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| IdB
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|---|---|---|---|---|---|---|---|
P57078
|
O14641
| 1
|
phosphorylation
|
up-regulates activity
| 0.44
|
Co-transfection of a RIPK4-GFP fusion increased the percentage of cells containing DVL2 puncta to more than 75% ( and ), suggesting that RIPK4 facilitates DVL2 signalosome formation.|Phosphorylation of DVL2 at Ser 298 and Ser 480 by RIPK4 favored canonical Wnt signaling.
|
SIGNOR-279756
|
O95198
|
Q9Y3S1
| 1
|
binding
|
down-regulates quantity by destabilization
| 0.44
|
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body.
|
SIGNOR-272120
|
Q8WVJ2
|
P43034
| 1
|
binding
|
up-regulates quantity by stabilization
| 0.44
|
The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic dynein, is critical for cell proliferation, survival, and neuronal migration. However, little is known about the regulation of LIS1. Here, we identify a previously uncharacterized mammalian homolog of Aspergillus NudC, NudCL2 (NudC-like protein 2), as a regulator of LIS1. NudCL2 is localized to the centrosome in interphase, and spindle poles and kinetochores during mitosis, a pattern similar to the localization of LIS1 and cytoplasmic dynein. Depletion of NudCL2 destabilized LIS1 and led to phenotypes resembling those of either dynein or LIS1 deficiency. NudCL2 complexed with and enhanced the interaction between LIS1 and Hsp90. Either disruption of the LIS1-Hsp90 interaction with the C terminus of NudCL2 or inhibition of Hsp90 chaperone function by geldanamycin decreased LIS1 stability.
|
SIGNOR-252167
|
Q5T447
|
Q9UNK0
| 1
|
polyubiquitination
|
down-regulates quantity by destabilization
| 0.44
|
Our co-immunoprecipitation experiments show that Syntaxin 8 directly interacts with HECTd3 and that the overexpression of HECTd3 promotes the ubiquitination of Syntaxin 8. Immunoprecipitates probed with the anti-ubiquitin (Santa Cruz) antibody could be recognized by the anti-ubiquin antibody (Fig. 3a), indicating that the shift of the His-syntaxin 8 protein bands were caused by polyubiquitin conjugations. Our data suggest that HECTd3 may function as an E3 ubiquitin-protein ligase to promote the ubiquitination and degradation of Syntaxin 8 through the proteasome pathway.
|
SIGNOR-271772
|
Q13237
|
P42261
| 1
|
phosphorylation
|
up-regulates activity
| 0.44
|
In cultured hippocampal neurons, activation of cGKII induces an accumulation of GluR1 on the cellular plasma membrane at extrasynaptic sites, and blockage of cGKII activity prevents the surface increase of GluR1, and also the increase in mEPSC frequency and amplitude, that follows a chemical form of LTP (chemLTP).|In this complex, cGKII phosphorylates GluR1 at serine 845 (S845), a site known to be phosphorylated also by PKA.
|
SIGNOR-278427
|
Q14164
|
P46937
| 1
|
phosphorylation
|
down-regulates quantity by destabilization
| 0.44
|
Virus-activated kinase IKKɛ phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response.
|
SIGNOR-277355
|
Q9HC78
|
P02771
| 1
|
transcriptional regulation
|
down-regulates quantity by repression
| 0.44
|
Zinc finger and BTB domain-containing 20 (ZBTB20), a member of BTB/POZ family, functions in neurogenesis and represses α-fetoprotein gene transcription in liver.
|
SIGNOR-266867
|
P00533
|
Q9UBN7
| 1
|
phosphorylation
|
down-regulates
| 0.44
|
A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.
|
SIGNOR-162431
|
Q02156
|
P61586
| 1
|
phosphorylation
|
up-regulates activity
| 0.439
|
Our laboratory reported that PKCepsilon modulates RhoA activity in HNSCC presumably through posttranslation phosphorylation .|Phosphopeptide mapping revealed that PKCepsilon phosphorylates RhoA at T127 and S188.
|
SIGNOR-279478
|
P17252
|
O60825
| 1
|
phosphorylation
|
up-regulates activity
| 0.439
|
The phosphorylation sites for both cAMP-dependent protein kinase and protein kinase C were located in a single peptide whose sequence was Arg-Arg-Asn-Ser-(P)-Phe-Thr-Pro-Leu-Ser-Ser-Ser-Asn-Thr(P)-Ile-Arg-Arg-Pro. The seryl residue nearest the N terminus was the residue specifically phosphorylated by cAMP-dependent protein kinase, whereas the threonine residue nearest the C terminus was phosphorylated by protein kinase C. | Phosphorylation of bovine heart Fru-6-P,B-kinase by either protein kinase C or CAMP-dependent protein kinase results in activation of the enzyme.
|
SIGNOR-248844
|
Q16236
|
P48507
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.439
|
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy
|
SIGNOR-279869
|
Q16539
|
P30307
| 1
|
phosphorylation
|
down-regulates activity
| 0.439
|
P38 binds and phosphorylates Cdc25B at serines 309 and 361, and Cdc25C at serine 216; phosphorylation of these residues is required for binding to 14-3-3 proteins.
|
SIGNOR-250091
|
Q9UM73
|
P40763
| 1
|
binding
|
up-regulates
| 0.439
|
Npm-alk has been shown to activate signal transducer and activator of transcription (stat) 3, a transcriptional regulator of cyclin d3.Proteins that interact with alk tyrosine kinase play important roles in mediating downstream cellular signals. Previously reported proteins in the alk signal pathway were identified including pi3-k, jak2, jak3, stat3, grb2, irs, and plcgamma1.
|
SIGNOR-139460
|
P24941
|
P23511
| 1
|
phosphorylation
|
up-regulates activity
| 0.439
|
Cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y. Cyclin A-cdk2 appears to associate with NF-Y both in vitro and in vivo. Furthermore, YA protein is phosphorylated in parallel with a cell cycle-dependent activation of cdk2 kinase and cyclin A expression. YA phosphorylation is unnecessary for heterotrimer formation with the YB-YC dimer. However, NF-Y containing a phosphorylation-deficient mutant form of YA, YA-aa, has its DNA binding activity impaired. \ To examine whether cdk2 phosphorylates the two serine residues at positions 320 and 326 in YA, we replaced either or both with alanine by site-directed mutagenesis. In a kinase assay using purified GST fusion proteins in vitro, cdk2 phosphorylated the wild type and both of the single-mutant proteins (YA-as and -sa), but not the double-mutant protein (YA-aa)
|
SIGNOR-250742
|
Q14164
|
Q04206
| 1
|
phosphorylation
|
up-regulates
| 0.439
|
Overexpressed ikkepsilon and tbk1 phosphorylate ser-536 in vivo and in vitro.
|
SIGNOR-129943
|
O75116
|
Q99962
| 1
|
phosphorylation
|
down-regulates
| 0.439
|
We identified the phosphorylation site of endophilin a1 at thr-14 endophilin t14d inhibited egf receptor internalization. Furthermore, phosphorylation of endophilin by rho-kinase inhibited the binding to cin85.
|
SIGNOR-140466
|
Q05209
|
P00519
| 1
|
dephosphorylation
|
down-regulates activity
| 0.439
|
Several experiments suggest that the pest-type ptps negatively regulate c-abl activity: c-abl was hyperphosphorylated in ptp-pest-deficient cells dephosphorylation of c-abl by pest-type ptp represents a novel mechanism by which c-abl activity is regulated.
|
SIGNOR-235568
|
Q13315
|
Q96S59
| 1
|
phosphorylation
|
up-regulates activity
| 0.439
|
We demonstrate that ATM phosphorylates RanBP9 in response to Ionizing Radiation and mediates its nuclear accumulation.
|
SIGNOR-279005
|
Q15042
|
P20336
| 1
|
gtpase-activating protein
|
down-regulates activity
| 0.439
|
Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).
|
SIGNOR-265580
|
Q00536
|
P46459
| 1
|
phosphorylation
|
down-regulates activity
| 0.439
|
Moreover, inhibition of Pctaire1 activity by transfecting its kinase-dead (KD) mutant into COS-7 cells enhances the self association of NSF.|We demonstrate that the D2 domain of NSF, which is required for the oligomerization of NSF subunits, binds directly to and is phosphorylated by Pctaire1 on serine 569.
|
SIGNOR-279511
|
Q02750
|
P55211
| 1
|
phosphorylation
|
down-regulates activity
| 0.439
|
Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2
|
SIGNOR-249385
|
Q9NR96
|
Q8IUC6
| 1
|
binding
|
up-regulates activity
| 0.439
|
To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group
|
SIGNOR-266749
|
P17252
|
Q92888
| 1
|
phosphorylation
|
up-regulates activity
| 0.439
|
We showed that the first and second phase of RhoA activity are dependent on p63 and Ca2+/PKC, respectively, and further identified phosphorylation of serine 240 on p115 RhoGEF by PKC to be the mechanistic link between PKC and RhoA.
|
SIGNOR-277530
|
P06239
|
Q9H204
| 1
|
phosphorylation
|
up-regulates
| 0.439
|
Y64 of magicin is phosphorylated by lck creating a sh2-grb2 binding motif
|
SIGNOR-148704
|
P17947
|
P17542
| 1
|
binding
|
down-regulates activity
| 0.439
|
PU.1/Spi-1 binds to the human TAL-1 silencer to mediate its activity.By expressing a mutant protein containing only the ETS domain of PU.1 in human erythroleukemic HEL cells, we demonstrated that PU.1 mediates the transcriptional repression activity of the silencer. Our data clearly demonstrate that PU.1 mediates TAL-1 silencer activity
|
SIGNOR-256048
|
Q9NR96
|
P58753
| 1
|
binding
|
up-regulates activity
| 0.439
|
To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group
|
SIGNOR-266748
|
P60484
|
P42229
| 1
|
dephosphorylation
|
down-regulates
| 0.439
|
The forced expression of pten in the eol-1r cells dephosphorylated akt, erk and stat5 /eol-1r cells showed epigenetic silencing of the phosphatase and tensin homolog deleted on chromosome ten (pten) gene. Exposure of eol-1r cells to imatinib failed to dephosphorylate akt, erk and stat5, although pdgfr? Was effectively inactivated. The forced expression of pten negatively regulated these signal pathways and sensitized eol-1r cells to imatinib.
|
SIGNOR-166481
|
Q5H9F3
|
Q9UQL6
| 1
|
binding
|
up-regulates activity
| 0.439
|
BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor.
|
SIGNOR-259113
|
P25116
|
O95837
| 1
|
binding
|
up-regulates activity
| 0.439
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257293
|
Q01974
|
P21333
| 1
|
binding
|
up-regulates
| 0.439
|
Additionally, the association of ror2 with the actin-binding protein filamin a is required for wnt5a-induced jnk activation and polarized cell migration.
|
SIGNOR-179668
|
Q13976
|
Q15637
| 1
|
phosphorylation
|
down-regulates activity
| 0.438
|
PKG phosphorylates SF1 at Ser20, which inhibits the SF1-U2AF65 interaction leading to a block of pre-spliceosome assembly. Mutation of Ser20 to Ala or Thr also inhibits the interaction with U2AF65, indicating that Ser20 is essential for binding.
|
SIGNOR-249018
|
Q9H2X6
|
P29590
| 1
|
phosphorylation
|
up-regulates
| 0.438
|
In response to dna damage, hipk2 phosphorylates pml at serines 8 and 38. he n-terminal phosphorylation sites contribute to the dna damage-induced pml sumoylation and are required for the ability of pml to cooperate with hipk2 for the induction of cell death.
|
SIGNOR-182428
|
P24666
|
P12931
| 1
|
dephosphorylation
|
up-regulates activity
| 0.438
|
LMWPTP dephosphorylated pY(527)-Src and pY(416)-Src in vitro, with greater specificity for pY(527)Src. Activation of LMWPTP produced strong activation of Src mediated by fast dephosphorylation of pY(527)-Src, followed by slower deactivation of this kinase via dephosphorylation of pY(416)Src.
|
SIGNOR-248454
|
P11309
|
P08183
| 1
|
dephosphorylation
|
up-regulates activity
| 0.438
|
Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function|P-gp is known to be phosphorylated at Ser667, Ser671, and Ser683 by PKA; at Ser661, Ser667, and Ser671 by PKC; and at Ser683 by Pim-1|simultaneous expression of PP5 and PPP2R3C reduced the phosphorylation detected by the antibodies that specifically recognize serine/threonine phosphorylated by PKA or serine phosphorylated by PKC. These results suggest that the PP5/PPP2R3C complex dephosphorylates PKA- and PKC-phosphorylated serine residues on P-gp
|
SIGNOR-272511
|
Q96GD4
|
Q9NS23
| 1
|
phosphorylation
|
down-regulates
| 0.438
|
Here, we show that aurora a and b associate with and phosphorylate rassf1a on serine 203 aurora a regulates prometaphase progression by inhibiting the ability of rassf1a to suppress apc-cdc20 activity.
|
SIGNOR-184561
|
P29597
|
Q13118
| 1
|
phosphorylation
|
down-regulates activity
| 0.438
|
These data strongly supported that Tyk2 phosphorylates TIEG1.|Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited TIEG1 nuclear translocation.
|
SIGNOR-279575
|
Q96GD4
|
P14136
| 1
|
phosphorylation
|
down-regulates activity
| 0.438
|
We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by aurora-b;thr-7/ser-13/ser-38 of gfap, and thr-16 of desmin are common with those related to rho-associated kinase (rho-kinase), which has been reported to phosphorylate gfap and desmin at cleavage furrow during cytokinesis. We identified ser-59 of desmin to be a specific site phosphorylated by aurora-b in vitro.
|
SIGNOR-100173
|
O43312
|
Q9UMX1
| 1
|
binding
|
up-regulates
| 0.438
|
We found that in vitro translated gli1 and sufu bind to gst-mim, but not gst-mim?N399 Or gst columns (fig. 4f). Indicative of the importance of the mim/gli complex interactions, the mim?N399 Mutant that fails to interact with gli and sufu showed a markedly reduced capacity to potentiate gli-dependent transcription (fig. 4g). Although these results indicate that a mim/gli/sufu complex is important for mim-mediated transcriptional potentiation
|
SIGNOR-130545
|
P01106
|
P26599
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.438
|
We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2,
|
SIGNOR-268689
|
Q15910
|
P31260
| 1
|
transcriptional regulation
|
down-regulates quantity by repression
| 0.438
|
These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.
|
SIGNOR-260070
|
O43791
|
P35659
| 1
|
binding
|
down-regulates quantity by destabilization
| 0.438
|
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E).
|
SIGNOR-272826
|
Q5T447
|
Q9H2D6
| 1
|
polyubiquitination
|
down-regulates quantity by destabilization
| 0.438
|
Here, we identify a novel Tara-binding protein HECTD3, a putative member of HECT E3 ubiquitin ligases. HECTD3 directly binds Tara in vitro and forms a complex with Tara in vivo. Overexpression of HECTD3 enhances the ubiquitination of Tara in vivo and promotes the turnover of Tara, whereas depletion of HECTD3 by small interfering RNA decreases Tara degradation.
|
SIGNOR-271770
|
P31749
|
Q15672
| 1
|
phosphorylation
|
up-regulates
| 0.438
|
Moreover, phosphorylation of twist-1 at ser42 was shown in vivo in various human cancer tissues, suggesting that this post-translational modification ensures functional activation of twist-1 after promotion of survival during carcinogenesis.
|
SIGNOR-164884
|
P11309
|
P39019
| 1
|
phosphorylation
|
up-regulates
| 0.438
|
The pim-1/rps19 interaction was demonstrated both in vitro and in living cells and led to phosphorylation of rps19 in an in vitro kinase assay.
|
SIGNOR-141411
|
P28069
|
P01222
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.438
|
CBP and Pit-1 acted synergistically in TRH stimulation of the TSH-β promoter. The human TSH-β promoter contains three well defined Pit-1 DNA-binding sites.
|
SIGNOR-267205
|
Q9Y4K3
|
P42345
| 1
|
ubiquitination
|
up-regulates activity
| 0.438
|
Together, these results demonstrate that mTOR polyubiquitination by TRAF6 modulates its activation in response to amino acids and point to a role for K63 ubiquitin modification as a sensor of nutrient status.
|
SIGNOR-278789
|
Q13535
|
Q8N163
| 1
|
phosphorylation
|
up-regulates activity
| 0.438
|
Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death.
|
SIGNOR-267662
|
Q9UBS0
|
Q53EL6
| 1
|
phosphorylation
|
down-regulates
| 0.438
|
Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.
|
SIGNOR-160992
|
P62714
|
P04637
| 1
|
dephosphorylation
|
up-regulates quantity by stabilization
| 0.437
|
A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55| In this study, we reported that the specific B regulatory subunits of PP2A B56gamma1 and B56gamma3 mediate dephosphorylation of p53 at Thr55. Ablation of the B56gamma protein by RNAi, which abolishes the Thr55 dephosphorylation in response to DNA damage, reduces p53 stabilization, Bax expression and cell apoptosis
|
SIGNOR-248583
|
Q9UBY5
|
P30679
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257406
|
P28222
|
P08754
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-256863
|
P35414
|
P63096
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-256681
|
P31749
|
Q16763
| 1
|
phosphorylation
|
up-regulates quantity by stabilization
| 0.437
|
Mechanistically, Akt1 physically interacted with and phosphorylated UBE2S at Thr 152, enhancing its stability by inhibiting proteasomal degradation.
|
SIGNOR-265078
|
Q99705
|
P08754
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257147
|
Q96HS1
|
Q99683
| 1
|
dephosphorylation
|
up-regulates activity
| 0.437
|
PGAM5 Is a Protein Ser/Thr Phosphatase That Activates ASK1. PGAM5 Dephosphorylates ASK1. This dephosphorylation unleashes phosphorylation ofThr-838 in the kinase domain, with activation of ASK1.
|
SIGNOR-277984
|
Q9BZL6
|
Q8WUI4
| 1
|
phosphorylation
|
up-regulates activity
| 0.437
|
Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].
|
SIGNOR-275933
|
Q9P0L2
|
P27816
| 1
|
phosphorylation
|
down-regulates activity
| 0.437
|
Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.
|
SIGNOR-250171
|
Q9Y5N1
|
P08754
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-256832
|
O75398
|
P08908
| 1
|
transcriptional regulation
|
down-regulates quantity by repression
| 0.437
|
The human 5-HT1A gene (HTR1A) rs6295 risk allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A autoreceptor transcription
|
SIGNOR-269064
|
P49841
|
P35659
| 1
|
phosphorylation
|
down-regulates quantity by destabilization
| 0.437
|
These data suggest that the E3 ligase SCFFbxw7-α degrades p-DEK in a GSK-3β–dependent manner.Therefore, the phosphorylation of DEK by GSK-3β is a crucial step to mediate Tpm RNA splicing.
|
SIGNOR-276303
|
P25105
|
P50148
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257387
|
Q86YT6
|
P53355
| 1
|
polyubiquitination
|
down-regulates quantity by destabilization
| 0.437
|
Transient expression of DIP-1 in HeLa cells antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis. These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitination by DIP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal degradation.
|
SIGNOR-272602
|
Q9Y5N1
|
P63096
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-256689
|
P31749
|
P35226
| 1
|
phosphorylation
|
up-regulates activity
| 0.437
|
The polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate
|
SIGNOR-252559
|
Q96EP0
|
P51843
| 1
|
monoubiquitination
|
up-regulates quantity by stabilization
| 0.437
|
RNF31 promotes monoubiquitination of DAX-1 in an RBR domain-dependent manner. In conclusion, our results suggest that the major DAX-1 modification observed in different experimental settings is likely to be monoubiquitination at one or more lysine residues (multiubiquitination) possibly located within the LBD of DAX-1. RNF31 stabilizes endogenous DAX-1.
|
SIGNOR-271786
|
Q5H9F3
|
Q13363
| 1
|
binding
|
up-regulates activity
| 0.437
|
BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay.
|
SIGNOR-259193
|
P00533
|
P09211
| 1
|
phosphorylation
|
up-regulates
| 0.437
|
Taken together, these results and those of the ms/ms analyses confirmed tyr-3, tyr-7, and tyr-198 to be primary residues phosphorylated by egfr in the gstp1 protein. The phosphorylation increased gstp1 enzymatic activity significantly,
|
SIGNOR-184387
|
P53350
|
Q9Y2Z0
| 1
|
phosphorylation
|
up-regulates activity
| 0.437
|
Plk1 phosphorylates Sgt1 at the kinetochores to promote timely kinetochore-microtubule attachment|Plk1 is required for the kinetochore localization of Sgt1 and phosphorylates serine 331 of Sgt1 at the kinetochores. This phosphorylation event enhances the association of the Hsp90-Sgt1 chaperone
|
SIGNOR-265222
|
P24530
|
O95837
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257428
|
Q5JTC6
|
P19544
| 1
|
binding
|
up-regulates
| 0.437
|
Wtx binds wt1, a zinc-finger transcription factor that is inactivated in wilms tumor. / the ability of wtx to enhance wt1-mediated transactivation suggests a physiologically significant interaction between these 2 tumor suppressors.
|
SIGNOR-185644
|
P20265
|
O75030
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.437
|
We further demonstrate that BRN2 induces MITF transcription through a binding site located at 50/36 of the MITF promoter
|
SIGNOR-249616
|
P18825
|
P19086
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257094
|
Q99705
|
P63096
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257034
|
P24530
|
P08754
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257166
|
P18089
|
P19086
| 1
|
binding
|
up-regulates activity
| 0.437
|
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
|
SIGNOR-257109
|
Q9UKA4
|
Q13576
| 1
|
binding
|
up-regulates activity
| 0.437
|
We show that IQGAP2 is regulated by an interaction with the A-kinase anchoring protein AKAP220. Phosphorylation of IQGAP2 via AKAP220-anchored PKA leads to enhanced Rac binding. Since AKAPs function to direct PKA toward specific substrates, we proposed that the formation of an IQGAP2/AKAP220/PKA ternary complex sharpens the response to cAMP.
|
SIGNOR-273740
|
Q01860
|
P26358
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.437
|
Oct4 and Nanog upregulate Dnmt1 through direct binding to its promoter, thereby leading to the repressed expression of p16 and p21 and genes associated with development and lineage differentiation
|
SIGNOR-253158
|
P17252
|
P04637
| 1
|
phosphorylation
|
up-regulates activity
| 0.437
|
Here, we demonstrate that cotransfection of p53 with either PKC alpha or PKC zeta increases p53's transcriptional activity. Mutagenesis of p53 indicates that serine 371 is the major site for phosphorylation by PKC alpha in vitro.
|
SIGNOR-248999
|
P22681
|
P36888
| 1
|
binding
|
down-regulates activity
| 0.436
|
Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.
|
SIGNOR-255739
|
P51451
|
P12318
| 1
|
phosphorylation
|
up-regulates activity
| 0.436
|
To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.
|
SIGNOR-249312
|
Q9H6Z9
|
P14618
| 1
|
hydroxylation
|
up-regulates activity
| 0.436
|
Interaction of PKM2 with prolyl hydroxylase 3 (PHD3) enhances PKM2 binding to HIF-1α and PKM2 coactivator function. Mass spectrometry and anti-hydroxyproline antibody assays demonstrate PKM2 hydroxylation on proline-403/408. PHD3 knockdown inhibits PKM2 coactivator function, reduces glucose uptake and lactate production, and increases O(2) consumption in cancer cells.
|
SIGNOR-267476
|
Q9UKB1
|
O00418
| 1
|
ubiquitination
|
down-regulates
| 0.436
|
Eef2k was degraded by the ubiquitin-proteasome system through the ubiquitin ligase scf(__trcp) (skp1-cul1-f-box protein, __-transducin repeat-containing protein) to enable rapid resumption of translation elongation. This event required autophosphorylation of eef2k on a canonical __trcp-binding domain
|
SIGNOR-197730
|
P41279
|
P36507
| 1
|
phosphorylation
|
up-regulates
| 0.436
|
Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases.
|
SIGNOR-129694
|
P06493
|
Q16512
| 1
|
phosphorylation
|
up-regulates activity
| 0.436
|
CDK1 phosphorylates PKN1 at S533, S537, S562, and S916 in vitro and in cells during drug-induced mitotic arrest. Immunofluorescence staining further confirmed that PKN1 phosphorylation occurs during normal mitosis in a CDK1-dependent manner.Knockdown of PKN1 significantly inhibited anchorage-independent growth and migration without affecting proliferation in multiple cancer cell lines.
|
SIGNOR-276831
|
O00187
|
P06681
| 1
|
cleavage
|
up-regulates activity
| 0.436
|
The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase
|
SIGNOR-263416
|
O14733
|
O15264
| 1
|
phosphorylation
|
up-regulates activity
| 0.436
|
p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.
|
SIGNOR-273954
|
Q92565
|
P01116
| 1
|
guanine nucleotide exchange factor
|
up-regulates
| 0.436
|
Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.
|
SIGNOR-183735
|
Q92565
|
P01111
| 1
|
guanine nucleotide exchange factor
|
up-regulates
| 0.436
|
Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.
|
SIGNOR-183738
|
Q96QU1
|
Q8TDI7
| 1
|
binding
|
up-regulates activity
| 0.436
|
Although several studies show that the tip links, composed of PCDH15 and CDH23, are required for normal mechanotransduction, it is unclear how they are coupled to the transduction machinery. Likewise, it has been demonstrated that the transmembrane channel-like proteins TMC1 and TMC2 are required for mechanosensitive responses in hair cells, but how they interact with other components of the mechanotransduction complex is not known. Here, we show that TMC1 and TMC2 can interact with PCDH15, thereby establishing a critical connection between the tip link and these putative components of the mechanotransduction channel in hair cells.
|
SIGNOR-262583
|
Q969H0
|
O96020
| 1
|
binding
|
down-regulates quantity by destabilization
| 0.436
|
Cdk2 (S384) and GSK3 (T380) prime cyclin E for destruction. The hyper-phosphorylated T380/S384 degron has high affinity for monomeric Fbw7α, which engages the remainder of the SCF to initiate cyclin E's ubiquitination by an E2 enzyme
|
SIGNOR-271642
|
Q13547
|
P49715
| 1
|
transcriptional regulation
|
down-regulates
| 0.436
|
These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome
|
SIGNOR-210013
|
Q15759
|
P15923
| 1
|
phosphorylation
|
up-regulates
| 0.436
|
Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription, while the nonphosphorylatable e47 mutant ser140ala fails to heterodimerize with myod and displays impaired myogenic potentia
|
SIGNOR-134190
|
Q9H6Z4
|
Q15796
| 1
|
relocalization
|
down-regulates activity
| 0.436
|
RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner.
|
SIGNOR-217634
|
P60484
|
P16220
| 1
|
dephosphorylation
|
down-regulates activity
| 0.436
|
Our study demonstrates that PTEN can dephosphorylate CREB at Ser133 and that PTEN protein phosphatase activity is required for CREB dephosphoryation.|Moreover, we use both in vitro and in vivo experiments to show PTEN can dephosphorylate CREB in a phosphatase-dependent manner, suggesting that CREB is a substrate of PTEN nuclear phosphatase. Loss of Pten results in an elevated RNA level of multiple CREB transcriptional targets and increased cell proliferation, which can be reversed by a nonphosphorylatable CREB mutant or knockdown of CREB. These data reveal a mechanism for PTEN modulation of CREB-mediated gene transcription and cell growth.
|
SIGNOR-248543
|
P49137
|
Q9UKV8
| 1
|
phosphorylation
|
up-regulates
| 0.436
|
Mk2 was found to phopsphorylate in vitro the ago2 protein in ser387, which was identified as the major ago2 phosphorylation site in cells.and mutation of ser387 to alanineimpairsago2 localization to therna-containing granules termedprocessing bodies
|
SIGNOR-166615
|
P62136
|
O14965
| 1
|
dephosphorylation
|
down-regulates
| 0.436
|
Pp1 is shown to dephosphorylate active stk15 and abolish its activity in vitro.
|
SIGNOR-110411
|
Q99835
|
P12931
| 1
|
phosphorylation
|
up-regulates
| 0.436
|
Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion.
|
SIGNOR-178610
|
Q13185
|
Q6KC79
| 1
|
binding
|
up-regulates activity
| 0.436
|
The heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus.
|
SIGNOR-264524
|
P27361
|
Q07820
| 1
|
phosphorylation
|
up-regulates
| 0.436
|
We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1.
|
SIGNOR-179812
|
Q8WU17
|
Q9Y5U4
| 1
|
ubiquitination
|
down-regulates quantity
| 0.436
|
Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner
|
SIGNOR-271956
|
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