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listlengths 2
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[
{
"location": {
"length": 99,
"offset": 0
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"text": "A specific human lysophospholipase: cDNA cloning, tissue distribution and kinetic characterization.",
"type": "title"
},
{
"location": {
"length": 1606,
"offset": 100
},
"text": "Lysophospholipases are critical enzymes that act on biological membranes to regulate the multifunctional lysophospholipids; increased levels of lysophospholipids are associated with a host of diseases. Herein we report the cDNA cloning of a human brain 25 kDa lysophospholipid-specific lysophospholipase (hLysoPLA). The enzyme (at both mRNA and protein levels) is widely distributed in tissues, but with quite different abundances. The hLysoPLA hydrolyzes lysophosphatidylcholine in both monomeric and micellar forms, and exhibits apparent cooperativity and surface dilution kinetics, but not interfacial activation. Detailed kinetic analysis indicates that the hLysoPLA binds first to the micellar surface and then to the substrate presented on the surface. The kinetic parameters associated with this surface dilution kinetic model are reported, and it is concluded that hLysoPLA has a single substrate binding site and a surface recognition site. The apparent cooperativity observed is likely due to the change of substrate presentation. In contrast to many non-specific lipolytic enzymes that exhibit lysophospholipase activity, hLysoPLA hydrolyzes only lysophospholipids and has no other significant enzymatic activity. Of special interest, hLysoPLA does not act on plasmenylcholine. Of the several inhibitors tested, only methyl arachidonyl fluorophosphonate (MAFP) potently and irreversibly inhibits the enzymatic activity. The inhibition by MAFP is consistent with the catalytic mechanism proposed for the enzyme - a serine hydrolase with a catalytic triad composed of Ser-119, Asp-174 and His-208.",
"type": "abstract"
}
] |
[
{
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"text": [
"lysophospholipid-specific lysophospholipase"
],
"type": "Gene"
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{
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{
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"text": [
"hLysoPLA"
],
"type": "Gene"
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{
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"text": [
"hLysoPLA"
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"type": "Gene"
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{
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"offsets": [
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"text": [
"hLysoPLA"
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"type": "Gene"
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{
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"text": [
"hLysoPLA"
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"type": "Gene"
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{
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"text": [
"hLysoPLA"
],
"type": "Gene"
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{
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}
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"text": [
"hLysoPLA"
],
"type": "Gene"
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{
"id": "3",
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{
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"db_name": "NCBIGene",
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}
],
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],
"text": [
"lysophospholipid-specific lysophospholipase"
],
"type": "Gene"
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{
"id": "4",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
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405,
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],
"text": [
"hLysoPLA"
],
"type": "Gene"
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{
"id": "5",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
536,
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]
],
"text": [
"hLysoPLA"
],
"type": "Gene"
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{
"id": "6",
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{
"db_id": "10434",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
762,
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]
],
"text": [
"hLysoPLA"
],
"type": "Gene"
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{
"id": "7",
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{
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"tax_id": null
}
],
"offsets": [
[
973,
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]
],
"text": [
"hLysoPLA"
],
"type": "Gene"
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{
"id": "9",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1233,
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]
],
"text": [
"hLysoPLA"
],
"type": "Gene"
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{
"id": "10",
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{
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"db_name": "NCBIGene",
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}
],
"offsets": [
[
1346,
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]
],
"text": [
"hLysoPLA"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 142,
"offset": 0
},
"text": "Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus.",
"type": "title"
},
{
"location": {
"length": 1323,
"offset": 143
},
"text": "The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Here we have investigated the functional domains of the proteins. The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species, and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences. Deletion of the SNH domain results in a more active transcriptional activator, suggesting that this domain acts as an inhibitor of the activation domain. The C-terminal SSX domain present in SYT-SSX translocation protein contributes a transcriptional repressor domain to the protein. Thus, the fusion protein has transcriptional activating and repressing domains. We demonstrate that the human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with SYT and SYT-SSX proteins in vitro. This interaction may provide an explanation of how the SYT protein activates gene transcription.",
"type": "abstract"
}
] |
[
{
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}
],
"offsets": [
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26,
29
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "13",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
34,
37
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "17",
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{
"db_id": "6595",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
123,
126
]
],
"text": [
"BRM"
],
"type": "Gene"
},
{
"id": "18",
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{
"db_id": "6760",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
240,
243
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "19",
"normalized": [
{
"db_id": "6756",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
298,
302
]
],
"text": [
"SSX1"
],
"type": "Gene"
},
{
"id": "20",
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{
"db_id": "6757",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
306,
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]
],
"text": [
"SSX2"
],
"type": "Gene"
},
{
"id": "21",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
337,
340
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "23",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
507,
510
]
],
"text": [
"SYT"
],
"type": "Gene"
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{
"id": "29",
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{
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"tax_id": null
}
],
"offsets": [
[
1011,
1014
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],
"text": [
"SYT"
],
"type": "Gene"
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{
"id": "34",
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{
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"tax_id": null
}
],
"offsets": [
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1231,
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],
"text": [
"SNF2"
],
"type": "Gene"
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{
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{
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"db_name": "NCBIGene",
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}
],
"offsets": [
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1236,
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],
"text": [
"Brahama"
],
"type": "Gene"
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{
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{
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}
],
"offsets": [
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1252,
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"text": [
"BRM"
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"type": "Gene"
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}
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"text": [
"SYT"
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"type": "Gene"
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}
],
"offsets": [
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1282,
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"text": [
"SYT"
],
"type": "Gene"
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"id": "40",
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}
],
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1335,
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"text": [
"SYT"
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"type": "Gene"
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}
],
"offsets": [
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1343,
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"text": [
"SYT"
],
"type": "Gene"
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{
"id": "43",
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{
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}
],
"offsets": [
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1425,
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"text": [
"SYT"
],
"type": "Gene"
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{
"id": "12",
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{
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}
],
"offsets": [
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26,
29
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "13",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
34,
37
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "17",
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{
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"tax_id": null
}
],
"offsets": [
[
123,
126
]
],
"text": [
"BRM"
],
"type": "Gene"
},
{
"id": "18",
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{
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"tax_id": null
}
],
"offsets": [
[
240,
243
]
],
"text": [
"SYT"
],
"type": "Gene"
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{
"id": "19",
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{
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"tax_id": null
}
],
"offsets": [
[
298,
302
]
],
"text": [
"SSX1"
],
"type": "Gene"
},
{
"id": "20",
"normalized": [
{
"db_id": "6757",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
306,
310
]
],
"text": [
"SSX2"
],
"type": "Gene"
},
{
"id": "21",
"normalized": [
{
"db_id": "6760",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
337,
340
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "23",
"normalized": [
{
"db_id": "6760",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
507,
510
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "29",
"normalized": [
{
"db_id": "6760",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1011,
1014
]
],
"text": [
"SYT"
],
"type": "Gene"
},
{
"id": "34",
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{
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"tax_id": null
}
],
"offsets": [
[
1231,
1235
]
],
"text": [
"SNF2"
],
"type": "Gene"
},
{
"id": "35",
"normalized": [
{
"db_id": "6595",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1236,
1243
]
],
"text": [
"Brahama"
],
"type": "Gene"
},
{
"id": "36",
"normalized": [
{
"db_id": "6595",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1252,
1255
]
],
"text": [
"BRM"
],
"type": "Gene"
},
{
"id": "37",
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{
"db_id": "6760",
"db_name": "NCBIGene",
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}
],
"offsets": [
[
1274,
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],
"text": [
"SYT"
],
"type": "Gene"
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{
"id": "38",
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}
],
"offsets": [
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1282,
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],
"text": [
"SYT"
],
"type": "Gene"
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{
"id": "40",
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{
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}
],
"offsets": [
[
1335,
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"text": [
"SYT"
],
"type": "Gene"
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{
"id": "41",
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{
"db_id": "6760",
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"tax_id": null
}
],
"offsets": [
[
1343,
1346
]
],
"text": [
"SYT"
],
"type": "Gene"
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{
"id": "43",
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{
"db_id": "6760",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1425,
1428
]
],
"text": [
"SYT"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 155,
"offset": 0
},
"text": "Identification and expression of delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium.",
"type": "title"
},
{
"location": {
"length": 1791,
"offset": 156
},
"text": "Despite its importance for the regulation of heart function, little is known about the isoform expression of the multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII) in human myocardium. In this study, we investigated the spectrum of CaMKII isoforms delta2, delta3, delta4, delta8, and delta9 in human striated muscle tissue. Isoform delta3 is characteristically expressed in cardiac muscle. In skeletal muscle, specific expression of a new isoform termed delta11 is demonstrated. Complete sequencing of human delta2 cDNA, representing all common features of the investigated CaMKII subclass, revealed its high homology to the corresponding rat cDNA. Comparative semiquantitative reverse transcription-polymerase chain reaction analyses from left ventricular tissues of normal hearts and from patients suffering from dilated cardiomyopathy showed a significant increase in transcript levels of isoform delta3 relative to the expression of glyceraldehyde-3-phosphate dehydrogenase in diseased hearts (101. 6+/-11.0% versus 64.9+/-9.9% in the nonfailing group; P < 0.05, n=6). Transcript levels of the other investigated cardiac CaMKII isoforms remained unchanged. At the protein level, by using a subclass-specific antibody, we observed a similar increase of a delta-CaMKII-specific signal (7.2+/-1.0 versus 3.8+/-0.7 optical density units in the nonfailing group; P < 0.05, n=4 through 6). The diseased state of the failing hearts was confirmed by a significant increase in transcript levels for atrial natriuretic peptide (292. 9+/-76.4% versus 40.1+/-3.2% in the nonfailing group; P < 0.05, n=3 through 6). Our data characterize for the first time the delta-CaMKII isoform expression pattern in human hearts and demonstrate changes in this expression pattern in heart failure.",
"type": "abstract"
}
] |
[
{
"id": "45",
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{
"db_id": "817",
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"tax_id": null
}
],
"offsets": [
[
33,
111
]
],
"text": [
"delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase"
],
"type": "Gene"
},
{
"id": "48",
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{
"db_id": "817",
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}
],
"offsets": [
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403,
461
]
],
"text": [
"CaMKII isoforms delta2, delta3, delta4, delta8, and delta9"
],
"type": "Gene"
},
{
"id": "50",
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{
"db_id": "2597",
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}
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"text": [
"glyceraldehyde-3-phosphate dehydrogenase"
],
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"db_id": "817",
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}
],
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1823,
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{
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}
],
"offsets": [
[
33,
111
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],
"text": [
"delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase"
],
"type": "Gene"
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{
"id": "48",
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{
"db_id": "817",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
403,
461
]
],
"text": [
"CaMKII isoforms delta2, delta3, delta4, delta8, and delta9"
],
"type": "Gene"
},
{
"id": "50",
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{
"db_id": "2597",
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"tax_id": null
}
],
"offsets": [
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1108,
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],
"text": [
"glyceraldehyde-3-phosphate dehydrogenase"
],
"type": "Gene"
},
{
"id": "52",
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{
"db_id": "817",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1429,
1441
]
],
"text": [
"delta-CaMKII"
],
"type": "Gene"
},
{
"id": "53",
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{
"db_id": "817",
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}
],
"offsets": [
[
1823,
1835
]
],
"text": [
"delta-CaMKII"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 97,
"offset": 0
},
"text": "Cloning and sequencing of the complete cDNA encoding the human insulin receptor related receptor.",
"type": "title"
},
{
"location": {
"length": 1198,
"offset": 98
},
"text": "The insulin receptor related receptor (IRR) is a heterotetrameric transmembrane receptor with intrinsic tyrosine kinase activity. The IRR shares large homology with the insulin and the insulin-like growth factor-1 (IGF-I) receptor with regard to amino acid sequence and protein structure. So far, only a partial human sequence containing the complete 3' end has been reported, although the full-length human IRR cDNA had been used for transfection studies and functional analysis of the receptor. We have isolated a full-length human IRR cDNA and report on the 5' translated and untranslated region of the human IRR gene. The full length IRR sequence contains 4150 bases and shares a high degree of homology with the guinea pig IRR cDNA sequence and rat IRR sequences that had been reported earlier on by others. Sequencing of the IRR cDNA revealed that the human IRR cDNA contains 341 bases corresponding to the IRR 5' end in addition to the bases that had been reported on before. Also, this sequence contains the start codon of translation. The full length cDNA for the human IRR can now be used for functional expression studies and to elucidate the nature of the ligand for this receptor type.",
"type": "abstract"
}
] |
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{
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63,
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232,
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267,
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"offsets": [
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"IRR"
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"id": "56",
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102,
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],
"offsets": [
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137,
140
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],
"text": [
"IRR"
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{
"id": "60",
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{
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"tax_id": null
}
],
"offsets": [
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232,
235
]
],
"text": [
"IRR"
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{
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}
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267,
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"text": [
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"id": "62",
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"db_id": "3645",
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"tax_id": null
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],
"offsets": [
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506,
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"text": [
"IRR"
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"type": "Gene"
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{
"id": "63",
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{
"db_id": "3645",
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"tax_id": null
}
],
"offsets": [
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632,
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"text": [
"IRR"
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"type": "Gene"
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{
"id": "64",
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{
"db_id": "3645",
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"tax_id": null
}
],
"offsets": [
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710,
713
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"text": [
"IRR"
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"type": "Gene"
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{
"id": "65",
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"tax_id": null
}
],
"offsets": [
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736,
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"text": [
"IRR"
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"id": "68",
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}
],
"offsets": [
[
929,
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],
"text": [
"IRR"
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"type": "Gene"
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"id": "69",
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{
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}
],
"offsets": [
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962,
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"text": [
"IRR"
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"type": "Gene"
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{
"id": "70",
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{
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}
],
"offsets": [
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1011,
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"text": [
"IRR"
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"type": "Gene"
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{
"id": "71",
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{
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}
],
"offsets": [
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1177,
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],
"text": [
"IRR"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 98,
"offset": 0
},
"text": "Isolation and chromosomal mapping of a novel human gene showing homology to Na+/PO4 cotransporter.",
"type": "title"
},
{
"location": {
"length": 724,
"offset": 99
},
"text": "We isolated a cDNA clone which shows a significant similarity with the renal Na+/phosphate cotransporter (NPT) from a human intestine mucosa cDNA library. The cDNA is 2626 bases long, with one open reading frame encoding a protein of 497 amino acids. The deduced amino acids sequence shows an overall homology of 48% with the human renal NPT1 protein. This gene is expressed in intestine, colon, liver, and pancreas. Thus, this gene may code for intestinal type NPT or closely related proteins. The chromosomal location of the gene was determined on the chromosome 6p21.3-p22 region by polymerase chain reaction-based analysis with both a human/rodent mono-chromosomal hybrid cell panel and a radiation hybrid mapping panel.",
"type": "abstract"
}
] |
[
{
"id": "76",
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}
],
"offsets": [
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437,
441
]
],
"text": [
"NPT1"
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"type": "Gene"
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{
"id": "77",
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{
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],
"offsets": [
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545,
564
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],
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{
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],
"offsets": [
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437,
441
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],
"text": [
"NPT1"
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{
"id": "77",
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],
"offsets": [
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545,
564
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],
"text": [
"intestinal type NPT"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 138,
"offset": 0
},
"text": "Cutting edge: immature dendritic cells generated from monocytes in the presence of TGF-beta 1 express functional C-C chemokine receptor 6.",
"type": "title"
},
{
"location": {
"length": 747,
"offset": 139
},
"text": "Although CD34+ progenitor-derived immature dendritic cells (DCs) express CCR6, several recent studies reported that monocyte-derived immature DCs do not do so. We observed that DCs generated from monocytes in the presence of GM-CSF, IL-4, and TGF-beta 1 consistently responded to liver and activation-regulated chemokine (LARC, also known as macrophage inflammatory protein-3 alpha). These immature DCs expressed one class of high-affinity binding sites for LARC, and expressed both CCR6 mRNA and protein. Therefore, LARC-CCR6 interaction presumably also contributes to the regulation of trafficking of monocyte-derived DCs, and utilization of TGF-beta can potentially provide a ready source of CCR6+ monocyte-derived DCs for therapeutic purposes.",
"type": "abstract"
}
] |
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{
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],
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83,
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113,
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212,
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],
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{
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364,
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"text": [
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372,
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382,
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"offsets": [
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419,
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],
"text": [
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"type": "Gene"
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],
"offsets": [
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461,
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],
"text": [
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{
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],
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481,
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"text": [
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597,
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],
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}
],
"offsets": [
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622,
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]
],
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"CCR6"
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"type": "Gene"
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"id": "91",
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}
],
"offsets": [
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656,
660
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],
"text": [
"LARC"
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"type": "Gene"
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{
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],
"offsets": [
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661,
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"offsets": [
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"text": [
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"type": "Gene"
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"id": "79",
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],
"offsets": [
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83,
93
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],
"text": [
"TGF-beta 1"
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"type": "Gene"
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{
"id": "80",
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{
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"tax_id": null
}
],
"offsets": [
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113,
137
]
],
"text": [
"C-C chemokine receptor 6"
],
"type": "Gene"
},
{
"id": "81",
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{
"db_id": "1235",
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"tax_id": null
}
],
"offsets": [
[
212,
216
]
],
"text": [
"CCR6"
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"type": "Gene"
},
{
"id": "82",
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"tax_id": null
}
],
"offsets": [
[
364,
370
]
],
"text": [
"GM-CSF"
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"type": "Gene"
},
{
"id": "83",
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"tax_id": null
}
],
"offsets": [
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372,
376
]
],
"text": [
"IL-4"
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"type": "Gene"
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{
"id": "84",
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"db_id": "7040",
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],
"offsets": [
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382,
392
]
],
"text": [
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"type": "Gene"
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{
"id": "85",
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}
],
"offsets": [
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419,
459
]
],
"text": [
"liver and activation-regulated chemokine"
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"type": "Gene"
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{
"id": "86",
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{
"db_id": "6364",
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"tax_id": null
}
],
"offsets": [
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461,
465
]
],
"text": [
"LARC"
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"type": "Gene"
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{
"id": "87",
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],
"offsets": [
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481,
520
]
],
"text": [
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"type": "Gene"
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{
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"db_id": "6364",
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"tax_id": null
}
],
"offsets": [
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597,
601
]
],
"text": [
"LARC"
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"type": "Gene"
},
{
"id": "90",
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{
"db_id": "1235",
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"tax_id": null
}
],
"offsets": [
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622,
626
]
],
"text": [
"CCR6"
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"type": "Gene"
},
{
"id": "91",
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{
"db_id": "6364",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
656,
660
]
],
"text": [
"LARC"
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"type": "Gene"
},
{
"id": "92",
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{
"db_id": "1235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
661,
665
]
],
"text": [
"CCR6"
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{
"id": "94",
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{
"db_id": "1235",
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}
],
"offsets": [
[
834,
838
]
],
"text": [
"CCR6"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 167,
"offset": 0
},
"text": "Identification and characterization of PKNbeta, a novel isoform of protein kinase PKN: expression and arachidonic acid dependency are different from those of PKNalpha.",
"type": "title"
},
{
"location": {
"length": 1426,
"offset": 168
},
"text": "The cDNA clone encoding a novel isoform of protein kinase PKN, termed PKNbeta, was isolated from a HeLa cDNA library. PKNbeta had high sequence homology with PKNalpha, originally isolated PKN, especially in the repeats of charged amino acid-rich region with leucine-zipper like sequences (CZ region/HR1), in the carboxyl-terminal catalytic domain, and in approximately 130 amino acid stretch (D region/HR2), located between CZ region/HR1 and the catalytic domain. However, the amino acid sequence of PKNbeta differed from that of PKNalpha in the region immediately amino-terminal to the catalytic domain, which contained two distinct proline-rich sequences consistent with the class II consensus sequence, PXXPXR, for binding to SH3 domain. Distribution of PKNbeta differed from that of PKNalpha in the following two respects: (1) Northern blotting indicated that PKNbeta mRNA could not be detected in human adult tissues, but was expressed abundantly in human cancer cell lines; (2) immunochemical analysis indicated that PKNbeta localized in nucleus and perinuclear Golgi apparatus, and was almost absent in cytoplasmic region in NIH3T3 cells. Recombinant PKNbeta expressed in COS7 cells displayed autophosphorylation and peptide kinase activity, but was found to be significantly less responsive to arachidonic acid than PKNalpha. The identification of this novel isoform underscores the diversity of PKN signaling pathway.",
"type": "abstract"
}
] |
[
{
"id": "96",
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}
],
"offsets": [
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39,
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],
"text": [
"PKNbeta"
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"type": "Gene"
},
{
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],
"offsets": [
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158,
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],
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{
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238,
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286,
293
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],
"text": [
"PKNbeta"
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"type": "Gene"
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{
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}
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"text": [
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}
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"offsets": [
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1191,
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"text": [
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{
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}
],
"offsets": [
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1326,
1333
]
],
"text": [
"PKNbeta"
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"type": "Gene"
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{
"id": "125",
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{
"db_id": "5585",
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}
],
"offsets": [
[
1492,
1500
]
],
"text": [
"PKNalpha"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 151,
"offset": 0
},
"text": "Coats' disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal angiogenesis.",
"type": "title"
},
{
"location": {
"length": 976,
"offset": 157
},
"text": "Coats' disease is characterized by abnormal retinal vascular development (so-called 'retinal telangiectasis') which results in massive intraretinal and subretinal lipid accumulation (exudative retinal detachment). The classical form of Coats' disease is almost invariably isolated, unilateral and seen in males. A female with a unilateral variant of Coats' disease gave birth to a son affected by Norrie disease. Both carried a missense mutation within the NDP gene on chromosome Xp11.2. Subsequently analysis of the retinas of nine enucleated eyes from males with Coats' disease demonstrated in one a somatic mutation in the NDP gene which was not present within non-retinal tissue. We suggest that Coats' telangiectasis is secondary to somatic mutation in the NDP gene which results in a deficiency of norrin (the protein product of the NDP gene) within the developing retina. This supports recent observations that the protein is critical for normal retinal vasculogenesis.",
"type": "abstract"
}
] |
[
{
"id": "128",
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{
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"tax_id": null
}
],
"offsets": [
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99,
102
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
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{
"db_id": "4693",
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}
],
"offsets": [
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120,
126
]
],
"text": [
"norrin"
],
"type": "Gene"
},
{
"id": "130",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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609,
612
]
],
"text": [
"NDP"
],
"type": "Gene"
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{
"id": "131",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
778,
781
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
"id": "132",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
914,
917
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
"id": "133",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
956,
962
]
],
"text": [
"norrin"
],
"type": "Gene"
},
{
"id": "134",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
991,
994
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
"id": "128",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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99,
102
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
"id": "129",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
120,
126
]
],
"text": [
"norrin"
],
"type": "Gene"
},
{
"id": "130",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
609,
612
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
"id": "131",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
778,
781
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
"id": "132",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
914,
917
]
],
"text": [
"NDP"
],
"type": "Gene"
},
{
"id": "133",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
956,
962
]
],
"text": [
"norrin"
],
"type": "Gene"
},
{
"id": "134",
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{
"db_id": "4693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
991,
994
]
],
"text": [
"NDP"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 152,
"offset": 0
},
"text": "A common polymorphic allele of the human luteinizing hormone beta-subunit gene: additional mutations and differential function of the promoter sequence.",
"type": "title"
},
{
"location": {
"length": 2223,
"offset": 153
},
"text": "A common genetic variant (V) of the human luteinizing hormone (LH) beta-subunit gene was recently discovered. The V-LH molecules have higher bioactivity in vitro, but shorter half-life in circulation, which apparently is related to the alterations of LH function observed in individuals homo- and heterozygous for the V-LHbeta allele. We have now studied whether additional mutations in the V-LHbeta promoter sequence could contribute to the altered physiology of the LH variant molecules. The 661 bp 5'-flanking region of the V-LHbeta gene, retrieved from human genomic DNA by PCR, contained eight single-nucleotide changes, as compared with the wild-type (wt) LHbeta promoter. The finding was consistent in DNA samples of different ethnic groups. Reporter constructs with various lengths of the wt- and V-LH promoter sequences, driving the firefly luciferase reporter gene, were transfected into an immortalized mouse pituitary cell line, LbetaT(2), known to express the endogenous LHbeta gene, and into a non-endocrine human embryonic kidney cell line, HEK 293. Basal expression levels of the V-LHbeta promoter constructs were on average 36% higher in LbetaT(2)cells ( P < 0.001; n = 29), and 40% higher in HEK 293 cells ( P < 0.001; n = 16), as compared with the respective wt sequences. Numerous qualitative and quantitative differences were found between the two cell lines in responses of the two promoter sequences to stimulation with 12- O -tetradecanoylphorbol-13-acetate, forskolin, 8-bromo-cAMP, progesterone and gonado- tropin-releasing hormone. In conclusion, the V-LHbeta promoter has higher basal activity, and differs in response to hormonal stimulation, as compared with the wt-LHbeta promoter. The altered promoter function of the V-LHbeta gene provides evidence for differences in regulation of the wt- and V-LHbeta genes, which may contribute to the differences observed in pituitary-gonadal function between carriers of the two LHbeta alleles. The findings also suggest a novel evolutionary mechanism whereby polymorphic changes resulting in altered bioactivity of a gene product may be compensated for by additional mutations in the cognate promoter sequence, changing transcription of the same gene.",
"type": "abstract"
}
] |
[
{
"id": "136",
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
41,
73
]
],
"text": [
"luteinizing hormone beta-subunit"
],
"type": "Gene"
},
{
"id": "137",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
195,
232
]
],
"text": [
"luteinizing hormone (LH) beta-subunit"
],
"type": "Gene"
},
{
"id": "138",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
473,
479
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "139",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
546,
552
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "140",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
682,
688
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "141",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
815,
821
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "142",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1137,
1143
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "143",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1251,
1257
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "148",
"normalized": [
{
"db_id": "2796",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1678,
1710
]
],
"text": [
"gonado- tropin-releasing hormone"
],
"type": "Gene"
},
{
"id": "149",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1733,
1739
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "150",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1849,
1855
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "151",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1905,
1911
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "152",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1982,
1988
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "153",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2103,
2109
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "136",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
41,
73
]
],
"text": [
"luteinizing hormone beta-subunit"
],
"type": "Gene"
},
{
"id": "137",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
195,
232
]
],
"text": [
"luteinizing hormone (LH) beta-subunit"
],
"type": "Gene"
},
{
"id": "138",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
473,
479
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "139",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
546,
552
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "140",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
682,
688
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "141",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
815,
821
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "142",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1137,
1143
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "143",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1251,
1257
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "148",
"normalized": [
{
"db_id": "2796",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1678,
1710
]
],
"text": [
"gonado- tropin-releasing hormone"
],
"type": "Gene"
},
{
"id": "149",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1733,
1739
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "150",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1849,
1855
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "151",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1905,
1911
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "152",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1982,
1988
]
],
"text": [
"LHbeta"
],
"type": "Gene"
},
{
"id": "153",
"normalized": [
{
"db_id": "3972",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2103,
2109
]
],
"text": [
"LHbeta"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 110,
"offset": 0
},
"text": "The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II.",
"type": "title"
},
{
"location": {
"length": 2023,
"offset": 111
},
"text": "Primary hyperoxaluria type II (PH2) is a rare monogenic disorder that is characterized by a lack of the enzyme that catalyzes the reduction of hydroxypyruvate to D-glycerate, the reduction of glyoxylate to glycolate and the oxidation of D-glycerate to hydroxypyruvate. The disease is characterized by an elevated urinary excretion of oxalate and L-glycerate. The increased oxalate excretion can cause nephrolithiasis and nephrocalci-nosis and can, in some cases, result in renal failure and systemic oxalate deposition. We identified a glyoxylate reductase/hydroxypyruvate reductase (GRHPR) cDNA clone from a human liver expressed sequence tag (EST) library. Nucleotide sequence analysis identified a 1198 nucleotide clone that encoded a 984 nucleotide open reading frame. The open reading frame encodes a predicted 328 amino acid protein with a mass of 35 563 Da. Transient transfection of the cDNA clone into COS cells verified that it encoded an enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Database analysis of human ESTs reveals widespread tissue expression, indicating that the enzyme may have a previously unrecognized role in metabolism. The genomic structure of the human GRHPR gene was determined and contains nine exons and eight introns and spans approximately 9 kb pericentromeric on chromosome 9. Four PH2 patients representing two pairs of siblings from two unrelated families were analyzed for mutations in GRHPR by single strand conformation polymorphism analysis. All four patients were homozygous for a single nucleotide deletion at codon 35 in exon 2, resulting in a premature stop codon at codon 45. The cDNA that we have identified represents the first characterization of an animal GRHPR sequence. The data we present will facilitate future genetic testing to confirm the clinical diagnosis of PH2. These data will also facilitate heterozygote testing and prenatal testing in families affected with PH2 to aid in genetic counseling.",
"type": "abstract"
}
] |
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{
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}
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18,
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{
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{
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}
],
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45,
50
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],
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"GRHPR"
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{
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{
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647,
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{
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{
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695,
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"GRHPR"
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"type": "Gene"
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{
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{
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{
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}
],
"offsets": [
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1360,
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],
"text": [
"GRHPR"
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"type": "Gene"
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{
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{
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}
],
"offsets": [
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1602,
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],
"text": [
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{
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"text": [
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"offsets": [
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18,
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],
"text": [
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45,
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],
"text": [
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{
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}
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"offsets": [
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647,
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],
"text": [
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{
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],
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668,
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],
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{
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],
"offsets": [
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695,
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],
"text": [
"GRHPR"
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"type": "Gene"
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{
"id": "161",
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{
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}
],
"offsets": [
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1100,
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],
"text": [
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}
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"offsets": [
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1360,
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"text": [
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{
"id": "164",
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{
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}
],
"offsets": [
[
1602,
1607
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],
"text": [
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{
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}
],
"offsets": [
[
1884,
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],
"text": [
"GRHPR"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 192,
"offset": 0
},
"text": "Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells.",
"type": "title"
},
{
"location": {
"length": 1354,
"offset": 193
},
"text": "Anhidrotic ectodermal dysplasia (EDA) is a human genetic disorder of impaired ectodermal appendage development. The EDA gene encodes isoforms of a novel transmembrane protein, ectodysplasin. The sequence of the longest isoform includes an interrupted collagenous domain of 19 Gly-X-Y repeats and a motif conserved in the tumor necrosis factor (TNF)-related ligand family. In order to understand better the function of the ectodysplasin protein molecule and its domains, we have studied the processing and localization of wild-type and mutated isoforms in transfected human fetal kidney 293 and monkey kidney COS-1 cells. Similar to other members of collagenous membrane proteins and members of TNF-related ligands, ectodysplasin is a type II membrane protein and it forms trimers. The membrane localization of ectodysplasin is asymmetrical: it is found on the apical and lateral surfaces of the cells where it co-localizes with cytoskeletal structures. The TNF-like motif and cysteines found near the C-terminus are necessary for correct transport to the cell membrane, but the intracellular and collagenous domains are not required for the localization pattern. Our results suggest that ectodysplasin is a new member in the TNF-related ligand family involved in the early epithelial-mesenchymal interaction that regulates ectodermal appendage formation.",
"type": "abstract"
}
] |
[
{
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"tax_id": null
}
],
"offsets": [
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0,
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]
],
"text": [
"Ectodysplasin"
],
"type": "Gene"
},
{
"id": "170",
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{
"db_id": "1896",
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"tax_id": null
}
],
"offsets": [
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204,
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]
],
"text": [
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],
"type": "Gene"
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{
"id": "171",
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{
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}
],
"offsets": [
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226,
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]
],
"text": [
"EDA"
],
"type": "Gene"
},
{
"id": "172",
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{
"db_id": "1896",
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}
],
"offsets": [
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309,
312
]
],
"text": [
"EDA"
],
"type": "Gene"
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{
"id": "173",
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{
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}
],
"offsets": [
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369,
382
]
],
"text": [
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"type": "Gene"
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{
"id": "177",
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{
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}
],
"offsets": [
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615,
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]
],
"text": [
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"type": "Gene"
},
{
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{
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}
],
"offsets": [
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908,
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],
"text": [
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"type": "Gene"
},
{
"id": "181",
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{
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}
],
"offsets": [
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1003,
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],
"text": [
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"type": "Gene"
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{
"id": "184",
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{
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}
],
"offsets": [
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1381,
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],
"text": [
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"type": "Gene"
},
{
"id": "167",
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{
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}
],
"offsets": [
[
0,
13
]
],
"text": [
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"type": "Gene"
},
{
"id": "170",
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{
"db_id": "1896",
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}
],
"offsets": [
[
204,
224
]
],
"text": [
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"type": "Gene"
},
{
"id": "171",
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{
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}
],
"offsets": [
[
226,
229
]
],
"text": [
"EDA"
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"type": "Gene"
},
{
"id": "172",
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{
"db_id": "1896",
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"tax_id": null
}
],
"offsets": [
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309,
312
]
],
"text": [
"EDA"
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},
{
"id": "173",
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{
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}
],
"offsets": [
[
369,
382
]
],
"text": [
"ectodysplasin"
],
"type": "Gene"
},
{
"id": "177",
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{
"db_id": "1896",
"db_name": "NCBIGene",
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}
],
"offsets": [
[
615,
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]
],
"text": [
"ectodysplasin"
],
"type": "Gene"
},
{
"id": "179",
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{
"db_id": "1896",
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}
],
"offsets": [
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908,
921
]
],
"text": [
"ectodysplasin"
],
"type": "Gene"
},
{
"id": "181",
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{
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}
],
"offsets": [
[
1003,
1016
]
],
"text": [
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"type": "Gene"
},
{
"id": "184",
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}
],
"offsets": [
[
1381,
1394
]
],
"text": [
"ectodysplasin"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 81,
"offset": 0
},
"text": "Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death.",
"type": "title"
},
{
"location": {
"length": 806,
"offset": 82
},
"text": "Bcl-2 is the best characterized inhibitor of apoptosis, although the molecular basis of this action is not fully understood. Using a protein interaction cloning procedure, we identified a human gene designated as bis (mapped to chromosome 10q25) that encoded a novel Bcl-2-interacting protein. Bis protein showed no significant homology with Bcl-2 family proteins and had no prominent functional motif. Co-immunoprecipitation analysis confirmed that Bis interacted with Bcl-2 in vivo. DNA transfection experiments indicated that Bis itself exerted only weak anti-apoptotic activity, but was synergistic with Bcl-2 in preventing Bax-induced and Fas-mediated apoptosis. These results suggest that Bis is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with Bcl-2.",
"type": "abstract"
}
] |
[
{
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}
],
"offsets": [
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0,
3
]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
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{
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}
],
"offsets": [
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50,
55
]
],
"text": [
"Bcl-2"
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"type": "Gene"
},
{
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{
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}
],
"offsets": [
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82,
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],
"text": [
"Bcl-2"
],
"type": "Gene"
},
{
"id": "191",
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{
"db_id": "9531",
"db_name": "NCBIGene",
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}
],
"offsets": [
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295,
298
]
],
"text": [
"bis"
],
"type": "Gene"
},
{
"id": "193",
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{
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}
],
"offsets": [
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376,
379
]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
"id": "195",
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{
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}
],
"offsets": [
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532,
535
]
],
"text": [
"Bis"
],
"type": "Gene"
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{
"id": "196",
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{
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}
],
"offsets": [
[
552,
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]
],
"text": [
"Bcl-2"
],
"type": "Gene"
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{
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{
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}
],
"offsets": [
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611,
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]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
"id": "198",
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{
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"tax_id": null
}
],
"offsets": [
[
690,
695
]
],
"text": [
"Bcl-2"
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"type": "Gene"
},
{
"id": "199",
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{
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}
],
"offsets": [
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710,
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]
],
"text": [
"Bax"
],
"type": "Gene"
},
{
"id": "200",
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{
"db_id": "355",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
726,
729
]
],
"text": [
"Fas"
],
"type": "Gene"
},
{
"id": "201",
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{
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"tax_id": null
}
],
"offsets": [
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777,
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]
],
"text": [
"Bis"
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"type": "Gene"
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{
"id": "202",
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}
],
"offsets": [
[
882,
887
]
],
"text": [
"Bcl-2"
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},
{
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}
],
"offsets": [
[
0,
3
]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
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{
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"tax_id": null
}
],
"offsets": [
[
50,
55
]
],
"text": [
"Bcl-2"
],
"type": "Gene"
},
{
"id": "190",
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{
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"tax_id": null
}
],
"offsets": [
[
82,
87
]
],
"text": [
"Bcl-2"
],
"type": "Gene"
},
{
"id": "191",
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{
"db_id": "9531",
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"tax_id": null
}
],
"offsets": [
[
295,
298
]
],
"text": [
"bis"
],
"type": "Gene"
},
{
"id": "193",
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{
"db_id": "9531",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
376,
379
]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
"id": "195",
"normalized": [
{
"db_id": "9531",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
532,
535
]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
"id": "196",
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{
"db_id": "596",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
552,
557
]
],
"text": [
"Bcl-2"
],
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},
{
"id": "197",
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{
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"tax_id": null
}
],
"offsets": [
[
611,
614
]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
"id": "198",
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{
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}
],
"offsets": [
[
690,
695
]
],
"text": [
"Bcl-2"
],
"type": "Gene"
},
{
"id": "199",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
710,
713
]
],
"text": [
"Bax"
],
"type": "Gene"
},
{
"id": "200",
"normalized": [
{
"db_id": "355",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
726,
729
]
],
"text": [
"Fas"
],
"type": "Gene"
},
{
"id": "201",
"normalized": [
{
"db_id": "9531",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
777,
780
]
],
"text": [
"Bis"
],
"type": "Gene"
},
{
"id": "202",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
882,
887
]
],
"text": [
"Bcl-2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 108,
"offset": 0
},
"text": "BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells.",
"type": "title"
},
{
"location": {
"length": 1892,
"offset": 109
},
"text": "BACKGROUND: Treatment of breast cancer with the antiestrogen tamoxifen is effective in approximately one half of the patients with estrogen receptor-positive disease, but tumors recur frequently because of the development of metastases that are resistant to tamoxifen. We have previously shown that mutagenesis of human estrogen-dependent ZR-75-1 breast cancer cells by insertion of a defective retrovirus genome caused the cells to become antiestrogen resistant. In this study, we isolated and characterized the crucial gene at the breast cancer antiestrogen resistance 1 (BCAR1) locus. METHODS/RESULTS: Transfer of the BCAR1 locus from retrovirus-mutated, antiestrogen-resistant cells to estrogen-dependent ZR-75-1 cells by cell fusion conferred an antiestrogen-resistant phenotype on the recipient cells. The complete coding sequence of BCAR1 was isolated by use of exon-trapping and complementary DNA (cDNA) library screening. Sequence analysis of human BCAR1 cDNA predicted a protein of 870 amino acids that was strongly homologous to rat p130Cas-adapter protein. Genomic analysis revealed that BCAR1 consists of seven exons and is located at chromosome 16q23.1. BCAR1 transcripts were detected in multiple human tissues and were similar in size to transcripts produced by retrovirus-mutated ZR-75-1 cells. Transfection of BCAR1 cDNA into ZR-75-1 cells again resulted in sustained cell proliferation in the presence of antiestrogens, confirming that BCAR1 was the responsible gene in the locus. CONCLUSIONS: Overexpression of the BCAR1 gene confers antiestrogen resistance on human ZR-75-1 breast cancer cells. Overexpression of BCAR1 in retrovirus-mutated cells appears to result from activation of the gene's promoter. The isolation and characterization of this gene open new avenues to elucidating mechanisms by which the growth of human breast cancer becomes independent of estrogen.",
"type": "abstract"
}
] |
[
{
"id": "204",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
5
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "205",
"normalized": [
{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
48,
55
]
],
"text": [
"p130Cas"
],
"type": "Gene"
},
{
"id": "206",
"normalized": [
{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
642,
681
]
],
"text": [
"breast cancer antiestrogen resistance 1"
],
"type": "Gene"
},
{
"id": "207",
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{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
683,
688
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "208",
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
730,
735
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "209",
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
949,
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]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
1067,
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]
],
"text": [
"BCAR1"
],
"type": "Gene"
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{
"id": "212",
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
1209,
1214
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "213",
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
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1277,
1282
]
],
"text": [
"BCAR1"
],
"type": "Gene"
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{
"id": "214",
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{
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}
],
"offsets": [
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1437,
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]
],
"text": [
"BCAR1"
],
"type": "Gene"
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"id": "215",
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{
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}
],
"offsets": [
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1564,
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],
"text": [
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"type": "Gene"
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{
"id": "216",
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{
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}
],
"offsets": [
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1644,
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]
],
"text": [
"BCAR1"
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"type": "Gene"
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{
"id": "217",
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{
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}
],
"offsets": [
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1743,
1748
]
],
"text": [
"BCAR1"
],
"type": "Gene"
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{
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{
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}
],
"offsets": [
[
0,
5
]
],
"text": [
"BCAR1"
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"type": "Gene"
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{
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{
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"tax_id": null
}
],
"offsets": [
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48,
55
]
],
"text": [
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],
"type": "Gene"
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{
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{
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"tax_id": null
}
],
"offsets": [
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642,
681
]
],
"text": [
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],
"type": "Gene"
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
683,
688
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
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{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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730,
735
]
],
"text": [
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],
"type": "Gene"
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"id": "209",
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{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
949,
954
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "210",
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
1067,
1072
]
],
"text": [
"BCAR1"
],
"type": "Gene"
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{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1209,
1214
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "213",
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{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1277,
1282
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "214",
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
1437,
1442
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "215",
"normalized": [
{
"db_id": "9564",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1564,
1569
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "216",
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{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
1644,
1649
]
],
"text": [
"BCAR1"
],
"type": "Gene"
},
{
"id": "217",
"normalized": [
{
"db_id": "9564",
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"tax_id": null
}
],
"offsets": [
[
1743,
1748
]
],
"text": [
"BCAR1"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 134,
"offset": 0
},
"text": "Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules.",
"type": "title"
},
{
"location": {
"length": 870,
"offset": 135
},
"text": "We have identified a type II Ca2+-dependent lectin displaying mannose-binding specificity, exclusively expressed by Langerhans cells (LC), and named Langerin. LC are uniquely characterized by Birbeck granules (BG), which are organelles consisting of superimposed and zippered membranes. Here, we have shown that Langerin is constitutively associated with BG and that antibody to Langerin is internalized into these structures. Remarkably, transfection of Langerin cDNA into fibroblasts created a compact network of membrane structures with typical features of BG. Langerin is thus a potent inducer of membrane superimposition and zippering leading to BG formation. Our data suggest that induction of BG is a consequence of the antigen-capture function of Langerin, allowing routing into these organelles and providing access to a nonclassical antigen-processing pathway.",
"type": "abstract"
}
] |
[
{
"id": "219",
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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0,
8
]
],
"text": [
"Langerin"
],
"type": "Gene"
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{
"id": "222",
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{
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}
],
"offsets": [
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284,
292
]
],
"text": [
"Langerin"
],
"type": "Gene"
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{
"id": "223",
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{
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}
],
"offsets": [
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447,
455
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],
"text": [
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"type": "Gene"
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{
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}
],
"offsets": [
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514,
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"text": [
"Langerin"
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"type": "Gene"
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{
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{
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}
],
"offsets": [
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590,
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]
],
"text": [
"Langerin"
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"type": "Gene"
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{
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}
],
"offsets": [
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699,
707
]
],
"text": [
"Langerin"
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"type": "Gene"
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}
],
"offsets": [
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890,
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"text": [
"Langerin"
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"type": "Gene"
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"id": "219",
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}
],
"offsets": [
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0,
8
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],
"text": [
"Langerin"
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"type": "Gene"
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"id": "222",
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"db_id": "50489",
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],
"offsets": [
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284,
292
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],
"text": [
"Langerin"
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"type": "Gene"
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{
"id": "223",
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{
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}
],
"offsets": [
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447,
455
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],
"text": [
"Langerin"
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"type": "Gene"
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{
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}
],
"offsets": [
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514,
522
]
],
"text": [
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"type": "Gene"
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{
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"tax_id": null
}
],
"offsets": [
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590,
598
]
],
"text": [
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"type": "Gene"
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{
"id": "226",
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{
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}
],
"offsets": [
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699,
707
]
],
"text": [
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"type": "Gene"
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{
"id": "227",
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}
],
"offsets": [
[
890,
898
]
],
"text": [
"Langerin"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 79,
"offset": 0
},
"text": "Cloning and characterisation of the Sry-related transcription factor gene Sox8.",
"type": "title"
},
{
"location": {
"length": 1233,
"offset": 80
},
"text": "SOX proteins form a large family of transcription factors related by a DNA-binding domain known as the HMG box. Some 30 Sox genes have been identified in mammals and orthologues have been found in a wide range of other metazoans. Sox genes are highly conserved and are known to play important roles in embryonic development, including roles in gonadal, central nervous system, neural crest and skeletal development. Several SOX genes have been implicated in human congenital diseases. We report here the isolation of Sox8 and its characterisation in mice and humans. This gene has a remarkably similar primary structure and genomic organisation to the campomelic dysplasia gene SOX9 and the Waardenburg-Shah syndrome gene SOX10. SOX8 protein is able to bind to canonical SOX target DNA sequences and activate transcription in vitro through two separate trans -activation regions. Further, Sox8 is expressed in the central nervous system, limbs, kidneys, gonads and craniofacial structures during mouse embryo development. Sox8 maps to the t complex on mouse chromosome 17 and to human chromosome 16p13.3, a region associated with the microphthalmia-cataract syndrome CATM and the alpha-thalassemia/mental retardation syndrome ATR-16.",
"type": "abstract"
}
] |
[
{
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"tax_id": null
}
],
"offsets": [
[
74,
78
]
],
"text": [
"Sox8"
],
"type": "Gene"
},
{
"id": "237",
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{
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}
],
"offsets": [
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597,
601
]
],
"text": [
"Sox8"
],
"type": "Gene"
},
{
"id": "238",
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}
],
"offsets": [
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758,
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]
],
"text": [
"SOX9"
],
"type": "Gene"
},
{
"id": "240",
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{
"db_id": "6663",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
802,
807
]
],
"text": [
"SOX10"
],
"type": "Gene"
},
{
"id": "241",
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{
"db_id": "30812",
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"tax_id": null
}
],
"offsets": [
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809,
813
]
],
"text": [
"SOX8"
],
"type": "Gene"
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{
"id": "243",
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{
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"tax_id": null
}
],
"offsets": [
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969,
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],
"text": [
"Sox8"
],
"type": "Gene"
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{
"id": "244",
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{
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}
],
"offsets": [
[
1102,
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]
],
"text": [
"Sox8"
],
"type": "Gene"
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{
"id": "230",
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"tax_id": null
}
],
"offsets": [
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74,
78
]
],
"text": [
"Sox8"
],
"type": "Gene"
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{
"id": "237",
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{
"db_id": "30812",
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"tax_id": null
}
],
"offsets": [
[
597,
601
]
],
"text": [
"Sox8"
],
"type": "Gene"
},
{
"id": "238",
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{
"db_id": "6662",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
758,
762
]
],
"text": [
"SOX9"
],
"type": "Gene"
},
{
"id": "240",
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{
"db_id": "6663",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
802,
807
]
],
"text": [
"SOX10"
],
"type": "Gene"
},
{
"id": "241",
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{
"db_id": "30812",
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"tax_id": null
}
],
"offsets": [
[
809,
813
]
],
"text": [
"SOX8"
],
"type": "Gene"
},
{
"id": "243",
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{
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}
],
"offsets": [
[
969,
973
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],
"text": [
"Sox8"
],
"type": "Gene"
},
{
"id": "244",
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{
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}
],
"offsets": [
[
1102,
1106
]
],
"text": [
"Sox8"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 61,
"offset": 0
},
"text": "Syntaphilin: a syntaxin-1 clamp that controls SNARE assembly.",
"type": "title"
},
{
"location": {
"length": 1006,
"offset": 62
},
"text": "Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machinery that forms the SNARE complex with VAMP/synaptobrevin and SNAP-25. Identifying proteins that modulate SNARE complex formation is critical for understanding the molecular mechanisms underlying neurotransmitter release and its modulation. We have cloned and characterized a protein called syntaphilin that is selectively expressed in brain. Syntaphilin competes with SNAP-25 for binding to syntaxin-1 and inhibits SNARE complex formation by absorbing free syntaxin-1. Transient overexpression of syntaphilin in cultured hippocampal neurons significantly reduces neurotransmitter release. Furthermore, introduction of syntaphilin into presynaptic superior cervical ganglion neurons in culture inhibits synaptic transmission. These findings suggest that syntaphilin may function as a molecular clamp that controls free syntaxin-1 availability for the assembly of the SNARE complex, and thereby regulates synaptic vesicle exocytosis.",
"type": "abstract"
}
] |
[
{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
11
]
],
"text": [
"Syntaphilin"
],
"type": "Gene"
},
{
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"normalized": [
{
"db_id": "6616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
198,
205
]
],
"text": [
"SNAP-25"
],
"type": "Gene"
},
{
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{
"db_id": "9751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
427,
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]
],
"text": [
"syntaphilin"
],
"type": "Gene"
},
{
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{
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}
],
"offsets": [
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479,
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]
],
"text": [
"Syntaphilin"
],
"type": "Gene"
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{
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"tax_id": null
}
],
"offsets": [
[
505,
512
]
],
"text": [
"SNAP-25"
],
"type": "Gene"
},
{
"id": "261",
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{
"db_id": "9751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
634,
645
]
],
"text": [
"syntaphilin"
],
"type": "Gene"
},
{
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{
"db_id": "9751",
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}
],
"offsets": [
[
755,
766
]
],
"text": [
"syntaphilin"
],
"type": "Gene"
},
{
"id": "263",
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{
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}
],
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901
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"text": [
"syntaphilin"
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"id": "246",
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0,
11
]
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"Syntaphilin"
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}
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198,
205
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"text": [
"SNAP-25"
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427,
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479,
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505,
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}
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]
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}
],
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755,
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"offsets": [
[
890,
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"text": [
"syntaphilin"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 132,
"offset": 0
},
"text": "Human follicle stimulating hormone receptor variants lacking transmembrane domains display altered post-translational conformations.",
"type": "title"
},
{
"location": {
"length": 2242,
"offset": 133
},
"text": "Variant splicing of gonadotropin receptor mRNA commonly occurs, however expression of receptor protein variants and their trafficking has yet to be studied in detail. To determine receptor variant trafficking and intracellular processing in mammalian cells, the intracellular fate of intentionally truncated variants of human follicle stimulating hormone receptor (hFSH-R) expressed in CHO cells was examined. Monoclonal antibodies (mAbs) were made against the hFSH-R's extracellular domain (ECD) expressed in insect cells. Four mAbs 106.156, 106.290, 106.318, and 106.263 were chosen as probes. Epitope mapping using synthetic peptides, and truncated hFSH-R variants revealed that mAb 106.156 bound to ECD residues 183-220, while mAbs 106.318, 106.290, 106.263 bound ECD residues 300-331. Immunofluorescence microscopy showed that mAbs 106.318 and 106.156 stained the surface of fixed, intact CHO cells expressing wild type hFSH-R. However, following cell permeabilization all four antibodies stained hFSH-R in Golgi and endoplasmic reticulum. Permeabilized cells expressing truncated variants ECD213 and ECD254 showed staining accumulated in the endoplasmic reticulum/nuclear envelope continuum. ECD335/His was found to accumulate in extended endoplasmic reticulum (ER). The ER location of ECD335/His was confirmed by double labeling experiments with concanavalin A and ECD mAb. Glycosidase digestion followed by Western blot analysis show ECD213 and ECD335/His to be glycosylated, but not ECD254. Both glycosylated truncated hFSH-R variants were sensitive to peptide-N-glycanase F and endoglycosidase H but insensitive to neuraminidase indicating that these variants possess high mannose type oligosaccharides. Thus truncated hFSH-R variants do not reach the medial or trans Golgi where high mannose oligosaccharides are trimmed and sialic acid is added. These data suggest that the conformation the ECD of the wild type receptor is different from the ECD alone expressed in the endoplasmic reticulum. This information suggests that the ECD serves two distinct roles; the first is to bind FSH and the other is likely to contact the endodomain of the receptor, which presumably leads to activation of the endodomain for signal transduction.",
"type": "abstract"
}
] |
[
{
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"tax_id": null
}
],
"offsets": [
[
0,
43
]
],
"text": [
"Human follicle stimulating hormone receptor"
],
"type": "Gene"
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{
"id": "269",
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{
"db_id": "2492",
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"tax_id": null
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],
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459,
496
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"text": [
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"type": "Gene"
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{
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{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
498,
504
]
],
"text": [
"hFSH-R"
],
"type": "Gene"
},
{
"id": "273",
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{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
785,
791
]
],
"text": [
"hFSH-R"
],
"type": "Gene"
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{
"id": "276",
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{
"db_id": "2492",
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"tax_id": null
}
],
"offsets": [
[
1058,
1064
]
],
"text": [
"hFSH-R"
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"type": "Gene"
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"id": "277",
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{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1135,
1141
]
],
"text": [
"hFSH-R"
],
"type": "Gene"
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"id": "280",
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{
"db_id": "2492",
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"tax_id": null
}
],
"offsets": [
[
1661,
1667
]
],
"text": [
"hFSH-R"
],
"type": "Gene"
},
{
"id": "281",
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{
"db_id": "4758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1758,
1771
]
],
"text": [
"neuraminidase"
],
"type": "Gene"
},
{
"id": "282",
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{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1862,
1868
]
],
"text": [
"hFSH-R"
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"type": "Gene"
},
{
"id": "267",
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{
"db_id": "2492",
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"tax_id": null
}
],
"offsets": [
[
0,
43
]
],
"text": [
"Human follicle stimulating hormone receptor"
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"type": "Gene"
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{
"id": "269",
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{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
459,
496
]
],
"text": [
"follicle stimulating hormone receptor"
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"type": "Gene"
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{
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{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
498,
504
]
],
"text": [
"hFSH-R"
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"type": "Gene"
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{
"id": "273",
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{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
785,
791
]
],
"text": [
"hFSH-R"
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"type": "Gene"
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{
"id": "276",
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{
"db_id": "2492",
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"tax_id": null
}
],
"offsets": [
[
1058,
1064
]
],
"text": [
"hFSH-R"
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"type": "Gene"
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"id": "277",
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"tax_id": null
}
],
"offsets": [
[
1135,
1141
]
],
"text": [
"hFSH-R"
],
"type": "Gene"
},
{
"id": "280",
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{
"db_id": "2492",
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"tax_id": null
}
],
"offsets": [
[
1661,
1667
]
],
"text": [
"hFSH-R"
],
"type": "Gene"
},
{
"id": "281",
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{
"db_id": "4758",
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"tax_id": null
}
],
"offsets": [
[
1758,
1771
]
],
"text": [
"neuraminidase"
],
"type": "Gene"
},
{
"id": "282",
"normalized": [
{
"db_id": "2492",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1862,
1868
]
],
"text": [
"hFSH-R"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 217,
"offset": 0
},
"text": "The pro-alpha3(V) collagen chain. Complete primary structure, expression domains in adult and developing tissues, and comparison to the structures and expression domains of the other types V and XI procollagen chains.",
"type": "title"
},
{
"location": {
"length": 1952,
"offset": 218
},
"text": "The low abundance fibrillar collagen type V is widely distributed in tissues as an alpha1(V)(2)alpha2(V) heterotrimer that helps regulate the diameters of fibrils of the abundant collagen type I. Mutations in the alpha1(V) and alpha2(V) chain genes have been identified in some cases of classical Ehlers-Danlos syndrome (EDS), in which aberrant collagen fibrils are associated with connective tissue fragility, particularly in skin and joints. Type V collagen also exists as an alpha1(V)alpha2(V)alpha3(V) heterotrimer that has remained poorly characterized chiefly due to inability to obtain the complete primary structure or nucleic acid probes for the alpha3(V) chain or its biosynthetic precursor, pro-alpha3(V). Here we provide human and mouse full-length pro-alpha3(V) sequences. Pro-alpha3(V) is shown to be closely related to the alpha1(V) precursor, pro-alpha1(V), but with marked differences in N-propeptide sequences, and collagenous domain features that provide insights into the low melting temperature of alpha1(V)alpha2(V)alpha3(V) heterotrimers, lack of heparin binding by alpha3(V) chains and the possibility that alpha1(V)alpha2(V)alpha3(V) heterotrimers are incorporated into heterotypic fibrils. In situ hybridization of mouse embryos detects alpha3(V) expression primarily in the epimysial sheaths of developing muscles and within nascent ligaments adjacent to forming bones and in joints. This distribution, and the association of alpha1(V), alpha2(V), and alpha3(V) chains in heterotrimers, suggests the human alpha3(V) gene COL5A3 as a candidate locus for at least some cases of classical EDS in which the alpha1(V) and alpha2(V) genes have been excluded, and for at least some cases of the hypermobility type of EDS, a condition marked by gross joint laxity and chronic musculoskeletal pain. COL5A3 is mapped to 19p13.2 near a polymorphic marker that should be useful in analyzing linkage with EDS and other disease phenotypes.",
"type": "abstract"
}
] |
[
{
"id": "288",
"normalized": [
{
"db_id": "50509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
4,
26
]
],
"text": [
"pro-alpha3(V) collagen"
],
"type": "Gene"
},
{
"id": "291",
"normalized": [
{
"db_id": "1289",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
301,
310
]
],
"text": [
"alpha1(V)"
],
"type": "Gene"
},
{
"id": "292",
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{
"db_id": "1290",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
313,
322
]
],
"text": [
"alpha2(V)"
],
"type": "Gene"
},
{
"id": "293",
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{
"db_id": "1289",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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431,
440
]
],
"text": [
"alpha1(V)"
],
"type": "Gene"
},
{
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}
],
"offsets": [
[
445,
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]
],
"text": [
"alpha2(V)"
],
"type": "Gene"
},
{
"id": "296",
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{
"db_id": "1289",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
696,
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]
],
"text": [
"alpha1(V)"
],
"type": "Gene"
},
{
"id": "297",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
705,
714
]
],
"text": [
"alpha2(V)"
],
"type": "Gene"
},
{
"id": "298",
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{
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}
],
"offsets": [
[
714,
723
]
],
"text": [
"alpha3(V)"
],
"type": "Gene"
},
{
"id": "299",
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{
"db_id": "50509",
"db_name": "NCBIGene",
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}
],
"offsets": [
[
873,
882
]
],
"text": [
"alpha3(V)"
],
"type": "Gene"
},
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"id": "300",
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{
"db_id": "50509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
920,
933
]
],
"text": [
"pro-alpha3(V)"
],
"type": "Gene"
},
{
"id": "301",
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{
"db_id": "50509",
"db_name": "NCBIGene",
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},
{
"db_id": "12831",
"db_name": "NCBIGene",
"tax_id": "10090"
}
],
"offsets": [
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979,
992
]
],
"text": [
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],
"type": "Gene"
},
{
"id": "302",
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{
"db_id": "50509",
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"tax_id": null
}
],
"offsets": [
[
1004,
1017
]
],
"text": [
"Pro-alpha3(V)"
],
"type": "Gene"
},
{
"id": "303",
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}
],
"offsets": [
[
1056,
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]
],
"text": [
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],
"type": "Gene"
},
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"id": "304",
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}
],
"offsets": [
[
1077,
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]
],
"text": [
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],
"type": "Gene"
},
{
"id": "306",
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"db_id": "1289",
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}
],
"offsets": [
[
1237,
1246
]
],
"text": [
"alpha1(V)"
],
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},
{
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}
],
"offsets": [
[
1246,
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]
],
"text": [
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],
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},
{
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}
],
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1255,
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]
],
"text": [
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}
],
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1307,
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]
],
"text": [
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}
],
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]
],
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"type": "Gene"
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{
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}
],
"offsets": [
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1358,
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]
],
"text": [
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"id": "312",
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}
],
"offsets": [
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1367,
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]
],
"text": [
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{
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}
],
"offsets": [
[
1671,
1680
]
],
"text": [
"alpha1(V)"
],
"type": "Gene"
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{
"id": "315",
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"tax_id": null
}
],
"offsets": [
[
1682,
1691
]
],
"text": [
"alpha2(V)"
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"type": "Gene"
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{
"id": "316",
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}
],
"offsets": [
[
1697,
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]
],
"text": [
"alpha3(V)"
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"type": "Gene"
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{
"id": "317",
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}
],
"offsets": [
[
1751,
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]
],
"text": [
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{
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}
],
"offsets": [
[
1766,
1772
]
],
"text": [
"COL5A3"
],
"type": "Gene"
},
{
"id": "319",
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{
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}
],
"offsets": [
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]
],
"text": [
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"type": "Gene"
},
{
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}
],
"offsets": [
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1862,
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]
],
"text": [
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],
"type": "Gene"
},
{
"id": "321",
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}
],
"offsets": [
[
2035,
2041
]
],
"text": [
"COL5A3"
],
"type": "Gene"
},
{
"id": "288",
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{
"db_id": "50509",
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"tax_id": null
}
],
"offsets": [
[
4,
26
]
],
"text": [
"pro-alpha3(V) collagen"
],
"type": "Gene"
},
{
"id": "291",
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{
"db_id": "1289",
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}
],
"offsets": [
[
301,
310
]
],
"text": [
"alpha1(V)"
],
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},
{
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}
],
"offsets": [
[
313,
322
]
],
"text": [
"alpha2(V)"
],
"type": "Gene"
},
{
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}
],
"offsets": [
[
431,
440
]
],
"text": [
"alpha1(V)"
],
"type": "Gene"
},
{
"id": "294",
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{
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}
],
"offsets": [
[
445,
454
]
],
"text": [
"alpha2(V)"
],
"type": "Gene"
},
{
"id": "296",
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}
],
"offsets": [
[
696,
705
]
],
"text": [
"alpha1(V)"
],
"type": "Gene"
},
{
"id": "297",
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{
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}
],
"offsets": [
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705,
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[
{
"location": {
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"offset": 0
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"text": "Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53.",
"type": "title"
},
{
"location": {
"length": 1261,
"offset": 77
},
"text": "Mdm2 has been shown to regulate p53 stability by targeting the p53 protein for proteasomal degradation. We now report that Mdm2 is a ubiquitin protein ligase (E3) for p53 and that its activity is dependent on its RING finger. Furthermore, we show that Mdm2 mediates its own ubiquitination in a RING finger-dependent manner, which requires no eukaryotic proteins other than ubiquitin-activating enzyme (E1) and an ubiquitin-conjugating enzyme (E2). It is apparent, therefore, that Mdm2 manifests an intrinsic capacity to mediate ubiquitination. Mutation of putative zinc coordination residues abrogated this activity, as did chelation of divalent cations. After cation chelation, the full activity could be restored by addition of zinc. We further demonstrate that the degradation of p53 and Mdm2 in cells requires additional potential zinc-coordinating residues beyond those required for the intrinsic activity of Mdm2 in vitro. Replacement of the Mdm2 RING with that of another protein (Praja1) reconstituted ubiquitination and proteasomal degradation of Mdm2. However, this RING was ineffective in ubiquitination and proteasomal targeting of p53, suggesting that there may be specificity at the level of the RING in the recognition of heterologous substrates.",
"type": "abstract"
}
] |
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200,
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244,
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450,
482
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557,
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"p53"
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] |
[
{
"location": {
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"offset": 0
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"text": "Identification of endoglycan, a member of the CD34/podocalyxin family of sialomucins.",
"type": "title"
},
{
"location": {
"length": 1284,
"offset": 86
},
"text": "CD34 and podocalyxin are structurally related sialomucins, which are expressed in multiple tissues including vascular endothelium and hematopoietic progenitors. These glycoproteins have been proposed to be involved in processes as diverse as glomerular filtration, inhibition of stem cell differentiation, and leukocyte-endothelial adhesion. Using homologies present in the cytoplasmic tails of these proteins, we have identified a novel member of this family, which we designate endoglycan. This protein shares a similar overall domain structure with the other family members including a sialomucin domain, but also possesses an extremely acidic amino-terminal region. In addition, endoglycan contains several potential glycosaminoglycan attachment sites and is modified with chondroitin sulfate. Endoglycan mRNA and protein were detected in both endothelial cells and CD34(+) bone marrow cells. Thus, CD34, podocalyxin, and endoglycan comprise a family of sialomucins sharing both structural similarity and sequence homology, which are expressed by both endothelium and multipotent hematopoietic progenitors. While the members of this family may perform overlapping functions at these sites, the unique structural features of endoglycan suggest distinct functions for this molecule.",
"type": "abstract"
}
] |
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],
"text": [
"endoglycan"
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"id": "367",
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{
"db_id": "50512",
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}
],
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[
1314,
1324
]
],
"text": [
"endoglycan"
],
"type": "Gene"
},
{
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{
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}
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18,
28
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],
"text": [
"endoglycan"
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{
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}
],
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46,
50
]
],
"text": [
"CD34"
],
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{
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"tax_id": null
}
],
"offsets": [
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51,
62
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],
"text": [
"podocalyxin"
],
"type": "Gene"
},
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"tax_id": null
}
],
"offsets": [
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86,
90
]
],
"text": [
"CD34"
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"type": "Gene"
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{
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{
"db_id": "5420",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
95,
106
]
],
"text": [
"podocalyxin"
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"type": "Gene"
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{
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{
"db_id": "50512",
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}
],
"offsets": [
[
566,
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"endoglycan"
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"tax_id": null
}
],
"offsets": [
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769,
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]
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"text": [
"endoglycan"
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{
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}
],
"offsets": [
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884,
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]
],
"text": [
"Endoglycan"
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}
],
"offsets": [
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989,
993
]
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"text": [
"CD34"
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"tax_id": null
}
],
"offsets": [
[
995,
1006
]
],
"text": [
"podocalyxin"
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],
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1012,
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"endoglycan"
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}
],
"offsets": [
[
1314,
1324
]
],
"text": [
"endoglycan"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 107,
"offset": 0
},
"text": "Identification of a human follicular dendritic cell molecule that stimulates germinal center B cell growth.",
"type": "title"
},
{
"location": {
"length": 1200,
"offset": 108
},
"text": "The initial interaction between B cells and follicular dendritic cells (FDCs) appears to be essential for germinal center (GC) formation. To identify molecules regulating this interaction, we generated FDC-staining monoclonal antibodies (mAbs) and screened them for their ability to block FDC-mediated costimulation of growth and differentiation of CD40-stimulated B cells. Using one of the inhibitory mAbs, 8D6, we expression cloned the cDNA encoding the 8D6 antigen (Ag) from a human FDC line, HK. The 8D6 Ag is a novel protein of 282 amino acids that is expressed abundantly on FDCs. Monolayers of COS cells transiently transfected with the 8D6 Ag cDNA stimulate B cell growth. The mAb 8D6 blocks the costimulatory function completely. The inhibitory activity of the mAb 8D6 was demonstrated to be due to an inhibition of cell cycle progression of CD40 ligand-stimulated GC B cells. In addition, the mAb 8D6 inhibits the growth of a lymphoma of GC origin, L3055, which depends on FDCs or HK cells for its growth. These findings suggest that the primary function of FDCs in the GC is to stimulate B cell growth. An FDC signal molecule, 8D6 Ag, may be an important molecule to mediate this function.",
"type": "abstract"
}
] |
[
{
"id": "369",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
516,
519
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "370",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
564,
580
]
],
"text": [
"8D6 antigen (Ag)"
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"type": "Gene"
},
{
"id": "371",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
612,
618
]
],
"text": [
"8D6 Ag"
],
"type": "Gene"
},
{
"id": "372",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
752,
758
]
],
"text": [
"8D6 Ag"
],
"type": "Gene"
},
{
"id": "373",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
797,
800
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "374",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
882,
885
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "375",
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{
"db_id": "958",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
959,
963
]
],
"text": [
"CD40"
],
"type": "Gene"
},
{
"id": "376",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1015,
1018
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "377",
"normalized": [
{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1246,
1252
]
],
"text": [
"8D6 Ag"
],
"type": "Gene"
},
{
"id": "369",
"normalized": [
{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
516,
519
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "370",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
564,
580
]
],
"text": [
"8D6 antigen (Ag)"
],
"type": "Gene"
},
{
"id": "371",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
612,
618
]
],
"text": [
"8D6 Ag"
],
"type": "Gene"
},
{
"id": "372",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
752,
758
]
],
"text": [
"8D6 Ag"
],
"type": "Gene"
},
{
"id": "373",
"normalized": [
{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
797,
800
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "374",
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{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
882,
885
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "375",
"normalized": [
{
"db_id": "958",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
959,
963
]
],
"text": [
"CD40"
],
"type": "Gene"
},
{
"id": "376",
"normalized": [
{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1015,
1018
]
],
"text": [
"8D6"
],
"type": "Gene"
},
{
"id": "377",
"normalized": [
{
"db_id": "51293",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1246,
1252
]
],
"text": [
"8D6 Ag"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 135,
"offset": 0
},
"text": "Neutrophil polarity and locomotion are associated with surface redistribution of leukosialin (CD43), an antiadhesive membrane molecule.",
"type": "title"
},
{
"location": {
"length": 1178,
"offset": 136
},
"text": "This study analyzed the behavior of an antiadhesive membrane molecule, CD43, in neutrophil polarization and locomotion. CD43 cross-linking by antibodies induced neutrophil locomotion, with CD43 molecules clustered at the uropod of polarized neutrophils. In contrast, CD11b/CD18 cross-linking by antibodies did not affect either cell polarization or locomotion. Stimulation of suspended or adherent neutrophils with chemotactic peptide results in cell polarization and locomotion and a concomitant redistribution of CD43 to the uropod. This process is entirely reversible. The study also investigated which actin-binding protein could be involved in CD43 lateral redistribution. alpha-Actinin and moesin are preferentially adsorbed on Sepharose beads bearing a recombinant CD43 intracellular domain. Analysis by immunofluorescence confocal microscopy shows a codistribution of moesin during CD43 lateral redistribution. By contrast, alpha-actinin is located at the leading edge, an area devoid of CD43. These results shed new light on the role of CD43 membrane redistribution, which appears to be directly related to neutrophil polarity and locomotion. (Blood. 2000;95:2462-2470)",
"type": "abstract"
}
] |
[
{
"id": "379",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
81,
92
]
],
"text": [
"leukosialin"
],
"type": "Gene"
},
{
"id": "380",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
94,
98
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "381",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
207,
211
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "382",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
256,
260
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "383",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
325,
329
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "384",
"normalized": [
{
"db_id": "3684",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
403,
408
]
],
"text": [
"CD11b"
],
"type": "Gene"
},
{
"id": "385",
"normalized": [
{
"db_id": "3689",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
409,
413
]
],
"text": [
"CD18"
],
"type": "Gene"
},
{
"id": "386",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
651,
655
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "388",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
785,
789
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "389",
"normalized": [
{
"db_id": "87",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
814,
827
]
],
"text": [
"alpha-Actinin"
],
"type": "Gene"
},
{
"id": "390",
"normalized": [
{
"db_id": "4478",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
832,
838
]
],
"text": [
"moesin"
],
"type": "Gene"
},
{
"id": "392",
"normalized": [
{
"db_id": "4478",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1012,
1018
]
],
"text": [
"moesin"
],
"type": "Gene"
},
{
"id": "393",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1026,
1030
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "394",
"normalized": [
{
"db_id": "87",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1068,
1081
]
],
"text": [
"alpha-actinin"
],
"type": "Gene"
},
{
"id": "395",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1132,
1136
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "396",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1182,
1186
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "379",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
81,
92
]
],
"text": [
"leukosialin"
],
"type": "Gene"
},
{
"id": "380",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
94,
98
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "381",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
207,
211
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "382",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
256,
260
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "383",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
325,
329
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "384",
"normalized": [
{
"db_id": "3684",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
403,
408
]
],
"text": [
"CD11b"
],
"type": "Gene"
},
{
"id": "385",
"normalized": [
{
"db_id": "3689",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
409,
413
]
],
"text": [
"CD18"
],
"type": "Gene"
},
{
"id": "386",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
651,
655
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "388",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
785,
789
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "389",
"normalized": [
{
"db_id": "87",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
814,
827
]
],
"text": [
"alpha-Actinin"
],
"type": "Gene"
},
{
"id": "390",
"normalized": [
{
"db_id": "4478",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
832,
838
]
],
"text": [
"moesin"
],
"type": "Gene"
},
{
"id": "392",
"normalized": [
{
"db_id": "4478",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1012,
1018
]
],
"text": [
"moesin"
],
"type": "Gene"
},
{
"id": "393",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1026,
1030
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "394",
"normalized": [
{
"db_id": "87",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1068,
1081
]
],
"text": [
"alpha-actinin"
],
"type": "Gene"
},
{
"id": "395",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1132,
1136
]
],
"text": [
"CD43"
],
"type": "Gene"
},
{
"id": "396",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1182,
1186
]
],
"text": [
"CD43"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 45,
"offset": 0
},
"text": "A G protein-coupled receptor for UDP-glucose.",
"type": "title"
},
{
"location": {
"length": 877,
"offset": 46
},
"text": "Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemical role as a glycosyl donor in the enzymatic biosynthesis of carbohydrates. It is less well known that UDP-glucose may possess pharmacological activity, suggesting that a receptor for this molecule may exist. Here, we show that UDP-glucose, and some closely related molecules, potently activate the orphan G protein-coupled receptor KIAA0001 heterologously expressed in yeast or mammalian cells. Nucleotides known to activate P2Y receptors were inactive, indicating the distinctly novel pharmacology of this receptor. The receptor is expressed in a wide variety of human tissues, including many regions of the brain. These data suggest that some sugar-nucleotides may serve important physiological roles as extracellular signaling molecules in addition to their familiar role in intermediary metabolism.",
"type": "abstract"
}
] |
[
{
"id": "405",
"normalized": [
{
"db_id": "9934",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
453,
461
]
],
"text": [
"KIAA0001"
],
"type": "Gene"
},
{
"id": "405",
"normalized": [
{
"db_id": "9934",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
453,
461
]
],
"text": [
"KIAA0001"
],
"type": "Gene"
}
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[
{
"location": {
"length": 78,
"offset": 0
},
"text": "Spinocerebellar ataxia type 6 mutation alters P-type calcium channel function.",
"type": "title"
},
{
"location": {
"length": 1472,
"offset": 79
},
"text": "Abnormal CAG repeat expansion in the alpha1A voltage-dependent calcium channel gene is associated with spinocerebellar ataxia type 6, an autosomal dominant cerebellar ataxia with a predominant loss of the Purkinje cell. A reverse transcriptase-polymerase chain reaction analysis of mRNA from mouse Purkinje cells revealed a predominant expression of the alpha1A channel lacking an asparagine-proline (NP) stretch in the domain IV (alpha1A(-NP)). Human alpha1A channels carrying various polyglutamine length with or without NP were expressed in HEK293 cells, and channel properties were compared using a whole-cell voltage clamp technique. alpha1A(-NP), corresponding to P-type channel, with 24 and 28 polyglutamines found in patients showed the voltage dependence of inactivation shifting negatively by 6 and 11 mV, respectively, from the 13 polyglutamine control. Contrarily, the alpha1A channel with NP (alpha1A(+NP)), corresponding to Q-type channel, with 28 polyglutamines exhibited a positive shift of 5 mV. These results suggest that altered function of alpha1A(-NP) may contribute to degeneration of Purkinje cells, which express predominantly alpha1A(-NP), due to the reduced Ca(2+) influx resulting from the negative shift of voltage-dependent inactivation. On the other hand, other types of neurons, expressing both alpha1A(-NP) and alpha1A(+NP), may survive because the positive shift of voltage-dependent inactivation of alpha1A(+NP) compensates Ca(2+) influx.",
"type": "abstract"
}
] |
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718,
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}
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1405,
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1422,
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}
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"offsets": [
[
1512,
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],
"text": [
"alpha1A"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 91,
"offset": 0
},
"text": "Structure, mapping and expression of the human gene encoding the homeodomain protein, SIX2.",
"type": "title"
},
{
"location": {
"length": 978,
"offset": 92
},
"text": "Vertebrate genes with sequence similarity to the Drosophila homeobox gene, sine oculis (so), constitute the SIX family. There is notable expression of members of this family in anterior neural structures, and several SIX genes have been shown to play roles in vertebrate and insect development, or have been implicated in maintenance of the differentiated state of tissues. Mutations in three of these genes in man (SIX5, SIX6 and SIX3) are associated with severe phenotypes, and therefore, the cloning of other human genes from this family is of interest. We have cloned and characterised the gene that encodes human SIX2, elucidated its gene structure and conducted expression studies in a range of tissues. SIX2 is widely expressed in the late first-trimester fetus, but has a limited range of expression sites in the adult. The expression pattern of SIX2 and its localisation to chromosome 2p15-p16 will be of use in assessing its candidacy in human developmental disorders.",
"type": "abstract"
}
] |
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86,
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],
"text": [
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{
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{
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],
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508,
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"text": [
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],
"offsets": [
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"text": [
"SIX2"
],
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}
] |
[
{
"location": {
"length": 96,
"offset": 0
},
"text": "Enhanced growth of MCF-7 breast cancer cells overexpressing parathyroid hormone-related peptide.",
"type": "title"
},
{
"location": {
"length": 2123,
"offset": 97
},
"text": "PTH-related peptide (PTHrP) is a secreted protein produced by breast cancer cells both in vivo and in vitro. Because of its structural similarity to PTH at the amino terminus, the two proteins interact with a common cell surface receptor, the PTH/PTHrP receptor. When overproduced by tumor cells, PTHrP enters the circulation, giving rise to the common paraneoplastic syndrome of humoral hypercalcemia of malignancy. Although initially discovered in malignancies, PTHrP is now known to be produced by most cells and tissues in the body. It acts as an autocrine and paracrine mediator of cell proliferation and differentiation, effects which are mediated via the PTH/PTHrP receptor. Recent evidence also has shown that, directly after translation, PTHrP is able to enter the nucleus and/or nucleolus and influence cell cycle progression and apoptosis. In this study, we have either overproduced PTHrP or inhibited endogenous PTHrP production in the breast cancer cell line, MCF-7. Overexpression of PTHrP was associated with an increase in mitogenesis, whereas inhibiting endogenous PTHrP production resulted in decreased cell proliferation. The overexpressed peptide targeted to the perinuclear space. In contrast, PTHrP interaction with the cell surface PTH/PTHrP receptor resulted in decreased cell proliferation in the same cell line. This latter effect is dependent on interaction with the receptor, in that exogenously added PTHrP moieties known not to interact with the receptor had no effect on cell growth. Furthermore, neutralization of added peptide with an anti-PTHrP antiserum completely abolished the growth inhibitory effects. In contrast, this antibody has no effect on the increased proliferation rate of the MCF-7 transfectants that overexpress PTHrP, compared with control cells. The net effect of autocrine/paracrine and intracrine effects of PTHrP in MCF-7 cells overproducing the peptide is accelerated cell growth. These findings have critical implications regarding the role of PTHrP in breast cancer, and they suggest that controlling PTHrP production in breast cancer may be useful therapeutically.",
"type": "abstract"
}
] |
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246,
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"PTH"
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340,
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394,
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759,
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"text": [
"PTHrP"
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] |
[
{
"location": {
"length": 112,
"offset": 0
},
"text": "Intracellular parasitism by the human granulocytic ehrlichiosis bacterium through the P-selectin ligand, PSGL-1.",
"type": "title"
},
{
"location": {
"length": 770,
"offset": 113
},
"text": "Human granulocytic ehrlichiosis (HGE) is a febrile tick-borne illness caused by a recently discovered intracellular bacterium remarkable for its tropism for professionally phagocytic neutrophils. Monoclonal antibodies against the P-selectin binding domain of the leukocyte P-selectin glycoprotein ligand, PSGL-1, prevented HGE cell binding and infection, as did enzymatic digestion of PSGL-1. Furthermore, simultaneous neoexpression in nonsusceptible cells of complementary DNAs for both PSGL-1 and its modifying alpha-(1,3) fucosyltransferase, Fuc-TVII, allowed binding and infection by HGE. Thus, the HGE bacterium specifically bound to fucosylated leukocyte PSGL-1. Selectin mimicry is likely central to the organism's unique ability to target and infect neutrophils.",
"type": "abstract"
}
] |
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86,
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343,
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"offsets": [
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],
"offsets": [
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658,
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],
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},
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}
],
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774,
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]
],
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"PSGL-1"
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}
],
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86,
103
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],
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],
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105,
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],
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],
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343,
353
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],
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386,
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418,
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],
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"PSGL-1"
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498,
504
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],
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601,
607
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],
"text": [
"PSGL-1"
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"type": "Gene"
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{
"id": "467",
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{
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}
],
"offsets": [
[
626,
656
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],
"text": [
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{
"id": "468",
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{
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],
"offsets": [
[
658,
666
]
],
"text": [
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"type": "Gene"
},
{
"id": "469",
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{
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}
],
"offsets": [
[
774,
780
]
],
"text": [
"PSGL-1"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 82,
"offset": 0
},
"text": "3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins.",
"type": "title"
},
{
"location": {
"length": 927,
"offset": 83
},
"text": "Human 3-methyladenine-DNA glycosylase (MPG protein) initiates base excision repair by severing the glycosylic bond of numerous damaged bases. In comparison, homologues of the Rad23 proteins (hHR23) and the hXPC protein are involved in the recognition of damaged bases in global genome repair, a subset of nucleotide excision repair. In this report, we show that the hHR23A and -B also interact with the MPG protein and can serve as accessory proteins for DNA damage recognition in base excision repair. Furthermore, the MPG.hHR23 protein complex elevates the rate of MPG protein-catalyzed excision from hypoxanthine-containing substrates. This increased excision rate is correlated with a greater binding affinity of the MPG protein-hHR23 protein complex for damaged DNA. These data suggest that the hHR23 proteins function as universal DNA damage recognition accessory proteins in both of these major excision repair pathways.",
"type": "abstract"
}
] |
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{
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"tax_id": null
}
],
"offsets": [
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0,
31
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],
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{
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}
],
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33,
36
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],
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"MPG"
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{
"id": "474",
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{
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],
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89,
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{
"id": "475",
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],
"offsets": [
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122,
125
]
],
"text": [
"MPG"
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"type": "Gene"
},
{
"id": "478",
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"db_id": "7508",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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289,
293
]
],
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"hXPC"
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},
{
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{
"db_id": "5887",
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],
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449,
462
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],
"text": [
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{
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}
],
"offsets": [
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486,
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],
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"MPG"
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}
],
"offsets": [
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603,
606
]
],
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"MPG"
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],
"offsets": [
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650,
653
]
],
"text": [
"MPG"
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{
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],
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804,
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]
],
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}
],
"offsets": [
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0,
31
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],
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}
],
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33,
36
]
],
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{
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}
],
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89,
120
]
],
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"type": "Gene"
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{
"id": "475",
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"db_id": "4350",
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}
],
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122,
125
]
],
"text": [
"MPG"
],
"type": "Gene"
},
{
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"db_id": "7508",
"db_name": "NCBIGene",
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}
],
"offsets": [
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289,
293
]
],
"text": [
"hXPC"
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},
{
"id": "479",
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{
"db_id": "5886",
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},
{
"db_id": "5887",
"db_name": "NCBIGene",
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}
],
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449,
462
]
],
"text": [
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],
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"tax_id": null
}
],
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486,
489
]
],
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"MPG"
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},
{
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}
],
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603,
606
]
],
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"MPG"
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{
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}
],
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650,
653
]
],
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}
],
"offsets": [
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804,
807
]
],
"text": [
"MPG"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 85,
"offset": 0
},
"text": "Expression, purification, and functional analysis of the human serine protease HtrA2.",
"type": "title"
},
{
"location": {
"length": 979,
"offset": 86
},
"text": "HumHtrA2 or Omi is a recently described member of a novel family of mammalian serine proteases homologous to the Escherichia coli htrA gene product. Although the physiological function of members of this new family is unclear, the current understanding is that as well as being involved with the degradation aberrantly folded proteins during conditions of cellular stress, they may possess a chaperone-like role under normal conditions. In this report we describe the overexpression of humHtrA2 in two heterologous systems comparing the merits of each. We found that molecular analysis of processing events in Sf9 cells allowed us to revisit E. coli expression systems which were initially unsuccessful. Using E. coli we were able to produce milligram amounts of >90% pure recombinant enzyme as determined by SDS-PAGE gels. By means of fluorescently labeled substrates alpha- and beta-casein and zymography, the proteolytic activity of recombinant HumHtrA2 was also demonstrated.",
"type": "abstract"
}
] |
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{
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}
],
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],
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],
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],
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],
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{
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}
],
"offsets": [
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86,
94
]
],
"text": [
"HumHtrA2"
],
"type": "Gene"
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"id": "491",
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{
"db_id": "27429",
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"tax_id": null
}
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[
98,
101
]
],
"text": [
"Omi"
],
"type": "Gene"
},
{
"id": "494",
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{
"db_id": "27429",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
572,
580
]
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"text": [
"humHtrA2"
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"type": "Gene"
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{
"db_id": "27429",
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}
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"offsets": [
[
1034,
1042
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"text": [
"HumHtrA2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 87,
"offset": 0
},
"text": "Repression of IL-2 promoter activity by the novel basic leucine zipper p21SNFT protein.",
"type": "title"
},
{
"location": {
"length": 911,
"offset": 88
},
"text": "IL-2 is the major autocrine and paracrine growth factor produced by T cells upon T cell stimulation. The inducible expression of IL-2 is highly regulated by multiple transcription factors, particularly AP-1, which coordinately activate the promoter. Described here is the ability of the novel basic leucine zipper protein p21SNFT to repress AP-1 activity and IL-2 transcription. A detailed analysis of the repression by p21SNFT repression on the IL-2 promoter distal NF-AT/AP-1 site demonstrates that it can bind DNA with NF-AT and Jun, strongly suggesting that it represses NF-AT/AP-1 activity by competing with Fos proteins for Jun dimerization. The importance of this repression is that p21SNFT inhibits the trans-activation potential of protein complexes that contain Jun, thereby demonstrating an additional level of control for the highly regulated, ubiquitous AP-1 transcription factor and the IL-2 gene.",
"type": "abstract"
}
] |
[
{
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
14,
18
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "499",
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{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
71,
78
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "500",
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
88,
92
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "502",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
217,
221
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "505",
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{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
410,
417
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "507",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
447,
451
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "508",
"normalized": [
{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
508,
515
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "509",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
534,
538
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "513",
"normalized": [
{
"db_id": "3725",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
623
]
],
"text": [
"Jun"
],
"type": "Gene"
},
{
"id": "516",
"normalized": [
{
"db_id": "2353",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
701,
704
]
],
"text": [
"Fos"
],
"type": "Gene"
},
{
"id": "517",
"normalized": [
{
"db_id": "3725",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
718,
721
]
],
"text": [
"Jun"
],
"type": "Gene"
},
{
"id": "518",
"normalized": [
{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
778,
785
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "519",
"normalized": [
{
"db_id": "3725",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
860,
863
]
],
"text": [
"Jun"
],
"type": "Gene"
},
{
"id": "521",
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
989,
993
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "497",
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
14,
18
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "499",
"normalized": [
{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
71,
78
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "500",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
88,
92
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "502",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
217,
221
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "505",
"normalized": [
{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
410,
417
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "507",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
447,
451
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "508",
"normalized": [
{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
508,
515
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "509",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
534,
538
]
],
"text": [
"IL-2"
],
"type": "Gene"
},
{
"id": "513",
"normalized": [
{
"db_id": "3725",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
623
]
],
"text": [
"Jun"
],
"type": "Gene"
},
{
"id": "516",
"normalized": [
{
"db_id": "2353",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
701,
704
]
],
"text": [
"Fos"
],
"type": "Gene"
},
{
"id": "517",
"normalized": [
{
"db_id": "3725",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
718,
721
]
],
"text": [
"Jun"
],
"type": "Gene"
},
{
"id": "518",
"normalized": [
{
"db_id": "55509",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
778,
785
]
],
"text": [
"p21SNFT"
],
"type": "Gene"
},
{
"id": "519",
"normalized": [
{
"db_id": "3725",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
860,
863
]
],
"text": [
"Jun"
],
"type": "Gene"
},
{
"id": "521",
"normalized": [
{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
989,
993
]
],
"text": [
"IL-2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 191,
"offset": 0
},
"text": "Identification of distinct surface-expressed and intracellular CXC-chemokine receptor 2 glycoforms in neutrophils: N-glycosylation is essential for maintenance of receptor surface expression.",
"type": "title"
},
{
"location": {
"length": 1820,
"offset": 192
},
"text": "The G protein-coupled CXC-chemokine receptor CXCR-2 mediates activation of neutrophil effector functions in response to multiple ligands, including IL-8 and neutrophil-activating peptide 2 (NAP-2). Although CXCR-2 has been successfully cloned and expressed in several cell lines, the molecular properties of the native neutrophil-expressed receptor have remained largely undefined. Here we report on the identification and characterization of distinct CXCR-2 glycoforms and their subcellular distribution in neutrophils. Immunoprecipitation and Western blot analyses of surface-expressed receptors covalently linked to IL-8 or NAP-2 as well as in their unloaded state revealed the occurrence of a single CXCR-2 variant with an apparent size of 56 kDa. According to deglycosylation experiments surface-expressed CXCR-2 carries two N-linked 9-kDa carbohydrate moieties that are both of complex structure. In addition, two other CXCR-2 variants of 38 and 40 kDa were found to occur exclusively intracellular and to carry N-glycosylations of high mannose or hybrid type. These receptors did not participate in ligand-induced receptor trafficking, while surface-expressed CXCR-2 was internalized and re-expressed following stimulation with NAP-2. By enzymatic removal of one 9-kDa carbohydrate moiety in surface-expressed CXCR-2 we can show that neither NAP-2-induced trafficking nor signaling of the receptor is dependent on its full glycosylation. Instead, glycosylation was found to protect CXCR-2 from proteolytic attack, as even partial deglycosylation is associated with serine protease-mediated disappearance of the receptor from the neutrophil surface. Thus, although not directly involved in signaling, glycosylation appears to be required to maintain neutrophil responsiveness to CXC-chemokines during inflammation.",
"type": "abstract"
}
] |
[
{
"id": "523",
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{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
63,
87
]
],
"text": [
"CXC-chemokine receptor 2"
],
"type": "Gene"
},
{
"id": "525",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
237,
243
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "526",
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{
"db_id": "3576",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
340,
344
]
],
"text": [
"IL-8"
],
"type": "Gene"
},
{
"id": "527",
"normalized": [
{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
349,
380
]
],
"text": [
"neutrophil-activating peptide 2"
],
"type": "Gene"
},
{
"id": "528",
"normalized": [
{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
382,
387
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "529",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
399,
405
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "531",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
644,
650
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "533",
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{
"db_id": "3576",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
811,
815
]
],
"text": [
"IL-8"
],
"type": "Gene"
},
{
"id": "534",
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{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
819,
824
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "535",
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{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
896,
902
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "536",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1003,
1009
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "537",
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{
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"tax_id": null
}
],
"offsets": [
[
1118,
1124
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
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"id": "539",
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{
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}
],
"offsets": [
[
1359,
1365
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "540",
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{
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"db_name": "NCBIGene",
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}
],
"offsets": [
[
1427,
1432
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "541",
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{
"db_id": "3579",
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"tax_id": null
}
],
"offsets": [
[
1509,
1515
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "542",
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{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1541,
1546
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "543",
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{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1681,
1687
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "523",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
63,
87
]
],
"text": [
"CXC-chemokine receptor 2"
],
"type": "Gene"
},
{
"id": "525",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
237,
243
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "526",
"normalized": [
{
"db_id": "3576",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
340,
344
]
],
"text": [
"IL-8"
],
"type": "Gene"
},
{
"id": "527",
"normalized": [
{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
349,
380
]
],
"text": [
"neutrophil-activating peptide 2"
],
"type": "Gene"
},
{
"id": "528",
"normalized": [
{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
382,
387
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "529",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
399,
405
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "531",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
644,
650
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "533",
"normalized": [
{
"db_id": "3576",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
811,
815
]
],
"text": [
"IL-8"
],
"type": "Gene"
},
{
"id": "534",
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{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
819,
824
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "535",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
896,
902
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "536",
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{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1003,
1009
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "537",
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{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1118,
1124
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "539",
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{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1359,
1365
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "540",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1427,
1432
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "541",
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{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1509,
1515
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
},
{
"id": "542",
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{
"db_id": "5473",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1541,
1546
]
],
"text": [
"NAP-2"
],
"type": "Gene"
},
{
"id": "543",
"normalized": [
{
"db_id": "3579",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1681,
1687
]
],
"text": [
"CXCR-2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 176,
"offset": 0
},
"text": "Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors.",
"type": "title"
},
{
"location": {
"length": 1631,
"offset": 177
},
"text": "Mechano-sensitive and fatty acid-activated K(+) belong to the structural class of K(+) channel with two pore domains. Here, we report the isolation and the characterization of a novel member of this family. This channel, called TREK2, is closely related to TREK1 (78% of homology). Its gene is located on chromosome 14q31. TREK2 is abundantly expressed in pancreas and kidney and to a lower level in brain, testis, colon, and small intestine. In the central nervous system, TREK2 has a widespread distribution with the highest levels of expression in cerebellum, occipital lobe, putamen, and thalamus. In transfected cells, TREK2 produces rapidly activating and non-inactivating outward rectifier K(+) currents. The single-channel conductance is 100 picosiemens at +40 mV in 150 mm K(+). The currents can be strongly stimulated by polyunsaturated fatty acid such as arachidonic, docosahexaenoic, and linoleic acids and by lysophosphatidylcholine. The channel is also activated by acidification of the intracellular medium. TREK2 is blocked by application of intracellular cAMP. As with TREK1, TREK2 is activated by the volatile general anesthetics chloroform, halothane, and isoflurane and by the neuroprotective agent riluzole. TREK2 can be positively or negatively regulated by a variety of neurotransmitter receptors. Stimulation of the G(s)-coupled receptor 5HT4sR or the G(q)-coupled receptor mGluR1 inhibits channel activity, whereas activation of the G(i)-coupled receptor mGluR2 increases TREK2 currents. These multiple types of regulations suggest that TREK2 plays an important role as a target of neurotransmitter action.",
"type": "abstract"
}
] |
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6,
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15,
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405,
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1263,
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1539,
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1674,
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] |
[
{
"location": {
"length": 119,
"offset": 0
},
"text": "SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells.",
"type": "title"
},
{
"location": {
"length": 1152,
"offset": 120
},
"text": "Our previous studies have shown that activation of a related adhesion focal tyrosine kinase (RAFTK) (also known as Pyk2) is required for dexamethasone (Dex)-induced apoptosis in multiple myeloma (MM) cells and that human interleukin-6 (IL-6), a known growth and survival factor for MM cells, blocks both RAFTK activation and apoptosis induced by Dex. However, the mechanism whereby IL-6 inhibits Dex-induced apoptosis is undefined. In this study, we demonstrate that protein-tyrosine phosphatase SHP2 mediates this protective effect. We show that IL-6 triggers selective activation of SHP2 and its association with RAFTK in Dex-treated MM cells. SHP2 interacts with RAFTK through a region other than its Src homology 2 domains. We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM.",
"type": "abstract"
}
] |
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"text": [
"IL-6"
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705,
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"RAFTK"
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"text": [
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]
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"text": [
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"offsets": [
[
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]
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"text": [
"SHP2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 83,
"offset": 0
},
"text": "Alpha(2) adrenoceptors regulate proliferation of human intestinal epithelial cells.",
"type": "title"
},
{
"location": {
"length": 2154,
"offset": 84
},
"text": "BACKGROUND AND AIMS: Previous studies on rodents have suggested that catecholamines stimulate proliferation of the intestinal epithelium through activation of alpha(2) adrenoceptors located on crypt cells. The occurrence of this effect awaits demonstration in humans and the molecular mechanisms involved have not yet been elucidated. Here, we examined the effect of alpha(2) agonists on a clone of Caco2 cells expressing the human alpha(2A) adrenoceptor. METHODS: Cells were transfected with a bicistronic plasmid containing the alpha2C10 and neomycin phosphotransferase genes. G418 resistant clones were assayed for receptor expression using radioligand binding. Receptor functionality was assessed by testing its ability to couple Gi proteins and to inhibit cAMP production. Mitogen activated protein kinase (MAPK) phosphorylation was followed by western blot, and cell proliferation was estimated by measuring protein and DNA content. RESULTS: Permanent transfection of Caco2 cells allowed us to obtain a clone (Caco2-3B) expressing alpha(2A) adrenoceptors at a density similar to that found in normal human intestinal epithelium. Caco2-3B retained morphological features and brush border enzyme expression characteristic of enterocytic differentiation. The receptor was coupled to Gi2/Gi3 proteins and its stimulation caused marked diminution of forskolin induced cAMP production. Treatment of Caco2-3B with UK14304 (alpha(2) agonist) induced a rapid increase in the phosphorylation state of MAPK, extracellular regulated protein kinase 1 (Erk1), and 2 (Erk2). This event was totally abolished in pertussis toxin treated cells and in the presence of kinase inhibitors (genistein or PD98059). It was unaffected by protein kinase C downregulation but correlated with a transient increase in Shc tyrosine phosphorylation. Finally, sustained exposure of Caco2-3B to UK14304 resulted in modest but significant acceleration of cell proliferation. None of these effects was observed in the parental cell line Caco2. CONCLUSION: The results obtained in the present study support a regulatory role for alpha(2) adrenoceptors in intestinal cell proliferation.",
"type": "abstract"
}
] |
[
{
"id": "607",
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{
"db_id": "150",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
516,
538
]
],
"text": [
"alpha(2A) adrenoceptor"
],
"type": "Gene"
},
{
"id": "608",
"normalized": [
{
"db_id": "150",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
614,
623
]
],
"text": [
"alpha2C10"
],
"type": "Gene"
},
{
"id": "616",
"normalized": [
{
"db_id": "5595",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1587,
1627
]
],
"text": [
"extracellular regulated protein kinase 1"
],
"type": "Gene"
},
{
"id": "617",
"normalized": [
{
"db_id": "5595",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1629,
1633
]
],
"text": [
"Erk1"
],
"type": "Gene"
},
{
"id": "618",
"normalized": [
{
"db_id": "5594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1643,
1647
]
],
"text": [
"Erk2"
],
"type": "Gene"
},
{
"id": "620",
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{
"db_id": "6464",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1878,
1881
]
],
"text": [
"Shc"
],
"type": "Gene"
},
{
"id": "607",
"normalized": [
{
"db_id": "150",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
516,
538
]
],
"text": [
"alpha(2A) adrenoceptor"
],
"type": "Gene"
},
{
"id": "608",
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{
"db_id": "150",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
614,
623
]
],
"text": [
"alpha2C10"
],
"type": "Gene"
},
{
"id": "616",
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{
"db_id": "5595",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1587,
1627
]
],
"text": [
"extracellular regulated protein kinase 1"
],
"type": "Gene"
},
{
"id": "617",
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{
"db_id": "5595",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1629,
1633
]
],
"text": [
"Erk1"
],
"type": "Gene"
},
{
"id": "618",
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{
"db_id": "5594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1643,
1647
]
],
"text": [
"Erk2"
],
"type": "Gene"
},
{
"id": "620",
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{
"db_id": "6464",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1878,
1881
]
],
"text": [
"Shc"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 68,
"offset": 0
},
"text": "IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines.",
"type": "title"
},
{
"location": {
"length": 1664,
"offset": 69
},
"text": "IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemoattractant (I-TAC) belong to the non-glutamate-leucine-arginine motif CXC chemokine family and act solely through the CXCR3 receptor for potent attraction of T lymphocytes. In this study, we evaluated the capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP-10, Mig, and I-TAC in cultured human keratinocytes and CXCR3 expression in T cells from allergic contact dermatitis (ACD). IL-4, but not IL-10 or IL-17, significantly up-regulated IFN-gamma- or TNF-alpha-induced IP-10, Mig, and I-TAC mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in keratinocyte supernatants. Immunohistochemistry of skin affected by ACD revealed that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining colocalized in CD4+ and CD8+ T cells. Nickel-specific CD4+ and CD8+ T cell lines established from ACD skin produced IFN-gamma and IL-4 and expressed moderate to high levels of CXCR3. Finally, CXCR3 agonistic chemokines released by stimulated keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4+ T cells and promoted their migration, with supernatant from keratinocyte cultures stimulated with IFN-gamma and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-gamma alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-gamma and TNF-alpha induction of IP-10, Mig, and I-TAC, which in turn may determine a prominent recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.",
"type": "abstract"
}
] |
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{
"id": "623",
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
4
]
],
"text": [
"IL-4"
],
"type": "Gene"
},
{
"id": "624",
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{
"db_id": "2833",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
41,
46
]
],
"text": [
"CXCR3"
],
"type": "Gene"
},
{
"id": "625",
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{
"db_id": "3627",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
69,
98
]
],
"text": [
"IFN-induced protein of 10 kDa"
],
"type": "Gene"
},
{
"id": "626",
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{
"db_id": "3627",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
100,
105
]
],
"text": [
"IP-10"
],
"type": "Gene"
},
{
"id": "627",
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{
"db_id": "4283",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
108,
137
]
],
"text": [
"monokine induced by IFN-gamma"
],
"type": "Gene"
},
{
"id": "628",
"normalized": [
{
"db_id": "4283",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
139,
142
]
],
"text": [
"Mig"
],
"type": "Gene"
},
{
"id": "629",
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{
"db_id": "6373",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
149,
191
]
],
"text": [
"IFN-inducible T-cell alpha-chemoattractant"
],
"type": "Gene"
},
{
"id": "630",
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{
"db_id": "6373",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
193,
198
]
],
"text": [
"I-TAC"
],
"type": "Gene"
},
{
"id": "633",
"normalized": [
{
"db_id": "2833",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
299,
313
]
],
"text": [
"CXCR3 receptor"
],
"type": "Gene"
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{
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{
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"tax_id": null
}
],
"offsets": [
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427,
431
]
],
"text": [
"IL-4"
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"type": "Gene"
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{
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{
"db_id": "3586",
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"tax_id": null
}
],
"offsets": [
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433,
438
]
],
"text": [
"IL-10"
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"type": "Gene"
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}
],
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444,
449
]
],
"text": [
"IL-17"
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"type": "Gene"
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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462,
467
]
],
"text": [
"IP-10"
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"type": "Gene"
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{
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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469,
472
]
],
"text": [
"Mig"
],
"type": "Gene"
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{
"id": "639",
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{
"db_id": "6373",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
478,
483
]
],
"text": [
"I-TAC"
],
"type": "Gene"
},
{
"id": "640",
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{
"db_id": "2833",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
520,
525
]
],
"text": [
"CXCR3"
],
"type": "Gene"
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{
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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588,
592
]
],
"text": [
"IL-4"
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"type": "Gene"
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"tax_id": null
}
],
"offsets": [
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602,
607
]
],
"text": [
"IL-10"
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"type": "Gene"
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{
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{
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"tax_id": null
}
],
"offsets": [
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611,
616
]
],
"text": [
"IL-17"
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"type": "Gene"
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{
"id": "644",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
645,
654
]
],
"text": [
"IFN-gamma"
],
"type": "Gene"
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{
"id": "645",
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{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
659,
668
]
],
"text": [
"TNF-alpha"
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"type": "Gene"
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
677,
682
]
],
"text": [
"IP-10"
],
"type": "Gene"
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{
"id": "647",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
684,
687
]
],
"text": [
"Mig"
],
"type": "Gene"
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{
"id": "648",
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{
"db_id": "6373",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
693,
698
]
],
"text": [
"I-TAC"
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"type": "Gene"
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{
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{
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"tax_id": null
}
],
"offsets": [
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762,
767
]
],
"text": [
"IP-10"
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"type": "Gene"
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"tax_id": null
}
],
"offsets": [
[
772,
775
]
],
"text": [
"Mig"
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"type": "Gene"
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}
],
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910,
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],
"text": [
"CXCR3"
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],
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925,
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],
"text": [
"CXCR3"
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"type": "Gene"
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],
"offsets": [
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1056,
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],
"text": [
"IFN-gamma"
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"type": "Gene"
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}
],
"offsets": [
[
1070,
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]
],
"text": [
"IL-4"
],
"type": "Gene"
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{
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}
],
"offsets": [
[
1116,
1121
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],
"text": [
"CXCR3"
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"type": "Gene"
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}
],
"offsets": [
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1132,
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"text": [
"CXCR3"
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"type": "Gene"
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"tax_id": null
}
],
"offsets": [
[
1362,
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]
],
"text": [
"IFN-gamma"
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"type": "Gene"
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{
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{
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}
],
"offsets": [
[
1376,
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],
"text": [
"IL-4"
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"type": "Gene"
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"tax_id": null
}
],
"offsets": [
[
1462,
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]
],
"text": [
"IFN-gamma"
],
"type": "Gene"
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{
"id": "660",
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{
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}
],
"offsets": [
[
1494,
1498
]
],
"text": [
"IL-4"
],
"type": "Gene"
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{
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{
"db_id": "3458",
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"tax_id": null
}
],
"offsets": [
[
1566,
1575
]
],
"text": [
"IFN-gamma"
],
"type": "Gene"
},
{
"id": "662",
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{
"db_id": "7124",
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"tax_id": null
}
],
"offsets": [
[
1580,
1589
]
],
"text": [
"TNF-alpha"
],
"type": "Gene"
},
{
"id": "663",
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{
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}
],
"offsets": [
[
1603,
1608
]
],
"text": [
"IP-10"
],
"type": "Gene"
},
{
"id": "664",
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{
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"Mig"
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"I-TAC"
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1681,
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"CXCR3"
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0,
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41,
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69,
98
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100,
105
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108,
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"text": [
"monokine induced by IFN-gamma"
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139,
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"Mig"
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[
149,
191
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193,
198
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299,
313
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427,
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444,
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462,
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469,
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478,
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520,
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588,
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602,
607
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],
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611,
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],
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645,
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"text": [
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],
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659,
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"text": [
"TNF-alpha"
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],
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[
677,
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],
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684,
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]
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}
],
"offsets": [
[
693,
698
]
],
"text": [
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"type": "Gene"
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}
],
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[
762,
767
]
],
"text": [
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"type": "Gene"
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],
"offsets": [
[
772,
775
]
],
"text": [
"Mig"
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"type": "Gene"
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],
"offsets": [
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910,
915
]
],
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],
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925,
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"id": "653",
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],
"offsets": [
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1056,
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],
"offsets": [
[
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}
],
"offsets": [
[
1116,
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],
"text": [
"CXCR3"
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"id": "656",
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}
],
"offsets": [
[
1132,
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}
],
"offsets": [
[
1362,
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]
],
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"IFN-gamma"
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"type": "Gene"
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"id": "658",
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}
],
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}
],
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[
1462,
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"IFN-gamma"
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"type": "Gene"
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}
],
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[
1494,
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],
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}
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1566,
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],
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}
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1580,
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],
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}
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1603,
1608
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],
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}
],
"offsets": [
[
1610,
1613
]
],
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"Mig"
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"type": "Gene"
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}
],
"offsets": [
[
1619,
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],
"text": [
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}
],
"offsets": [
[
1681,
1686
]
],
"text": [
"CXCR3"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 181,
"offset": 0
},
"text": "The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q.",
"type": "title"
},
{
"location": {
"length": 1449,
"offset": 182
},
"text": "We have isolated the human GRAF gene (for GTPase regulator associated with the focal adhesion kinase pp125(FAK)). This gene was fused with MLL in a unique t(5;11)(q31;q23) that occurred in an infant with juvenile myelomonocytic leukemia. GRAF encodes a member of the Rho family of the GTPase-activating protein (GAP) family. On the protein level, it is 90% homologous to the recently described chicken GRAF gene that functions as a GAP of RhoA in vivo and is thus a critical component of the integrin signaling transduction pathway. The particular position of the human GRAF gene at 5q31 and the proposed antiproliferative and tumor suppressor properties of its avian homologue suggest that it also might be pathogenetically relevant for hematologic malignancies with deletions of 5q. To investigate this possibility, we sequenced 4-5 individual cDNA clones from 13 cases in which one allele of GRAF was deleted. We found point mutations within the GAP domain of the second GRAF allele in one patient. In two additional patients we found an insertion of 52 or 74 bp within the GRAF cDNA that generates a reading frame shift followed by a premature stop codon. GRAF maps outside the previously defined commonly deleted 5q31 region. Nevertheless, inactivation of both alleles in at least some cases suggests that deletions and mutations of the GRAF gene may be instrumental in the development and progression of hematopoeitic disorders with a del(5q).",
"type": "abstract"
}
] |
[
{
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"tax_id": null
}
],
"offsets": [
[
10,
14
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "669",
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{
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}
],
"offsets": [
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32,
35
]
],
"text": [
"MLL"
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"type": "Gene"
},
{
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{
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}
],
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209,
213
]
],
"text": [
"GRAF"
],
"type": "Gene"
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{
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}
],
"offsets": [
[
321,
324
]
],
"text": [
"MLL"
],
"type": "Gene"
},
{
"id": "676",
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}
],
"offsets": [
[
420,
424
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "683",
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{
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}
],
"offsets": [
[
752,
756
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
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{
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}
],
"offsets": [
[
1077,
1081
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "686",
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{
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}
],
"offsets": [
[
1156,
1160
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "687",
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{
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"tax_id": null
}
],
"offsets": [
[
1259,
1263
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "688",
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{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1342,
1346
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "689",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1524,
1528
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "668",
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{
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"tax_id": null
}
],
"offsets": [
[
10,
14
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "669",
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{
"db_id": "4297",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
32,
35
]
],
"text": [
"MLL"
],
"type": "Gene"
},
{
"id": "670",
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{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
209,
213
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "675",
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{
"db_id": "4297",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
321,
324
]
],
"text": [
"MLL"
],
"type": "Gene"
},
{
"id": "676",
"normalized": [
{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
420,
424
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "683",
"normalized": [
{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
752,
756
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "684",
"normalized": [
{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1077,
1081
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "686",
"normalized": [
{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1156,
1160
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "687",
"normalized": [
{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1259,
1263
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "688",
"normalized": [
{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1342,
1346
]
],
"text": [
"GRAF"
],
"type": "Gene"
},
{
"id": "689",
"normalized": [
{
"db_id": "23092",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1524,
1528
]
],
"text": [
"GRAF"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 70,
"offset": 0
},
"text": "LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8.",
"type": "title"
},
{
"location": {
"length": 1031,
"offset": 71
},
"text": "Liver-expressed chemokine (LEC) is an unusually large CC chemokine, which is also known as LMC, HCC-4, NCC-4, and CCL16. Previously, LEC was shown to induce leukocyte migration but the responsible signaling receptors were not characterized. We report chemotaxis and competitive binding studies that show LEC binds to and activates CCR1 and CCR8 transfected HEK-293 cells. LEC induced maximal migration of CCR1 and CCR8 transfected cells at 89.3 nmol/L and cell adhesion at 5.6 nmol/L. The molar concentration of LEC required to induce maximum cell migration is 20- to 200-fold greater than that required for RANTES or I309, respectively. All 3 chemokines induced maximal static adhesion at 5 to 7 nmol/L. A neutralizing polyclonal antibody to LEC was developed to demonstrate that the unusually high concentration of LEC required to induce chemotaxis was a property of LEC and not as a result of an irrelevant protein contamination. This study suggests that LEC may be a more effective inducer of cell adhesion than cell migration.",
"type": "abstract"
}
] |
[
{
"id": "691",
"normalized": [
{
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] |
[
{
"location": {
"length": 124,
"offset": 0
},
"text": "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B.",
"type": "title"
},
{
"location": {
"length": 1398,
"offset": 125
},
"text": "Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The mutant ataxin-3 forms intranuclear inclusions in cultured cells as well as in diseased human brain and also causes cell death in transfected cells. However, the normal function of ataxin-3 remains unknown. To explore the function of ataxin-3, we used the two-hybrid system to screen for the protein(s) that interacts with ataxin-3. We found that ataxin-3 interacts with two human homologs of the yeast DNA repair protein RAD23, HHR23A and HHR23B. Furthermore, we confirmed that ataxin-3 interacts with the -ubiquitin-like domain at the N-terminus of the HHR23 proteins, which is important for nucleotide excision repair; however, ataxin-3 does not interact with -ubiquitin, implying that ataxin-3 might be functionally associated with the HHR23 proteins through this specific interaction. The normal and mutant ataxin-3 proteins show no difference in their ability to bind to the HHR23 proteins. However, in 293 cells HHR23A is recruited to intranuclear inclusions formed by the mutant ataxin-3 through its interaction with ataxin-3. These results suggest that this interaction is associated with the normal function of ataxin-3 and that some functional abnormality of the HHR23 proteins might exist in MJD.",
"type": "abstract"
}
] |
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18
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1436,
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"text": [
"ataxin-3"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 136,
"offset": 0
},
"text": "Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells.",
"type": "title"
},
{
"location": {
"length": 1659,
"offset": 137
},
"text": "X-linked retinoschisis is characterized by microcystic-like changes of the macular region and schisis within the inner retinal layers, leading to visual deterioration in males. Many missense and protein-truncating mutations of the causative gene RS1 have now been identified and are thought to be inactivating. RS1 encodes a 224 amino acid protein, retinoschisin, which contains a discoidin domain but is of unknown function. We have generated a polyclonal antibody against a peptide from a unique region within retinoschisin, which detects a protein of approximately 28 kDa in retinal samples reduced with dithiothreitol, but multimers sized >40 kDa under non-reducing conditions. A screen of human tissues with this antibody reveals retinoschisin to be retina specific and the antibody detects a protein of similar size in bovine and murine retinae. We investigated the expression pattern in the retina of both RS1 mRNA (using in situ hybridization with riboprobes) and retinoschisin (using immunohistochemistry). The antisense riboprobe detected RS1 mRNA only in the photoreceptor layer but the protein product of the gene was present both in the photoreceptors and within the inner portions of the retina. Furthermore, differentiated retinoblastoma cells (Weri-Rb1 cells) were found to express RS1 mRNA and to release retinoschisin. These results suggest that retinoschisin is released by photo-receptors and has functions within the inner retinal layers. Thus, X-linked retinoschisis is caused by abnormalities in a putative secreted photoreceptor protein and is the first example of a secreted photo-receptor protein associated with a retinal dystrophy.",
"type": "abstract"
}
] |
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0,
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19,
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383,
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137,
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383,
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448,
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486,
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649,
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872,
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1050,
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}
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1109,
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1186,
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1435,
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1501,
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}
],
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[
1603,
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]
],
"text": [
"X-linked retinoschisis"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 85,
"offset": 0
},
"text": "Identification of a common protein association region in the neuronal Cdk5 activator.",
"type": "title"
},
{
"location": {
"length": 1433,
"offset": 86
},
"text": "Cyclin-dependent protein kinase 5 (Cdk5) depends on the association with neuronal Cdk5 activator (Nck5a) for kinase activity. A variety of cellular proteins have been shown to undergo high affinity association with Nck5a, including three novel proteins, C42, C48, and C53 found by a yeast two-hybrid screen (Ching, Y. P., Qi, Z., and Wang, J. H. (2000) Gene 242, 285-294). The three proteins show competitive binding to Nck5a suggesting that they bind at a common site. The binding site has been mapped to a region of 26 amino acid residues (residues 145 to 170) at the N-terminal boundary of the kinase activation domain of Nck5a. This region of Nck5a contains an amphipathic alpha-helix whose hydrophobic face is involved in Cdk5 activation (Chin, K. T., Ohki, S, Tang, D., Cheng, H. C., Wang, J. H. , and Zhang, M. (1999) J. Biol. Chem. 274, 7120-7127). Several lines of evidence suggest that Nck5a interacts with the binding proteins at the hydrophilic face of the amphipathic alpha-helix. First, the Nck5a-(145-170) peptide can bind Cdk5 and Nck5a-binding proteins simultaneously. Second, the association of Nck5a-(145-170) to C48 can be markedly reduced by high ionic strength whereas the interaction between Nck5a and Cdk5 is not affected. Third, substitution of Glu(157) by glutamine in Nck5a-(145-170) abolishes the peptide's ability to bind to the three Nck5a-binding proteins without diminishing its Cdk5 binding activity.",
"type": "abstract"
}
] |
[
{
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}
],
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[
61,
84
]
],
"text": [
"neuronal Cdk5 activator"
],
"type": "Gene"
},
{
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{
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}
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[
86,
119
]
],
"text": [
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"type": "Gene"
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{
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}
],
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121,
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{
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159,
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]
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"text": [
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}
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"offsets": [
[
184,
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]
],
"text": [
"Nck5a"
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}
],
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]
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}
],
"offsets": [
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340,
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]
],
"text": [
"C42"
],
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{
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}
],
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345,
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]
],
"text": [
"C48"
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{
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}
],
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354,
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]
],
"text": [
"C53"
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}
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]
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}
],
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]
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}
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}
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}
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[
{
"location": {
"length": 283,
"offset": 0
},
"text": "CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor: chemotaxis and adhesion induced by its ligands, interferon gamma-inducible protein 10 and monokine induced by interferon gamma.",
"type": "title"
},
{
"location": {
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"offset": 284
},
"text": "CXC chemokine receptor 3 (CXCR3), which is known to be expressed predominately on memory and activated T lymphocytes, is a receptor for both interferon gamma (IFN-gamma)-inducible protein 10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report the novel finding that CXCR3 is also expressed on CD34(+) hematopoietic progenitors from human cord blood stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) but not on freshly isolated CD34(+) progenitors. Freshly isolated CD34(+) progenitors expressed low levels of CXCR3 messenger RNA, but this expression was highly up-regulated by GM-CSF, as indicated by a real-time quantitative reverse transcriptase-polymerase chain reaction technique. gamma IP-10 and Mig induced chemotaxis of GM-CSF-stimulated CD34(+) progenitors by means of CXCR3, since an anti-CXCR3 monoclonal antibody (mAb) was found to block gamma IP-10-induced and Mig-induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 mAb blocked these functions of gammaIP-10 and Mig but not of chemokine stromal cell-derived factor 1 alpha. gamma IP-10-induced and Mig-induced up-regulation of integrins (CD49a and CD49b) was found to play a crucial role in adhesion of GM-CSF-stimulated CD34(+) progenitors. Moreover, gamma IP-10 and Mig stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment for the physiologic and pathophysiologic events of differentiation of CD34(+) hematopoietic progenitors into lymphoid and myeloid stem cells, subsequently immune and inflammatory cells. These processes include transmigration, relocation, differentiation, and maturation of CD34(+) hematopoietic progenitors. (Blood. 2000;96:1230-1238)",
"type": "abstract"
}
] |
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"text": "The immune dysfunction and cell destruction that occur in the human immunodeficiency virus (HIV)-infected host appear to result from the direct cytopathic effects of viral infection and the effects of viral proteins on uninfected bystander cells. Recently, the alpha-chemokine receptor CXCR4 has been reported to mediate apoptosis in neuronal cells and in CD4(+) and CD8(+) T cells after its binding to HIV-1 envelope proteins. In the current study, it was observed that human umbilical vein endothelial cells (HUVEC) undergo apoptosis after their treatment with the HIV-1 envelope proteins gp120/160. Anti-CXCR4 monoclonal antibody decreased HIV-1 gp120/160-induced apoptosis, suggesting that the CXCR4 chemokine receptor mediates the apoptotic effects of these HIV envelope glycoproteins. Further studies revealed that caspases play an important role in this process because the pretreatment of cells with a general caspase enzyme inhibitor decreased the extent of HUVEC apoptosis induced by gp120/160. In addition, it was found that caspase-3 was activated on HIV-1 gp120/160 treatment of these cells. It was also observed that gp120/160 treatment slightly increased the expression of the pro-apoptotic molecule Bax. These results suggest that HIV-1 envelope glycoproteins can disrupt endothelial integrity through the interaction with CXCR4, thereby facilitating virus transit out of the bloodstream and contributing to the vascular injury syndromes seen in acquired immunodeficiency syndrome. (Blood. 2000;96:1438-1442)",
"type": "abstract"
}
] |
[
{
"id": "853",
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{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
357,
387
]
],
"text": [
"alpha-chemokine receptor CXCR4"
],
"type": "Gene"
},
{
"id": "857",
"normalized": [
{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
703,
708
]
],
"text": [
"CXCR4"
],
"type": "Gene"
},
{
"id": "859",
"normalized": [
{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
794,
799
]
],
"text": [
"CXCR4"
],
"type": "Gene"
},
{
"id": "863",
"normalized": [
{
"db_id": "836",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1132,
1141
]
],
"text": [
"caspase-3"
],
"type": "Gene"
},
{
"id": "866",
"normalized": [
{
"db_id": "581",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1311,
1314
]
],
"text": [
"Bax"
],
"type": "Gene"
},
{
"id": "868",
"normalized": [
{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1435,
1440
]
],
"text": [
"CXCR4"
],
"type": "Gene"
},
{
"id": "853",
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{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
357,
387
]
],
"text": [
"alpha-chemokine receptor CXCR4"
],
"type": "Gene"
},
{
"id": "857",
"normalized": [
{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
703,
708
]
],
"text": [
"CXCR4"
],
"type": "Gene"
},
{
"id": "859",
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{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
794,
799
]
],
"text": [
"CXCR4"
],
"type": "Gene"
},
{
"id": "863",
"normalized": [
{
"db_id": "836",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1132,
1141
]
],
"text": [
"caspase-3"
],
"type": "Gene"
},
{
"id": "866",
"normalized": [
{
"db_id": "581",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1311,
1314
]
],
"text": [
"Bax"
],
"type": "Gene"
},
{
"id": "868",
"normalized": [
{
"db_id": "7852",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1435,
1440
]
],
"text": [
"CXCR4"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 194,
"offset": 0
},
"text": "Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome).",
"type": "title"
},
{
"location": {
"length": 1308,
"offset": 195
},
"text": "Knobloch syndrome (KS) is an autosomal recessive disorder defined by the occurrence of high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele. The KS causative gene had been assigned to a 4.3 cM interval at 21q22.3 by linkage analysis of a large consanguineous Brazilian family. We reconstructed the haplotypes of this family with ten additional markers (five were novel) and narrowed the candidate interval to a region of < 245 kb, which contains 24 expressed sequence tags, the KIAA0958 gene and the 5' end of the COL18A1 gene. We identified a homozygous mutation at the AG consensus acceptor splice site of COL18A1 intron 1 exclusively among the 12 KS patients, which was not found among 140 control chromosomes. This mutation predicts the creation of a stop codon in exon 4 and therefore the truncation of the alpha1(XVIII) collagen short form, which was expressed in human adult retina. These findings provide evidence that KS is caused by mutations in COL18A1 which, therefore, has a major role in determining the retinal structure as well as in the closure of the neural tube. Therefore, we show for the first time that the absence of a collagen isoform impairs embryonic cell proliferation and/or migration as a primary or secondary effect.",
"type": "abstract"
}
] |
[
{
"id": "870",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
14
]
],
"text": [
"Collagen XVIII"
],
"type": "Gene"
},
{
"id": "872",
"normalized": [
{
"db_id": "23275",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
735,
743
]
],
"text": [
"KIAA0958"
],
"type": "Gene"
},
{
"id": "873",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
771,
778
]
],
"text": [
"COL18A1"
],
"type": "Gene"
},
{
"id": "875",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
865,
872
]
],
"text": [
"COL18A1"
],
"type": "Gene"
},
{
"id": "876",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1069,
1091
]
],
"text": [
"alpha1(XVIII) collagen"
],
"type": "Gene"
},
{
"id": "877",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1213,
1220
]
],
"text": [
"COL18A1"
],
"type": "Gene"
},
{
"id": "870",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
14
]
],
"text": [
"Collagen XVIII"
],
"type": "Gene"
},
{
"id": "872",
"normalized": [
{
"db_id": "23275",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
735,
743
]
],
"text": [
"KIAA0958"
],
"type": "Gene"
},
{
"id": "873",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
771,
778
]
],
"text": [
"COL18A1"
],
"type": "Gene"
},
{
"id": "875",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
865,
872
]
],
"text": [
"COL18A1"
],
"type": "Gene"
},
{
"id": "876",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1069,
1091
]
],
"text": [
"alpha1(XVIII) collagen"
],
"type": "Gene"
},
{
"id": "877",
"normalized": [
{
"db_id": "80781",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1213,
1220
]
],
"text": [
"COL18A1"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 74,
"offset": 0
},
"text": "CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.",
"type": "title"
},
{
"location": {
"length": 1369,
"offset": 75
},
"text": "Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKgamma in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.",
"type": "abstract"
}
] |
[
{
"id": "879",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
4
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "895",
"normalized": [
{
"db_id": "1147",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
523,
531
]
],
"text": [
"IKKalpha"
],
"type": "Gene"
},
{
"id": "896",
"normalized": [
{
"db_id": "3551",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
536,
543
]
],
"text": [
"IKKbeta"
],
"type": "Gene"
},
{
"id": "898",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
635,
639
]
],
"text": [
"NEMO"
],
"type": "Gene"
},
{
"id": "899",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
641,
670
]
],
"text": [
"NF-kappaB essential modulator"
],
"type": "Gene"
},
{
"id": "900",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
672,
680
]
],
"text": [
"IKKgamma"
],
"type": "Gene"
},
{
"id": "902",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
826,
830
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "906",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
923,
927
]
],
"text": [
"NEMO"
],
"type": "Gene"
},
{
"id": "907",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
928,
936
]
],
"text": [
"IKKgamma"
],
"type": "Gene"
},
{
"id": "908",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
975,
979
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "915",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1178,
1182
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "919",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1258,
1262
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "879",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
4
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "895",
"normalized": [
{
"db_id": "1147",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
523,
531
]
],
"text": [
"IKKalpha"
],
"type": "Gene"
},
{
"id": "896",
"normalized": [
{
"db_id": "3551",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
536,
543
]
],
"text": [
"IKKbeta"
],
"type": "Gene"
},
{
"id": "898",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
635,
639
]
],
"text": [
"NEMO"
],
"type": "Gene"
},
{
"id": "899",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
641,
670
]
],
"text": [
"NF-kappaB essential modulator"
],
"type": "Gene"
},
{
"id": "900",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
672,
680
]
],
"text": [
"IKKgamma"
],
"type": "Gene"
},
{
"id": "902",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
826,
830
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "906",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
923,
927
]
],
"text": [
"NEMO"
],
"type": "Gene"
},
{
"id": "907",
"normalized": [
{
"db_id": "8517",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
928,
936
]
],
"text": [
"IKKgamma"
],
"type": "Gene"
},
{
"id": "908",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
975,
979
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "915",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1178,
1182
]
],
"text": [
"CIKS"
],
"type": "Gene"
},
{
"id": "919",
"normalized": [
{
"db_id": "10758",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1258,
1262
]
],
"text": [
"CIKS"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 96,
"offset": 0
},
"text": "Functional consequences of tumorigenic missense mutations in the amino-terminal domain of Smad4.",
"type": "title"
},
{
"location": {
"length": 1590,
"offset": 97
},
"text": "Smads, the intracellular effectors of transforming growth factor-beta (TGF-beta) family members, are somatically mutated at high frequency in particular types of human cancers. Certain of these mutations affect the Smad amino-terminal domain, which, in the case of Smad3 and Smad4, binds DNA. We investigated the functional consequences of four missense mutations in the Smad4 amino-terminal domain found in human tumors. The mutant proteins were found to have impaired abilities to bind DNA although they were fully capable of forming complexes with Smad3. All four Smad4 mutants showed decreased protein stability compared to wild-type Smad4. Two of the Smad4 mutants (G65V and P130S) were translocated to the nucleus and were capable of transactivating a Smad-dependent promoter in a ligand-dependent manner. In contrast, the L43S and R100T mutants were not translocated efficiently to the nucleus and consequently resulted in severely defective transcriptional responses to TGF-beta. Moreover, we demonstrate here the critical importance of two basic residues in the beta-hairpin loop of Smad3 or Smad4 for DNA binding, consistent with predictions from the Smad3 crystal structure. In addition, our results reveal that in the TGF-beta-induced heteromeric signaling complex, loss of DNA binding of Smad4 can be compensated by Smad3, however, both Smad3 and Smad4 are needed for efficient DNA binding and signaling. In conclusion, mutations in the amino-terminal domain of Smad4, that are found in cancer, show loss of multiple functional properties which may contribute to tumorigenesis.",
"type": "abstract"
}
] |
[
{
"id": "923",
"normalized": [
{
"db_id": "4089",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
90,
95
]
],
"text": [
"Smad4"
],
"type": "Gene"
},
{
"id": "929",
"normalized": [
{
"db_id": "4088",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
362,
367
]
],
"text": [
"Smad3"
],
"type": "Gene"
},
{
"id": "930",
"normalized": [
{
"db_id": "4089",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
372,
377
]
],
"text": [
"Smad4"
],
"type": "Gene"
},
{
"id": "931",
"normalized": [
{
"db_id": "4089",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
468,
473
]
],
"text": [
"Smad4"
],
"type": "Gene"
},
{
"id": "933",
"normalized": [
{
"db_id": "4088",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
648,
653
]
],
"text": [
"Smad3"
],
"type": "Gene"
},
{
"id": "934",
"normalized": [
{
"db_id": "4089",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
664,
669
]
],
"text": [
"Smad4"
],
"type": "Gene"
},
{
"id": "935",
"normalized": [
{
"db_id": "4089",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
735,
740
]
],
"text": [
"Smad4"
],
"type": "Gene"
},
{
"id": "936",
"normalized": [
{
"db_id": "4089",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
753,
758
]
],
"text": [
"Smad4"
],
"type": "Gene"
},
{
"id": "940",
"normalized": [
{
"db_id": "4088",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1189,
1194
]
],
"text": [
"Smad3"
],
"type": "Gene"
},
{
"id": "941",
"normalized": [
{
"db_id": "4089",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1198,
1203
]
],
"text": [
"Smad4"
],
"type": "Gene"
},
{
"id": "942",
"normalized": [
{
"db_id": "4088",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1258,
1263
]
],
"text": [
"Smad3"
],
"type": "Gene"
},
{
"id": "944",
"normalized": [
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"Smad4"
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] |
[
{
"location": {
"length": 75,
"offset": 0
},
"text": "Interaction between LIS1 and doublecortin, two lissencephaly gene products.",
"type": "title"
},
{
"location": {
"length": 1138,
"offset": 76
},
"text": "Mutations in either LIS1 or DCX are the most common cause for type I lissencephaly. Here we report that LIS1 and DCX interact physically both in vitro and in vivo. Epitope-tagged DCX transiently expressed in COS cells can be co-immunoprecipitated with endogenous LIS1. Furthermore, endogenous DCX could be co-immunoprecipitated with endogenous LIS1 in embryonic brain extracts, demonstrating an in vivo association. The two protein products also co-localize in transfected cells and in primary neuronal cells. In addition, we demonstrate homodimerization of DCX in vitro. Using fragments of both LIS1 and DCX, the domains of interaction were mapped. LIS1 and DCX interact with tubulin and microtubules. Our results suggest that addition of DCX and LIS1 to tubulin enhances polymerization in an additive fashion. In in vitro competition assays, when LIS1 is added first, DCX competes with LIS1 in its binding to microtubules, but when DCX is added prior to the addition of LIS1 it enhances the binding of LIS1 to microtubules. We conclude that LIS1 and DCX cross-talk is important to microtubule function in the developing cerebral cortex.",
"type": "abstract"
}
] |
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"type": "Gene"
},
{
"id": "976",
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{
"db_id": "5048",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1119,
1123
]
],
"text": [
"LIS1"
],
"type": "Gene"
},
{
"id": "977",
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{
"db_id": "1641",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1128,
1131
]
],
"text": [
"DCX"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 127,
"offset": 0
},
"text": "Localization and enhanced current density of the Kv4.2 potassium channel by interaction with the actin-binding protein filamin.",
"type": "title"
},
{
"location": {
"length": 1543,
"offset": 128
},
"text": "Kv4.2 potassium channels play a critical role in postsynaptic excitability. Immunocytochemical studies reveal a somatodendritic Kv4.2 expression pattern, with the channels concentrated mainly at dendritic spines. The molecular mechanism that underlies the localization of Kv4.2 to this subcellular region is unknown. We used the yeast two-hybrid system to identify the Kv4.2-associated proteins that are involved in channel localization. Here we demonstrate a direct interaction between Kv4.2 and the actin-binding protein, filamin. We show that Kv4.2 and filamin can be coimmunoprecipitated both in vitro and in brain and that Kv4.2 and filamin share an overlapping expression pattern in the cerebellum and cultured hippocampal neurons. To examine the functional consequences of this interaction, we expressed Kv4.2 in filamin(+) and filamin(-) cells and performed immunocytochemical and electrophysiological analyses. Our results indicate that Kv4.2 colocalizes with filamin at filopodial roots in filamin(+) cells but shows a nonspecific expression pattern in filamin(-) cells, with no localization to filopodial roots. Furthermore, the magnitude of whole-cell Kv4.2 current density is approximately 2.7-fold larger in filamin(+) cells as compared with these currents in filamin(-) cells. We propose that filamin may function as a scaffold protein in the postsynaptic density, mediating a direct link between Kv4.2 and the actin cytoskeleton, and that this interaction is essential for the generation of appropriate Kv4.2 current densities.",
"type": "abstract"
}
] |
[
{
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
49,
54
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "982",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
128,
133
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "983",
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{
"db_id": "3751",
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"tax_id": null
}
],
"offsets": [
[
256,
261
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "984",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
400,
405
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "985",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
497,
502
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "986",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
615,
620
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "989",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
674,
679
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "991",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
756,
761
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "993",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
939,
944
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "994",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1074,
1079
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "996",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1292,
1297
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "998",
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{
"db_id": "3751",
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"tax_id": null
}
],
"offsets": [
[
1540,
1545
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "999",
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{
"db_id": "3751",
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"tax_id": null
}
],
"offsets": [
[
1647,
1652
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "979",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
49,
54
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "982",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
128,
133
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "983",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
256,
261
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "984",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
400,
405
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "985",
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{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
497,
502
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "986",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
615,
620
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "989",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
674,
679
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "991",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
756,
761
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "993",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
939,
944
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "994",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1074,
1079
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "996",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1292,
1297
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "998",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1540,
1545
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
},
{
"id": "999",
"normalized": [
{
"db_id": "3751",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1647,
1652
]
],
"text": [
"Kv4.2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 145,
"offset": 0
},
"text": "Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness.",
"type": "title"
},
{
"location": {
"length": 984,
"offset": 146
},
"text": "Approximately 50% of childhood deafness is caused by mutations in specific genes. Autosomal recessive loci account for approximately 80% of nonsyndromic genetic deafness. Here we report the identification of a new transmembrane serine protease (TMPRSS3; also known as ECHOS1) expressed in many tissues, including fetal cochlea, which is mutated in the families used to describe both the DFNB10 and DFNB8 loci. An 8-bp deletion and insertion of 18 monomeric (approximately 68-bp) beta-satellite repeat units, normally present in tandem arrays of up to several hundred kilobases on the short arms of acrocentric chromosomes, causes congenital deafness (DFNB10). A mutation in a splice-acceptor site, resulting in a 4-bp insertion in the mRNA and a frameshift, was detected in childhood onset deafness (DFNB8). This is the first description of beta-satellite insertion into an active gene resulting in a pathogenic state, and the first description of a protease involved in hearing loss.",
"type": "abstract"
}
] |
[
{
"id": "1003",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
391,
398
]
],
"text": [
"TMPRSS3"
],
"type": "Gene"
},
{
"id": "1004",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
414,
420
]
],
"text": [
"ECHOS1"
],
"type": "Gene"
},
{
"id": "1005",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
533,
539
]
],
"text": [
"DFNB10"
],
"type": "Gene"
},
{
"id": "1006",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
544,
549
]
],
"text": [
"DFNB8"
],
"type": "Gene"
},
{
"id": "1007",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
797,
803
]
],
"text": [
"DFNB10"
],
"type": "Gene"
},
{
"id": "1009",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
946,
951
]
],
"text": [
"DFNB8"
],
"type": "Gene"
},
{
"id": "1003",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
391,
398
]
],
"text": [
"TMPRSS3"
],
"type": "Gene"
},
{
"id": "1004",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
414,
420
]
],
"text": [
"ECHOS1"
],
"type": "Gene"
},
{
"id": "1005",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
533,
539
]
],
"text": [
"DFNB10"
],
"type": "Gene"
},
{
"id": "1006",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
544,
549
]
],
"text": [
"DFNB8"
],
"type": "Gene"
},
{
"id": "1007",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
797,
803
]
],
"text": [
"DFNB10"
],
"type": "Gene"
},
{
"id": "1009",
"normalized": [
{
"db_id": "64699",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
946,
951
]
],
"text": [
"DFNB8"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 102,
"offset": 0
},
"text": "A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression.",
"type": "title"
},
{
"location": {
"length": 883,
"offset": 103
},
"text": "Germline mutations of the human BRCA2 gene confer susceptibility to breast cancer. Although the function of the BRCA2 protein remains to be determined, murine cells homozygous for BRCA2 inactivation display chromosomal aberrations. We have isolated a 2 MDa BRCA2-containing complex and identified a structural DNA binding component, designated as BRCA2-Associated Factor 35 (BRAF35). BRAF35 contains a nonspecific DNA binding HMG domain and a kinesin-like coiled coil domain. Similar to BRCA2, BRAF35 mRNA expression levels in mouse embryos are highest in proliferating tissues with high mitotic index. Strikingly, nuclear staining revealed a close association of BRAF35/BRCA2 complex with condensed chromatin coincident with histone H3 phosphorylation. Importantly, antibody microinjection experiments suggest a role for BRCA2/BRAF35 complex in modulation of cell cycle progression.",
"type": "abstract"
}
] |
[
{
"id": "1011",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
8,
13
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1012",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
135,
140
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1013",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
215,
220
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1016",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
450,
476
]
],
"text": [
"BRCA2-Associated Factor 35"
],
"type": "Gene"
},
{
"id": "1017",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
478,
484
]
],
"text": [
"BRAF35"
],
"type": "Gene"
},
{
"id": "1018",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
487,
493
]
],
"text": [
"BRAF35"
],
"type": "Gene"
},
{
"id": "1021",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
590,
595
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1023",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
767,
773
]
],
"text": [
"BRAF35"
],
"type": "Gene"
},
{
"id": "1024",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
774,
779
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1025",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
925,
930
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1026",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
931,
937
]
],
"text": [
"BRAF35"
],
"type": "Gene"
},
{
"id": "1011",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
8,
13
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1012",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
135,
140
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1013",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
215,
220
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1016",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
450,
476
]
],
"text": [
"BRCA2-Associated Factor 35"
],
"type": "Gene"
},
{
"id": "1017",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
478,
484
]
],
"text": [
"BRAF35"
],
"type": "Gene"
},
{
"id": "1018",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
487,
493
]
],
"text": [
"BRAF35"
],
"type": "Gene"
},
{
"id": "1021",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
590,
595
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1023",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
767,
773
]
],
"text": [
"BRAF35"
],
"type": "Gene"
},
{
"id": "1024",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
774,
779
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1025",
"normalized": [
{
"db_id": "675",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
925,
930
]
],
"text": [
"BRCA2"
],
"type": "Gene"
},
{
"id": "1026",
"normalized": [
{
"db_id": "10362",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
931,
937
]
],
"text": [
"BRAF35"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 108,
"offset": 0
},
"text": "Cloning, expression and chromosomal location of NKX6B TO 10Q26, a region frequently deleted in brain tumors.",
"type": "title"
},
{
"location": {
"length": 1105,
"offset": 109
},
"text": "Nkx6-2 (former Gtx) is a murine-homeobox-containing gene localized distally on Chromosome (Chr) 7. Analysis of the expression pattern, together with DNA binding assays, suggests that this gene product might be important for differentiated oligodendrocyte function and in the regulation of myelin gene expression. We now report on the cloning and characterization of the human homolog (NKX6B). DNA sequence analysis of an 11-kb genomic fragment revealed that the complete human gene spans 1.2 kb and is composed of three exons. NKX6B is predicted to encode a polypeptide of 277 amino acids with 97% identity to mouse Nkx6-2. Northern blot experiments showed that NKX6B expression is tightly controlled in a tissue-specific fashion with the highest site of expression being the brain. Finally, using STS content mapping and RH analyis, we demonstrated that NKX6B maps to the 10q26, a region where frequent loss of heterozygosity has been observed in various malignant brain tumors. These results may implicate NKX6B as a candidate tumor suppressor gene for brain tumors, particularly for oligodendrogliomas.",
"type": "abstract"
}
] |
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[
{
"location": {
"length": 132,
"offset": 0
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"text": "Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells.",
"type": "title"
},
{
"location": {
"length": 980,
"offset": 133
},
"text": "Tumour progression is regulated by the balance of proliferation and apoptosis in the tumour cell population. To date, the role of vascular endothelial growth factor (VEGF) in tumour growth has been attributed to the induction of angiogenesis. VEGF has been shown to be a survival factor for endothelial cells, preventing apoptosis by inducing Bcl-2 expression. In both murine (4T1) and human (MDA-MB-231) metastatic mammary carcinoma cell lines, we found that VEGF upregulated Bcl-2 expression and anti-VEGF antibodies reduced Bcl-2 expression. These alterations in Bcl-2 expression were reflected by the levels of tumour cell apoptosis. VEGF resulted in reduced tumour cell apoptosis, whereas its inhibition with anti-VEGF neutralizing antibodies induced apoptosis directly in tumour cells. Therefore, in addition to its role in angiogenesis and vessel permeability, VEGF acts as a survival factor for tumour cells, inducing Bcl-2 expression and inhibiting tumour cell apoptosis.",
"type": "abstract"
}
] |
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] |
[
{
"location": {
"length": 114,
"offset": 0
},
"text": "Endothelial cell costimulation of T cell activation through CD58-CD2 interactions involves lipid raft aggregation.",
"type": "title"
},
{
"location": {
"length": 1463,
"offset": 115
},
"text": "Human endothelial cells (EC) costimulate CD4(+) memory T cell activation through CD58-CD2 interactions. In this study we tested the hypothesis that EC activate distinct costimulatory pathways in T cells that target specific transcription factors. AP-1, composed of fos and jun proteins, is a critical effector of TCR signaling and binds several sites in the IL-2 promoter. EC augment c-fos promoter activity in T cells; however, deletion analysis reveals no transcription factor binding sites in the promoter uniquely responsive to EC costimulation. Overexpression of AP-1 proteins in T cells augments the activity of an AP-1-luciferase reporter gene equally in the absence or the presence of EC costimulation. Interestingly, EC stimulate a similar 2- to 3-fold up-regulation of AP-1, NF-AT, NF-kappaB, and NF-IL-2-luciferase reporters. CD2 mAbs completely block EC effects on all of these pathways, as well as costimulation of IL-2 secretion. We conclude that EC costimulation through CD2 does not trigger a single distinct costimulatory pathway in T cells, but rather, it amplifies several pathways downstream of the TCR. Indeed, we find that early EC costimulation acts \" upstream \" of the TCR by promoting lipid raft aggregation, thus amplifying TCR signaling. Soluble CD2 mAbs block EC-induced raft aggregation, whereas cross-linking CD2 promotes aggregation. These data are consistent with the critical role of CD2 in organizing the T cell-APC contact zone.",
"type": "abstract"
}
] |
[
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],
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"text": [
"CD58"
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],
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"CD4"
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],
"text": [
"CD58"
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],
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201,
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],
"text": [
"CD2"
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}
],
"offsets": [
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380,
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],
"text": [
"fos"
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"type": "Gene"
},
{
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{
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}
],
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]
],
"text": [
"jun"
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],
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473,
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],
"text": [
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{
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}
],
"offsets": [
[
499,
504
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],
"text": [
"c-fos"
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"type": "Gene"
},
{
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{
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952,
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"text": [
"CD2"
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"text": [
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1101,
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"CD2"
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[
1388,
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"text": [
"CD2"
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"id": "1077",
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"offsets": [
[
1454,
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"text": [
"CD2"
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"id": "1078",
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"offsets": [
[
1532,
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"text": [
"CD2"
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"id": "1056",
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],
"offsets": [
[
60,
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"text": [
"CD58"
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"id": "1057",
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{
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65,
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"text": [
"CD2"
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[
156,
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]
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"text": [
"CD4"
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"id": "1059",
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{
"db_id": "965",
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[
196,
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]
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"text": [
"CD58"
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"id": "1060",
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{
"db_id": "914",
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"offsets": [
[
201,
204
]
],
"text": [
"CD2"
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"id": "1063",
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{
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}
],
"offsets": [
[
380,
383
]
],
"text": [
"fos"
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"type": "Gene"
},
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"id": "1064",
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{
"db_id": "3725",
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}
],
"offsets": [
[
388,
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]
],
"text": [
"jun"
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"type": "Gene"
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{
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}
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[
473,
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"text": [
"IL-2"
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{
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}
],
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[
499,
504
]
],
"text": [
"c-fos"
],
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[
952,
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"CD2"
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"IL-2"
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1101,
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"CD2"
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}
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[
1388,
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"text": [
"CD2"
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"type": "Gene"
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}
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[
1454,
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"text": [
"CD2"
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"type": "Gene"
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"id": "1078",
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}
],
"offsets": [
[
1532,
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]
],
"text": [
"CD2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 148,
"offset": 0
},
"text": "Protocadherin LKC, a new candidate for a tumor suppressor of colon and liver cancers, its association with contact inhibition of cell proliferation.",
"type": "title"
},
{
"location": {
"length": 1574,
"offset": 149
},
"text": "Protocadherins are a major subfamily of the cadherin superfamily, but little is known about their functions and intracellular signal transduction. We cloned a novel human protocadherin gene, containing seven EC domains, and identified functional aspects of this gene. The gene was predominantly expressed in liver, kidney and colon tissues, and was thus designated Protocadherin LKC. The expression of Protocadherin LKC is markedly reduced in cancers arising from these tissues at both transcriptional and protein levels. To investigate the effects of Protocadherin LKC expression in colon cancer, we introduced the gene into colon cancer cell line HCT116, which does not express this gene. Significantly, Protocadherin LKC expression induced contact inhibition of cell proliferation although it did not affect growth rate. When grown to post-confluence in monolayer cells cultures, Protocadherin LKC-expressing HCT116 no longer formed multiple cell layers and showed the typical paving stone morphology of normal epithelial cells. Furthermore, expression of Protocadherin LKC suppressed tumor formation of HCT116 cells in a nude mouse model. In addition, we identified a protein, hMAST205 (microtubule-associated serine/threonine kinase-205 kDa), which interacted with Protocadherin LKC; the interaction occurring between the PDZ domain of hMAST205 and C-terminal tail of Protocadherin LKC. Our results suggest that Protocadherin LKC, which directly binds PDZ protein, is a molecular switch for contact inhibition of epithelial cells in the liver, kidney and colon tissues.",
"type": "abstract"
}
] |
[
{
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}
],
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[
0,
17
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
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514,
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],
"type": "Gene"
},
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551,
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},
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],
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701,
718
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],
"type": "Gene"
},
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}
],
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855,
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"type": "Gene"
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{
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}
],
"offsets": [
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1032,
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],
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"Protocadherin LKC"
],
"type": "Gene"
},
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{
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}
],
"offsets": [
[
1208,
1225
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1113",
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{
"db_id": "23139",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1330,
1338
]
],
"text": [
"hMAST205"
],
"type": "Gene"
},
{
"id": "1114",
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{
"db_id": "23139",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1340,
1394
]
],
"text": [
"microtubule-associated serine/threonine kinase-205 kDa"
],
"type": "Gene"
},
{
"id": "1115",
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{
"db_id": "54825",
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}
],
"offsets": [
[
1419,
1436
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
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{
"db_id": "23139",
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}
],
"offsets": [
[
1490,
1498
]
],
"text": [
"hMAST205"
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"type": "Gene"
},
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{
"db_id": "54825",
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}
],
"offsets": [
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1522,
1539
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
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{
"db_id": "54825",
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}
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1566,
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]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
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"id": "1121",
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}
],
"offsets": [
[
1606,
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]
],
"text": [
"PDZ protein"
],
"type": "Gene"
},
{
"id": "1101",
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{
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}
],
"offsets": [
[
0,
17
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1107",
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"db_id": "54825",
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}
],
"offsets": [
[
514,
531
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
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"id": "1108",
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{
"db_id": "54825",
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}
],
"offsets": [
[
551,
568
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1109",
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{
"db_id": "54825",
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}
],
"offsets": [
[
701,
718
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1110",
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{
"db_id": "54825",
"db_name": "NCBIGene",
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}
],
"offsets": [
[
855,
872
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1111",
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{
"db_id": "54825",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1032,
1049
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1112",
"normalized": [
{
"db_id": "54825",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1208,
1225
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1113",
"normalized": [
{
"db_id": "23139",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1330,
1338
]
],
"text": [
"hMAST205"
],
"type": "Gene"
},
{
"id": "1114",
"normalized": [
{
"db_id": "23139",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1340,
1394
]
],
"text": [
"microtubule-associated serine/threonine kinase-205 kDa"
],
"type": "Gene"
},
{
"id": "1115",
"normalized": [
{
"db_id": "54825",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1419,
1436
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1117",
"normalized": [
{
"db_id": "23139",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1490,
1498
]
],
"text": [
"hMAST205"
],
"type": "Gene"
},
{
"id": "1119",
"normalized": [
{
"db_id": "54825",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1522,
1539
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1120",
"normalized": [
{
"db_id": "54825",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1566,
1583
]
],
"text": [
"Protocadherin LKC"
],
"type": "Gene"
},
{
"id": "1121",
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{
"db_id": "10207",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1606,
1617
]
],
"text": [
"PDZ protein"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 140,
"offset": 0
},
"text": "Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek.",
"type": "title"
},
{
"location": {
"length": 1374,
"offset": 141
},
"text": "Human Daxx is a protein that functions, in part, as a transcriptional co-repressor through its interaction with a growing number of nuclear, DNA-associated proteins. To determine the mechanism by which hDaxx represses transcription, we used conventional chromatography to isolate endogenous hDaxx. We determined that hDaxx has an apparent molecular weight of 360 kDa, which is consistent with the fact that multiple domains of hDaxx are required for transcriptional repression and suggests that hDaxx associates with multiple proteins. Using co-fractionation and co-immunoprecipitation we demonstrate that hDaxx associates with proteins that are critical for transcriptional repression, such as histone deacetylase II, constituents of chromatin such as core histones H2A, H2B, H3 and H4, and Dek, a chromatin-associated protein reported to change the topology of DNA in chromatin in vitro. We also demonstrate a requirement for the SPT domain and the first paired amphipathic helix of hDaxx for its association with histone deacetylase II and acetylated histone H4, respectively. Finally, we provide evidence suggesting that the association of hDaxx with chromatin-related proteins is dependent on the post-translational phosphorylation status of hDaxx. A working model for the repressive action of hDaxx through its association with chromatin related proteins is presented.",
"type": "abstract"
}
] |
[
{
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
4
]
],
"text": [
"Daxx"
],
"type": "Gene"
},
{
"id": "1124",
"normalized": [
{
"db_id": "3066",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
9,
31
]
],
"text": [
"histone deacetylase II"
],
"type": "Gene"
},
{
"id": "1125",
"normalized": [
{
"db_id": "7913",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
107,
139
]
],
"text": [
"chromatin-associated protein Dek"
],
"type": "Gene"
},
{
"id": "1126",
"normalized": [
{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
147,
151
]
],
"text": [
"Daxx"
],
"type": "Gene"
},
{
"id": "1129",
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
343,
348
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1130",
"normalized": [
{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
432,
437
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1131",
"normalized": [
{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
458,
463
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1132",
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
568,
573
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1133",
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
636,
641
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1134",
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
747,
752
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1135",
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{
"db_id": "3066",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
836,
858
]
],
"text": [
"histone deacetylase II"
],
"type": "Gene"
},
{
"id": "1139",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1126,
1131
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1140",
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{
"db_id": "3066",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1157,
1179
]
],
"text": [
"histone deacetylase II"
],
"type": "Gene"
},
{
"id": "1142",
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1285,
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]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1144",
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1388,
1393
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1145",
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{
"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1440,
1445
]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
{
"id": "1123",
"normalized": [
{
"db_id": "1616",
"db_name": "NCBIGene",
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}
],
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0,
4
]
],
"text": [
"Daxx"
],
"type": "Gene"
},
{
"id": "1124",
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{
"db_id": "3066",
"db_name": "NCBIGene",
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}
],
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9,
31
]
],
"text": [
"histone deacetylase II"
],
"type": "Gene"
},
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"id": "1125",
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"db_id": "7913",
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"offsets": [
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107,
139
]
],
"text": [
"chromatin-associated protein Dek"
],
"type": "Gene"
},
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"db_id": "1616",
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147,
151
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"text": [
"Daxx"
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343,
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],
"text": [
"hDaxx"
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"hDaxx"
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}
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]
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"hDaxx"
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"db_name": "NCBIGene",
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}
],
"offsets": [
[
568,
573
]
],
"text": [
"hDaxx"
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}
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]
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"hDaxx"
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}
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]
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"hDaxx"
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}
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"offsets": [
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836,
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]
],
"text": [
"histone deacetylase II"
],
"type": "Gene"
},
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"id": "1139",
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"db_id": "1616",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1126,
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]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
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"id": "1140",
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"db_name": "NCBIGene",
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}
],
"offsets": [
[
1157,
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]
],
"text": [
"histone deacetylase II"
],
"type": "Gene"
},
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"id": "1142",
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"db_name": "NCBIGene",
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}
],
"offsets": [
[
1285,
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]
],
"text": [
"hDaxx"
],
"type": "Gene"
},
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"id": "1144",
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"db_id": "1616",
"db_name": "NCBIGene",
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}
],
"offsets": [
[
1388,
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]
],
"text": [
"hDaxx"
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"type": "Gene"
},
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"id": "1145",
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"db_name": "NCBIGene",
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}
],
"offsets": [
[
1440,
1445
]
],
"text": [
"hDaxx"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 65,
"offset": 0
},
"text": "Regulation of human separase by securin binding and autocleavage.",
"type": "title"
},
{
"location": {
"length": 1575,
"offset": 66
},
"text": "BACKGROUND: Sister chromatid separation is initiated by separase, a protease that cleaves cohesin and thereby dissolves sister chromatid cohesion. Separase is activated by the degradation of its inhibitor securin and by the removal of inhibitory phosphates. In human cells, separase activation also coincides with the cleavage of separase, but it is not known if this reaction activates separase, which protease cleaves separase, and how separase cleavage is regulated.RESULTS: Inhibition of separase expression in human cells by RNA interference causes the formation of polyploid cells with large lobed nuclei. In mitosis, many of these cells contain abnormal chromosome plates with unseparated sister chromatids. Inhibitor binding experiments in vitro reveal that securin prevents the access of substrate analogs to the active site of separase. Upon securin degradation, the active site of full-length separase becomes accessible, allowing rapid autocatalytic cleavage of separase at one of three sites. The resulting N- and C-terminal fragments remain associated and can be reinhibited by securin. A noncleavable separase mutant retains its ability to cleave cohesin in vitro.CONCLUSIONS: Our results suggest that separase is required for sister chromatid separation during mitosis in human cells. Our data further indicate that securin inhibits separase by blocking the access of substrates to the active site of separase. Securin proteolysis allows autocatalytic processing of separase into a cleaved form, but separase cleavage is not essential for separase activation.",
"type": "abstract"
}
] |
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
20,
28
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1149",
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{
"db_id": "9232",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
32,
39
]
],
"text": [
"securin"
],
"type": "Gene"
},
{
"id": "1150",
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{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
122,
130
]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1151",
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{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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213,
221
]
],
"text": [
"Separase"
],
"type": "Gene"
},
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"id": "1152",
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{
"db_id": "9232",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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271,
278
]
],
"text": [
"securin"
],
"type": "Gene"
},
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"id": "1153",
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"db_id": "9700",
"db_name": "NCBIGene",
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}
],
"offsets": [
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340,
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]
],
"text": [
"separase"
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"type": "Gene"
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"id": "1154",
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"db_id": "9700",
"db_name": "NCBIGene",
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}
],
"offsets": [
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396,
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]
],
"text": [
"separase"
],
"type": "Gene"
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"id": "1155",
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"db_id": "9700",
"db_name": "NCBIGene",
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}
],
"offsets": [
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453,
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]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1156",
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{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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486,
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]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1157",
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{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
504,
512
]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1158",
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"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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558,
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]
],
"text": [
"separase"
],
"type": "Gene"
},
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"db_id": "9232",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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832,
839
]
],
"text": [
"securin"
],
"type": "Gene"
},
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"id": "1160",
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"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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903,
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]
],
"text": [
"separase"
],
"type": "Gene"
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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918,
925
]
],
"text": [
"securin"
],
"type": "Gene"
},
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"db_name": "NCBIGene",
"tax_id": null
}
],
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970,
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]
],
"text": [
"separase"
],
"type": "Gene"
},
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"tax_id": null
}
],
"offsets": [
[
1040,
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]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1164",
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1158,
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]
],
"text": [
"securin"
],
"type": "Gene"
},
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"id": "1165",
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1182,
1190
]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1166",
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}
],
"offsets": [
[
1283,
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]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1167",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1398,
1405
]
],
"text": [
"securin"
],
"type": "Gene"
},
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"id": "1168",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1415,
1423
]
],
"text": [
"separase"
],
"type": "Gene"
},
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"id": "1169",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1483,
1491
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1170",
"normalized": [
{
"db_id": "9232",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1493,
1500
]
],
"text": [
"Securin"
],
"type": "Gene"
},
{
"id": "1171",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1548,
1556
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1172",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1582,
1590
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1173",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1621,
1629
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1148",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
20,
28
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1149",
"normalized": [
{
"db_id": "9232",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
32,
39
]
],
"text": [
"securin"
],
"type": "Gene"
},
{
"id": "1150",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
122,
130
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1151",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
213,
221
]
],
"text": [
"Separase"
],
"type": "Gene"
},
{
"id": "1152",
"normalized": [
{
"db_id": "9232",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
271,
278
]
],
"text": [
"securin"
],
"type": "Gene"
},
{
"id": "1153",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
340,
348
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1154",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
396,
404
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1155",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
453,
461
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1156",
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{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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486,
494
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1157",
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{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
504,
512
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1158",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
558,
566
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1159",
"normalized": [
{
"db_id": "9232",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
832,
839
]
],
"text": [
"securin"
],
"type": "Gene"
},
{
"id": "1160",
"normalized": [
{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
903,
911
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1161",
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"tax_id": null
}
],
"offsets": [
[
918,
925
]
],
"text": [
"securin"
],
"type": "Gene"
},
{
"id": "1162",
"normalized": [
{
"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
970,
978
]
],
"text": [
"separase"
],
"type": "Gene"
},
{
"id": "1163",
"normalized": [
{
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}
],
"offsets": [
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1040,
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]
],
"text": [
"separase"
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"type": "Gene"
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"id": "1164",
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}
],
"offsets": [
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1158,
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]
],
"text": [
"securin"
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"type": "Gene"
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}
],
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1182,
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]
],
"text": [
"separase"
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"type": "Gene"
},
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"id": "1166",
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}
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1283,
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]
],
"text": [
"separase"
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"type": "Gene"
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"id": "1167",
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"tax_id": null
}
],
"offsets": [
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1398,
1405
]
],
"text": [
"securin"
],
"type": "Gene"
},
{
"id": "1168",
"normalized": [
{
"db_id": "9700",
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}
],
"offsets": [
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1415,
1423
]
],
"text": [
"separase"
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"type": "Gene"
},
{
"id": "1169",
"normalized": [
{
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}
],
"offsets": [
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1483,
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]
],
"text": [
"separase"
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"type": "Gene"
},
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"id": "1170",
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"tax_id": null
}
],
"offsets": [
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1493,
1500
]
],
"text": [
"Securin"
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"type": "Gene"
},
{
"id": "1171",
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"tax_id": null
}
],
"offsets": [
[
1548,
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]
],
"text": [
"separase"
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"type": "Gene"
},
{
"id": "1172",
"normalized": [
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"db_id": "9700",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1582,
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]
],
"text": [
"separase"
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"type": "Gene"
},
{
"id": "1173",
"normalized": [
{
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}
],
"offsets": [
[
1621,
1629
]
],
"text": [
"separase"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 88,
"offset": 0
},
"text": "Contribution of CD3 gamma to TCR regulation and signaling in human mature T lymphocytes.",
"type": "title"
},
{
"location": {
"length": 1169,
"offset": 89
},
"text": "CD3 proteins may have redundant as well as specific contributions to the intracellular propagation and final effector responses of TCR-mediated signals at different checkpoints during T cell differentiation. We report here on the participation of CD3 gamma in the activation and effector function of human mature T lymphocytes at the antigen recognition checkpoint. Following TCR-CD3 engagement of human CD3 gamma-deficient T cell lines, and despite their lower TCR-CD3 surface levels compared to normal controls, mature T cell responses such as protein tyrosine phosphorylation and the regulation of expression of several cell surface molecules, including the TCR-CD3 itself, were either normal or only slightly affected. In contrast, other physiological responses like the specific adhesion and concomitant cell polarization on ICAM-1-coated dishes were selectively defective, and activation-induced cell death was increased. Our data indicate that CD3 gamma contributes essential specialized signaling functions to certain mature T cell responses. Failure to generate appropriate interactions may abort cytoskeleton reorganization and initiate an apoptotic response.",
"type": "abstract"
}
] |
[
{
"id": "1175",
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{
"db_id": "917",
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"tax_id": null
}
],
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[
16,
25
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"CD3 gamma"
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},
{
"id": "1179",
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{
"db_id": "917",
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}
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[
336,
345
]
],
"text": [
"CD3 gamma"
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"type": "Gene"
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{
"id": "1182",
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{
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493,
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"CD3 gamma"
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}
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919,
925
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"ICAM-1"
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1040,
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"CD3 gamma"
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16,
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"CD3 gamma"
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336,
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"CD3 gamma"
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493,
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"CD3 gamma"
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{
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}
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"offsets": [
[
919,
925
]
],
"text": [
"ICAM-1"
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{
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"offsets": [
[
1040,
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],
"text": [
"CD3 gamma"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 103,
"offset": 0
},
"text": "ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles.",
"type": "title"
},
{
"location": {
"length": 1388,
"offset": 104
},
"text": "Cells can release membrane components in a soluble form and as membrane vesicles. L1, an important molecule for cell migration of neural and tumor cells, is released by membrane-proximal cleavage, and soluble L1 promotes cell migration. Release of L1 is enhanced by shedding inducers such as phorbol ester and pervanadate, but it is also enhanced by depletion of cellular cholesterol with methyl-beta-cyclodextrin (MCD). How such different compounds can induce shedding is presently unknown. We show here that ADAM10 is involved in L1 cleavage, which occurs at the cell surface and in the Golgi apparatus. MCD and pervanadate treatment induced the release of microvesicles containing full-length L1 and the active form of ADAM10. L1 cleavage occurred in isolated vesicles. L1-containing microvesicles could trigger haptotactic cell migration. Only the neural L1 form carrying the RSLE signal for clathrin-dependent endocytosis was recruited and cleaved in vesicles. Phorbol ester treatment activated L1 cleavage predominantly at the cell surface. Our results provide evidence for two pathways of L1 cleavage, based on ADAM10 localization, that can be activated differentially: 1) direct cleavage at the cell surface, and 2) release and cleavage in secretory vesicles most likely derived from the Golgi apparatus. The findings establish a novel role for ADAM10 as a vesicle-based protease.",
"type": "abstract"
}
] |
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}
],
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[
0,
6
]
],
"text": [
"ADAM10"
],
"type": "Gene"
},
{
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{
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28,
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},
{
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{
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}
],
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186,
188
]
],
"text": [
"L1"
],
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},
{
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{
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],
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313,
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"L1"
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{
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{
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}
],
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352,
354
]
],
"text": [
"L1"
],
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},
{
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{
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}
],
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614,
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"ADAM10"
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{
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],
"offsets": [
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636,
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]
],
"text": [
"L1"
],
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{
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}
],
"offsets": [
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800,
802
]
],
"text": [
"L1"
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}
],
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826,
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"ADAM10"
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{
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}
],
"offsets": [
[
834,
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],
"text": [
"L1"
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"type": "Gene"
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{
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{
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}
],
"offsets": [
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877,
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]
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"text": [
"L1"
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{
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{
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}
],
"offsets": [
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963,
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"text": [
"L1"
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{
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}
],
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1104,
1106
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"L1"
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}
],
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1200,
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"L1"
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}
],
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1222,
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"text": [
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],
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0,
6
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],
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28,
48
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],
"text": [
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}
],
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186,
188
]
],
"text": [
"L1"
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}
],
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313,
315
]
],
"text": [
"L1"
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"type": "Gene"
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],
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352,
354
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],
"text": [
"L1"
],
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}
],
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614,
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],
"text": [
"ADAM10"
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}
],
"offsets": [
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636,
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]
],
"text": [
"L1"
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}
],
"offsets": [
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800,
802
]
],
"text": [
"L1"
],
"type": "Gene"
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{
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}
],
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826,
832
]
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"text": [
"ADAM10"
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}
],
"offsets": [
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834,
836
]
],
"text": [
"L1"
],
"type": "Gene"
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{
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"tax_id": null
}
],
"offsets": [
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877,
879
]
],
"text": [
"L1"
],
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}
],
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963,
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],
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"L1"
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}
],
"offsets": [
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1104,
1106
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],
"text": [
"L1"
],
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}
],
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1200,
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}
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1222,
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"text": [
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}
],
"offsets": [
[
1457,
1463
]
],
"text": [
"ADAM10"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 38,
"offset": 0
},
"text": "Yaf2 inhibits Myc biological function.",
"type": "title"
},
{
"location": {
"length": 822,
"offset": 39
},
"text": "The proto-oncogenes of the myelocytomatosis viral oncogene homolog (MYC) family, including MYC, MYCN and MYCL, encode nuclear proteins that act as transcription factors. The Myc protein is the best studied member of this family and is involved in cell cycle regulation, differentiation and cell death. We have previously demonstrated that the zinc-finger protein Yaf2 interacts with the central region of MycN and enhances MycN dependent transcriptional activation. Here we show that Yaf2 also binds to the Myc protein in vivo and in vitro. In contrast to the activating effect on MycN function, Yaf2 inhibits Myc mediated transactivation and transformation. This differential influence on two members of the Myc family gives insight into a new mechanism to modulate the biological activities of Myc transcription factors.",
"type": "abstract"
}
] |
[
{
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
4
]
],
"text": [
"Yaf2"
],
"type": "Gene"
},
{
"id": "1210",
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{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
14,
17
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1214",
"normalized": [
{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
130,
133
]
],
"text": [
"MYC"
],
"type": "Gene"
},
{
"id": "1215",
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{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
135,
139
]
],
"text": [
"MYCN"
],
"type": "Gene"
},
{
"id": "1216",
"normalized": [
{
"db_id": "4610",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
144,
148
]
],
"text": [
"MYCL"
],
"type": "Gene"
},
{
"id": "1217",
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{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
213,
216
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1219",
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{
"db_id": "10138",
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"tax_id": null
}
],
"offsets": [
[
402,
406
]
],
"text": [
"Yaf2"
],
"type": "Gene"
},
{
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{
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"tax_id": null
}
],
"offsets": [
[
444,
448
]
],
"text": [
"MycN"
],
"type": "Gene"
},
{
"id": "1221",
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{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
462,
466
]
],
"text": [
"MycN"
],
"type": "Gene"
},
{
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{
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}
],
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523,
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]
],
"text": [
"Yaf2"
],
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{
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}
],
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[
546,
549
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1224",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
624
]
],
"text": [
"MycN"
],
"type": "Gene"
},
{
"id": "1225",
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{
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"tax_id": null
}
],
"offsets": [
[
635,
639
]
],
"text": [
"Yaf2"
],
"type": "Gene"
},
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{
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"tax_id": null
}
],
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[
649,
652
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1227",
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{
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"tax_id": null
}
],
"offsets": [
[
748,
751
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1228",
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{
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"tax_id": null
}
],
"offsets": [
[
835,
838
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1209",
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{
"db_id": "10138",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
4
]
],
"text": [
"Yaf2"
],
"type": "Gene"
},
{
"id": "1210",
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{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
14,
17
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1214",
"normalized": [
{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
130,
133
]
],
"text": [
"MYC"
],
"type": "Gene"
},
{
"id": "1215",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
135,
139
]
],
"text": [
"MYCN"
],
"type": "Gene"
},
{
"id": "1216",
"normalized": [
{
"db_id": "4610",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
144,
148
]
],
"text": [
"MYCL"
],
"type": "Gene"
},
{
"id": "1217",
"normalized": [
{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
213,
216
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1219",
"normalized": [
{
"db_id": "10138",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
402,
406
]
],
"text": [
"Yaf2"
],
"type": "Gene"
},
{
"id": "1220",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
444,
448
]
],
"text": [
"MycN"
],
"type": "Gene"
},
{
"id": "1221",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
462,
466
]
],
"text": [
"MycN"
],
"type": "Gene"
},
{
"id": "1222",
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{
"db_id": "10138",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
523,
527
]
],
"text": [
"Yaf2"
],
"type": "Gene"
},
{
"id": "1223",
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{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
546,
549
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1224",
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{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
624
]
],
"text": [
"MycN"
],
"type": "Gene"
},
{
"id": "1225",
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{
"db_id": "10138",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
635,
639
]
],
"text": [
"Yaf2"
],
"type": "Gene"
},
{
"id": "1226",
"normalized": [
{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
649,
652
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1227",
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{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
748,
751
]
],
"text": [
"Myc"
],
"type": "Gene"
},
{
"id": "1228",
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{
"db_id": "4609",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
835,
838
]
],
"text": [
"Myc"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 59,
"offset": 0
},
"text": "Expression cloning of a human dual-specificity phosphatase.",
"type": "title"
},
{
"location": {
"length": 1106,
"offset": 60
},
"text": "Using an expression cloning strategy, we isolated a cDNA encoding a human protein-tyrosine-phosphatase. Bacteria expressing the kinase domain of the keratinocyte growth factor receptor (bek/fibroblast growth factor receptor 2) were infected with a fibroblast cDNA library in a phagemid prokaryotic expression vector and screened with a monoclonal anti-phosphotyrosine antibody. Among several clones showing decreased anti-phosphotyrosine recognition, one displayed phosphatase activity toward the kinase in vitro. The 4.1-kilobase cDNA encoded a deduced protein of 185 amino acids with limited sequence similarity to the vaccinia virus phosphatase VH1. The purified recombinant protein dephosphorylated several activated growth factor receptors, as well as serine-phosphorylated casein, in vitro. Both serine and tyrosine phosphatase activities were completely abolished by mutagenesis of a single cysteine residue conserved in VH1 and the VH1-related (VHR) human protein. These properties suggest that VHR is capable of regulating intracellular events mediated by both tyrosine and serine phosphorylation.",
"type": "abstract"
}
] |
[
{
"id": "1233",
"normalized": [
{
"db_id": "2263",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
209,
244
]
],
"text": [
"keratinocyte growth factor receptor"
],
"type": "Gene"
},
{
"id": "1234",
"normalized": [
{
"db_id": "2263",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
246,
249
]
],
"text": [
"bek"
],
"type": "Gene"
},
{
"id": "1235",
"normalized": [
{
"db_id": "2263",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
250,
285
]
],
"text": [
"fibroblast growth factor receptor 2"
],
"type": "Gene"
},
{
"id": "1241",
"normalized": [
{
"db_id": "1845",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1000,
1031
]
],
"text": [
"VH1-related (VHR) human protein"
],
"type": "Gene"
},
{
"id": "1242",
"normalized": [
{
"db_id": "1845",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1063,
1066
]
],
"text": [
"VHR"
],
"type": "Gene"
},
{
"id": "1233",
"normalized": [
{
"db_id": "2263",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
209,
244
]
],
"text": [
"keratinocyte growth factor receptor"
],
"type": "Gene"
},
{
"id": "1234",
"normalized": [
{
"db_id": "2263",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
246,
249
]
],
"text": [
"bek"
],
"type": "Gene"
},
{
"id": "1235",
"normalized": [
{
"db_id": "2263",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
250,
285
]
],
"text": [
"fibroblast growth factor receptor 2"
],
"type": "Gene"
},
{
"id": "1241",
"normalized": [
{
"db_id": "1845",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1000,
1031
]
],
"text": [
"VH1-related (VHR) human protein"
],
"type": "Gene"
},
{
"id": "1242",
"normalized": [
{
"db_id": "1845",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1063,
1066
]
],
"text": [
"VHR"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 128,
"offset": 0
},
"text": "Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor.",
"type": "title"
},
{
"location": {
"length": 835,
"offset": 129
},
"text": "The Ah (dioxin) receptor binds a number of widely disseminated environmental pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons, and mediates their carcinogenic effects. The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). The Ah receptor nuclear translocator protein (Arnt) is required for Ah receptor function. Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. Furthermore, Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. Arnt contains a basic helix-loop-helix motif, which may be responsible for interacting with both the XRE and the ligand-binding subunit.",
"type": "abstract"
}
] |
[
{
"id": "1244",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
22,
54
]
],
"text": [
"Ah receptor nuclear translocator"
],
"type": "Gene"
},
{
"id": "1245",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
64,
68
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1246",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
116,
127
]
],
"text": [
"Ah receptor"
],
"type": "Gene"
},
{
"id": "1247",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
133,
153
]
],
"text": [
"Ah (dioxin) receptor"
],
"type": "Gene"
},
{
"id": "1249",
"normalized": [
{
"db_id": "1543",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
386,
393
]
],
"text": [
"Cyp 1a1"
],
"type": "Gene"
},
{
"id": "1250",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
512,
544
]
],
"text": [
"Ah receptor nuclear translocator"
],
"type": "Gene"
},
{
"id": "1251",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
554,
558
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1252",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
576,
587
]
],
"text": [
"Ah receptor"
],
"type": "Gene"
},
{
"id": "1253",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
598,
602
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1254",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
676,
687
]
],
"text": [
"Ah receptor"
],
"type": "Gene"
},
{
"id": "1255",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
702,
706
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1256",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
828,
832
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1244",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
22,
54
]
],
"text": [
"Ah receptor nuclear translocator"
],
"type": "Gene"
},
{
"id": "1245",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
64,
68
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1246",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
116,
127
]
],
"text": [
"Ah receptor"
],
"type": "Gene"
},
{
"id": "1247",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
133,
153
]
],
"text": [
"Ah (dioxin) receptor"
],
"type": "Gene"
},
{
"id": "1249",
"normalized": [
{
"db_id": "1543",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
386,
393
]
],
"text": [
"Cyp 1a1"
],
"type": "Gene"
},
{
"id": "1250",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
512,
544
]
],
"text": [
"Ah receptor nuclear translocator"
],
"type": "Gene"
},
{
"id": "1251",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
554,
558
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1252",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
576,
587
]
],
"text": [
"Ah receptor"
],
"type": "Gene"
},
{
"id": "1253",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
598,
602
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1254",
"normalized": [
{
"db_id": "196",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
676,
687
]
],
"text": [
"Ah receptor"
],
"type": "Gene"
},
{
"id": "1255",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
702,
706
]
],
"text": [
"Arnt"
],
"type": "Gene"
},
{
"id": "1256",
"normalized": [
{
"db_id": "405",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
828,
832
]
],
"text": [
"Arnt"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 150,
"offset": 0
},
"text": "Characterization of SAF-A, a novel nuclear DNA binding protein from HeLa cells with high affinity for nuclear matrix/scaffold attachment DNA elements.",
"type": "title"
},
{
"location": {
"length": 911,
"offset": 151
},
"text": "We identified four proteins in nuclear extracts from HeLa cells which specifically bind to a scaffold attachment region (SAR) element from the human genome. Of these four proteins, SAF-A (scaffold attachment factor A), shows the highest affinity for several homologous and heterologous SAR elements from vertebrate cells. SAF-A is an abundant nuclear protein and a constituent of the nuclear matrix and scaffold. The homogeneously purified protein is a novel double stranded DNA binding protein with an apparent molecular weight of 120 kDa. SAF-A binds at multiple sites to the human SAR element; competition studies with synthetic polynucleotides indicate that these sites most probably reside in the multitude of A/T-stretches which are distributed throughout this element. In addition we show by electron microscopy that the protein forms large aggregates and mediates the formation of looped DNA structures.",
"type": "abstract"
}
] |
[
{
"id": "1259",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
20,
25
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1261",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
244,
270
]
],
"text": [
"scaffold attachment region"
],
"type": "Gene"
},
{
"id": "1262",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
272,
275
]
],
"text": [
"SAR"
],
"type": "Gene"
},
{
"id": "1263",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
332,
337
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1264",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
339,
367
]
],
"text": [
"scaffold attachment factor A"
],
"type": "Gene"
},
{
"id": "1265",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
437,
440
]
],
"text": [
"SAR"
],
"type": "Gene"
},
{
"id": "1266",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
473,
478
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1268",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
692,
697
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1269",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
735,
738
]
],
"text": [
"SAR"
],
"type": "Gene"
},
{
"id": "1259",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
20,
25
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1261",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
244,
270
]
],
"text": [
"scaffold attachment region"
],
"type": "Gene"
},
{
"id": "1262",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
272,
275
]
],
"text": [
"SAR"
],
"type": "Gene"
},
{
"id": "1263",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
332,
337
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1264",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
339,
367
]
],
"text": [
"scaffold attachment factor A"
],
"type": "Gene"
},
{
"id": "1265",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
437,
440
]
],
"text": [
"SAR"
],
"type": "Gene"
},
{
"id": "1266",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
473,
478
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1268",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
692,
697
]
],
"text": [
"SAF-A"
],
"type": "Gene"
},
{
"id": "1269",
"normalized": [
{
"db_id": "8856",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
735,
738
]
],
"text": [
"SAR"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 188,
"offset": 0
},
"text": "Expression cloning of a cDNA encoding UDP-GlcNAc:Gal beta 1-3-GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase by gene transfer into CHO cells expressing polyoma large tumor antigen.",
"type": "title"
},
{
"location": {
"length": 1612,
"offset": 189
},
"text": "A cDNA encoding UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase (EC 2.4.1.102), which forms critical branches in O-glycans, has been isolated by an expression cloning approach using Chinese hamster ovary (CHO) cells. Increased activity of this enzyme and the concomitant occurrence of the O-glycan core 2 structure [Gal beta 1-3(GlcNAc beta 1-6)GalNAc] has been observed in a variety of biological processes, such as T-cell activation and immunodeficiency due to the Wiskott-Aldrich syndrome and AIDS. Since CHO cells do not express this enzyme, CHO cell lines were established to stably express polyoma large tumor (T) antigen, which enables transient expression cloning. Because the antibody used was found to detect most efficiently the oligosaccharide products attached to leukosialin, the CHO cells were also stably transfected with leukosialin cDNA. By using this particular CHO cell line, a cDNA that encodes a protein determining the formation of the core 2 structure was isolated from an HL-60 cDNA library. The cDNA sequence predicts a protein with type II membrane topology, as has been found for all other mammalian glycosyltransferases cloned to date. The expression of the presumed catalytic domain as a fusion protein with the IgG binding domain of protein A enabled us to demonstrate unequivocally that the cDNA encodes the core 2 beta-1,6-N-acetylglucosaminyltransferase, the enzyme responsible for the formation of Gal beta 1-3(GlcNAc beta 1-6)GalNAc structures. No activity with this enzyme was detected toward the acceptors for other beta 1-6GlcNAc transferases.",
"type": "abstract"
}
] |
[
{
"id": "1271",
"normalized": [
{
"db_id": "2650",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
38,
116
]
],
"text": [
"UDP-GlcNAc:Gal beta 1-3-GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase"
],
"type": "Gene"
},
{
"id": "1272",
"normalized": [
{
"db_id": "2650",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
205,
282
]
],
"text": [
"UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase"
],
"type": "Gene"
},
{
"id": "1276",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
996,
1007
]
],
"text": [
"leukosialin"
],
"type": "Gene"
},
{
"id": "1277",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1057,
1068
]
],
"text": [
"leukosialin"
],
"type": "Gene"
},
{
"id": "1280",
"normalized": [
{
"db_id": "2650",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1559,
1606
]
],
"text": [
"core 2 beta-1,6-N-acetylglucosaminyltransferase"
],
"type": "Gene"
},
{
"id": "1271",
"normalized": [
{
"db_id": "2650",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
38,
116
]
],
"text": [
"UDP-GlcNAc:Gal beta 1-3-GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase"
],
"type": "Gene"
},
{
"id": "1272",
"normalized": [
{
"db_id": "2650",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
205,
282
]
],
"text": [
"UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase"
],
"type": "Gene"
},
{
"id": "1276",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
996,
1007
]
],
"text": [
"leukosialin"
],
"type": "Gene"
},
{
"id": "1277",
"normalized": [
{
"db_id": "6693",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1057,
1068
]
],
"text": [
"leukosialin"
],
"type": "Gene"
},
{
"id": "1280",
"normalized": [
{
"db_id": "2650",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1559,
1606
]
],
"text": [
"core 2 beta-1,6-N-acetylglucosaminyltransferase"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 170,
"offset": 0
},
"text": "Cloning of a novel tumor necrosis factor-alpha-inducible primary response gene that is differentially expressed in development and capillary tube-like formation in vitro.",
"type": "title"
},
{
"location": {
"length": 1895,
"offset": 171
},
"text": "TNF is a proinflammatory cytokine that has pleiotropic effects on cells and tissues, mediated in large part by alterations in target tissue gene expression. We have used the technique of differential hybridization to identify several primary response genes induced by TNF in human umbilical vein endothelial (HUVE) cells, a cell type that is profoundly activated by cytokine treatment. One of these cDNA, designated B94, detects a rapidly and transiently induced 4-kb transcript in TNF-treated HUVE cells, and this transcript is superinduced in the concomitant presence of cycloheximide. Other proinflammatory stimuli including IL-1 beta and LPS are also able to induce B94 mRNA expression. Nuclear run-on experiments demonstrate that TNF induction of B94 transcript occurs primarily at the level of transcriptional activation. Further, B94 is shown to be a single copy gene that is evolutionarily conserved. The gene is localized to the q32 region of chromosome 14, a region that is often rearranged in lymphoid neoplasms. B94 transcript expression is also found to be regulated during mouse development and in an in vitro model of endothelial capillary tube formation. Developmental regulation occurs most prominently in mouse embryonic liver and kidney, and a second smaller form of B94 transcript is detected in the placenta and testes. B94 and other TNF-responsive transcripts are also induced during capillary tube formation suggesting overlap between genes induced by TNF and those induced during angiogenesis. Sequence analysis of the B94 cDNA reveals an open reading frame encoding a 73-kDa polypeptide that has no homology to any known protein. Polyclonal antisera directed against the carboxyl-terminal portion of the B94 protein immunoprecipitates a protein of the predicted molecular mass both from COS cells transfected with a B94 expression vector and from TNF-treated HUVE cells.",
"type": "abstract"
}
] |
[
{
"id": "1284",
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{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
19,
46
]
],
"text": [
"tumor necrosis factor-alpha"
],
"type": "Gene"
},
{
"id": "1285",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
171,
174
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1286",
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{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
439,
442
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1287",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
587,
590
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1288",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
653,
656
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1289",
"normalized": [
{
"db_id": "3553",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
799,
808
]
],
"text": [
"IL-1 beta"
],
"type": "Gene"
},
{
"id": "1290",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
841,
844
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1291",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
906,
909
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1292",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
923,
926
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1293",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1008,
1011
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1294",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "21928",
"db_name": "NCBIGene",
"tax_id": "10090"
}
],
"offsets": [
[
1195,
1198
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1295",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1457,
1460
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1296",
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{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1512,
1515
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1297",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1526,
1529
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1298",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1646,
1649
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1299",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1714,
1717
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1300",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1900,
1903
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1301",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2012,
2015
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1302",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2043,
2046
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1284",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
19,
46
]
],
"text": [
"tumor necrosis factor-alpha"
],
"type": "Gene"
},
{
"id": "1285",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
171,
174
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1286",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
439,
442
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1287",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
587,
590
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1288",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
653,
656
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1289",
"normalized": [
{
"db_id": "3553",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
799,
808
]
],
"text": [
"IL-1 beta"
],
"type": "Gene"
},
{
"id": "1290",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
841,
844
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1291",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
906,
909
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1292",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
923,
926
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1293",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1008,
1011
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1294",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "21928",
"db_name": "NCBIGene",
"tax_id": "10090"
}
],
"offsets": [
[
1195,
1198
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1295",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1457,
1460
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1296",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1512,
1515
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1297",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1526,
1529
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1298",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1646,
1649
]
],
"text": [
"TNF"
],
"type": "Gene"
},
{
"id": "1299",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1714,
1717
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1300",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1900,
1903
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1301",
"normalized": [
{
"db_id": "7127",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2012,
2015
]
],
"text": [
"B94"
],
"type": "Gene"
},
{
"id": "1302",
"normalized": [
{
"db_id": "7124",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2043,
2046
]
],
"text": [
"TNF"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 102,
"offset": 0
},
"text": "Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins.",
"type": "title"
},
{
"location": {
"length": 1817,
"offset": 103
},
"text": "Advanced glycosylation end products of proteins (AGEs) are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. A approximately 35-kDa polypeptide with a unique NH2-terminal sequence has been isolated from bovine lung and found to be present on the surface of endothelial cells where it mediates the binding of AGEs (receptor for advanced glycosylation end product or RAGE). Using an oligonucleotide probe based on the amino-terminal sequence of RAGE, an apparently full-length cDNA of 1.5 kilobases was isolated from a bovine lung cDNA library. This cDNA encoded a 394 amino acid mature protein comprised of the following putative domains: an extracellular domain of 332 amino acids, a single hydrophobic membrane spanning domain of 19 amino acids, and a carboxyl-terminal domain of 43 amino acids. A partial clone encoding the human counterpart of RAGE, isolated from a human lung library, was found to be approximately 90% homologous to the bovine molecule. Based on computer analysis of the amino acid sequence of RAGE and comparison with databases, RAGE is a new member of the immunoglobulin superfamily of cell surface molecules and shares significant homology with MUC 18, NCAM, and the cytoplasmic domain of CD20. Expression of the RAGE cDNA in 293 cells allowed them to bind 125I-AGE-albumin in a saturable and dose-dependent manner (Kd approximately 100 nM), blocked by antibody to RAGE. Western blots of 293 cells transfected with RAGE cDNA probed with anti-RAGE IgG demonstrated expression of immunoreactive protein compared to its absence in mock-transfected cells. These results suggest that RAGE functions as a cell surface receptor for AGEs, which could potentially mediate cellular effects of this class of glycosylated proteins.",
"type": "abstract"
}
] |
[
{
"id": "1312",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
542,
546
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1313",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
624
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1317",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1024,
1028
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1318",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1192,
1196
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1319",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1228,
1232
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1321",
"normalized": [
{
"db_id": "4162",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1346,
1352
]
],
"text": [
"MUC 18"
],
"type": "Gene"
},
{
"id": "1322",
"normalized": [
{
"db_id": "4684",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1354,
1358
]
],
"text": [
"NCAM"
],
"type": "Gene"
},
{
"id": "1324",
"normalized": [
{
"db_id": "931",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1390,
1394
]
],
"text": [
"CD20"
],
"type": "Gene"
},
{
"id": "1325",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1414,
1418
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1328",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1566,
1570
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1329",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1616,
1620
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1330",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1643,
1647
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1331",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1780,
1784
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1312",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
542,
546
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1313",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
624
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1317",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1024,
1028
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1318",
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{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1192,
1196
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1319",
"normalized": [
{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1228,
1232
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1321",
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{
"db_id": "4162",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1346,
1352
]
],
"text": [
"MUC 18"
],
"type": "Gene"
},
{
"id": "1322",
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{
"db_id": "4684",
"db_name": "NCBIGene",
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}
],
"offsets": [
[
1354,
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]
],
"text": [
"NCAM"
],
"type": "Gene"
},
{
"id": "1324",
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{
"db_id": "931",
"db_name": "NCBIGene",
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}
],
"offsets": [
[
1390,
1394
]
],
"text": [
"CD20"
],
"type": "Gene"
},
{
"id": "1325",
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{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1414,
1418
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
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"id": "1328",
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{
"db_id": "177",
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"tax_id": null
}
],
"offsets": [
[
1566,
1570
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1329",
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{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1616,
1620
]
],
"text": [
"RAGE"
],
"type": "Gene"
},
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"id": "1330",
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{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1643,
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]
],
"text": [
"RAGE"
],
"type": "Gene"
},
{
"id": "1331",
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{
"db_id": "177",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1780,
1784
]
],
"text": [
"RAGE"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 114,
"offset": 0
},
"text": "Structure of the CD59-encoding gene: further evidence of a relationship to murine lymphocyte antigen Ly-6 protein.",
"type": "title"
},
{
"location": {
"length": 1149,
"offset": 115
},
"text": "The gene for CD59 [membrane inhibitor of reactive lysis (MIRL), protectin], a phosphatidylinositol-linked surface glycoprotein that regulates the formation of the polymeric C9 complex of complement and that is deficient on the abnormal hematopoietic cells of patients with paroxysmal nocturnal hemoglobinuria, consists of four exons spanning 20 kilobases. The untranslated first exon is preceded by a G+C-rich promoter region that lacks a consensus TATA or CAAT motif. The second exon encodes the hydrophobic leader sequence of the protein, and the third exon encodes the amino-terminal portion of the mature protein. The fourth exon encodes the remainder of the mature protein, including the hydrophobic sequence necessary for glycosyl-phosphatidylinositol anchor attachment. The structure of the CD59 gene is very similar to that encoding Ly-6, a murine glycoprotein with which CD59 has some structural similarity. The striking similarity in gene structure is further evidence that the two proteins belong to a superfamily of proteins that may also include the urokinase plasminogen-activator receptor and a squid glycoprotein of unknown function.",
"type": "abstract"
}
] |
[
{
"id": "1335",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
17,
21
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1338",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
128,
132
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1339",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
134,
170
]
],
"text": [
"membrane inhibitor of reactive lysis"
],
"type": "Gene"
},
{
"id": "1340",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
172,
176
]
],
"text": [
"MIRL"
],
"type": "Gene"
},
{
"id": "1341",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
179,
188
]
],
"text": [
"protectin"
],
"type": "Gene"
},
{
"id": "1345",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
913,
917
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1347",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
995,
999
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1348",
"normalized": [
{
"db_id": "5329",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1178,
1218
]
],
"text": [
"urokinase plasminogen-activator receptor"
],
"type": "Gene"
},
{
"id": "1335",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
17,
21
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1338",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
128,
132
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1339",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
134,
170
]
],
"text": [
"membrane inhibitor of reactive lysis"
],
"type": "Gene"
},
{
"id": "1340",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
172,
176
]
],
"text": [
"MIRL"
],
"type": "Gene"
},
{
"id": "1341",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
179,
188
]
],
"text": [
"protectin"
],
"type": "Gene"
},
{
"id": "1345",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
913,
917
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1347",
"normalized": [
{
"db_id": "966",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
995,
999
]
],
"text": [
"CD59"
],
"type": "Gene"
},
{
"id": "1348",
"normalized": [
{
"db_id": "5329",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1178,
1218
]
],
"text": [
"urokinase plasminogen-activator receptor"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 83,
"offset": 0
},
"text": "Cloning and chromosome mapping of the human interleukin-1 receptor antagonist gene.",
"type": "title"
},
{
"location": {
"length": 1093,
"offset": 84
},
"text": "By screening a human genomic library with an interleukin-1 receptor antagonist (IL-1ra) cDNA probe, we have isolated a 15 kb clone which contains the entire coding region of the gene as expressed in monocytes, and includes 6 kb of 5'-upstream sequence. The gene contains four exons which code for the secreted form of the IL-1ra, however, our clone does not contain the alternative first exon used to generate an intracellular form of the protein as the protein as found in epithelial cells. Analysis of the sequence reveals a consensus TATA box, and three Alu repeats, two of which are in the upstream region and one in intron 3. The sequence also reveals an 86 bp motif tandomly repeated four times within intron 2, and may reflect the polymorphism known to exist in this region of the gene. By in-situ fluorescence hybridization we have shown that the IL-1ra gene is found on the long arm of chromosome 2 and maps to 2q13-14.1. Previous studies have revealed that IL-1 alpha, and IL-1 beta and both type I and type II forms of the IL-1 receptor all map close to this region of chromosome 2.",
"type": "abstract"
}
] |
[
{
"id": "1350",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
44,
77
]
],
"text": [
"interleukin-1 receptor antagonist"
],
"type": "Gene"
},
{
"id": "1351",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
129,
162
]
],
"text": [
"interleukin-1 receptor antagonist"
],
"type": "Gene"
},
{
"id": "1352",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
164,
170
]
],
"text": [
"IL-1ra"
],
"type": "Gene"
},
{
"id": "1353",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
406,
412
]
],
"text": [
"IL-1ra"
],
"type": "Gene"
},
{
"id": "1355",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
939,
945
]
],
"text": [
"IL-1ra"
],
"type": "Gene"
},
{
"id": "1356",
"normalized": [
{
"db_id": "3552",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1051,
1061
]
],
"text": [
"IL-1 alpha"
],
"type": "Gene"
},
{
"id": "1357",
"normalized": [
{
"db_id": "3553",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1067,
1076
]
],
"text": [
"IL-1 beta"
],
"type": "Gene"
},
{
"id": "1358",
"normalized": [
{
"db_id": "3554",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "7850",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1086,
1131
]
],
"text": [
"type I and type II forms of the IL-1 receptor"
],
"type": "Gene"
},
{
"id": "1350",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
44,
77
]
],
"text": [
"interleukin-1 receptor antagonist"
],
"type": "Gene"
},
{
"id": "1351",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
129,
162
]
],
"text": [
"interleukin-1 receptor antagonist"
],
"type": "Gene"
},
{
"id": "1352",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
164,
170
]
],
"text": [
"IL-1ra"
],
"type": "Gene"
},
{
"id": "1353",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
406,
412
]
],
"text": [
"IL-1ra"
],
"type": "Gene"
},
{
"id": "1355",
"normalized": [
{
"db_id": "3557",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
939,
945
]
],
"text": [
"IL-1ra"
],
"type": "Gene"
},
{
"id": "1356",
"normalized": [
{
"db_id": "3552",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1051,
1061
]
],
"text": [
"IL-1 alpha"
],
"type": "Gene"
},
{
"id": "1357",
"normalized": [
{
"db_id": "3553",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1067,
1076
]
],
"text": [
"IL-1 beta"
],
"type": "Gene"
},
{
"id": "1358",
"normalized": [
{
"db_id": "3554",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "7850",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1086,
1131
]
],
"text": [
"type I and type II forms of the IL-1 receptor"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 109,
"offset": 0
},
"text": "Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.",
"type": "title"
},
{
"location": {
"length": 1370,
"offset": 110
},
"text": "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is an autosomal recessive neurodegenerative disorder characterized by early-onset ataxia, ocular motor apraxia, and hypoalbuminemia. Recently, the causative gene for EAOH, APTX, has been identified. Of the two splicing variants of APTX mRNA, the short and the long forms, long-form APTX mRNA was found to be the major isoform. Aprataxin is mainly located in the nucleus, and, furthermore, the first nuclear localization signal located near the amino terminus of the long-form aprataxin is essential for its nuclear localization. We found, based on the yeast two-hybrid and coimmunoprecipitation experiments, that the long-form but not the short-form aprataxin interacts with XRCC1 (x-ray repair cross-complementing group 1). Interestingly the amino terminus of the long-form aprataxin is homologous with polynucleotidekinase-3'-phosphatase, which has been demonstrated to be involved in base excision repair, a subtype of single-strand DNA break repair, through interaction with XRCC1, DNA polymerase beta, and DNA ligase III. These results strongly support the possibility that aprataxin and XRCC1 constitute a multiprotein complex and are involved in single-strand DNA break repair, and furthermore, that accumulation of unrepaired damaged DNA underlies the pathophysiological mechanisms of EAOH.",
"type": "abstract"
}
] |
[
{
"id": "1360",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
0,
9
]
],
"text": [
"Aprataxin"
],
"type": "Gene"
},
{
"id": "1361",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
37,
41
]
],
"text": [
"EAOH"
],
"type": "Gene"
},
{
"id": "1363",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
110,
174
]
],
"text": [
"Early-onset ataxia with ocular motor apraxia and hypoalbuminemia"
],
"type": "Gene"
},
{
"id": "1364",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
176,
180
]
],
"text": [
"EAOH"
],
"type": "Gene"
},
{
"id": "1365",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
348,
352
]
],
"text": [
"EAOH"
],
"type": "Gene"
},
{
"id": "1366",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
354,
358
]
],
"text": [
"APTX"
],
"type": "Gene"
},
{
"id": "1367",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
413,
417
]
],
"text": [
"APTX"
],
"type": "Gene"
},
{
"id": "1368",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
464,
468
]
],
"text": [
"APTX"
],
"type": "Gene"
},
{
"id": "1369",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
509,
518
]
],
"text": [
"Aprataxin"
],
"type": "Gene"
},
{
"id": "1370",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
658,
667
]
],
"text": [
"aprataxin"
],
"type": "Gene"
},
{
"id": "1371",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
832,
841
]
],
"text": [
"aprataxin"
],
"type": "Gene"
},
{
"id": "1372",
"normalized": [
{
"db_id": "7515",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
857,
862
]
],
"text": [
"XRCC1"
],
"type": "Gene"
},
{
"id": "1373",
"normalized": [
{
"db_id": "7515",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
864,
904
]
],
"text": [
"x-ray repair cross-complementing group 1"
],
"type": "Gene"
},
{
"id": "1374",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
957,
966
]
],
"text": [
"aprataxin"
],
"type": "Gene"
},
{
"id": "1375",
"normalized": [
{
"db_id": "11284",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
986,
1021
]
],
"text": [
"polynucleotidekinase-3'-phosphatase"
],
"type": "Gene"
},
{
"id": "1376",
"normalized": [
{
"db_id": "7515",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1161,
1166
]
],
"text": [
"XRCC1"
],
"type": "Gene"
},
{
"id": "1377",
"normalized": [
{
"db_id": "5423",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1168,
1187
]
],
"text": [
"DNA polymerase beta"
],
"type": "Gene"
},
{
"id": "1378",
"normalized": [
{
"db_id": "3980",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1193,
1207
]
],
"text": [
"DNA ligase III"
],
"type": "Gene"
},
{
"id": "1379",
"normalized": [
{
"db_id": "54840",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1261,
1270
]
],
"text": [
"aprataxin"
],
"type": "Gene"
},
{
"id": "1380",
"normalized": [
{
"db_id": "7515",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1275,
1280
]
],
"text": [
"XRCC1"
],
"type": "Gene"
},
{
"id": "1381",
"normalized": [
{
"db_id": "54840",
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37,
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110,
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176,
180
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"EAOH"
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348,
352
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"EAOH"
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354,
358
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"text": [
"APTX"
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{
"id": "1367",
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413,
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"APTX"
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464,
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"APTX"
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509,
518
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"Aprataxin"
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{
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658,
667
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"aprataxin"
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{
"id": "1371",
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{
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[
832,
841
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"aprataxin"
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"offsets": [
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857,
862
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"text": [
"XRCC1"
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"id": "1373",
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"offsets": [
[
864,
904
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"text": [
"x-ray repair cross-complementing group 1"
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"offsets": [
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957,
966
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],
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"aprataxin"
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"id": "1375",
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986,
1021
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"text": [
"polynucleotidekinase-3'-phosphatase"
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{
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1161,
1166
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"XRCC1"
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"id": "1377",
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1168,
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"text": [
"DNA polymerase beta"
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1193,
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"text": [
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1261,
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1275,
1280
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"text": [
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"id": "1381",
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}
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"offsets": [
[
1475,
1479
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],
"text": [
"EAOH"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 70,
"offset": 0
},
"text": "Analysis of APAF-1 expression in human cutaneous melanoma progression.",
"type": "title"
},
{
"location": {
"length": 1015,
"offset": 71
},
"text": "APAF-1 plays a pivotal role in mitochondria-dependent apoptosis, binding to cytochrome c and favoring activation of caspase-9. It has been shown that epigenetic silencing of the APAF-1 gene is a common event in several metastatic melanoma cells in vitro. We determined, by Western blot, variation in the level of expression of APAF-1 in several human melanoma cell lines and, by immunohistochemistry, in a group of 106 histological samples including benign and malignant melanocytic lesions. We observed APAF-1 down-regulation or loss of expression in two metastatic melanoma cell lines, compared to primary melanoma cell lines. The immunohistochemical analysis revealed a significant difference in APAF-1 staining between nevi and melanomas. In addition, we found a significant negative correlation between APAF-1 expression level and tumor thickness and between primary melanomas and metastases. We conclude that loss of APAF-1 expression can be considered as an indicator of malignant transformation in melanoma.",
"type": "abstract"
}
] |
[
{
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
12,
18
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],
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"APAF-1"
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{
"id": "1384",
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{
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}
],
"offsets": [
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71,
77
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],
"text": [
"APAF-1"
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"type": "Gene"
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{
"id": "1385",
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{
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}
],
"offsets": [
[
147,
159
]
],
"text": [
"cytochrome c"
],
"type": "Gene"
},
{
"id": "1386",
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{
"db_id": "842",
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"tax_id": null
}
],
"offsets": [
[
187,
196
]
],
"text": [
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{
"id": "1387",
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{
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],
"offsets": [
[
249,
255
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],
"text": [
"APAF-1"
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"type": "Gene"
},
{
"id": "1388",
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{
"db_id": "317",
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}
],
"offsets": [
[
398,
404
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],
"text": [
"APAF-1"
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"type": "Gene"
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{
"id": "1389",
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{
"db_id": "317",
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}
],
"offsets": [
[
575,
581
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],
"text": [
"APAF-1"
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"type": "Gene"
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{
"id": "1390",
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{
"db_id": "317",
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}
],
"offsets": [
[
770,
776
]
],
"text": [
"APAF-1"
],
"type": "Gene"
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{
"id": "1391",
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{
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}
],
"offsets": [
[
879,
885
]
],
"text": [
"APAF-1"
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"type": "Gene"
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{
"id": "1392",
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{
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}
],
"offsets": [
[
994,
1000
]
],
"text": [
"APAF-1"
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"type": "Gene"
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{
"id": "1383",
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{
"db_id": "317",
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"tax_id": null
}
],
"offsets": [
[
12,
18
]
],
"text": [
"APAF-1"
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"type": "Gene"
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{
"id": "1384",
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{
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}
],
"offsets": [
[
71,
77
]
],
"text": [
"APAF-1"
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"type": "Gene"
},
{
"id": "1385",
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{
"db_id": "54205",
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"tax_id": null
}
],
"offsets": [
[
147,
159
]
],
"text": [
"cytochrome c"
],
"type": "Gene"
},
{
"id": "1386",
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{
"db_id": "842",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
187,
196
]
],
"text": [
"caspase-9"
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"type": "Gene"
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{
"id": "1387",
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{
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"tax_id": null
}
],
"offsets": [
[
249,
255
]
],
"text": [
"APAF-1"
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"type": "Gene"
},
{
"id": "1388",
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{
"db_id": "317",
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"tax_id": null
}
],
"offsets": [
[
398,
404
]
],
"text": [
"APAF-1"
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"type": "Gene"
},
{
"id": "1389",
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{
"db_id": "317",
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"tax_id": null
}
],
"offsets": [
[
575,
581
]
],
"text": [
"APAF-1"
],
"type": "Gene"
},
{
"id": "1390",
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{
"db_id": "317",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
770,
776
]
],
"text": [
"APAF-1"
],
"type": "Gene"
},
{
"id": "1391",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
879,
885
]
],
"text": [
"APAF-1"
],
"type": "Gene"
},
{
"id": "1392",
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{
"db_id": "317",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
994,
1000
]
],
"text": [
"APAF-1"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 84,
"offset": 0
},
"text": "A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition.",
"type": "title"
},
{
"location": {
"length": 998,
"offset": 85
},
"text": "A human cDNA was cloned that encodes a DNA-binding protein (SATB1) that is expressed predominantly in thymus and binds selectively to the nuclear matrix/scaffold-associating DNAs (MARs/SARs). Missing nucleoside experiments showed that SATB1 selectively binds in a special AT-rich sequence context where one strand consists of mixed A's, T's, and C's, excluding G's (ATC sequences). When this feature is destroyed by mutation, SATB1 binding is greatly reduced even if the direct contact sequence remains intact. Conjunctional SATB1-binding sequences become stably unpaired in supercoiled DNA. Specific mutations that diminish the unwinding potential greatly reduce SATB1 binding. However, SATB1 does not bind single-stranded DNA. Chemical interference assays show that SATB1 binds along the minor groove with very little contact with the bases. This suggests that SATB1 recognizes the ATC sequence indirectly through the altered sugar-phosphate backbone structure present in the double-stranded DNA.",
"type": "abstract"
}
] |
[
{
"id": "1396",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
145,
150
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1397",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
320,
325
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1398",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
511,
516
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1399",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
610,
615
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1400",
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{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
749,
754
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1401",
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{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
773,
778
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1402",
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{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
853,
858
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1403",
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{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
948,
953
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1396",
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{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
145,
150
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1397",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
320,
325
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1398",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
511,
516
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1399",
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{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
610,
615
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1400",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
749,
754
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1401",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
773,
778
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1402",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
853,
858
]
],
"text": [
"SATB1"
],
"type": "Gene"
},
{
"id": "1403",
"normalized": [
{
"db_id": "6304",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
948,
953
]
],
"text": [
"SATB1"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 71,
"offset": 0
},
"text": "Cloning and characterization of a human angiotensin II type 1 receptor.",
"type": "title"
},
{
"location": {
"length": 916,
"offset": 72
},
"text": "A human liver cDNA library was screened using a rat type 1 angiotensin II receptor cDNA coding sequence as a probe. cDNA clones were isolated which encoded a protein of 359 amino acids that shared 94.4% and 95.3% identify to rat and bovine type 1 angiotensin II receptors, respectively. Ligand binding studies of the cloned receptor expressed in COS cells suggested that it is pharmacologically a type 1 angiotensin II receptor subtype. Electrophysiological studies of the receptor expressed in Xenopus laevis oocytes revealed that it could functionally couple to a second messenger system leading to the mobilization of intracellular stores of calcium. Southern and Northern blot analyses indicated that the cloned receptor is represented as a single copy in the human genome and is expressed in many tissues of different histogenic origin with the exception of brain, where mRNA transcripts were barely detectable.",
"type": "abstract"
}
] |
[
{
"id": "1405",
"normalized": [
{
"db_id": "185",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
40,
70
]
],
"text": [
"angiotensin II type 1 receptor"
],
"type": "Gene"
},
{
"id": "1408",
"normalized": [
{
"db_id": "185",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
469,
499
]
],
"text": [
"type 1 angiotensin II receptor"
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"type": "Gene"
},
{
"id": "1405",
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{
"db_id": "185",
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"tax_id": null
}
],
"offsets": [
[
40,
70
]
],
"text": [
"angiotensin II type 1 receptor"
],
"type": "Gene"
},
{
"id": "1408",
"normalized": [
{
"db_id": "185",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
469,
499
]
],
"text": [
"type 1 angiotensin II receptor"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 129,
"offset": 0
},
"text": "Cloning, expression and localization of an RNA helicase gene from a human lymphoid cell line with chromosomal breakpoint 11q23.3.",
"type": "title"
},
{
"location": {
"length": 488,
"offset": 130
},
"text": "A gene encoding a putative human RNA helicase, p54, has been cloned and mapped to the band q23.3 of chromosome 11. The predicted amino acid sequence shares a striking homology (75% identical) with the female germline-specific RNA helicase ME31B gene of Drosophila. Unlike ME31B, however, the new gene expresses an abundant transcript in a large number of adult tissues and its 5' non-coding region was found split in a t(11;14)(q23.3;q32.3) cell line from a diffuse large B-cell lymphoma.",
"type": "abstract"
}
] |
[
{
"id": "1412",
"normalized": [
{
"db_id": "1656",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
177,
180
]
],
"text": [
"p54"
],
"type": "Gene"
},
{
"id": "1412",
"normalized": [
{
"db_id": "1656",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
177,
180
]
],
"text": [
"p54"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 117,
"offset": 0
},
"text": "Mutually exclusive expression of a helix-loop-helix gene and N-myc in human neuroblastomas and in normal development.",
"type": "title"
},
{
"location": {
"length": 1308,
"offset": 118
},
"text": "We have isolated a novel human gene encoding a helix-loop-helix (HLH) protein by molecularly cloning chromosome 1p36-specific CpG islands. The gene termed heir-1 was localized to the neuroblastoma consensus deletion at 1p36.2-p36.12. Its predicted protein is 95.8% identical to the mouse HLH462 protein and has clear homology to the mouse Id and Drosophila emc proteins. Heir-1 does not encode a basic DNA binding domain as found in basic HLH proteins. The gene is expressed specifically at high abundance in adult lung, kidney and adrenal medulla, but not in adult brain. Despite prominent heir-1 expression in adrenal medulla, which is a prime target for neuroblastomas, 10 out of 12 neuroblastoma-derived cell lines revealed very low levels of heir-1 mRNA. Low heir-1 expression was generally found in tumor cell lines with N-myc overexpression, whereas the two cell lines displaying high heir-1 levels did not overexpress N-myc. Mutually exclusive expression of both genes was also found by in situ hybridization in developing mouse tissues, particularly in the forebrain neuroectoderm. We conclude that heir-1 expression is reduced specifically in the majority of neuroblastomas and suggest an inverse correlation between heir-1 and N-myc expression in neuroblastoma tumors and in embryonic development.",
"type": "abstract"
}
] |
[
{
"id": "1418",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
61,
66
]
],
"text": [
"N-myc"
],
"type": "Gene"
},
{
"id": "1421",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
273,
279
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1425",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
489,
495
]
],
"text": [
"Heir-1"
],
"type": "Gene"
},
{
"id": "1428",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
709,
715
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1429",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
865,
871
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1430",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
882,
888
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1431",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
945,
950
]
],
"text": [
"N-myc"
],
"type": "Gene"
},
{
"id": "1432",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1010,
1016
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1433",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1044,
1049
]
],
"text": [
"N-myc"
],
"type": "Gene"
},
{
"id": "1434",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1226,
1232
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1435",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1345,
1351
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1436",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1356,
1361
]
],
"text": [
"N-myc"
],
"type": "Gene"
},
{
"id": "1418",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
61,
66
]
],
"text": [
"N-myc"
],
"type": "Gene"
},
{
"id": "1421",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
273,
279
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1425",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
489,
495
]
],
"text": [
"Heir-1"
],
"type": "Gene"
},
{
"id": "1428",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
709,
715
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1429",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
865,
871
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1430",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
882,
888
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1431",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
945,
950
]
],
"text": [
"N-myc"
],
"type": "Gene"
},
{
"id": "1432",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1010,
1016
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1433",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1044,
1049
]
],
"text": [
"N-myc"
],
"type": "Gene"
},
{
"id": "1434",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1226,
1232
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1435",
"normalized": [
{
"db_id": "3399",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1345,
1351
]
],
"text": [
"heir-1"
],
"type": "Gene"
},
{
"id": "1436",
"normalized": [
{
"db_id": "4613",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1356,
1361
]
],
"text": [
"N-myc"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 91,
"offset": 0
},
"text": "Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box.",
"type": "title"
},
{
"location": {
"length": 1722,
"offset": 92
},
"text": "Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to influence the structure of hnRNA and participate in the processing of hnRNA to mRNA. The hnRNP U protein is an abundant nucleoplasmic phosphoprotein that is the largest of the major hnRNP proteins (120 kDa by SDS-PAGE). HnRNP U binds pre-mRNA in vivo and binds both RNA and ssDNA in vitro. Here we describe the cloning and sequencing of a cDNA encoding the hnRNP U protein, the determination of its amino acid sequence and the delineation of a region in this protein that confers RNA binding. The predicted amino acid sequence of hnRNP U contains 806 amino acids (88,939 Daltons), and shows no extensive homology to any known proteins. The N-terminus is rich in acidic residues and the C-terminus is glycine-rich. In addition, a glutamine-rich stretch, a putative NTP binding site and a putative nuclear localization signal are present. It could not be defined from the sequence what segment of the protein confers its RNA binding activity. We identified an RNA binding activity within the C-terminal glycine-rich 112 amino acids. This region, designated U protein glycine-rich RNA binding region (U-gly), can by itself bind RNA. Furthermore, fusion of U-gly to a heterologous bacterial protein (maltose binding protein) converts this fusion protein into an RNA binding protein. A 26 amino acid peptide within U-gly is necessary for the RNA binding activity of the U protein. Interestingly, this peptide contains a cluster of RGG repeats with characteristic spacing and this motif is found also in several other RNA binding proteins. We have termed this region the RGG box and propose that it is an RNA binding motif and a predictor of RNA binding activity.",
"type": "abstract"
}
] |
[
{
"id": "1438",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
46,
53
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
},
{
"id": "1442",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
246,
253
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
},
{
"id": "1444",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
377,
384
]
],
"text": [
"HnRNP U"
],
"type": "Gene"
},
{
"id": "1445",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
514,
521
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
},
{
"id": "1446",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
687,
694
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
},
{
"id": "1438",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
46,
53
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
},
{
"id": "1442",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
246,
253
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
},
{
"id": "1444",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
377,
384
]
],
"text": [
"HnRNP U"
],
"type": "Gene"
},
{
"id": "1445",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
514,
521
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
},
{
"id": "1446",
"normalized": [
{
"db_id": "3192",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
687,
694
]
],
"text": [
"hnRNP U"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 149,
"offset": 0
},
"text": "Identification, cloning, and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1.",
"type": "title"
},
{
"location": {
"length": 1303,
"offset": 150
},
"text": "We have isolated a cDNA encoding a third type of protein-tyrosine-phosphatase. We screened human megakaryoblastic cell line (MEG-01) an umbilical vein endothelial cell cDNA libraries to obtain a 3.7-kilobase cDNA designated PTPase MEG. Northern blot analysis of MEG-01 RNA detected a 3.7-kilobase transcript, suggesting that a full-length cDNA has been identified. PTPase MEG cDNA contains an open reading frame of 926 amino acids. The cDNA has a G+C-rich 5' untranslated region of 771 nucleotides that has the potential to form stable stem-loop structures and has two upstream ATG codons. The predicted protein (Mr = 105,910) has no apparent membrane-spanning region and contains a single protein-tyrosine-phosphatase domain (amino acids 659-909) that is 35-40% identical to previously described tyrosine-phosphatase domains. The recombinant phosphatase domain possesses protein-tyrosine-phosphatase activity when expressed in Escherichia coli. The amino-terminal region (amino acids 31-367) is 45% identical to the amino terminus of human erythrocyte protein 4.1, a cytoskeletal protein. The identification of a protein-tyrosine-phosphatase that is related to cytoskeletal proteins implies that cell signaling activities reside not only in transmembrane receptors but in cytoskeletal elements as well.",
"type": "abstract"
}
] |
[
{
"id": "1465",
"normalized": [
{
"db_id": "2035",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
124,
148
]
],
"text": [
"cytoskeletal protein 4.1"
],
"type": "Gene"
},
{
"id": "1467",
"normalized": [
{
"db_id": "5775",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
374,
384
]
],
"text": [
"PTPase MEG"
],
"type": "Gene"
},
{
"id": "1468",
"normalized": [
{
"db_id": "5775",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
515,
525
]
],
"text": [
"PTPase MEG"
],
"type": "Gene"
},
{
"id": "1475",
"normalized": [
{
"db_id": "2035",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1191,
1214
]
],
"text": [
"erythrocyte protein 4.1"
],
"type": "Gene"
},
{
"id": "1465",
"normalized": [
{
"db_id": "2035",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
124,
148
]
],
"text": [
"cytoskeletal protein 4.1"
],
"type": "Gene"
},
{
"id": "1467",
"normalized": [
{
"db_id": "5775",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
374,
384
]
],
"text": [
"PTPase MEG"
],
"type": "Gene"
},
{
"id": "1468",
"normalized": [
{
"db_id": "5775",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
515,
525
]
],
"text": [
"PTPase MEG"
],
"type": "Gene"
},
{
"id": "1475",
"normalized": [
{
"db_id": "2035",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1191,
1214
]
],
"text": [
"erythrocyte protein 4.1"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 45,
"offset": 0
},
"text": "The receptor for ciliary neurotrophic factor.",
"type": "title"
},
{
"location": {
"length": 1075,
"offset": 46
},
"text": "Although neurotrophic factors were originally isolated on the basis of their ability to support the survival of neurons, these molecules are now thought to influence many aspects of the development and maintenance of the nervous system. Identifying the receptors for these neurotrophic factors should aid in identifying the cells on which these factors act and in understanding their precise mechanisms of action. A \" tagged-ligand panning \" procedure was used to clone a receptor for ciliary neurotrophic factor (CNTF). This receptor is expressed exclusively within the nervous system and skeletal muscle. The CNTF receptor has a structure unrelated to the receptors utilized by the nerve growth factor family of neurotrophic molecules, but instead is most homologous to the receptor for a cytokine, interleukin-6. This similarity suggestes that the CNTF receptor, like the interleukin-6 receptor, requires a second, signal-transducing component. In contrast to all known receptors, the CNTF receptor is anchored to cell membranes by a glycosyl-phosphatidylinositol linkage.",
"type": "abstract"
}
] |
[
{
"id": "1480",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
4,
44
]
],
"text": [
"receptor for ciliary neurotrophic factor"
],
"type": "Gene"
},
{
"id": "1483",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
518,
558
]
],
"text": [
"receptor for ciliary neurotrophic factor"
],
"type": "Gene"
},
{
"id": "1484",
"normalized": [
{
"db_id": "1270",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
560,
564
]
],
"text": [
"CNTF"
],
"type": "Gene"
},
{
"id": "1485",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
657,
670
]
],
"text": [
"CNTF receptor"
],
"type": "Gene"
},
{
"id": "1488",
"normalized": [
{
"db_id": "3569",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
847,
860
]
],
"text": [
"interleukin-6"
],
"type": "Gene"
},
{
"id": "1489",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
897,
910
]
],
"text": [
"CNTF receptor"
],
"type": "Gene"
},
{
"id": "1490",
"normalized": [
{
"db_id": "3570",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
921,
943
]
],
"text": [
"interleukin-6 receptor"
],
"type": "Gene"
},
{
"id": "1491",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1034,
1047
]
],
"text": [
"CNTF receptor"
],
"type": "Gene"
},
{
"id": "1480",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
4,
44
]
],
"text": [
"receptor for ciliary neurotrophic factor"
],
"type": "Gene"
},
{
"id": "1483",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
518,
558
]
],
"text": [
"receptor for ciliary neurotrophic factor"
],
"type": "Gene"
},
{
"id": "1484",
"normalized": [
{
"db_id": "1270",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
560,
564
]
],
"text": [
"CNTF"
],
"type": "Gene"
},
{
"id": "1485",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
657,
670
]
],
"text": [
"CNTF receptor"
],
"type": "Gene"
},
{
"id": "1488",
"normalized": [
{
"db_id": "3569",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
847,
860
]
],
"text": [
"interleukin-6"
],
"type": "Gene"
},
{
"id": "1489",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
897,
910
]
],
"text": [
"CNTF receptor"
],
"type": "Gene"
},
{
"id": "1490",
"normalized": [
{
"db_id": "3570",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
921,
943
]
],
"text": [
"interleukin-6 receptor"
],
"type": "Gene"
},
{
"id": "1491",
"normalized": [
{
"db_id": "1271",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1034,
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"text": [
"CNTF receptor"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 116,
"offset": 0
},
"text": "A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR.",
"type": "title"
},
{
"location": {
"length": 831,
"offset": 117
},
"text": "The vitamin A derivative retinoic acid exerts its effects on transcription through two distinct classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). We provide evidence that expression of the gene for cellular retinol-binding protein type II (CRBPII), a key protein in the intestinal absorption of vitamin A, is dramatically up-regulated by retinoic acid in the presence of RXR but not RAR. This regulation is conferred through a specific cis element in the CRBPII promoter that contains five nearly perfect tandem repeats of the sequence AGGTCA spaced by a single nucleotide. The discovery of this new RX response element provides a means for distinguishing between the two retinoid receptor systems and suggests that an RXR-mediated pathway exists for modulating vitamin A metabolism.",
"type": "abstract"
}
] |
[
{
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{
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"tax_id": null
}
],
"offsets": [
[
23,
63
]
],
"text": [
"cellular retinol-binding protein type II"
],
"type": "Gene"
},
{
"id": "1494",
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{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
104,
107
]
],
"text": [
"RXR"
],
"type": "Gene"
},
{
"id": "1498",
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{
"db_id": "6256",
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"tax_id": null
}
],
"offsets": [
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284,
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]
],
"text": [
"retinoid X receptor"
],
"type": "Gene"
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{
"id": "1499",
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{
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"tax_id": null
}
],
"offsets": [
[
305,
308
]
],
"text": [
"RXR"
],
"type": "Gene"
},
{
"id": "1500",
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{
"db_id": "5948",
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"tax_id": null
}
],
"offsets": [
[
363,
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]
],
"text": [
"cellular retinol-binding protein type II"
],
"type": "Gene"
},
{
"id": "1501",
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{
"db_id": "5948",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
405,
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]
],
"text": [
"CRBPII"
],
"type": "Gene"
},
{
"id": "1502",
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{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
536,
539
]
],
"text": [
"RXR"
],
"type": "Gene"
},
{
"id": "1504",
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{
"db_id": "5948",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
626
]
],
"text": [
"CRBPII"
],
"type": "Gene"
},
{
"id": "1505",
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{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
884,
887
]
],
"text": [
"RXR"
],
"type": "Gene"
},
{
"id": "1493",
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{
"db_id": "5948",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
23,
63
]
],
"text": [
"cellular retinol-binding protein type II"
],
"type": "Gene"
},
{
"id": "1494",
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{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
104,
107
]
],
"text": [
"RXR"
],
"type": "Gene"
},
{
"id": "1498",
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{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
284,
303
]
],
"text": [
"retinoid X receptor"
],
"type": "Gene"
},
{
"id": "1499",
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{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
305,
308
]
],
"text": [
"RXR"
],
"type": "Gene"
},
{
"id": "1500",
"normalized": [
{
"db_id": "5948",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
363,
403
]
],
"text": [
"cellular retinol-binding protein type II"
],
"type": "Gene"
},
{
"id": "1501",
"normalized": [
{
"db_id": "5948",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
405,
411
]
],
"text": [
"CRBPII"
],
"type": "Gene"
},
{
"id": "1502",
"normalized": [
{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
536,
539
]
],
"text": [
"RXR"
],
"type": "Gene"
},
{
"id": "1504",
"normalized": [
{
"db_id": "5948",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
620,
626
]
],
"text": [
"CRBPII"
],
"type": "Gene"
},
{
"id": "1505",
"normalized": [
{
"db_id": "6256",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
884,
887
]
],
"text": [
"RXR"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 110,
"offset": 0
},
"text": "Cloning, expression and chromosomal localization of a new putative receptor-like protein tyrosine phosphatase.",
"type": "title"
},
{
"location": {
"length": 1488,
"offset": 111
},
"text": "We have isolated a mouse cDNA of 5.7 kb, encoding a new member of the family of receptor-like protein tyrosine phosphatases, termed mRPTP mu. The cDNA predicts a protein of 1432 amino acids (not including signal peptide) with a calculated Mr of 161,636. In addition, we have cloned the human homologue, hRPTP mu, which shows 98.7% amino acid identity to mRPTP mu. The predicted mRPTP mu protein consists of a 722 amino acid extracellular region, containing 13 potential N-glycosylation sites, a single transmembrane domain and a 688 amino acid intracellular part containing 2 tandem repeats homologous to the catalytic domains of other tyrosine phosphatases. The N-terminal extracellular part contains a region of about 170 amino acids with no sequence similarities to known proteins, followed by one Ig-like domain and 4 fibronectin type III-like domains. The intracellular part is unique in that the region between the transmembrane domain and the first catalytic domain is about twice as large as in other receptor-like protein tyrosine phosphatases. RNA blot analysis reveals a single transcript, that is most abundant in lung and present in much lower amounts in brain and heart. Transfection of the mRPTP mu cDNA into COS cells results in the synthesis of a protein with an apparent Mr of 195,000, as detected in immunoblots using an antipeptide antibody. The human RPTP mu gene is localized on chromosome 18pter-q11, a region with frequent abnormalities implicated in human cancer.",
"type": "abstract"
}
] |
[
{
"id": "1512",
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{
"db_id": "5797",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
414,
422
]
],
"text": [
"hRPTP mu"
],
"type": "Gene"
},
{
"id": "1525",
"normalized": [
{
"db_id": "5797",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1483,
1490
]
],
"text": [
"RPTP mu"
],
"type": "Gene"
},
{
"id": "1512",
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{
"db_id": "5797",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
414,
422
]
],
"text": [
"hRPTP mu"
],
"type": "Gene"
},
{
"id": "1525",
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{
"db_id": "5797",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1483,
1490
]
],
"text": [
"RPTP mu"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 117,
"offset": 0
},
"text": "Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor.",
"type": "title"
},
{
"location": {
"length": 1083,
"offset": 118
},
"text": "Cytotoxic lymphocyte maturation factor (CLMF) is a disulfide-bonded heterodimeric lymphokine that (i) acts as a growth factor for activated T cells independent of interleukin 2 and (ii) synergizes with suboptimal concentrations of interleukin 2 to induce lymphokine-activated killer cells. We now report the cloning and expression of both human CLMF subunit cDNAs from a lymphoblastoid B-cell line, NC-37. The two subunits represent two distinct and unrelated gene products whose mRNAs are coordinately induced upon activation of NC-37 cells. Coexpression of the two subunit cDNAs in COS cells is necessary for the secretion of biologically active CLMF; COS cells transfected with either subunit cDNA alone do not secrete bioactive CLMF. Recombinant CLMF expressed in mammalian cells displays biologic activities essentially identical to natural CLMF, and its activities can be neutralized by monoclonal antibodies prepared against natural CLMF. Since this heterodimeric protein displays the properties of an interleukin, we propose that CLMF be given the designation interleukin 12.",
"type": "abstract"
}
] |
[
{
"id": "1527",
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{
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
78,
116
]
],
"text": [
"cytotoxic lymphocyte maturation factor"
],
"type": "FamilyName"
},
{
"id": "1528",
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{
"db_id": "3592",
"db_name": "NCBIGene",
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},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
118,
156
]
],
"text": [
"Cytotoxic lymphocyte maturation factor"
],
"type": "FamilyName"
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{
"id": "1529",
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{
"db_id": "3592",
"db_name": "NCBIGene",
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
158,
162
]
],
"text": [
"CLMF"
],
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},
{
"id": "1531",
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
281,
294
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],
"text": [
"interleukin 2"
],
"type": "Gene"
},
{
"id": "1532",
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
349,
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],
"text": [
"interleukin 2"
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"type": "Gene"
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{
"id": "1533",
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
463,
467
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1534",
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{
"db_id": "3592",
"db_name": "NCBIGene",
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
766,
770
]
],
"text": [
"CLMF"
],
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{
"id": "1535",
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{
"db_id": "3592",
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
850,
854
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1536",
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{
"db_id": "3592",
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
868,
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]
],
"text": [
"CLMF"
],
"type": "FamilyName"
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{
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{
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"db_name": "NCBIGene",
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},
{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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964,
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]
],
"text": [
"CLMF"
],
"type": "FamilyName"
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{
"id": "1538",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1058,
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]
],
"text": [
"CLMF"
],
"type": "Gene"
},
{
"id": "1540",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1156,
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]
],
"text": [
"CLMF"
],
"type": "FamilyName"
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{
"id": "1541",
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{
"db_id": "3592",
"db_name": "NCBIGene",
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1186,
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]
],
"text": [
"interleukin 12"
],
"type": "FamilyName"
},
{
"id": "1527",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
78,
116
]
],
"text": [
"cytotoxic lymphocyte maturation factor"
],
"type": "FamilyName"
},
{
"id": "1528",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
118,
156
]
],
"text": [
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],
"type": "FamilyName"
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{
"id": "1529",
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{
"db_id": "3592",
"db_name": "NCBIGene",
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{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
158,
162
]
],
"text": [
"CLMF"
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"type": "FamilyName"
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{
"id": "1531",
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
281,
294
]
],
"text": [
"interleukin 2"
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"type": "Gene"
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{
"id": "1532",
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{
"db_id": "3558",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
349,
362
]
],
"text": [
"interleukin 2"
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"type": "Gene"
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{
"id": "1533",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
463,
467
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1534",
"normalized": [
{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
766,
770
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1535",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
850,
854
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1536",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
868,
872
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1537",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
964,
968
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1538",
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{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1058,
1062
]
],
"text": [
"CLMF"
],
"type": "Gene"
},
{
"id": "1540",
"normalized": [
{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1156,
1160
]
],
"text": [
"CLMF"
],
"type": "FamilyName"
},
{
"id": "1541",
"normalized": [
{
"db_id": "3592",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "3593",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1186,
1200
]
],
"text": [
"interleukin 12"
],
"type": "FamilyName"
}
] |
[
{
"location": {
"length": 220,
"offset": 0
},
"text": "Structure, expression, and genetic linkage of the mouse BCM1 (OX45 or Blast-1) antigen. Evidence for genetic duplication giving rise to the BCM1 region on mouse chromosome 1 and the CD2/LFA3 region on mouse chromosome 3.",
"type": "title"
},
{
"location": {
"length": 1886,
"offset": 221
},
"text": "The mouse BCM1 (OX45, Blast-1) antigen has been cDNA cloned and sequenced to provide data supporting the view that BCM1, LFA3, and CD2 constitute a subgroup within the Ig superfamily. Mouse BCM1 is widely expressed on leukocytes and is likely to be anchored to the cell surface by a glycosyl-phosphatidylinositol anchor, as is the case for rat and human BCM1 antigen. Genetic linkage studies by recombination and pulse field analysis showed the BCM1 locus (Bcm-1) to be on distal mouse chromosome 1 and to be linked within 1,600 kb to the locus for an ATPase alpha chain gene (Atpa-3). A similar relationship was established between the human BCM1 locus (BCM1) and ATP1A2, and other markers on chromosome 1q. Conservation of genomic organization within a segment of human chromosome 1q and mouse chromosome 1 was demonstrated. A similar situation is seen in the region of the CD2 and LFA3 genes between mouse chromosome 3 and human chromosome 1p. Furthermore, the CD2/LFA3 genes are linked within 580 kb to Atpa-1/ATP1A1 genes to provide a parallel situation to the linkage between Bcm-1/BCM1 and Atpa-3/ATP1A2 on chromosomes 1 (mouse) and 1q (human). Taken together, the data suggest duplication of a chromosome region including the precursors of the genes for BCM1, CD2, and LFA3, and the ATPase genes to give rise to the linkage groups now observed. The duplicated regions may have stayed together on chromosome 1 in the human (with the insertion of a centromere), while in the mouse, the genetic regions are proposed to have become dispersed in the formation of chromosomes 1 and 3. CD2 and LFA3 are more dissimilar in sequence than BCM1 and LFA3, and if the precursors of the CD2 and LFA3 loci formed before the proposed chromosome segment duplication, then a gene encoding a recognizer molecule for BCM1 may exist in linkage with Bcm-1/BCM1 on chromosome 1 (mouse) and 1q (human).",
"type": "abstract"
}
] |
[
{
"id": "1546",
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{
"db_id": "962",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
140,
144
]
],
"text": [
"BCM1"
],
"type": "Gene"
},
{
"id": "1547",
"normalized": [
{
"db_id": "914",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
182,
185
]
],
"text": [
"CD2"
],
"type": "Gene"
},
{
"id": "1548",
"normalized": [
{
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"db_name": "NCBIGene",
"tax_id": null
}
],
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[
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] |
[
{
"location": {
"length": 214,
"offset": 0
},
"text": "Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor.",
"type": "title"
},
{
"location": {
"length": 2205,
"offset": 215
},
"text": "Two proteins which specifically bind tumor necrosis factor (TNF) have recently been isolated from human urine in our laboratory. The two proteins cross-react immunologically with two species of cell surface TNF receptors (TNF-R). Antibodies against one of the two TNF binding proteins (TBPI) were found to have effects characteristic of TNF, including stimulating phosphorylation of specific cellular proteins. Oligonucleotide probes designed on the basis of the NH2-terminal amino acid sequence of TBPI were used to clone the cDNA for the structurally related cell surface type 1 TNF-R. It is notable that although this receptor can signal the phosphorylation of cellular proteins, it appears from its amino acid sequence to be devoid of intrinsic protein kinase activity. The extracellular domain of the receptor is composed of four internal cysteine-rich repeats, homologous to structures repeated four times in the extracellular domains of the nerve growth factor receptor and the B lymphocytes surface antigen CDw40. The amino acid composition and size of the extracellular domain of the type I TNF-R closely resemble those of TBPI. The COOH-terminal amino acid sequence of the four cysteine rich repeats within the extracellular domain of the type I TNF-R matches the COOH-terminal sequence of TBPI. Amino acid sequences in the extracellular domain also fully match other sequences found in TBPI. On the other hand, amino acid sequences in the soluble form of the type II TNF-R (TBPII), while indicating a marked homology of structure, did not suggest any identity between this protein and the extracellular domain of the type I TNF-R. CHO cells transfected with type I TNF-R cDNA produced both cell surface and soluble forms of the receptor. The receptor produced by CHO cells was recognized by several monoclonal antibodies against TBPI, reacting with several distinct epitopes in this molecule. These data suggest that the soluble forms of the TNF-Rs are structurally identical to the extracellular cytokine binding domains of these receptors and are consistent with the notion that the soluble forms are, at least partly, derived from the same transcripts that encode the cell surface receptors.",
"type": "abstract"
}
] |
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1884,
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76,
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252,
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275,
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"TNF"
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776,
801
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"cell surface type 1 TNF-R"
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1308,
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"TBPII"
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1843,
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1884,
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],
"text": [
"type I TNF-R"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 171,
"offset": 0
},
"text": "A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44.",
"type": "title"
},
{
"location": {
"length": 1532,
"offset": 172
},
"text": "TSG-6 cDNA was isolated by differential screening of a lambda cDNA library prepared from tumor necrosis factor (TNF)-treated human diploid FS-4 fibroblasts. We show that TSG-6 mRNA was not detectable in untreated cells, but became readily induced by TNF in normal human fibroblast lines and in peripheral blood mononuclear cells. In contrast, TSG-6 mRNA was undetectable in either control or TNF-treated human vascular endothelial cells and a variety of tumor-derived or virus-transformed cell lines. The sequence of full-length TSG-6 cDNA revealed one major open reading frame predicting a polypeptide of 277 amino acids, including a typical cleavable signal peptide. The NH2-terminal half of the predicted TSG-6 protein sequence shows a significant homology with a region implicated in hyaluronate binding, present in cartilage link protein, proteoglycan core proteins, and the adhesion receptor CD44. The most extensive sequence homology exists between the predicted TSG-6 protein and CD44. Western blot analysis with an antiserum raised against a TSG-6 fusion protein detected a 39-kD glycoprotein in the supernatants of TNF-treated FS-4 cells and of cells transfected with TSG-6 cDNA. Binding of the TSG-6 protein to hyaluronate was demonstrated by coprecipitation. Our data indicate that the inflammatory cytokine (TNF or IL-1)-inducible, secretory TSG-6 protein is a novel member of the family of hyaluronate binding proteins, possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis.",
"type": "abstract"
}
] |
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59,
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166,
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342,
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422,
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515,
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],
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564,
567
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"TNF"
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{
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],
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701,
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1142,
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1350,
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1377,
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1493,
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}
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1500,
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1527,
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59,
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}
],
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166,
170
]
],
"text": [
"CD44"
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],
"offsets": [
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172,
177
]
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"text": [
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}
],
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261,
282
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284,
287
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342,
347
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],
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422,
425
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515,
520
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}
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564,
567
]
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"TNF"
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"type": "Gene"
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{
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"tax_id": null
}
],
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[
701,
706
]
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"TSG-6"
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}
],
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880,
885
]
],
"text": [
"TSG-6"
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{
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"tax_id": null
}
],
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[
992,
1014
]
],
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"db_id": "960",
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"tax_id": null
}
],
"offsets": [
[
1070,
1074
]
],
"text": [
"CD44"
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},
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}
],
"offsets": [
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1142,
1147
]
],
"text": [
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}
],
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1160,
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]
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"text": [
"CD44"
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}
],
"offsets": [
[
1223,
1228
]
],
"text": [
"TSG-6"
],
"type": "Gene"
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}
],
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1297,
1300
]
],
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}
],
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1350,
1355
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],
"text": [
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}
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}
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}
],
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1500,
1504
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],
"text": [
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{
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}
],
"offsets": [
[
1527,
1532
]
],
"text": [
"TSG-6"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 107,
"offset": 0
},
"text": "Cloning and antisense oligodeoxynucleotide inhibition of a human homolog of cdc2 required in hematopoiesis.",
"type": "title"
},
{
"location": {
"length": 2044,
"offset": 108
},
"text": "Mechanisms triggering the commitment of pluripotent bone marrow stem cells to differentiated lineages such as mononuclear macrophages or multinucleated megakaryocytes are still unknown, although several lines of evidence suggested correlation between cholinergic signaling and hematopoietic differentiation. We now present cloning of a cDNA coding for CHED (cholinesterase-related cell division controller), a human homolog of the Schizosaccharomyces pombe cell division cycle 2 (cdc2)-like kinases, universal controllers of the mitotic cell cycle. Library screening, RNA blot hybridization, and direct PCR amplification of cDNA reverse-transcribed from cellular mRNA revealed that CHED mRNA is expressed in multiple tissues, including bone marrow. The CHED protein includes the consensus ATP binding and phosphorylation domains characteristic of kinases, displays 34-42% identically aligned amino acid residues with other cdc2-related kinases, and is considerably longer at its amino and carboxyl termini. An antisense oligodeoxynucleotide designed to interrupt CHED's expression (AS-CHED) significantly reduced the ratio between CHED mRNA and actin mRNA within 1 hr of its addition to cultures, a reduction that persisted for 4 days. AS-CHED treatment selectively inhibited megakaryocyte development in murine bone marrow cultures but did not prevent other hematopoietic pathways, as evidenced by increasing numbers of mononuclear cells. An oligodeoxynucleotide blocking production of the acetylcholine-hydrolyzing enzyme, butyrylcholinesterase, displayed a similar inhibition of megakaryocytopoiesis. In contrast, an oligodeoxynucleotide blocking production of the human 2Hs cdc2 homolog interfered with production of the human 2Hs cdc2 homolog interfered with cellular proliferation without altering the cell-type composition of these cultures. Therefore, these findings strengthen the link between cholinergic signaling and cell division control in hematopoiesis and implicate both CHED and cholinesterases in this differentiation process.",
"type": "abstract"
}
] |
[
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}
],
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[
76,
80
]
],
"text": [
"cdc2"
],
"type": "Gene"
},
{
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}
],
"offsets": [
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],
"text": [
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}
],
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],
"text": [
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}
],
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"text": [
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}
],
"offsets": [
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],
"text": [
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},
{
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}
],
"offsets": [
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],
"text": [
"CHED"
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"CHED"
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1239,
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"CHED"
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1347,
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"CHED"
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],
"offsets": [
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1633,
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"text": [
"butyrylcholinesterase"
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"type": "Gene"
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"text": [
"cdc2"
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"cdc2"
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2095,
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"text": [
"CHED"
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"text": [
"cdc2"
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{
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]
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"text": [
"CHED"
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],
"offsets": [
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466,
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],
"text": [
"cholinesterase-related cell division controller"
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"CHED"
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}
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"offsets": [
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1633,
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"text": [
"butyrylcholinesterase"
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}
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"offsets": [
[
1786,
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"text": [
"cdc2"
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}
],
"offsets": [
[
1843,
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]
],
"text": [
"cdc2"
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"type": "Gene"
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{
"id": "1670",
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{
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}
],
"offsets": [
[
2095,
2099
]
],
"text": [
"CHED"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 99,
"offset": 0
},
"text": "Structural analysis and expression of human desmoglein: a cadherin-like component of the desmosome.",
"type": "title"
},
{
"location": {
"length": 2255,
"offset": 100
},
"text": "Desmosomes are adhesive cell junctions found in great abundance in tissues that experience mechanical stress. The transmembrane desmosomal glycoproteins have been proposed to play a role in cell adhesion; desmoglein I (DGI) is a major member of this class of desmosomal molecules. However, evidence supporting a role for DGI in cell adhesion or in the plaque is lacking. In order to begin to understand DGI function we have identified human cDNA clones encoding the entire mature polypeptide of 1000 amino acids. Our data suggest that like the bovine DGI molecule human DGI is highly related to the calcium-dependent class of cell adhesion molecules known as cadherins. Four related extracellular domains located in the amino-terminal domain of the molecule contain putative calcium binding sites originally identified in the cadherins. The highest degree of similarity between human N-cadherin and human DGI, and likewise between bovine DGI and human DGI, is greatest in the most amino-terminal extracellular domain. This suggests a conserved functional role for the extracellular domains, perhaps in calcium-mediated cell adhesion. The cytoplasmic portion of the molecule contains a cadherin-like region and, like bovine DGI, a carboxy-terminal tail that is not present in the cadherins, comprising three additional domains. One of these contains a novel repeating motif of 29 +/- 1 residues, first identified in bovine DGI. Each of the highly homologous repeating units is likely to consist of two beta-strands and two turns with special characteristics. Five amino acids that are identical in bovine and human DGI lie in the second of the two predicted beta-strands, and intriguingly contain putative target sites for protein kinase C. On the basis of structural analysis, a model predicting the disposition of human DGI domains in the desmosome is proposed. Northern analysis suggests that unlike bovine epidermis, which expresses a single mRNA of reported size approximately 7.6 kb, human foreskin and cultured keratinocytes display a complex pattern with bands of approximately 7.2, 4.0 and 3.0 kb. Each of these cross-hybridizing mRNAs is coordinately expressed in normal human keratinocytes in response to long-term culture and increased calcium.",
"type": "abstract"
}
] |
[
{
"id": "1673",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
305,
317
]
],
"text": [
"desmoglein I"
],
"type": "Gene"
},
{
"id": "1674",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
319,
322
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1675",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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421,
424
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1676",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
503,
506
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1678",
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{
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"tax_id": null
}
],
"offsets": [
[
670,
673
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1682",
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{
"db_id": "1000",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
984,
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]
],
"text": [
"N-cadherin"
],
"type": "Gene"
},
{
"id": "1683",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1005,
1008
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1685",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1052,
1055
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1692",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1714,
1717
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1673",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
305,
317
]
],
"text": [
"desmoglein I"
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"type": "Gene"
},
{
"id": "1674",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
319,
322
]
],
"text": [
"DGI"
],
"type": "Gene"
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{
"id": "1675",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
421,
424
]
],
"text": [
"DGI"
],
"type": "Gene"
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{
"id": "1676",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
503,
506
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1678",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
670,
673
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1682",
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{
"db_id": "1000",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
984,
994
]
],
"text": [
"N-cadherin"
],
"type": "Gene"
},
{
"id": "1683",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1005,
1008
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1685",
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{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1052,
1055
]
],
"text": [
"DGI"
],
"type": "Gene"
},
{
"id": "1692",
"normalized": [
{
"db_id": "1828",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1714,
1717
]
],
"text": [
"DGI"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 110,
"offset": 0
},
"text": "Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins.",
"type": "title"
},
{
"location": {
"length": 2170,
"offset": 111
},
"text": "We have isolated and characterized a full-length cDNA clone encoding human loricrin. Curiously, this protein displays major differences from the recently described mouse loricrin (Mehrel, T., Hohl, D., Nakazawa, H., Rothnagel, J.A., Longley, M.A., Bundman, D., Cheng, C.K., Lichti, U., Bisher, M.E., Steven, A. C., Steinert, P.M., Yuspa, S.H., and Roop, D.R. (1990) Cell 61, 1103-1112). Although both proteins are glycine-serine-cysteine-rich, the sequences have not been conserved. However, analysis of the sequences reveals a common motif of quasi-peptide repeats of an aliphatic or aromatic amino acid residue followed by several glycine and/or serine and cysteine residues. These sequences are interspersed and flanked by short glutamine- or glutamine/lysine-rich peptides. Thus loricrins consist of a family of cell envelope proteins of highly variable sequences that nevertheless retain common structural elements. We show that unlike all other putative protein components of the cell envelope, loricrins are highly insoluble, due at least in part to cross-linking by disulfide bonds. Furthermore, we have isolated four peptides from purified human cell envelopes that contain recognizable loricrin sequences and which are cross-linked by the N epsilon-(gamma-glutamyl)lysine isodipeptide bond. The presence of such bonds thus affords an explanation for the extraordinary insolubility of loricrin by cross-linking to the cell envelope and can also explain the low steady-state levels of monomeric loricrin in cytoskeletal extracts of epidermis. This study represents the first report of this isodipeptide cross-link in a protein component of the cornified cell envelope. We propose a model for the structure of loricrin in which (i) the unusual glycine-serine-rich sequences adopt a flexible loop conformation, indexed on the recurrent aliphatic residues; (ii) inter- or intramolecular isodipeptide and disulfide cross-links induce or stabilize folding of loricrin so as to form a more compact rosette-like structure; and (iii) the presence of the flexible glycine-rich loops necessarily will impact a flexible character to the cell envelope and entire epithelium.",
"type": "abstract"
}
] |
[
{
"id": "1696",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
26,
34
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1698",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
186,
194
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1700",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1307,
1315
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1701",
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{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1505,
1513
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1702",
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{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1614,
1622
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1703",
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{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1828,
1836
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1704",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2073,
2081
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1696",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
26,
34
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1698",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
186,
194
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1700",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1307,
1315
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1701",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1505,
1513
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1702",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1614,
1622
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1703",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1828,
1836
]
],
"text": [
"loricrin"
],
"type": "Gene"
},
{
"id": "1704",
"normalized": [
{
"db_id": "4014",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
2073,
2081
]
],
"text": [
"loricrin"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 94,
"offset": 0
},
"text": "Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter.",
"type": "title"
},
{
"location": {
"length": 1165,
"offset": 95
},
"text": "At most synapses, chemical signalling is terminated by a rapid reaccumulation of neurotransmitter into presynaptic terminals. Uptake systems for the biogenic amines are the initial site of action for therapeutic antidepressants and drugs such as cocaine and the amphetamines. We have isolated a complementary DNA clone encoding a human noradrenaline transporter. The cDNA sequence predicts a protein of 617 amino acids, with 12-13 highly hydrophobic regions compatible with membrane-spanning domains. Expression of the cDNA clone in transfected HeLa cells indicates that noradrenaline transport activity is sodium-dependent and sensitive to selective noradrenaline transport inhibitors. Transporter RNA is localized to the brainstem and the adrenal gland. The predicted protein sequence demonstrates significant amino-acid identity with the Na+/gamma-aminobutyric acid transporter, thus identifying a new gene family for neurotransmitter transporter proteins. Analysis of its structure and function may lead to structure-based drug design for the treatment of human depression and could help determine whether transporter abnormalities underlie affective disorders.",
"type": "abstract"
}
] |
[
{
"id": "1706",
"normalized": [
{
"db_id": "6530",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
24,
93
]
],
"text": [
"cocaine- and antidepressant-sensitive human noradrenaline transporter"
],
"type": "Gene"
},
{
"id": "1707",
"normalized": [
{
"db_id": "6530",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
431,
456
]
],
"text": [
"noradrenaline transporter"
],
"type": "Gene"
},
{
"id": "1706",
"normalized": [
{
"db_id": "6530",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
24,
93
]
],
"text": [
"cocaine- and antidepressant-sensitive human noradrenaline transporter"
],
"type": "Gene"
},
{
"id": "1707",
"normalized": [
{
"db_id": "6530",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
431,
456
]
],
"text": [
"noradrenaline transporter"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 97,
"offset": 0
},
"text": "Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments.",
"type": "title"
},
{
"location": {
"length": 844,
"offset": 98
},
"text": "A set of 11 clones encoding putative GTP binding proteins highly homologous to the yeast YPT1/SEC4 gene products have been isolated from an MDCK cell cDNA library. We localized three of the corresponding proteins in mammalian cells by using affinity-purified antibodies in immunofluorescence and immunoelectron microscopy studies. One, the MDCK homolog of rab2, is associated with a structure having the characteristics of an intermediate compartment between the endoplasmic reticulum and the Golgi apparatus. The second, rab5, is located at the cytoplasmic surface of the plasma membrane and on early endosomes, while the third, rab7, is found on late endosomes. These findings provide evidence that members of the YPT1/SEC4 subfamily of GTP binding proteins are localized to specific exocytic and endocytic subcompartments in mammalian cells.",
"type": "abstract"
}
] |
[
{
"id": "1717",
"normalized": [
{
"db_id": "5862",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
454,
458
]
],
"text": [
"rab2"
],
"type": "Gene"
},
{
"id": "1719",
"normalized": [
{
"db_id": "5868",
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"text": [
"rab5"
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"type": "Gene"
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"id": "1720",
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{
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"text": [
"rab7"
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}
],
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454,
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"text": [
"rab2"
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"type": "Gene"
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{
"id": "1719",
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{
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],
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620,
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"text": [
"rab5"
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"type": "Gene"
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{
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}
],
"offsets": [
[
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],
"text": [
"rab7"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 45,
"offset": 0
},
"text": "A human homologue of the yeast HDEL receptor.",
"type": "title"
},
{
"location": {
"length": 1039,
"offset": 46
},
"text": "Retention of resident proteins in the lumen of the endoplasmic reticulum is achieved in both yeast and animal cells by their continual retrieval from the cis-Golgi, or a pre-Golgi compartment. Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, usually Lys-Asp-Glu-Leu (KDEL in the single letter code) in animal cells, His-Asp-Glu-Leu (HDEL) in Saccharomyces cerevisiae. There is evidence that the ERD2 gene encodes the sorting receptor that recognizes HDEL in yeast; its product is an integral membrane protein of relative molecular mass 26,000 (26K) that is not glycosylated. In contrast, Vaux et al. suggest that the mammalian KDEL receptor is a 72K glycoprotein that they detected using an anti-idiotypic antibody approach. If this were so, it would indicate a surprising divergence of the retrieval machinery between yeast and animal cells. We report here that human cells express a protein similar in sequence, size and properties to the ERD2 product, and propose that this protein is the human KDEL receptor.",
"type": "abstract"
}
] |
[
{
"id": "1732",
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{
"db_id": "10945",
"db_name": "NCBIGene",
"tax_id": null
}
],
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700,
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]
],
"text": [
"KDEL receptor"
],
"type": "Gene"
},
{
"id": "1733",
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{
"db_id": "10945",
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"tax_id": null
}
],
"offsets": [
[
1014,
1018
]
],
"text": [
"ERD2"
],
"type": "Gene"
},
{
"id": "1734",
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{
"db_id": "10945",
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"tax_id": null
}
],
"offsets": [
[
1071,
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],
"text": [
"KDEL receptor"
],
"type": "Gene"
},
{
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{
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],
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700,
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"text": [
"KDEL receptor"
],
"type": "Gene"
},
{
"id": "1733",
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{
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"tax_id": null
}
],
"offsets": [
[
1014,
1018
]
],
"text": [
"ERD2"
],
"type": "Gene"
},
{
"id": "1734",
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{
"db_id": "10945",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1071,
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]
],
"text": [
"KDEL receptor"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 83,
"offset": 0
},
"text": "Primary structure and functional expression of rat and human stem cell factor DNAs.",
"type": "title"
},
{
"location": {
"length": 707,
"offset": 84
},
"text": "Partial cDNA and genomic clones of rat stem cell factor (SCF) have been isolated. Using probes based on the rat sequence, partial and full-length cDNA and genomic clones of human SCF have been isolated. Based on the primary structure of the 164 amino acid protein purified from BRL-3A cells, truncated forms of the rat and human proteins have been expressed in E. coli and mammalian cells and have been shown to possess biological activity. SCF is able to augment the proliferation of both myeloid and lymphoid hematopoietic progenitors in bone marrow cultures. SCF exhibits potent synergistic activities in conjunction with colony-stimulating factors, resulting in increased colony numbers and colony size.",
"type": "abstract"
}
] |
[
{
"id": "1736",
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{
"db_id": "4254",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
61,
77
]
],
"text": [
"stem cell factor"
],
"type": "Gene"
},
{
"id": "1739",
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{
"db_id": "4254",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
263,
266
]
],
"text": [
"SCF"
],
"type": "Gene"
},
{
"id": "1740",
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{
"db_id": "4254",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
525,
528
]
],
"text": [
"SCF"
],
"type": "Gene"
},
{
"id": "1741",
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{
"db_id": "4254",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
646,
649
]
],
"text": [
"SCF"
],
"type": "Gene"
},
{
"id": "1736",
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{
"db_id": "4254",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
61,
77
]
],
"text": [
"stem cell factor"
],
"type": "Gene"
},
{
"id": "1739",
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{
"db_id": "4254",
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"tax_id": null
}
],
"offsets": [
[
263,
266
]
],
"text": [
"SCF"
],
"type": "Gene"
},
{
"id": "1740",
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{
"db_id": "4254",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
525,
528
]
],
"text": [
"SCF"
],
"type": "Gene"
},
{
"id": "1741",
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{
"db_id": "4254",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
646,
649
]
],
"text": [
"SCF"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 160,
"offset": 0
},
"text": "Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis.",
"type": "title"
},
{
"location": {
"length": 1428,
"offset": 161
},
"text": "Autoantibodies to a novel nuclear Ag, Sp100, have recently been described that recognize a nuclear protein with an apparent molecular mass of 95 to 100 kDa and a dot-like distribution within cell nuclei. By immunoscreening of a lambda gt11 cDNA expression library derived from HeLa cells with an anti-Sp100 autoimmune serum a 0.7-kb cDNA (Sp26) coding for a fragment of Sp100 was isolated. Expression of this cDNA and use of the recombinant protein in ELISA revealed that the fragment carries major Sp100 autoepitopes and that anti-Sp100 autoantibodies predominantly occur in patients suffering from primary biliary cirrhosis (50/184). The Sp26 cDNA was used as hybridization probe for isolation of longer cDNA from human liver- and placenta-derived lambda gt10 cDNA libraries. Overlapping fragments were assembled to generate a full length cDNA coding for a protein with a molecular mass of 53 kDa and an isoelectric point of 4.7. The Sp100 autoantigen expressed in vitro from this cDNA and authenticated by a capture immunoblot assay, comigrated in SDS-PAGE with the authentic HeLa autoantigen of 95 to 100 kDa and thus showed an aberrant electrophoretic mobility. Computer based protein sequence analysis of the Sp100 autoantigen revealed regions of striking sequence similarities to the alpha 1 and alpha 2 domains of various human and non-human MHC class I Ag and to several transacting transcriptional regulatory proteins.",
"type": "abstract"
}
] |
[
{
"id": "1744",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
199,
204
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1745",
"normalized": [
{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
462,
467
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1746",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
531,
536
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1747",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
660,
665
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1748",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
693,
698
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1749",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1097,
1102
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1750",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1376,
1381
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1752",
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{
"db_id": "4276",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1511,
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],
"text": [
"MHC class I Ag"
],
"type": "Gene"
},
{
"id": "1744",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
199,
204
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1745",
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{
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"tax_id": null
}
],
"offsets": [
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462,
467
]
],
"text": [
"Sp100"
],
"type": "Gene"
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{
"id": "1746",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
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531,
536
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],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1747",
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{
"db_id": "6672",
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"tax_id": null
}
],
"offsets": [
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660,
665
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1748",
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{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
693,
698
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1749",
"normalized": [
{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1097,
1102
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1750",
"normalized": [
{
"db_id": "6672",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1376,
1381
]
],
"text": [
"Sp100"
],
"type": "Gene"
},
{
"id": "1752",
"normalized": [
{
"db_id": "4276",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1511,
1525
]
],
"text": [
"MHC class I Ag"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 50,
"offset": 0
},
"text": "Expression cloning of a human Fc receptor for IgA.",
"type": "title"
},
{
"location": {
"length": 893,
"offset": 51
},
"text": "IgA, the predominant isotype in secretions, mediates the neutralization and removal of environmental antigens from mucosal sites. Although cell surface receptors for the Fc region of IgA (Fc alpha R) have been implicated in a variety of immune effector mechanisms, the molecular features of Fc alpha R remain only marginally characterized. In this report, we describe the isolation of a clone from a myeloid cell line cDNA library that directs the expression of a cell surface molecule with IgA binding specificity. The cDNA encodes a peptide of Mr 30,000 including a putative transmembrane region with features atypical of conventional membrane-anchored proteins. Databank searches indicate that the human myeloid cell Fc alpha R sequence is unique, is a member of the immunoglobulin gene superfamily, and is related to Fc receptors for IgG (Fc gamma RI, II, and III) and IgE (Fc epsilon RI).",
"type": "abstract"
}
] |
[
{
"id": "1761",
"normalized": [
{
"db_id": "2204",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
239,
249
]
],
"text": [
"Fc alpha R"
],
"type": "Gene"
},
{
"id": "1762",
"normalized": [
{
"db_id": "2204",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
342,
352
]
],
"text": [
"Fc alpha R"
],
"type": "Gene"
},
{
"id": "1766",
"normalized": [
{
"db_id": "2204",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
771,
781
]
],
"text": [
"Fc alpha R"
],
"type": "Gene"
},
{
"id": "1770",
"normalized": [
{
"db_id": "2209",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "2212",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "2214",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
894,
918
]
],
"text": [
"Fc gamma RI, II, and III"
],
"type": "Gene"
},
{
"id": "1772",
"normalized": [
{
"db_id": "2205",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
929,
942
]
],
"text": [
"Fc epsilon RI"
],
"type": "Gene"
},
{
"id": "1761",
"normalized": [
{
"db_id": "2204",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
239,
249
]
],
"text": [
"Fc alpha R"
],
"type": "Gene"
},
{
"id": "1762",
"normalized": [
{
"db_id": "2204",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
342,
352
]
],
"text": [
"Fc alpha R"
],
"type": "Gene"
},
{
"id": "1766",
"normalized": [
{
"db_id": "2204",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
771,
781
]
],
"text": [
"Fc alpha R"
],
"type": "Gene"
},
{
"id": "1770",
"normalized": [
{
"db_id": "2209",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "2212",
"db_name": "NCBIGene",
"tax_id": null
},
{
"db_id": "2214",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
894,
918
]
],
"text": [
"Fc gamma RI, II, and III"
],
"type": "Gene"
},
{
"id": "1772",
"normalized": [
{
"db_id": "2205",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
929,
942
]
],
"text": [
"Fc epsilon RI"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 78,
"offset": 0
},
"text": "Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase.",
"type": "title"
},
{
"location": {
"length": 914,
"offset": 79
},
"text": "The cDNA encoding human ferrochelatase [EC 4.99.1.1] was isolated from a human placenta cDNA library in bacteriophage lambda gt11 by screening with a radiolabeled fragment of mouse ferrochelatase cDNA. The cDNA had an open reading frame of 1269 base pairs (bp) encoding a protein of 423 amino acid residues (Mr. 47,833) with alternative putative polyadenylation signals in the 3' non-coding regions and poly (A) tails. Amino acid sequencing showed that the mature protein consists of 369 amino acid residues (Mr. 42,158) with a putative leader sequence of 54 amino acid residues. The human enzyme showed an 88% identity to mouse enzyme and 46% to yeast enzyme. Northern blot analysis showed two mRNAs of about 2500 and 1600 bp for ferrochelatase in K562 and HepG2 cells. As full-length cDNA for human ferrochelatase is now available, molecular lesions related to erythropoietic protoporphyria can be characterized.",
"type": "abstract"
}
] |
[
{
"id": "1774",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
63,
77
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
},
{
"id": "1775",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
103,
117
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
},
{
"id": "1776",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
119,
130
]
],
"text": [
"EC 4.99.1.1"
],
"type": "Gene"
},
{
"id": "1778",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
810,
824
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
},
{
"id": "1779",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
880,
894
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
},
{
"id": "1774",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
63,
77
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
},
{
"id": "1775",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
103,
117
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
},
{
"id": "1776",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
119,
130
]
],
"text": [
"EC 4.99.1.1"
],
"type": "Gene"
},
{
"id": "1778",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
810,
824
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
},
{
"id": "1779",
"normalized": [
{
"db_id": "2235",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
880,
894
]
],
"text": [
"ferrochelatase"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 101,
"offset": 0
},
"text": "Sequence identity between human pancreatic cholesterol esterase and bile salt-stimulated milk lipase.",
"type": "title"
},
{
"location": {
"length": 910,
"offset": 102
},
"text": "Three overlapping cDNA clones covering the entire primary sequence of the bile salt stimulated lipase in human milk were isolated from a human breast lambda gt10 cDNA library by screening with the rat pancreatic cholesterol esterase cDNA. Nucleotide sequencing of the cDNA showed that the human milk lipase mRNA encodes a 748-residue protein, including a 23-residue signal peptide. The human milk lipase cDNA is highly homologous to rat pancreatic cholesterol esterase, suggesting that the milk lipase may be identical to the cholesterol esterase in human pancreas. This conclusion was confirmed by isolation and sequencing of the cDNA for human pancreatic cholesterol esterase. Analysis of the sequence for the human cholesterol esterase/milk lipase revealed similarities to other serine esterases in three distinct regions of the protein. These domains may represent the active site triads of these proteins.",
"type": "abstract"
}
] |
[
{
"id": "1781",
"normalized": [
{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
32,
63
]
],
"text": [
"pancreatic cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1782",
"normalized": [
{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
68,
100
]
],
"text": [
"bile salt-stimulated milk lipase"
],
"type": "Gene"
},
{
"id": "1785",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
397,
408
]
],
"text": [
"milk lipase"
],
"type": "Gene"
},
{
"id": "1786",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
494,
505
]
],
"text": [
"milk lipase"
],
"type": "Gene"
},
{
"id": "1788",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
592,
603
]
],
"text": [
"milk lipase"
],
"type": "Gene"
},
{
"id": "1789",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
628,
648
]
],
"text": [
"cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1790",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
748,
779
]
],
"text": [
"pancreatic cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1791",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
820,
840
]
],
"text": [
"cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1792",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
841,
852
]
],
"text": [
"milk lipase"
],
"type": "Gene"
},
{
"id": "1781",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
32,
63
]
],
"text": [
"pancreatic cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1782",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
68,
100
]
],
"text": [
"bile salt-stimulated milk lipase"
],
"type": "Gene"
},
{
"id": "1785",
"normalized": [
{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
397,
408
]
],
"text": [
"milk lipase"
],
"type": "Gene"
},
{
"id": "1786",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
494,
505
]
],
"text": [
"milk lipase"
],
"type": "Gene"
},
{
"id": "1788",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
592,
603
]
],
"text": [
"milk lipase"
],
"type": "Gene"
},
{
"id": "1789",
"normalized": [
{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
628,
648
]
],
"text": [
"cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1790",
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{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
748,
779
]
],
"text": [
"pancreatic cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1791",
"normalized": [
{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
820,
840
]
],
"text": [
"cholesterol esterase"
],
"type": "Gene"
},
{
"id": "1792",
"normalized": [
{
"db_id": "1056",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
841,
852
]
],
"text": [
"milk lipase"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 225,
"offset": 0
},
"text": "Maple syrup urine disease. Complete primary structure of the E1 beta subunit of human branched chain alpha-ketoacid dehydrogenase complex deduced from the nucleotide sequence and a gene analysis of patients with this disease.",
"type": "title"
},
{
"location": {
"length": 1577,
"offset": 226
},
"text": "A defect in the E1 beta subunit of the branched chain alpha-ketoacid dehydrogenase (BCKDH) complex is one cause of maple syrup urine disease (MSUD). In an attempt to elucidate the molecular basis of MSUD, we isolated and characterized a 1.35 kbp cDNA clone encoding the entire precursor of the E1 beta subunit of BCKDH complex from a human placental cDNA library. Nucleotide sequence analysis revealed that the isolated cDNA clone (lambda hBE1 beta-1) contained a 5'-untranslated sequence of four nucleotides, the translated sequence of 1,176 nucleotides and the 3'-untranslated sequence of 169 nucleotides. Comparison of the amino acid sequence predicted from the nucleotide sequence of the cDNA insert of the clone with the NH2-terminal amino acid sequence of the purified mature bovine BCKDH-E1 beta subunit showed that the cDNA insert encodes for a 342-amino acid subunit with a Mr = 37,585. The subunit is synthesized as the precursor with a leader sequence of 50 amino acids and is processed at the NH2 terminus. A search for protein homology revealed that the primary structure of human BCKDH-E1 beta was similar to the bovine BCKDH-E1 beta and to the E1 beta subunit of human pyruvate dehydrogenase complex, in all regions. The structures and functions of mammalian alpha-ketoacid dehydrogenase complexes are apparently highly conserved. Genomic DNA from lymphoblastoid cell lines derived from normal and five MSUD patients, in whom E1 beta was not detected by immunoblot analysis, gave the same restriction maps on Southern blot analysis. The gene has at least 80 kbp.",
"type": "abstract"
}
] |
[
{
"id": "1795",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
61,
76
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1797",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
242,
257
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1800",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
520,
535
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1802",
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{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
665,
676
]
],
"text": [
"hBE1 beta-1"
],
"type": "Gene"
},
{
"id": "1806",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1326,
1333
]
],
"text": [
"E1 beta"
],
"type": "Gene"
},
{
"id": "1808",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1385,
1400
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1811",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1667,
1674
]
],
"text": [
"E1 beta"
],
"type": "Gene"
},
{
"id": "1795",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
61,
76
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1797",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
242,
257
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1800",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
520,
535
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1802",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
665,
676
]
],
"text": [
"hBE1 beta-1"
],
"type": "Gene"
},
{
"id": "1806",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1326,
1333
]
],
"text": [
"E1 beta"
],
"type": "Gene"
},
{
"id": "1808",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1385,
1400
]
],
"text": [
"E1 beta subunit"
],
"type": "Gene"
},
{
"id": "1811",
"normalized": [
{
"db_id": "594",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1667,
1674
]
],
"text": [
"E1 beta"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 63,
"offset": 0
},
"text": "Sequence and expression of a human type II mesothelial keratin.",
"type": "title"
},
{
"location": {
"length": 1052,
"offset": 64
},
"text": "Using mRNA from cultured human mesothelial cells, we constructed bacterial plasmids and lambda phage vectors that contained cDNA sequences specific for the keratins expressed in these cells. A cloned cDNA encoding keratin K7 (55 kD) was identified by positive hybrid selection. Southern Blot analysis indicated that this sequence is represented only once in the human genome, and Northern Blot analysis demonstrated that the gene encoding K7 is expressed in abundance in cultured bronchial and mesothelial cells, but only weakly in cultured epidermal cells and not at all in liver, colon, or exocervical tissue. The predicted amino acid sequence of this keratin has revealed a striking difference between this keratin and the type II keratins expressed in epidermal cells: whereas all of the epidermal type II keratins thus far sequenced have long nonhelical termini rich in glycine and serine, this mesothelial type II keratin has amino and carboxy terminal regions that are unusually short and lack the inexact repeats of glycine and serine residues.",
"type": "abstract"
}
] |
[
{
"id": "1813",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
35,
62
]
],
"text": [
"type II mesothelial keratin"
],
"type": "Gene"
},
{
"id": "1815",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
286,
288
]
],
"text": [
"K7"
],
"type": "Gene"
},
{
"id": "1816",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
503,
505
]
],
"text": [
"K7"
],
"type": "Gene"
},
{
"id": "1819",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
964,
991
]
],
"text": [
"mesothelial type II keratin"
],
"type": "Gene"
},
{
"id": "1813",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
35,
62
]
],
"text": [
"type II mesothelial keratin"
],
"type": "Gene"
},
{
"id": "1815",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
286,
288
]
],
"text": [
"K7"
],
"type": "Gene"
},
{
"id": "1816",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
503,
505
]
],
"text": [
"K7"
],
"type": "Gene"
},
{
"id": "1819",
"normalized": [
{
"db_id": "3855",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
964,
991
]
],
"text": [
"mesothelial type II keratin"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 114,
"offset": 0
},
"text": "Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence.",
"type": "title"
},
{
"location": {
"length": 1535,
"offset": 115
},
"text": "p97 is a cell-surface glycoprotein that is present in most human melanomas but only in trace amounts in normal adult tissues. To determine the structure of this tumor-associated antigen and to identify its functional domains, we have purified and cloned p97 mRNA and determined its nucleotide sequence. The mRNA encodes a 738-residue precursor, which contains the previously determined N-terminal amino acid sequence of p97. After removal of a 19-residue signal peptide, the mature p97 molecule comprises extracellular domains of 342 and 352 residues and a C-terminal 25-residue stretch of predominantly uncharged and hydrophobic amino acids, which we believe acts as a membrane anchor. Each extracellular domain contains 14 cysteine residues, which form seven intradomain disulfide bridges, and one or two potential N-glycosylation sites. Protease digestion studies show that the three major antigenic determinants of p97 are present on the N-terminal domain. The domains are strikingly homologous to each other (46% amino acid sequence homology) and to the corresponding domains of human serum transferrin (39% homology). Conservation of disulfide bridges and of amino acids thought to compose the iron binding pockets suggests that p97 is also related to transferrin in tertiary structure and function. We propose that p97 be renamed melanotransferrin to denote its original identification in melanoma cells and its evolutionary relationship to serotransferrin and lactotransferrin, the other members of the transferrin superfamily.",
"type": "abstract"
}
] |
[
{
"id": "1822",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
31,
62
]
],
"text": [
"melanoma-associated antigen p97"
],
"type": "Gene"
},
{
"id": "1823",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
64,
81
]
],
"text": [
"melanotransferrin"
],
"type": "Gene"
},
{
"id": "1824",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
115,
118
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1826",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
369,
372
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1827",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
535,
538
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1828",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
597,
600
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1832",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1034,
1037
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1834",
"normalized": [
{
"db_id": "7018",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1211,
1222
]
],
"text": [
"transferrin"
],
"type": "Gene"
},
{
"id": "1835",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1350,
1353
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1836",
"normalized": [
{
"db_id": "7018",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1373,
1384
]
],
"text": [
"transferrin"
],
"type": "Gene"
},
{
"id": "1837",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1437,
1440
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1838",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1452,
1469
]
],
"text": [
"melanotransferrin"
],
"type": "Gene"
},
{
"id": "1839",
"normalized": [
{
"db_id": "7018",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1563,
1578
]
],
"text": [
"serotransferrin"
],
"type": "Gene"
},
{
"id": "1840",
"normalized": [
{
"db_id": "4057",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1583,
1599
]
],
"text": [
"lactotransferrin"
],
"type": "Gene"
},
{
"id": "1841",
"normalized": [
{
"db_id": "7018",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1626,
1637
]
],
"text": [
"transferrin"
],
"type": "Gene"
},
{
"id": "1822",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
31,
62
]
],
"text": [
"melanoma-associated antigen p97"
],
"type": "Gene"
},
{
"id": "1823",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
64,
81
]
],
"text": [
"melanotransferrin"
],
"type": "Gene"
},
{
"id": "1824",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
115,
118
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1826",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
369,
372
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1827",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
535,
538
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1828",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
597,
600
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1832",
"normalized": [
{
"db_id": "4241",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1034,
1037
]
],
"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1834",
"normalized": [
{
"db_id": "7018",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1211,
1222
]
],
"text": [
"transferrin"
],
"type": "Gene"
},
{
"id": "1835",
"normalized": [
{
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}
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"text": [
"p97"
],
"type": "Gene"
},
{
"id": "1836",
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{
"db_id": "7018",
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}
],
"offsets": [
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1373,
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],
"text": [
"transferrin"
],
"type": "Gene"
},
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}
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1437,
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"text": [
"p97"
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}
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1452,
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"text": [
"melanotransferrin"
],
"type": "Gene"
},
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}
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1563,
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"text": [
"serotransferrin"
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},
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}
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1583,
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"text": [
"lactotransferrin"
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"type": "Gene"
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}
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"offsets": [
[
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],
"text": [
"transferrin"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 143,
"offset": 0
},
"text": "Isolation and sequence of a cDNA clone for human calcineurin B, the Ca2+-binding subunit of the Ca2+/calmodulin-stimulated protein phosphatase.",
"type": "title"
},
{
"location": {
"length": 933,
"offset": 144
},
"text": "We have identified and cloned human cDNA for the Ca2+-binding subunit of calcineurin, the brain isozyme of the Ca2+/calmodulin-stimulated protein phosphatase. The 2.5-kb cDNA has an open reading frame of 510 bp, a leader sequence of at least 500 bp, and a 1,277-bp 3'-noncoding sequence. The deduced sequence of the human protein differs from bovine brain calcineurin B by an additional valine at the carboxyl terminus and substitution of Met-11 and Ser-153 by cysteine. A partial clone of the mouse protein corresponding to amino acids 75-150 was also isolated. This portion of the human and mouse protein sequence is identical, with the DNA sequences showing 94% identity. The respective mRNAs in human and mouse are also of similar size. As was observed with protein levels, mRNA abundance in brain is 20-60 times that found in other tissues with the exception of HeLa cells which, like brain, contain abundant calcineurin B mRNA.",
"type": "abstract"
}
] |
[
{
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{
"db_id": "5534",
"db_name": "NCBIGene",
"tax_id": null
}
],
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49,
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],
"text": [
"calcineurin B"
],
"type": "Gene"
},
{
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{
"db_id": "5534",
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"offsets": [
[
193,
228
]
],
"text": [
"Ca2+-binding subunit of calcineurin"
],
"type": "Gene"
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{
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500,
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],
"text": [
"calcineurin B"
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}
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1058,
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"text": [
"calcineurin B"
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49,
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"text": [
"calcineurin B"
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{
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"db_id": "5534",
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"offsets": [
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193,
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]
],
"text": [
"Ca2+-binding subunit of calcineurin"
],
"type": "Gene"
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{
"db_id": "5534",
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"offsets": [
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500,
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]
],
"text": [
"calcineurin B"
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"type": "Gene"
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{
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{
"db_id": "5534",
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}
],
"offsets": [
[
1058,
1071
]
],
"text": [
"calcineurin B"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 122,
"offset": 0
},
"text": "Human liver serine dehydratase. cDNA cloning and sequence homology with hydroxyamino acid dehydratases from other sources.",
"type": "title"
},
{
"location": {
"length": 1077,
"offset": 123
},
"text": "Rat liver serine dehydratase cDNA was used to screen a human liver cDNA library in lambda gt11. One positive clone occurred in every 5,000 clones. Fifteen positive clones were plaque purified. The largest cDNA obtained contained an open reading frame of 987 base pairs, and 5' and 3' noncoding regions of 89 and 317 base pairs, respectively. The deduced amino acid sequence, with a calculated Mr of 34,615, was similar to that of rat liver serine dehydratase except for the absence of a segment consisting of 36 amino acid residues. In vitro transcription/translation with the cDNA resulted in the formation of a polypeptide with an Mr of approximately 35,000, which cross-reacted with the anti-rat serine dehydratase antibody. These results suggest that the human serine dehydratase is structurally cognate with the rat enzyme. Moreover, portions of the sequence postulated to be essential for activity in microbial threonine dehydratases are found in the mammalian serine dehydratases, suggesting that hydroxyamino and dehydratases may have originated from a common ancestor.",
"type": "abstract"
}
] |
[
{
"id": "1851",
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{
"db_id": "10993",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
12,
30
]
],
"text": [
"serine dehydratase"
],
"type": "Gene"
},
{
"id": "1856",
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{
"db_id": "10993",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
888,
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]
],
"text": [
"serine dehydratase"
],
"type": "Gene"
},
{
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{
"db_id": "10993",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
12,
30
]
],
"text": [
"serine dehydratase"
],
"type": "Gene"
},
{
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{
"db_id": "10993",
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}
],
"offsets": [
[
888,
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]
],
"text": [
"serine dehydratase"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 80,
"offset": 0
},
"text": "rac, a novel ras-related family of proteins that are botulinum toxin substrates.",
"type": "title"
},
{
"location": {
"length": 1724,
"offset": 81
},
"text": "A new family of ras-related proteins, designated rac (ras-related C3 botulinum toxin substrate) has been identified. rac1 and rac2 cDNA clones were isolated from a differentiated HL-60 library and encode proteins that are 92% homologous and share 58% and 26-30% amino acid homology with human rhos and ras, respectively. Nucleotide sequence analysis predicts both rac1 and rac2 proteins to contain 192 amino acids with molecular masses of 21,450 and 21,429 daltons, respectively. rac1 and rac2 possess four of the five conserved functional domains in ras associated with binding and hydrolysis of guanine nucleotides. They also contain the COOH-terminal consensus sequence Cys-X-X-X-COOH which localizes ras to the inner plasma membrane and the residues Gly12 and Ala59, at which sites mutations elicit transforming potential to ras. The rac transcripts, particularly rac2, display relative myeloid tissue selectivity. Both rac1 transcripts (2.4 and 1.1 kilobases (kb] increase when HL-60 cells differentiate to neutrophil-like morphology. In contrast, differentiation of U937 cells to monocyte-like morphology causes no change in the 2.4-kb mRNA and a decrease in the 1.1-kb mRNA species. rac2 mRNA (1.45 kb) increases 7-9-fold and 3-fold upon differentiation of HL-60 and U937 cells, respectively. Neither rac mRNAs are present in a Jurkat T cell line, and unlike rac1, rac2 mRNA is absent in human brain and liver tissue. Transfection experiments permitted the demonstration that rac1 and rac2 are substrates for ADP-ribosylation by the C3 component of botulinum toxin. The data suggest that racs are plasma membrane-associated GTP-binding proteins which could regulate secretory processes, particularly in myeloid cells.",
"type": "abstract"
}
] |
[
{
"id": "1864",
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{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
198,
202
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1865",
"normalized": [
{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
207,
211
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1866",
"normalized": [
{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
445,
449
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1867",
"normalized": [
{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
454,
458
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1868",
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{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
561,
565
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1869",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
570,
574
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1872",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
949,
953
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1873",
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{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1005,
1009
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1874",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1271,
1275
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1876",
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{
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"tax_id": null
}
],
"offsets": [
[
1447,
1451
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
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{
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"tax_id": null
}
],
"offsets": [
[
1453,
1457
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
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{
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"tax_id": null
}
],
"offsets": [
[
1564,
1568
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1879",
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1573,
1577
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1864",
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{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
198,
202
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1865",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
207,
211
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1866",
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{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
445,
449
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1867",
"normalized": [
{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
454,
458
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1868",
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{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
561,
565
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1869",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
570,
574
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1872",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
949,
953
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1873",
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{
"db_id": "5879",
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"tax_id": null
}
],
"offsets": [
[
1005,
1009
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1874",
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{
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"tax_id": null
}
],
"offsets": [
[
1271,
1275
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1876",
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{
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"tax_id": null
}
],
"offsets": [
[
1447,
1451
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1877",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1453,
1457
]
],
"text": [
"rac2"
],
"type": "Gene"
},
{
"id": "1878",
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{
"db_id": "5879",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1564,
1568
]
],
"text": [
"rac1"
],
"type": "Gene"
},
{
"id": "1879",
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{
"db_id": "5880",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
1573,
1577
]
],
"text": [
"rac2"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 131,
"offset": 0
},
"text": "Human gastric cathepsin E. Predicted sequence, localization to chromosome 1, and sequence homology with other aspartic proteinases.",
"type": "title"
},
{
"location": {
"length": 1831,
"offset": 132
},
"text": "The predicted sequence of human gastric cathepsin E (CTSE) was determined by analysis of cDNA clones isolated from a library constructed with poly(A+) RNA from a gastric adenocarcinoma cell line. The CTSE cDNA clones were identified using a set of complementary 18-base oligonucleotide probes specific for a 6-residue sequence surrounding the first active site of all previously characterized human aspartic proteinases. Sequence analysis of CTSE cDNA clones revealed a 1188-base pair open reading frame that exhibited 59% sequence identity with human pepsinogen A. The predicted CTSE amino acid sequence includes a 379-residue proenzyme (Mr = 40,883) and a 17-residue signal peptide. The predicted CTSE amino acid composition was consistent with that of purified material from gastric mucosa and gastric adenocarcinoma cell lines. Additional evidence for the identification of the CTSE cDNA clones was obtained by analysis of poly(A+) RNA isolated from CTSE-producing and -nonproducing gastric adenocarcinoma cell subclones. Three RNA transcripts (3.6, 2.6, and 2.1 kilobases) were identified in poly(A+) RNA isolated from a gastric adenocarcinoma cell line that produced CTSE that were absent from nonproducing subclones. CTSE contains 7 cysteine residues, of which 6 were localized by comparative maximal alignment analysis with pepsinogen A to conserved residues that form intrachain disulfide bonds. The seventh cysteine residue of CTSE is located within the activation peptide region of the proenzyme. We suspect that this residue forms an interchain disulfide bond and thereby determines the dimerization of CTSE proenzyme molecules that is observed under native conditions. The CTSE gene was localized to human chromosome 1 by concurrent cytogenetic and cDNA probe analyses of a panel of human x mouse somatic cell hybrids.",
"type": "abstract"
}
] |
[
{
"id": "1883",
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{
"db_id": "1510",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
14,
25
]
],
"text": [
"cathepsin E"
],
"type": "Gene"
},
{
"id": "1885",
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{
"db_id": "1510",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
172,
183
]
],
"text": [
"cathepsin E"
],
"type": "Gene"
},
{
"id": "1886",
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{
"db_id": "1510",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
185,
189
]
],
"text": [
"CTSE"
],
"type": "Gene"
},
{
"id": "1887",
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{
"db_id": "1510",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
332,
336
]
],
"text": [
"CTSE"
],
"type": "Gene"
},
{
"id": "1889",
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{
"db_id": "1510",
"db_name": "NCBIGene",
"tax_id": null
}
],
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574,
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]
],
"text": [
"CTSE"
],
"type": "Gene"
},
{
"id": "1890",
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{
"db_id": "1510",
"db_name": "NCBIGene",
"tax_id": null
}
],
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712,
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]
],
"text": [
"CTSE"
],
"type": "Gene"
},
{
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{
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"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
831,
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]
],
"text": [
"CTSE"
],
"type": "Gene"
},
{
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{
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"tax_id": null
}
],
"offsets": [
[
1014,
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]
],
"text": [
"CTSE"
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"type": "Gene"
},
{
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{
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"tax_id": null
}
],
"offsets": [
[
1086,
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]
],
"text": [
"CTSE"
],
"type": "Gene"
},
{
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}
],
"offsets": [
[
1305,
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]
],
"text": [
"CTSE"
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"type": "Gene"
},
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}
],
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]
],
"text": [
"CTSE"
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},
{
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}
],
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]
],
"text": [
"CTSE"
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},
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}
],
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[
1747,
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]
],
"text": [
"CTSE"
],
"type": "Gene"
},
{
"id": "1898",
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{
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}
],
"offsets": [
[
1818,
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]
],
"text": [
"CTSE"
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"type": "Gene"
},
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}
],
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],
"text": [
"cathepsin E"
],
"type": "Gene"
},
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"id": "1885",
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"text": [
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]
],
"text": [
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}
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[
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"CTSE"
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}
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[
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]
],
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"CTSE"
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{
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}
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[
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]
],
"text": [
"CTSE"
],
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{
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}
],
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[
1818,
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]
],
"text": [
"CTSE"
],
"type": "Gene"
}
] |
[
{
"location": {
"length": 94,
"offset": 0
},
"text": "Homology between a region of the human retinoblastoma gene and L1 family repetitive sequences.",
"type": "title"
},
{
"location": {
"length": 660,
"offset": 95
},
"text": "Five clones that hybridized weakly with the human retinoblastoma (Rb) gene were obtained by screening a human genomic library in a non-stringent condition. The DNAs of two of these clones were partially sequenced and found to contain a region with considerable homology to part of the Rb gene. These two clones were found to contain L1 family repeating sequences. This finding is discussed in relation with possible functions of the L1 family. As the L1 family is transposable, the Rb gene may be inactivated by recombination at this homologous region. Another possibility related with the DNA binding properties of Rb and L1 family proteins is also discussed.",
"type": "abstract"
}
] |
[
{
"id": "1900",
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{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
39,
53
]
],
"text": [
"retinoblastoma"
],
"type": "Gene"
},
{
"id": "1902",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
145,
159
]
],
"text": [
"retinoblastoma"
],
"type": "Gene"
},
{
"id": "1903",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
161,
163
]
],
"text": [
"Rb"
],
"type": "Gene"
},
{
"id": "1904",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
380,
382
]
],
"text": [
"Rb"
],
"type": "Gene"
},
{
"id": "1908",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
577,
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]
],
"text": [
"Rb"
],
"type": "Gene"
},
{
"id": "1909",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
711,
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]
],
"text": [
"Rb"
],
"type": "Gene"
},
{
"id": "1900",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
39,
53
]
],
"text": [
"retinoblastoma"
],
"type": "Gene"
},
{
"id": "1902",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
145,
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]
],
"text": [
"retinoblastoma"
],
"type": "Gene"
},
{
"id": "1903",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
161,
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]
],
"text": [
"Rb"
],
"type": "Gene"
},
{
"id": "1904",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
380,
382
]
],
"text": [
"Rb"
],
"type": "Gene"
},
{
"id": "1908",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
577,
579
]
],
"text": [
"Rb"
],
"type": "Gene"
},
{
"id": "1909",
"normalized": [
{
"db_id": "5925",
"db_name": "NCBIGene",
"tax_id": null
}
],
"offsets": [
[
711,
713
]
],
"text": [
"Rb"
],
"type": "Gene"
}
] |
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