GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P21127	Q9UQ88	0	phosphorylation	up-regulates	0.305	Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58)	SIGNOR-169628
Q5JWF2	P63244	2	binding	down-regulates activity	0.2	The results showed that RACK1 severed as an oncogene to enhance the proliferation capacity of liver cancer cell lines, meanwhile, downregulated GNA14 expression in Huh7 cell lines reversed the effects of RACK1 on cell proliferation	SIGNOR-278048
Q08345	P30408	2	binding	up-regulates activity	0.424	Gao et al have demonstrated that in metastatic breast cancer cell, DDR1 interacts with cell surface Transmembrane 4 L Six Family Member 1 (TM4SF1) and regulates tumor dormancy and reactivation [3]. The interaction between DDR1 and TM4SF1 is collagen dependent and control Protein Kinase C Alpha (PKCa) mediated downstream JAK-STAT signaling pathway [3] (Figure 3). Interestingly the data also showed that TM4SF1 failed to interact with DDR2.	SIGNOR-272400
Q9Y6E2	P05198	2	binding	up-regulates activity	0.253	BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro	SIGNOR-261220
P54253	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.334	NICD and MDM2 ubiquitinate and degrade ATXN1.\|These results suggest that NICD and MDM2 synergistically reduce ATXN1 expression at the posttranscriptional level.	SIGNOR-278823
P06493	P40337	1	phosphorylation	up-regulates activity	0.2	Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1.\|PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo.	SIGNOR-280207
Q9UKV8	Q9UPQ9	2	binding	up-regulates activity	0.796	The assay showed that full-length TNRC6B binds full-length human AGO2. We have identified and molecularly dissected important sequence and structure features in the conserved Ago hooks of S. pombe Tas3 and human TNRC6B. The effect of Ago hook peptides from the shuttling P-body component TNRC6B in our miRNA-mediated translational repression assay (Fig. 5b), in particular, hints at a novel regulatory role of Ago hooks in miRNA-mediated gene repression mechanisms.	SIGNOR-269680
Q9NTX7	O95271	1	ubiquitination	down-regulates quantity	0.723	We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation.	SIGNOR-260004
P04264	Q03405	2	binding	up-regulates activity	0.288	Cytokeratin 1 binds to both gC1qR and u-PAR. Our data suggest that formation of HK (and Factor XII) binding sites along endothelial cell membranes consists of bimolecular com-plexes of gC1qR-cytokeratin 1 and u-PAR-cytokeratin 1, with gC1qR binding being favored.	SIGNOR-251880
P36508	P20226	2	binding	down-regulates activity	0.399	We identified ZNF76 as a novel transcriptional repressor that targets TBP. ZNF76 interacts with TBP through both its N and C termini. ZNF76 targets TBP for transcriptional repression.	SIGNOR-224650
Q04726	P98170	0	ubiquitination	up-regulates activity	0.507	These findings suggest that TLE3 ubiquitylation by XIAP may be required during Wnt pathway activation to facilitate its dissociation from TCF/Lef, allowing subsequent beta-catenin binding and transcriptional activation.	SIGNOR-278528
P16885	P51451	0	phosphorylation	up-regulates activity	0.557	Lyn, Syk, Btk, and Blk can also phosphorylate and enhance the activation of phospholipase C gamma 2 (PLCgamma2), which hydrolyzes PI (4,5) P2 to create inositol 3,4,5-trisphosphate (IP3) and diacylglycerol (DAG), stimulating Ca 2+ mobilization and protein kinase C (PKC), respectively.	SIGNOR-280195
P09471	Q9UKP6	2	binding	up-regulates activity	0.265	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-257252
Q9BWF3	P19544	2	binding	down-regulates	0.364	Wilm's tumor protein 1 (wt1), a protein implicated in various cancers and developmental disorders, consists of two major isoforms: wt1(-kts), a transcription factor, and wt1(+kts), a post-transcriptional regulator that binds to rna and can interact with splicing components. Here we show that wt1 interacts with the novel splicing regulator rbm4. / we conclude that the (+kts) form of wt1 is able to inhibit the effect of rbm4 on alternative splicing.	SIGNOR-149166
P42226	Q9UHD2	0	phosphorylation	up-regulates	0.674	We now show that stat6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger sting (also named mita/eris) to recruit stat6 to the endoplasmic reticulum, leading to stat6 phosphorylation on ser(407) by tbk1 and tyr(641), independent of jaks. Phosphorylated stat6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing.	SIGNOR-176775
O15151	O96017	0	phosphorylation	down-regulates	0.723	Phosphorylation of s342 and s367 in vivo require the chk2 kinase. Chk2 also stimulates mdmx ubiquitination and degradation by mdm2	SIGNOR-140417
O96017	P04637	1	phosphorylation	up-regulates quantity by stabilization	0.791	Chk1/chk2 and atm/atr also phosphorylate the effector p53, increasing its stability.We Have demonstrated that the human homologs of the checkpoint kinases, chk1 and chk2/hcds1, phosphorylate at least three dna damage-inducible phosphorylation sites in p53.	SIGNOR-74831
P30519	P68400	0	phosphorylation	up-regulates activity	0.335	Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. \| CK2 activation is abolished by the S79A mutation but preserved in S179A and T248A mutations, indicating that S79 is the target of CK2-dependent activation of HO2	SIGNOR-250895
Q03113	P30411	2	binding	up-regulates activity	0.2	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-257344
P06241	O14522	1	phosphorylation	down-regulates activity	0.414	Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT	SIGNOR-275543
O95996	O15169	2	binding	up-regulates	0.771	Human axin (haxin) binds directly to beta-catenin, gsk3 beta, and apc in vitro, and the endogenous proteins are found in a complex in cells.	SIGNOR-57673
Q8N1I0	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.586	DOCK4 (dedicator for cytokinesis 4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, is one of few genes that are associated with both ASD and dyslexia.	SIGNOR-266823
O00418	Q15418	0	phosphorylation	down-regulates activity	0.513	We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity	SIGNOR-109708
P17252	Q9HBA0	1	phosphorylation	up-regulates activity	0.38	We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.	SIGNOR-260882
P52797	Q15375	2	binding	up-regulates	0.802	The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion	SIGNOR-52384
Q8N163	P68400	0	phosphorylation	up-regulates activity	0.2	CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. \|In our results, CK2alpha affected the\|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1	SIGNOR-267666
Q06413	P68400	0	phosphorylation	up-regulates activity	0.333	We show that serine 59 located between the MADS and MEF2 domains of MEF2C is phosphorylated in vivo and can be phosphorylated in vitro by casein kinase-II (CKII). Phosphorylation of this site enhanced the DNA binding and transcriptional activity of MEF2C by increasing its DNA binding activity 5-fold.	SIGNOR-250914
P16615	O00631	2	binding	down-regulates activity	0.505	The structure suggests a mechanism for selective Ca2+ loading and activation of SERCA, and provides new insight into how SLN and PLB inhibition arises from stabilization of this E1 intermediate state without bound Ca2+.	SIGNOR-264779
O60548	P10644	1	transcriptional regulation	up-regulates quantity by expression	0.2	Elevating the amounts of FOXD2 expression vector up to 12-fold relative to the RIα1b reporter construct demonstrated that maximal induction of the RIα1b promoter by FOXD2 was at least 5.8-fold	SIGNOR-261605
P16104	P61088	0	ubiquitination	up-regulates	0.2	In an h2ax- and mdc1-dependent manner , rnf8/ubc13 complexes go to sites of dna damage through their fha domain and initiate the synthesis of k63 polyubiquitin chains on chromatin that recruit the brca1 a complex through the uim domains of rap80.	SIGNOR-159880
O75581	P49840	0	phosphorylation	up-regulates activity	0.632	Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493	SIGNOR-275398
Q96AQ6	P40424	2	binding	down-regulates activity	0.331	This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences.	SIGNOR-273666
O95363	Q2TAL8	0	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269403
P17947	Q03164	0	methylation	up-regulates quantity by expression	0.441	Furthermore, we show that both MLL and AML1/CBFβ are required for maintaining the H3K4-me3 mark at the PU.1 upstream regulatory element (URE) and promoter region, and for full PU.1 gene expression.	SIGNOR-255874
O95476	Q13873	2	binding	down-regulates	0.426	We show that dullard promotes the ubiquitin-mediated proteosomal degradation of bmp receptors	SIGNOR-151001
O43186	O15265	2	binding	down-regulates activity	0.607	We found that ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation.	SIGNOR-223226
Q8TCQ1	P01903	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.	SIGNOR-271412
P22894	P02671	1	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. \|Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.\|MMP-8 20ADSGEGD a-chain \| 442LRTGKEKV a-chain	SIGNOR-263625
P46937	O75385	0	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, hypoxia stimulates ULK1 to translocate into nucleus, where it interacts with and phosphorylates yes-associated protein (YAP) at Ser227, resulting in YAP stabilization through blockade of ubiquitin-proteasome system (UPS), which in turn facilitates PKM2 transcription, glycolysis, cell proliferation in vitro as well as PDAC growth in mice.	SIGNOR-277570
Q9NRC8	Q13315	1	deacetylation	down-regulates activity	0.36	Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. \|Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016	SIGNOR-275890
P49841	O60341	1	phosphorylation	up-regulates activity	0.265	GSK3beta phosphorylates KDM1A serine 683 upon priming phosphorylation of KDM1A serine 687 by CK1alpha.\|Together, these results support the notion that GSK3\u03b2 stabilizes KDM1A by decreasing its ubiquitination.	SIGNOR-278225
Q13627	O43524	1	phosphorylation	down-regulates	0.359	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity phosphorylation of foxos by akt, ikk, erk, ck1, cdk2, and dyrk1a universally leads to foxo's inhibition.	SIGNOR-183674
Q02750	Q02750	2	phosphorylation	up-regulates activity	0.2	MEK1 and MEK2 can also be activated by autophosphorylation. Tyrosine 304 may be a candidate for the autophosphorylation site in MEK1.	SIGNOR-251415
P63096	P48145	2	binding	up-regulates activity	0.435	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-256675
Q96FA3	P53355	0	phosphorylation	down-regulates quantity by destabilization	0.2	DAPK1, which directly binds to and phosphorylates Pellino1 at Ser39, leading to Pellino1 poly-ubiquitination and turnover.	SIGNOR-277531
P62136	P41236	2	binding	down-regulates	0.785	Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.	SIGNOR-160651
P05129	P17302	1	phosphorylation	down-regulates activity	0.568	Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.\|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.	SIGNOR-249050
P67775	P06730	1	dephosphorylation	down-regulates	0.347	A recent study using genetically engineered mouse models has clearly shown that mnk-mediated eif4e phosphorylation is absolutely required for eif4e's oncogenic action. Taken together, we conclude that pp2a negatively regulates eif4e phosphorylation and eif4f complex assembly through dephosphorylation of mnk and eif4e, thus suggesting a novel mechanism by which pp2a exerts its tumor-suppressive function.	SIGNOR-168306
P06493	Q96Q89	1	phosphorylation	up-regulates activity	0.41	Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1.	SIGNOR-262695
P14210	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.	SIGNOR-251739
Q00987	Q9Y6B2	1	polyubiquitination	down-regulates quantity by destabilization	0.424	Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.	SIGNOR-272582
Q86WG3	Q9UNE7	0	polyubiquitination	down-regulates quantity by destabilization	0.378	CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.	SIGNOR-272651
Q08499-2	P28482	0	phosphorylation	down-regulates	0.353	The pde4d2 isoform is inhibited by erk2 phosphorylation	SIGNOR-77563
Q96SR6	Q8NFU7	0	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259095
Q6GQQ9	Q13546	1	deubiquitination	down-regulates activity	0.538	NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne\|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.	SIGNOR-268411
Q9Y478	Q8N122	1	phosphorylation	down-regulates	0.466	Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.	SIGNOR-173041
P43405	P16885	1	phosphorylation	up-regulates activity	0.753	Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase C\u03b32 (PLC\u03b32).\|Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase Cgamma2 (PLCgamma2).	SIGNOR-278995
P09341	Q99835	2	binding	up-regulates	0.2	We found that smo, by virtue of what appears to be constitutive activity, activates all members of the g(i) family but does not activate members of the g(s), g(q), and g(12) families.	SIGNOR-148484
Q7LBC6	Q16695	1	demethylation	down-regulates activity	0.2	We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.	SIGNOR-266635
Q13153	Q13233	1	phosphorylation	up-regulates activity	0.538	We found that pak1 phosphorylated mekk1 on serine 67 of its amino-terminal regulatory domain. mekk1 activity was increased modestly following pak phosphorylation.	SIGNOR-236006
Q9Y365	P68400	0	phosphorylation	down-regulates	0.409	Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity	SIGNOR-155740
O15033	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.316	These experiments suggested that GSK3beta phosphorylation of FIEL1 is required for PIAS4 targeting, and FIEL1 residues P779 and phosphorylated T783 are both required for PIAS4 interaction \|FIEL1 T783A mutant overexpression completely failed to decrease PIAS4 protein level.	SIGNOR-275528
Q13315	P15374	1	phosphorylation	up-regulates activity	0.331	Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM.	SIGNOR-279794
Q14596	P49841	0	phosphorylation	down-regulates activity	0.428	The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation\|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.	SIGNOR-261795
Q05655	P31749	0	phosphorylation	up-regulates activity	0.26	Of note, the amino acid sequence adjacent to Ser204 phosphorylation site matches the minimal AKT substrate motif (RxxpS) suggesting that AKT1 could potentially directly regulate PRKCD through phosphorylation.\|This integrative analysis allowed us to confirm that the enrichment of PRKCD centered network is likely the result of elevated phosphorylation of PRKCD by AKT1.	SIGNOR-280175
P53675	Q676U5	2	binding	up-regulates	0.304	Clathrin heavy-chain interacts with atg16l1, and is involved in the formation of atg16l1-positive early autophagosome precursors	SIGNOR-166705
P24864	O94955	2	binding	down-regulates quantity by destabilization	0.406	Here we show that RhoBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. Depletion of RhoBTB3 arrested cells in S phase, triggered Golgi fragmentation, and elevated cyclin E levels. On the Golgi, RhoBTB3 bound cyclin E as part of a Cullin3 (CUL3)-dependent RING-E3 ubiquitin ligase complex comprised of RhoBTB3, CUL3, and RBX1.	SIGNOR-272131
Q4G0J3	O94992	2	binding	down-regulates activity	0.686	To investigate whether LARP7 is part of the known 7SK RNP implicated in the regulation of transcription, co‐immunoprecipitation studies were performed using the nuclear extracts of HeLa cells (Fig 3A, lanes 1–4). Antibodies against LARP7, CDK9 and HEXIM1 efficiently precipitated 7SK RNA, whereas no RNA was found in the control (Fig 3A, lower panel, lanes 1–4). Interestingly, HEXIM1, CDK9, CYCT1 and LARP7 were present in all immunopurifications, as determined by mass spectrometry of silver‐stained gels (Fig 3A; data not shown) and western blotting. In conclusion, these experiments show that LARP7 negatively regulates not only viral but also cellular POLII class genes through the 7SK P‐TEFb system.	SIGNOR-261183
Q00987	P33981	0	phosphorylation	up-regulates activity	0.264	(D and E) MDM2 was phosphorylated by hMps1 at Thr4, Thr306 and Ser307 in vitro.\|In support, the MDM2 Ser307 to Ala mutant was less stable than the wild-type protein when coexpressed with hMps1 (Supplementary Figure S2B and C). hMps1 promotes MDM2-mediated H2B ubiquitination. (A) wild-type but not kinase-dead mutant hMps1 promotes MDM2-mediated H2B ubiquitination. 293T cells were transfected with the indicated plasmids and lysates were prepared for the Ni-NTA bead pulldown assay. 46999999="S307A"}	SIGNOR-279315
O43303	P41208	2	binding	up-regulates activity	0.698	We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.	SIGNOR-265967
P17612	Q6PIY7	1	phosphorylation	down-regulates activity	0.2	We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition.	SIGNOR-259402
P17612	Q9BZE0	1	phosphorylation	down-regulates activity	0.283	Protein kinase a (pka) and glycogen synthase kinase 3beta sequentially phosphorylate gli2 at multiple sites, identified by mutagenesis, thus resulting in a reduction of its transcriptional activity	SIGNOR-145131
Q13315	Q96GD4	0	phosphorylation	up-regulates	0.431	Aurora-b mediated atm serine 1403 phosphorylation is required for mitotic atm activation and the spindle checkpoint	SIGNOR-177280
O95819	Q12933	1	phosphorylation	down-regulates quantity	0.521	A key finding of our study is that HGK induces lysosomal degradation of TRAF2 by directly phosphorylating TRAF2 Ser35.\|Conversely, TRAF2 levels were decreased by ectopically expressed HGK in an overexpression system (XREF_FIG).	SIGNOR-279536
Q02779	P15923	1	phosphorylation	down-regulates	0.2	Mlk2 inhibits e47 transactivation activity on the trkb promote	SIGNOR-161544
P31749	O15111	1	phosphorylation	up-regulates	0.668	Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta	SIGNOR-187006
Q7Z6M2	P67809	2	binding	down-regulates quantity by destabilization	0.381	Here we identify FBX33 as a component of an SCF E3-ubiquitin ligase that targets the multifunctional regulator Y-box binding protein 1 (YB-1)/dbpB/p50 for polyubiquitination and destruction by the proteasome. By targeting YB-1 for proteasomal degradation, FBX33 negatively interferes with YB-1 mediated functions. FBX33 recruits Skp-1/Cul1 to YB-1	SIGNOR-271604
Q9UQM7	Q05682	1	phosphorylation	down-regulates	0.2	Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii	SIGNOR-22635
P63096	P11229	2	binding	up-regulates activity	0.399	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-256735
Q13535	Q92900	1	phosphorylation	up-regulates activity	0.368	Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage.	SIGNOR-278911
O14746	Q92630	0	phosphorylation	down-regulates activity	0.444	Dyrk2 phosphorylates TERT protein, a catalytic subunit of telomerase.\|In this study, we found that dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (Dyrk2) negatively regulates telomerase activity.	SIGNOR-279611
P29597	Q13261	0	null	up-regulates	0.245	Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated	SIGNOR-256253
Q5QNW6	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265394
P00533	P01135	2	binding	up-regulates activity	0.899	Our data indicate that a subset of cell lines is dependent on TGF-_-mediated activation of the EGFR for cell proliferation and strongly suggest that pancreatic tumors expressing high levels of TGF-_ and phosphorylated (activated) EGFR are EGFR-dependent in vitro and in vivo.	SIGNOR-93199
Q9HBE1	P78317	2	binding	down-regulates	0.511	In vitro and in vivo interaction between rnf4 and patz was demonstrated / patz acted as a transcriptional repressor, whereas its partner rnf4 behaved as a transcriptional activator./ the association of patz with rnf4 switches activation to repression	SIGNOR-75775
O14713	P05106	2	binding	down-regulates activity	0.308	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257656
P49841	P24385	1	phosphorylation	down-regulates	0.783	Phosphorylation of cyclin d1 on a single threonine residue near the carboxyl terminus (thr-286) positively regulates proteasomal degradation of d1. Now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover.	SIGNOR-144818
Q76N32	Q96SN8	1	relocalization	up-regulates activity	0.452	We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. \|Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215	SIGNOR-275624
P04637	O43293	0	phosphorylation	up-regulates	0.406	A cell-free ser(20) phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser(20) kinases.Evaluation of these calcium calmodulin kinase superfamily members as candidate ser(20) kinases in vivo has shown that only chk1 or dapk-1 can stimulate p53 transactivation and induce ser(20) phosphorylation of p53.	SIGNOR-153495
Q14344	P61586	2	binding	up-regulates	0.574	Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism.	SIGNOR-192111
O75030	P10415	1	transcriptional regulation	up-regulates quantity by expression	0.475	MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF	SIGNOR-249618
Q38SD2	P51149	1	phosphorylation	up-regulates activity	0.386	Overall, these data suggest that LRRK1 is able to phosphorylate endogenous Rab7A at Ser72.	SIGNOR-278212
Q13131	P56524	1	phosphorylation	down-regulates	0.272	We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases.	SIGNOR-173689
O15554	P22392	0	phosphorylation	up-regulates	0.419	We previously showed that nucleoside diphosphate kinase beta (ndpk-b), a mammalian histidine kinase, is required for kca3.1 channel activation in human cd4 t lymphocytes.	SIGNOR-181083
O00422	Q9UMX1	2	binding	up-regulates	0.673	Here we report that the mouse homolog of su(fu) [msu(fu)] specifically interacts with sap18, a component of the msin3 and histone deacetylase complex. In addition, we demonstrate that msu(fu) functionally cooperates with sap18 to repress transcription by recruiting the sap18-msin3 complex to promoters containing the gli-binding element.	SIGNOR-117311
Q96EB6	Q6UUV9	1	deacetylation	up-regulates	0.281	Sirt1 deacetylates and activates torc1	SIGNOR-191568
O95471	Q13363	0	transcriptional regulation	down-regulates quantity by repression	0.2	ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.	SIGNOR-254105
Q969F2	P01135	2	binding	up-regulates quantity by stabilization	0.449	Here, we show that Naked2 is a short-lived protein with a half-life of 60 min caused by its rapid ubiquitin-mediated proteasomal degradation. Overexpression of TGF-alpha stabilizes Naked2 protein in an EGF receptor (EGFR)-independent manner; a physical interaction between the cytoplasmic tail of TGF-alpha and Naked2 is necessary and sufficient for this protection. We have identified a RING finger protein, AO7/RNF25, as a ubiquitin ligase for Naked2, and we have shown that overexpression of TGF-alpha reduces binding of AO7 to Naked2.	SIGNOR-271739
Q8IZD2-8	O95944	2	binding	up-regulates activity	0.505	We identify natural cytotoxicity receptor NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is excluded from the nucleus, but expressed at the cell-surface level; its subcellular localization is being associated with the presence of a specific C-terminal motif. Strikingly, NKp44L has not been detected on circulating cells isolated from healthy individuals, but it is expressed on a large panel of the tumor and transformed cells.	SIGNOR-260042
Q12772	P28482	0	phosphorylation	up-regulates	0.358	Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.	SIGNOR-123045

P21127

Q9UQ88

0

phosphorylation

up-regulates

0.305

Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58)

SIGNOR-169628

Q5JWF2

P63244

2

binding

down-regulates activity

0.2

The results showed that RACK1 severed as an oncogene to enhance the proliferation capacity of liver cancer cell lines, meanwhile, downregulated GNA14 expression in Huh7 cell lines reversed the effects of RACK1 on cell proliferation

SIGNOR-278048

Q08345

P30408

2

binding

up-regulates activity

0.424

Gao et al have demonstrated that in metastatic breast cancer cell, DDR1 interacts with cell surface Transmembrane 4 L Six Family Member 1 (TM4SF1) and regulates tumor dormancy and reactivation [3]. The interaction between DDR1 and TM4SF1 is collagen dependent and control Protein Kinase C Alpha (PKCa) mediated downstream JAK-STAT signaling pathway [3] (Figure 3). Interestingly the data also showed that TM4SF1 failed to interact with DDR2.

SIGNOR-272400

Q9Y6E2

P05198

2

binding

up-regulates activity

0.253

BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro

SIGNOR-261220

P54253

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.334

NICD and MDM2 ubiquitinate and degrade ATXN1.|These results suggest that NICD and MDM2 synergistically reduce ATXN1 expression at the posttranscriptional level.

SIGNOR-278823

P06493

P40337

1

phosphorylation

up-regulates activity

0.2

Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1.|PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo.

SIGNOR-280207

Q9UKV8

Q9UPQ9

2

binding

up-regulates activity

0.796

The assay showed that full-length TNRC6B binds full-length human AGO2. We have identified and molecularly dissected important sequence and structure features in the conserved Ago hooks of S. pombe Tas3 and human TNRC6B. The effect of Ago hook peptides from the shuttling P-body component TNRC6B in our miRNA-mediated translational repression assay (Fig. 5b), in particular, hints at a novel regulatory role of Ago hooks in miRNA-mediated gene repression mechanisms.

SIGNOR-269680

Q9NTX7

O95271

1

ubiquitination

down-regulates quantity

0.723

We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation.

SIGNOR-260004

P04264

Q03405

2

binding

up-regulates activity

0.288

Cytokeratin 1 binds to both gC1qR and u-PAR. Our data suggest that formation of HK (and Factor XII) binding sites along endothelial cell membranes consists of bimolecular com-plexes of gC1qR-cytokeratin 1 and u-PAR-cytokeratin 1, with gC1qR binding being favored.

SIGNOR-251880

P36508

P20226

2

binding

down-regulates activity

0.399

We identified ZNF76 as a novel transcriptional repressor that targets TBP. ZNF76 interacts with TBP through both its N and C termini. ZNF76 targets TBP for transcriptional repression.

SIGNOR-224650

Q04726

P98170

0

ubiquitination

up-regulates activity

0.507

These findings suggest that TLE3 ubiquitylation by XIAP may be required during Wnt pathway activation to facilitate its dissociation from TCF/Lef, allowing subsequent beta-catenin binding and transcriptional activation.

SIGNOR-278528

P16885

P51451

0

phosphorylation

up-regulates activity

0.557

Lyn, Syk, Btk, and Blk can also phosphorylate and enhance the activation of phospholipase C gamma 2 (PLCgamma2), which hydrolyzes PI (4,5) P2 to create inositol 3,4,5-trisphosphate (IP3) and diacylglycerol (DAG), stimulating Ca 2+ mobilization and protein kinase C (PKC), respectively.

SIGNOR-280195

P09471

Q9UKP6

2

binding

up-regulates activity

0.265

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-257252

Q9BWF3

P19544

2

binding

down-regulates

0.364

Wilm's tumor protein 1 (wt1), a protein implicated in various cancers and developmental disorders, consists of two major isoforms: wt1(-kts), a transcription factor, and wt1(+kts), a post-transcriptional regulator that binds to rna and can interact with splicing components. Here we show that wt1 interacts with the novel splicing regulator rbm4. / we conclude that the (+kts) form of wt1 is able to inhibit the effect of rbm4 on alternative splicing.

SIGNOR-149166

P42226

Q9UHD2

0

phosphorylation

up-regulates

0.674

We now show that stat6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger sting (also named mita/eris) to recruit stat6 to the endoplasmic reticulum, leading to stat6 phosphorylation on ser(407) by tbk1 and tyr(641), independent of jaks. Phosphorylated stat6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing.

SIGNOR-176775

O15151

O96017

0

phosphorylation

down-regulates

0.723

Phosphorylation of s342 and s367 in vivo require the chk2 kinase. Chk2 also stimulates mdmx ubiquitination and degradation by mdm2

SIGNOR-140417

O96017

P04637

1

phosphorylation

up-regulates quantity by stabilization

0.791

Chk1/chk2 and atm/atr also phosphorylate the effector p53, increasing its stability.We Have demonstrated that the human homologs of the checkpoint kinases, chk1 and chk2/hcds1, phosphorylate at least three dna damage-inducible phosphorylation sites in p53.

SIGNOR-74831

P30519

P68400

0

phosphorylation

up-regulates activity

0.335

Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. | CK2 activation is abolished by the S79A mutation but preserved in S179A and T248A mutations, indicating that S79 is the target of CK2-dependent activation of HO2

SIGNOR-250895

Q03113

P30411

2

binding

up-regulates activity

0.2

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-257344

P06241

O14522

1

phosphorylation

down-regulates activity

0.414

Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT

SIGNOR-275543

O95996

O15169

2

binding

up-regulates

0.771

Human axin (haxin) binds directly to beta-catenin, gsk3 beta, and apc in vitro, and the endogenous proteins are found in a complex in cells.

SIGNOR-57673

Q8N1I0

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.586

DOCK4 (dedicator for cytokinesis 4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, is one of few genes that are associated with both ASD and dyslexia.

SIGNOR-266823

O00418

Q15418

0

phosphorylation

down-regulates activity

0.513

We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity

SIGNOR-109708

P17252

Q9HBA0

1

phosphorylation

up-regulates activity

0.38

We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.

SIGNOR-260882

P52797

Q15375

2

binding

up-regulates

0.802

The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion

SIGNOR-52384

Q8N163

P68400

0

phosphorylation

up-regulates activity

0.2

CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. |In our results, CK2alpha affected the|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1

SIGNOR-267666

Q06413

P68400

0

phosphorylation

up-regulates activity

0.333

We show that serine 59 located between the MADS and MEF2 domains of MEF2C is phosphorylated in vivo and can be phosphorylated in vitro by casein kinase-II (CKII). Phosphorylation of this site enhanced the DNA binding and transcriptional activity of MEF2C by increasing its DNA binding activity 5-fold.

SIGNOR-250914

P16615

O00631

2

binding

down-regulates activity

0.505

The structure suggests a mechanism for selective Ca2+ loading and activation of SERCA, and provides new insight into how SLN and PLB inhibition arises from stabilization of this E1 intermediate state without bound Ca2+.

SIGNOR-264779

O60548

P10644

1

transcriptional regulation

up-regulates quantity by expression

0.2

Elevating the amounts of FOXD2 expression vector up to 12-fold relative to the RIα1b reporter construct demonstrated that maximal induction of the RIα1b promoter by FOXD2 was at least 5.8-fold

SIGNOR-261605

P16104

P61088

0

ubiquitination

up-regulates

0.2

In an h2ax- and mdc1-dependent manner , rnf8/ubc13 complexes go to sites of dna damage through their fha domain and initiate the synthesis of k63 polyubiquitin chains on chromatin that recruit the brca1 a complex through the uim domains of rap80.

SIGNOR-159880

O75581

P49840

0

phosphorylation

up-regulates activity

0.632

Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493

SIGNOR-275398

Q96AQ6

P40424

2

binding

down-regulates activity

0.331

This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences.

SIGNOR-273666

O95363

Q2TAL8

0

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269403

P17947

Q03164

0

methylation

up-regulates quantity by expression

0.441

Furthermore, we show that both MLL and AML1/CBFβ are required for maintaining the H3K4-me3 mark at the PU.1 upstream regulatory element (URE) and promoter region, and for full PU.1 gene expression.

SIGNOR-255874

O95476

Q13873

2

binding

down-regulates

0.426

We show that dullard promotes the ubiquitin-mediated proteosomal degradation of bmp receptors

SIGNOR-151001

O43186

O15265

2

binding

down-regulates activity

0.607

We found that ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation.

SIGNOR-223226

Q8TCQ1

P01903

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.

SIGNOR-271412

P22894

P02671

1

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. |Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.|MMP-8 20ADSGEGD a-chain | 442LRTGKEKV a-chain

SIGNOR-263625

P46937

O75385

0

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, hypoxia stimulates ULK1 to translocate into nucleus, where it interacts with and phosphorylates yes-associated protein (YAP) at Ser227, resulting in YAP stabilization through blockade of ubiquitin-proteasome system (UPS), which in turn facilitates PKM2 transcription, glycolysis, cell proliferation in vitro as well as PDAC growth in mice.

SIGNOR-277570

Q9NRC8

Q13315

1

deacetylation

down-regulates activity

0.36

Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. |Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016

SIGNOR-275890

P49841

O60341

1

phosphorylation

up-regulates activity

0.265

GSK3beta phosphorylates KDM1A serine 683 upon priming phosphorylation of KDM1A serine 687 by CK1alpha.|Together, these results support the notion that GSK3\u03b2 stabilizes KDM1A by decreasing its ubiquitination.

SIGNOR-278225

Q13627

O43524

1

phosphorylation

down-regulates

0.359

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity phosphorylation of foxos by akt, ikk, erk, ck1, cdk2, and dyrk1a universally leads to foxo's inhibition.

SIGNOR-183674

Q02750

2

phosphorylation

up-regulates activity

0.2

MEK1 and MEK2 can also be activated by autophosphorylation. Tyrosine 304 may be a candidate for the autophosphorylation site in MEK1.

SIGNOR-251415

P63096

P48145

2

binding

up-regulates activity

0.435

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-256675

Q96FA3

P53355

0

phosphorylation

down-regulates quantity by destabilization

0.2

DAPK1, which directly binds to and phosphorylates Pellino1 at Ser39, leading to Pellino1 poly-ubiquitination and turnover.

SIGNOR-277531

P62136

P41236

2

binding

down-regulates

0.785

Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.

SIGNOR-160651

P05129

P17302

1

phosphorylation

down-regulates activity

0.568

Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.

SIGNOR-249050

P67775

P06730

1

dephosphorylation

down-regulates

0.347

A recent study using genetically engineered mouse models has clearly shown that mnk-mediated eif4e phosphorylation is absolutely required for eif4e's oncogenic action. Taken together, we conclude that pp2a negatively regulates eif4e phosphorylation and eif4f complex assembly through dephosphorylation of mnk and eif4e, thus suggesting a novel mechanism by which pp2a exerts its tumor-suppressive function.

SIGNOR-168306

P06493

Q96Q89

1

phosphorylation

up-regulates activity

0.41

Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1.

SIGNOR-262695

P14210

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.

SIGNOR-251739

Q00987

Q9Y6B2

1

polyubiquitination

down-regulates quantity by destabilization

0.424

Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.

SIGNOR-272582

Q86WG3

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.378

CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.

SIGNOR-272651

Q08499-2

P28482

0

phosphorylation

down-regulates

0.353

The pde4d2 isoform is inhibited by erk2 phosphorylation

SIGNOR-77563

Q96SR6

Q8NFU7

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.

SIGNOR-259095

Q6GQQ9

Q13546

1

deubiquitination

down-regulates activity

0.538

NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.

SIGNOR-268411

Q9Y478

Q8N122

1

phosphorylation

down-regulates

0.466

Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.

SIGNOR-173041

P43405

P16885

1

phosphorylation

up-regulates activity

0.753

Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase C\u03b32 (PLC\u03b32).|Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase Cgamma2 (PLCgamma2).

SIGNOR-278995

P09341

Q99835

2

binding

up-regulates

0.2

We found that smo, by virtue of what appears to be constitutive activity, activates all members of the g(i) family but does not activate members of the g(s), g(q), and g(12) families.

SIGNOR-148484

Q7LBC6

Q16695

1

demethylation

down-regulates activity

0.2

We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.

SIGNOR-266635

Q13153

Q13233

1

phosphorylation

up-regulates activity

0.538

We found that pak1 phosphorylated mekk1 on serine 67 of its amino-terminal regulatory domain. mekk1 activity was increased modestly following pak phosphorylation.

SIGNOR-236006

Q9Y365

P68400

0

phosphorylation

down-regulates

0.409

Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity

SIGNOR-155740

O15033

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.316

These experiments suggested that GSK3beta phosphorylation of FIEL1 is required for PIAS4 targeting, and FIEL1 residues P779 and phosphorylated T783 are both required for PIAS4 interaction |FIEL1 T783A mutant overexpression completely failed to decrease PIAS4 protein level.

SIGNOR-275528

Q13315

P15374

1

phosphorylation

up-regulates activity

0.331

Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM.

SIGNOR-279794

Q14596

P49841

0

phosphorylation

down-regulates activity

0.428

The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.

SIGNOR-261795

Q05655

P31749

0

phosphorylation

up-regulates activity

0.26

Of note, the amino acid sequence adjacent to Ser204 phosphorylation site matches the minimal AKT substrate motif (RxxpS) suggesting that AKT1 could potentially directly regulate PRKCD through phosphorylation.|This integrative analysis allowed us to confirm that the enrichment of PRKCD centered network is likely the result of elevated phosphorylation of PRKCD by AKT1.

SIGNOR-280175

P53675

Q676U5

2

binding

up-regulates

0.304

Clathrin heavy-chain interacts with atg16l1, and is involved in the formation of atg16l1-positive early autophagosome precursors

SIGNOR-166705

P24864

O94955

2

binding

down-regulates quantity by destabilization

0.406

Here we show that RhoBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. Depletion of RhoBTB3 arrested cells in S phase, triggered Golgi fragmentation, and elevated cyclin E levels. On the Golgi, RhoBTB3 bound cyclin E as part of a Cullin3 (CUL3)-dependent RING-E3 ubiquitin ligase complex comprised of RhoBTB3, CUL3, and RBX1.

SIGNOR-272131

Q4G0J3

O94992

2

binding

down-regulates activity

0.686

To investigate whether LARP7 is part of the known 7SK RNP implicated in the regulation of transcription, co‐immunoprecipitation studies were performed using the nuclear extracts of HeLa cells (Fig 3A, lanes 1–4). Antibodies against LARP7, CDK9 and HEXIM1 efficiently precipitated 7SK RNA, whereas no RNA was found in the control (Fig 3A, lower panel, lanes 1–4). Interestingly, HEXIM1, CDK9, CYCT1 and LARP7 were present in all immunopurifications, as determined by mass spectrometry of silver‐stained gels (Fig 3A; data not shown) and western blotting. In conclusion, these experiments show that LARP7 negatively regulates not only viral but also cellular POLII class genes through the 7SK P‐TEFb system.

SIGNOR-261183

Q00987

P33981

0

phosphorylation

up-regulates activity

0.264

(D and E) MDM2 was phosphorylated by hMps1 at Thr4, Thr306 and Ser307 in vitro.|In support, the MDM2 Ser307 to Ala mutant was less stable than the wild-type protein when coexpressed with hMps1 (Supplementary Figure S2B and C). hMps1 promotes MDM2-mediated H2B ubiquitination. (A) wild-type but not kinase-dead mutant hMps1 promotes MDM2-mediated H2B ubiquitination. 293T cells were transfected with the indicated plasmids and lysates were prepared for the Ni-NTA bead pulldown assay. 46999999="S307A"}

SIGNOR-279315

O43303

P41208

2

binding

up-regulates activity

0.698

We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.

SIGNOR-265967

P17612

Q6PIY7

1

phosphorylation

down-regulates activity

0.2

We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition.

SIGNOR-259402

P17612

Q9BZE0

1

phosphorylation

down-regulates activity

0.283

Protein kinase a (pka) and glycogen synthase kinase 3beta sequentially phosphorylate gli2 at multiple sites, identified by mutagenesis, thus resulting in a reduction of its transcriptional activity

SIGNOR-145131

Q13315

Q96GD4

0

phosphorylation

up-regulates

0.431

Aurora-b mediated atm serine 1403 phosphorylation is required for mitotic atm activation and the spindle checkpoint

SIGNOR-177280

O95819

Q12933

1

phosphorylation

down-regulates quantity

0.521

A key finding of our study is that HGK induces lysosomal degradation of TRAF2 by directly phosphorylating TRAF2 Ser35.|Conversely, TRAF2 levels were decreased by ectopically expressed HGK in an overexpression system (XREF_FIG).

SIGNOR-279536

Q02779

P15923

1

phosphorylation

down-regulates

0.2

Mlk2 inhibits e47 transactivation activity on the trkb promote

SIGNOR-161544

P31749

O15111

1

phosphorylation

up-regulates

0.668

Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta

SIGNOR-187006

Q7Z6M2

P67809

2

binding

down-regulates quantity by destabilization

0.381

Here we identify FBX33 as a component of an SCF E3-ubiquitin ligase that targets the multifunctional regulator Y-box binding protein 1 (YB-1)/dbpB/p50 for polyubiquitination and destruction by the proteasome. By targeting YB-1 for proteasomal degradation, FBX33 negatively interferes with YB-1 mediated functions. FBX33 recruits Skp-1/Cul1 to YB-1

SIGNOR-271604

Q9UQM7

Q05682

1

phosphorylation

down-regulates

0.2

Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii

SIGNOR-22635

P63096

P11229

2

binding

up-regulates activity

0.399

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-256735

Q13535

Q92900

1

phosphorylation

up-regulates activity

0.368

Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage.

SIGNOR-278911

O14746

Q92630

0

phosphorylation

down-regulates activity

0.444

Dyrk2 phosphorylates TERT protein, a catalytic subunit of telomerase.|In this study, we found that dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (Dyrk2) negatively regulates telomerase activity.

SIGNOR-279611

P29597

Q13261

0

null

up-regulates

0.245

Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated

SIGNOR-256253

Q5QNW6

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265394

P00533

P01135

2

binding

up-regulates activity

0.899

Our data indicate that a subset of cell lines is dependent on TGF-_-mediated activation of the EGFR for cell proliferation and strongly suggest that pancreatic tumors expressing high levels of TGF-_ and phosphorylated (activated) EGFR are EGFR-dependent in vitro and in vivo.

SIGNOR-93199

Q9HBE1

P78317

2

binding

down-regulates

0.511

In vitro and in vivo interaction between rnf4 and patz was demonstrated / patz acted as a transcriptional repressor, whereas its partner rnf4 behaved as a transcriptional activator./ the association of patz with rnf4 switches activation to repression

SIGNOR-75775

O14713

P05106

2

binding

down-regulates activity

0.308

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257656

P49841

P24385

1

phosphorylation

down-regulates

0.783

Phosphorylation of cyclin d1 on a single threonine residue near the carboxyl terminus (thr-286) positively regulates proteasomal degradation of d1. Now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover.

SIGNOR-144818

Q76N32

Q96SN8

1

relocalization

up-regulates activity

0.452

We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215

SIGNOR-275624

P04637

O43293

0

phosphorylation

up-regulates

0.406

A cell-free ser(20) phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser(20) kinases.Evaluation of these calcium calmodulin kinase superfamily members as candidate ser(20) kinases in vivo has shown that only chk1 or dapk-1 can stimulate p53 transactivation and induce ser(20) phosphorylation of p53.

SIGNOR-153495

Q14344

P61586

2

binding

up-regulates

0.574

Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism.

SIGNOR-192111

O75030

P10415

1

transcriptional regulation

up-regulates quantity by expression

0.475

MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF

SIGNOR-249618

Q38SD2

P51149

1

phosphorylation

up-regulates activity

0.386

Overall, these data suggest that LRRK1 is able to phosphorylate endogenous Rab7A at Ser72.

SIGNOR-278212

Q13131

P56524

1

phosphorylation

down-regulates

0.272

We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases.

SIGNOR-173689

O15554

P22392

0

phosphorylation

up-regulates

0.419

We previously showed that nucleoside diphosphate kinase beta (ndpk-b), a mammalian histidine kinase, is required for kca3.1 channel activation in human cd4 t lymphocytes.

SIGNOR-181083

O00422

Q9UMX1

2

binding

up-regulates

0.673

Here we report that the mouse homolog of su(fu) [msu(fu)] specifically interacts with sap18, a component of the msin3 and histone deacetylase complex. In addition, we demonstrate that msu(fu) functionally cooperates with sap18 to repress transcription by recruiting the sap18-msin3 complex to promoters containing the gli-binding element.

SIGNOR-117311

Q96EB6

Q6UUV9

1

deacetylation

up-regulates

0.281

Sirt1 deacetylates and activates torc1

SIGNOR-191568

O95471

Q13363

0

transcriptional regulation

down-regulates quantity by repression

0.2

ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.

SIGNOR-254105

Q969F2

P01135

2

binding

up-regulates quantity by stabilization

0.449

Here, we show that Naked2 is a short-lived protein with a half-life of 60 min caused by its rapid ubiquitin-mediated proteasomal degradation. Overexpression of TGF-alpha stabilizes Naked2 protein in an EGF receptor (EGFR)-independent manner; a physical interaction between the cytoplasmic tail of TGF-alpha and Naked2 is necessary and sufficient for this protection. We have identified a RING finger protein, AO7/RNF25, as a ubiquitin ligase for Naked2, and we have shown that overexpression of TGF-alpha reduces binding of AO7 to Naked2.

SIGNOR-271739

Q8IZD2-8

O95944

2

binding

up-regulates activity

0.505

We identify natural cytotoxicity receptor NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is excluded from the nucleus, but expressed at the cell-surface level; its subcellular localization is being associated with the presence of a specific C-terminal motif. Strikingly, NKp44L has not been detected on circulating cells isolated from healthy individuals, but it is expressed on a large panel of the tumor and transformed cells.

SIGNOR-260042

Q12772

P28482

0

phosphorylation

up-regulates

0.358

Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.

SIGNOR-123045