GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q96A26	Q16665	transcriptional regulation	up-regulates quantity by expression	0.282	In this work, we report the identification of an HIF-1 alpha-responsive proapoptotic molecule, HGTD-P. Its expression was directly regulated by HIF-1 alpha through a hypoxia-responsive element on the HGTD-P promoter region.	SIGNOR-260292
P08754	P21728	binding	up-regulates activity	0.282	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-257181
P20336	Q9UJD0	relocalization	up-regulates activity	0.282	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264379
Q03113	P28336	binding	up-regulates	0.282	These neuropeptides, including gastrin-releasing peptide, neuromedin b, neurotensin, gastrin, cholecystokinin and arginine vasopressin bind seven transmembrane-spanning receptors that couple to heterotrimeric g proteins. Studies with human small cell lung cancer (sclc) cells support a requirement for balanced signaling through g(q) and g(12/13) proteins leading to intracellular ca2+ mobilization, pkc activation and regulation of the erk and jnk map kinase pathways.	SIGNOR-107025
Q8TDR2	Q05D32	dephosphorylation	up-regulates quantity by stabilization	0.282	We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).	SIGNOR-273775
Q07954	P00734	binding	up-regulates	0.282	In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp	SIGNOR-41090
Q9H4A3	Q9BYP7	phosphorylation	up-regulates activity	0.282	We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro.	SIGNOR-260789
P08754	P21918	binding	up-regulates activity	0.282	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-257156
Q13562	O00712	transcriptional regulation	up-regulates quantity	0.282	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268897
P35354	Q14934	transcriptional regulation	up-regulates quantity by expression	0.282	NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration	SIGNOR-264027
O14867	Q8NEZ5	ubiquitination	down-regulates quantity	0.282	Here, we show that heme triggers the degradation of Bach1, a pro-metastatic transcription factor, by promoting its interaction with the ubiquitin ligase Fbxo22.	SIGNOR-259331
P62714	Q01105	binding	down-regulates	0.282	Here we report that both the amino terminal fragment (i(2ntf);aa 1-175) and the carboxy terminal fragment (i(2ctf);aa 176-277) of i(2)(pp2a) inhibit pp2a by binding to its catalytic subunit pp2ac	SIGNOR-175722
Q12959	P24941	phosphorylation	up-regulates	0.282	We also show that dlg1 is phosphorylated by both cdk1 and cdk2 on ser158 and ser442. These phosphorylated sites together affect the nuclear localisation of the protein, and implicate the role of phosphorylation on ser158 and ser442 in its putative nuclear functions as a tumour suppressor. phosphorylation on ser158 and ser442 enhances nuclear expression of dlg1	SIGNOR-182765
Q05516	P24941	phosphorylation	down-regulates	0.282	Here we show that the main cyclin-dependent kinase involved at the g(1) to s transition (cdk2) phosphorylates plzf at two consensus sites found within pest domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of plzf, which impairs plzf transcriptional repression ability and antagonizes its growth inhibitory effects.	SIGNOR-160630
Q6IQ49	Q9NZJ0	binding	down-regulates quantity by destabilization	0.282	Here, we identify human SDE2 as a new genome surveillance factor regulated by PCNA interaction. The cleaved SDE2 products need to be degraded by the CRL4CDT2 ubiquitin E3 ligase in a cell cycle- and DNA damage-dependent manner, and failure to degrade SDE2 impairs S phase progression and cellular survival.	SIGNOR-272807
Q7L5N1	P31749	phosphorylation	up-regulates	0.282	Mechanistic studies show that akt causes csn6 phosphorylation at ser 60, which, in turn, reduces ubiquitin-mediated protein degradation of csn6.	SIGNOR-252532
P29401	P31749	phosphorylation	up-regulates activity	0.282	Akt phosphorylates TKT on Thr382, markedly enhancing enzyme activity and increasing carbon flow through the nonoxidative PPP, thereby increasing purine synthesis.	SIGNOR-265101
Q9UJD0	O15034	binding	down-regulates activity	0.282	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264371
P01106	P48729	phosphorylation	down-regulates quantity by destabilization	0.282	Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation.	SIGNOR-276387
P35367	Q9UQM7	phosphorylation	down-regulates	0.282	As we have shown previously, human h1r can be phosphorylated in vitro by several kinases includingpka, pkc, pkg, and camk ii in summary, these data suggest that thr140, thr142, ser396, ser398, and thr478 can be phosphorylated by the kinases described above (table 2).	SIGNOR-124348
Q8TB45	P27361	phosphorylation	up-regulates quantity by stabilization	0.282	Screening the DEPTOR interactome identified that the association of USP-7 deubiquitinase with DEPTOR was dependent upon S235 phosphorylation. Inhibition of USP-7 activity resulted in DEPTOR polyubiquitination and degradation. A scansite search suggested that ERK1 may be responsible for S235 phosphorylation, which was confirmed through the use of inhibitors, ERK1 knockdown, and an in vitro kinase assay.	SIGNOR-277587
Q9P212	P50148	binding	up-regulates	0.282	Typically galfas stimulates adenylyl cyclase and increases levels of cyclic amp (camp), whereas galfai inhibits adenylyl cyclase and lowers camp levels, and members of the galfaq family bind to and activate phospholipase c (plc), which cleaves phosphatidylinositol bisphosphate (pip2) into diacylglycerol and inositol triphosphate (ip3). The gbeta subunits and ggamma subunits function as a dimer to activate manymolecules, including phospholipases, ion channels and lipid kinases.	SIGNOR-152609
O75874	P36956	transcriptional regulation	up-regulates quantity by expression	0.282	IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells\|evidence that IDH1 may regulate lipogenesis in hepatic cells	SIGNOR-253132
Q13263	O14757	phosphorylation	up-regulates activity	0.282	These data suggested that KAP1 Ser473 phosphorylation by Chk1 and Chk2 does not take place predominantly at sites of DNA damage, and are consistent with previous work indicating that, following their DNA-damage-localized phosphorylation and activation by ATR and ATM, Chk1 and Chk2 dissociate from chromatin to phosphorylate their substrates , ].\|These results therefore indicated that both Chk1 and Chk2 can target KAP1 Ser473, and are in agreement with IR triggering both the ATM and Chk2 and ATR and Chk1 pathways .	SIGNOR-280226
P63096	P34969	binding	up-regulates activity	0.281	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-257055
P46527	Q06124	dephosphorylation	up-regulates activity	0.281	Moreover, SHP-2 was strongly activated on G-CSF stimulation and specifically dephosphorylated p27(Kip1) in vitro.\|Most importantly, we could illustrate that SHP-2 modulates p27 (Kip1) stability and contributes to p27 (Kip1)-mediated cell cycle progression.	SIGNOR-277168
P19793	P24468	binding	up-regulates	0.281	Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site	SIGNOR-79446
O94953	P04637	transcriptional regulation	up-regulates quantity by expression	0.281	KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter.	SIGNOR-263729
Q9HAW9	P20823	transcriptional regulation	up-regulates quantity by expression	0.281	Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.	SIGNOR-253972
O60674	P54764	phosphorylation	up-regulates activity	0.281	EphA4 phosphorylates JAK2.\|These findings suggest that EphA4 activates not only growth hormone receptor, as shown above, but also JAK2 by direct phosphorylation.	SIGNOR-279040
O43474	P15941	binding	up-regulates activity	0.281	Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. Our results show that MUC1-C binds constitutively to KLF4, occupies PE21 with KLF4, and enhances the KLF4 occupancy of PE21.	SIGNOR-270543
Q9Y4X5	Q13619	binding	up-regulates activity	0.281	Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin.	SIGNOR-268847
Q9UQD0	Q13557	phosphorylation	up-regulates activity	0.281	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275792
P05091	Q02156	phosphorylation	up-regulates activity	0.281	Post-translational enhancement of ALDH2 activity can be achieved by serine/threonine phosphorylation by epsilon protein kinase C (epsilonPKC). \|e identified S279 as a critical εPKC phosphorylation site in the activation of ALDH2. The critical catalytic site, cysteine 302 (C302) of ALDH2 is susceptible to adduct formation by reactive aldehyde, 4HNE, which readily renders the enzyme inactive. We show that phosphomimetic mutations of T185E, S279E and T412E confer protection of ALDH2 against 4HNE-induced inactivation, indicating that phosphorylation on these three sites by εPKC likely also protects the enzyme against reactive aldehydes.	SIGNOR-271864
P37173	P12931	phosphorylation	up-regulates	0.281	Tbetarii can also be phosphorylated by src, a non-rtk, on y284, which can serve as a docking site for the recruitment of grb2 and shc, thereby bridging tbetarii to mapk activation.	SIGNOR-182963
P46531	P41240	binding	up-regulates	0.281	We found that the notch-1-furin interaction is regulated by the non-receptor tyrosine kinase, c-src. c-src and notch-1 are physically associated, and this association is responsible for notch-1 processing and activation	SIGNOR-196824
Q96PG8	P04626	phosphorylation	down-regulates activity	0.281	These results show for the first time that PUMA can be phosphorylated at tyrosine residues directly by HER2.\|Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein.	SIGNOR-278224
Q03164	Q13535	phosphorylation	up-regulates	0.281	Mll is phosphorylated at serine 516 by atr in response to genotoxic stress in the s phase, which disrupts its interaction with, and hence its degradation by, the scf(skp2) e3 ligase, leading to its accumulation.	SIGNOR-25151
Q6UUV9	Q96EB6	deacetylation	up-regulates	0.281	Sirt1 deacetylates and activates torc1	SIGNOR-191568
Q9BXH1	P04626	phosphorylation	down-regulates quantity by destabilization	0.281	HER2 phosphorylates and destabilizes pro-apoptotic PUMA. Using an intracellular assay, we found PUMA to be phosphorylated in breast cancer cells with activated HER2. Via cell-free HER2 kinase assay, we observed that PUMA was directly phosphorylated by HER2. Activation of HER2 decreased PUMA protein half-life.	SIGNOR-276474
O75676	P68400	phosphorylation	up-regulates activity	0.281	Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.	SIGNOR-276268
P55265	P31749	phosphorylation	down-regulates activity	0.281	AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively	SIGNOR-276193
P08754	P34969	binding	up-regulates activity	0.281	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-257168
O00443	P06493	phosphorylation	down-regulates activity	0.281	Mitotic and stress-induced phosphorylation of HsPI3K-C2alpha targets the protein for degradation. Stress-dependent and mitotic phosphorylation of hspik3-c2alpha occurs on the same serine residue (ser259) within a recognition motif for proline-directed kinases. Mitotic phosphorylation of hspik3-c2alpha can be attributed to cdc2 activity, and stress-induced phosphorylation of hspik3-c2alpha is mediated by jnk/sapk	SIGNOR-100903
P49279	P12931	phosphorylation	up-regulates activity	0.281	In this study, we provide evidence that SLC11A1 is phosphorylated by Src family kinases at tyrosine 15 present in a conserved tyrosine-based motif (YGSI) among all species.	SIGNOR-278500
Q92769	P67775	dephosphorylation	down-regulates activity	0.281	In contrast, in the present work, PPP2CA reduced HDAC2 S394 phosphorylation.\|We postulated that PPP2CA would negatively regulate phospho dependent HDAC2 activity.	SIGNOR-277049
P45984	P14778	phosphorylation	up-regulates activity	0.281	Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab	SIGNOR-249514
Q00653	P62877	ubiquitination	up-regulates	0.281	Mechanism of processing of the nf-kappa b2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of nedd8-modification on the scf(beta-trcp) ubiquitin ligase.	SIGNOR-120342
P05231	P11831	null	up-regulates	0.281	Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.	SIGNOR-255966
Q99618	O60729	dephosphorylation	up-regulates	0.281	The phosphatase cdc14b translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase apc/ccdh1	SIGNOR-179664
Q9UKX5	P14921	null	up-regulates quantity by expression	0.281	We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.	SIGNOR-253352
P54132	Q86YT6	ubiquitination	down-regulates quantity by destabilization	0.281	BLM is Ubiquitinated by E3 Ligase MIB1.\|Moreover, MIB1 mediated BLM degradation in G1 phase appears to be important for DNA double-strand break repair.	SIGNOR-278548
Q9Y4K3	Q15654	binding	up-regulates activity	0.28	Our results revealed that TRIP6 could enhance TRAF6 oligomerization and TRAF6 autoubiquitination through its interaction	SIGNOR-280455
P17480	Q8IWS0	binding	down-regulates	0.28	We demonstrate that phf6 is a nucleolus, ribosomal rna promoter-associated protein. Phf6 directly interacts with upstream binding factor (ubf) through its phd1 domain and suppresses ribosomal rna (rrna) transcription by affecting the protein level of ubf	SIGNOR-200133
P08567	P17252	phosphorylation	up-regulates	0.28	To determine the role of pkc-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in cos cells. Phosphorylation was found to occur almost exclusively on ser-113 and ser-117. Replacing all these sites with glycine decreased phosphorylation by > 90% and reduced pleckstrin's ability to inhibit phosphoinositide hydrolysis by as much as 80%.	SIGNOR-40048
P09471	P35346	binding	up-regulates activity	0.28	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-256969
Q9BYG3	P06493	phosphorylation	up-regulates activity	0.28	The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.	SIGNOR-262696
Q14289	P08581	phosphorylation	up-regulates activity	0.28	In this study, using a protein array approach, we found that c-Met phosphorylates FAK and Pyk2 in medulloblastoma cells.\|Our study shows for the first time that c-Met activates FAK and Pyk2 and that FAK and Pyk2 mediate the effects of c-Met in medulloblastoma.	SIGNOR-280040
Q99933	Q8NI51	transcriptional regulation	up-regulates quantity by expression	0.28	DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation	SIGNOR-254107
P51170	P27361	phosphorylation	down-regulates quantity by destabilization	0.28	Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.	SIGNOR-249449
O00763	Q9NPA3	binding	up-regulates activity	0.28	Recently, we reported the discovery that MIG12, a 183 amino acid protein, binds to ACC1 and ACC2, which induces polymerization and subsequently increases the enzymatic activity of the protein	SIGNOR-267112
P08754	P28335	binding	up-regulates activity	0.28	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-256877
P19883	Q9UJU2	transcriptional regulation	up-regulates quantity by expression	0.28	We further demonstrate that Fst is a direct target of the WNT/β-catenin pathway. Activation and inactivation of β-catenin induced and inhibited Fst expression, respectively, in both C2C12 cells and mouse embryos. Specific TCF/LEF1 binding sites within the promoter and intron 1 region of the Fst gene were required for RSPO2 and WNT/β-catenin-induced Fst expression.	SIGNOR-251722
P42772	Q9HCX3	transcriptional regulation	down-regulates quantity by repression	0.28	Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.	SIGNOR-266099
P63000	P36897	null	up-regulates activity	0.28	Thus, TGF-_1 rapidly stimulates activity of both RhoA and Rac1 and this activation requires ALK5/T_RI kinase activity.	SIGNOR-227496
Q9NWB1	P51608	transcriptional regulation	down-regulates quantity by repression	0.28	MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.	SIGNOR-264681
Q9H4B6	O00506	phosphorylation	down-regulates activity	0.28	STK25 inhibits the ability of SAV1 to counteract STRIPAK.\|Using this antibody, we confirmed that SAV1 WT was indeed phosphorylated by STK25 at T26 in human cells (XREF_FIG).	SIGNOR-278369
O60341	Q99814	transcriptional regulation	down-regulates quantity by repression	0.28	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271588
Q12888	Q16539	phosphorylation	down-regulates activity	0.28	Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.\|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks \|phosphorylation of T1609 is likely to be mediated by p38 MAPK	SIGNOR-264446
P09471	P43115	binding	up-regulates activity	0.28	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-256995
O95551	P36896	phosphorylation	up-regulates activity	0.28	ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.	SIGNOR-262612
Q14814	P11802	binding	down-regulates	0.28	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.	SIGNOR-176524
P17676	Q8N2I9	binding	down-regulates quantity by destabilization	0.28	The COP1-interacting protein STK40 (Durzynska et al., 2017), which was detected in c/EBPβ complexes from BMDMs (Figure 1B), also appeared to contribute to the suppression of c/EBPβ in microglia. Specifically, deletion of the STK40 pseudokinase increased the amount of c/EBPβ protein without increasing the amount of Cebpb mRNA	SIGNOR-261925
Q99683	P11309	phosphorylation	down-regulates	0.28	Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation	SIGNOR-187905
P21580	Q96J02	binding	up-regulates activity	0.28	Here we demonstrate that the regulatory molecule tax1bp1 recruited the e3 ligase itch to a20 via two 'ppxy' motifs. Itch was essential for the termination of tumor necrosis factor receptor signaling by controlling a20-mediated recruitment and inactivation of rip1. (abstract)	SIGNOR-160621
P37231	P03372	transcriptional regulation	down-regulates quantity by repression	0.28	Our data show for the first time that eralpha binds to ppar response element and represses its transactivation	SIGNOR-140233
P60709	O95631	post transcriptional regulation	up-regulates quantity	0.28	Netrin-1 induces β-actin translation driven by its 3’UTR.	SIGNOR-268161
Q16637	Q93008	deubiquitination	up-regulates quantity by stabilization	0.28	Ubiquitin-specific Protease 9x Deubiquitinates and Stabilizes the Spinal Muscular Atrophy Protein-Survival Motor Neuron	SIGNOR-253113
P31749	Q9P0U3	desumoylation	down-regulates quantity by destabilization	0.28	Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity.	SIGNOR-252736
Q9BXW4	Q96A56	binding	up-regulates	0.28	These data indicate that cell death observed after tp53inp1-lc3 interaction depends on both autophagy and caspase activity. We conclude that tp53inp1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy.	SIGNOR-196676
P35354	Q12968	transcriptional regulation	up-regulates quantity by expression	0.279	NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration	SIGNOR-264028
P35499	Q96PU5	ubiquitination	down-regulates quantity by destabilization	0.279	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253460
Q13308	P12931	phosphorylation	up-regulates activity	0.279	Because Ptk7 lacks intrinsic kinase activitiy, we suggest a positive feedback model in which pre-existing active Src phosphorylates PTK7 enabling it to interact with the SH2 domain of additional Src molecules to result in further activation.	SIGNOR-279123
Q93008	P06493	phosphorylation	up-regulates activity	0.279	Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.	SIGNOR-275608
Q13422	P62136	dephosphorylation	up-regulates	0.279	Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway	SIGNOR-174859
Q14164	P35813	dephosphorylation	down-regulates activity	0.279	PPM1A directly dephosphorylates both MAVS and TBK1 and IKKepsilon.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.	SIGNOR-277072
Q9UQD0	Q9UQM7	phosphorylation	up-regulates activity	0.279	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275785
P62745	P52306	binding	up-regulates	0.279	Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob	SIGNOR-171615
P14618	P24666	dephosphorylation	up-regulates activity	0.279	Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.\|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.\|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm	SIGNOR-277134
P17987	P52747	transcriptional regulation	up-regulates quantity by expression	0.279	The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.	SIGNOR-266220
P18669	Q8IXJ6	deacetylation	up-regulates activity	0.279	Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.	SIGNOR-266517
Q00987	Q01130	transcriptional regulation	up-regulates quantity by expression	0.279	Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2.	SIGNOR-260076
P04839	P15976	transcriptional regulation	up-regulates quantity	0.279	These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils.	SIGNOR-259947
Q13043	Q9UL54	phosphorylation	up-regulates	0.279	In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2	SIGNOR-201330
P04406	Q13043	phosphorylation	up-regulates activity	0.279	Interestingly, GAPDH is phosphorylated by Mst1 to a comparable extent as its known substrate MBP, suggesting that GAPDH is a good substrate of Mst1 at least in vitro.\|Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells.	SIGNOR-279295
P08754	P29275	binding	up-regulates activity	0.279	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-257152
Q99607	O15550	transcriptional regulation	down-regulates quantity by repression	0.279	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260031
P00519	P33981	phosphorylation	down-regulates	0.279	Ttk phosphorylation of thr735 was associated with partial inhibition of nuclear targeting of c-abl.	SIGNOR-181064
Q14353	P51608	post transcriptional regulation	up-regulates quantity by expression	0.279	MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.	SIGNOR-264678
P38405	P28336	binding	up-regulates activity	0.278	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-256918

Q96A26

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.282

In this work, we report the identification of an HIF-1 alpha-responsive proapoptotic molecule, HGTD-P. Its expression was directly regulated by HIF-1 alpha through a hypoxia-responsive element on the HGTD-P promoter region.

SIGNOR-260292

P08754

P21728

0

binding

up-regulates activity

0.282

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-257181

P20336

Q9UJD0

0

relocalization

up-regulates activity

0.282

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264379

Q03113

P28336

0

binding

up-regulates

0.282

These neuropeptides, including gastrin-releasing peptide, neuromedin b, neurotensin, gastrin, cholecystokinin and arginine vasopressin bind seven transmembrane-spanning receptors that couple to heterotrimeric g proteins. Studies with human small cell lung cancer (sclc) cells support a requirement for balanced signaling through g(q) and g(12/13) proteins leading to intracellular ca2+ mobilization, pkc activation and regulation of the erk and jnk map kinase pathways.

SIGNOR-107025

Q8TDR2

Q05D32

0

dephosphorylation

up-regulates quantity by stabilization

0.282

We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).

SIGNOR-273775

Q07954

P00734

0

binding

up-regulates

0.282

In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp

SIGNOR-41090

Q9H4A3

Q9BYP7

0

phosphorylation

up-regulates activity

0.282

We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro.

SIGNOR-260789

P08754

P21918

0

binding

up-regulates activity

0.282

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-257156

Q13562

O00712

0

transcriptional regulation

up-regulates quantity

0.282

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268897

P35354

Q14934

0

transcriptional regulation

up-regulates quantity by expression

0.282

NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration

SIGNOR-264027

O14867

Q8NEZ5

0

ubiquitination

down-regulates quantity

0.282

Here, we show that heme triggers the degradation of Bach1, a pro-metastatic transcription factor, by promoting its interaction with the ubiquitin ligase Fbxo22.

SIGNOR-259331

P62714

Q01105

0

binding

down-regulates

0.282

Here we report that both the amino terminal fragment (i(2ntf);aa 1-175) and the carboxy terminal fragment (i(2ctf);aa 176-277) of i(2)(pp2a) inhibit pp2a by binding to its catalytic subunit pp2ac

SIGNOR-175722

Q12959

P24941

0

phosphorylation

up-regulates

0.282

We also show that dlg1 is phosphorylated by both cdk1 and cdk2 on ser158 and ser442. These phosphorylated sites together affect the nuclear localisation of the protein, and implicate the role of phosphorylation on ser158 and ser442 in its putative nuclear functions as a tumour suppressor. phosphorylation on ser158 and ser442 enhances nuclear expression of dlg1

SIGNOR-182765

Q05516

P24941

0

phosphorylation

down-regulates

0.282

Here we show that the main cyclin-dependent kinase involved at the g(1) to s transition (cdk2) phosphorylates plzf at two consensus sites found within pest domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of plzf, which impairs plzf transcriptional repression ability and antagonizes its growth inhibitory effects.

SIGNOR-160630

Q6IQ49

Q9NZJ0

0

binding

down-regulates quantity by destabilization

0.282

Here, we identify human SDE2 as a new genome surveillance factor regulated by PCNA interaction. The cleaved SDE2 products need to be degraded by the CRL4CDT2 ubiquitin E3 ligase in a cell cycle- and DNA damage-dependent manner, and failure to degrade SDE2 impairs S phase progression and cellular survival.

SIGNOR-272807

Q7L5N1

P31749

0

phosphorylation

up-regulates

0.282

Mechanistic studies show that akt causes csn6 phosphorylation at ser 60, which, in turn, reduces ubiquitin-mediated protein degradation of csn6.

SIGNOR-252532

P29401

P31749

0

phosphorylation

up-regulates activity

0.282

Akt phosphorylates TKT on Thr382, markedly enhancing enzyme activity and increasing carbon flow through the nonoxidative PPP, thereby increasing purine synthesis.

SIGNOR-265101

Q9UJD0

O15034

0

binding

down-regulates activity

0.282

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264371

P01106

P48729

0

phosphorylation

down-regulates quantity by destabilization

0.282

Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation.

SIGNOR-276387

P35367

Q9UQM7

0

phosphorylation

down-regulates

0.282

As we have shown previously, human h1r can be phosphorylated in vitro by several kinases includingpka, pkc, pkg, and camk ii in summary, these data suggest that thr140, thr142, ser396, ser398, and thr478 can be phosphorylated by the kinases described above (table 2).

SIGNOR-124348

Q8TB45

P27361

0

phosphorylation

up-regulates quantity by stabilization

0.282

Screening the DEPTOR interactome identified that the association of USP-7 deubiquitinase with DEPTOR was dependent upon S235 phosphorylation. Inhibition of USP-7 activity resulted in DEPTOR polyubiquitination and degradation. A scansite search suggested that ERK1 may be responsible for S235 phosphorylation, which was confirmed through the use of inhibitors, ERK1 knockdown, and an in vitro kinase assay.

SIGNOR-277587

Q9P212

P50148

0

binding

up-regulates

0.282

Typically galfas stimulates adenylyl cyclase and increases levels of cyclic amp (camp), whereas galfai inhibits adenylyl cyclase and lowers camp levels, and members of the galfaq family bind to and activate phospholipase c (plc), which cleaves phosphatidylinositol bisphosphate (pip2) into diacylglycerol and inositol triphosphate (ip3). The gbeta subunits and ggamma subunits function as a dimer to activate manymolecules, including phospholipases, ion channels and lipid kinases.

SIGNOR-152609

O75874

P36956

0

transcriptional regulation

up-regulates quantity by expression

0.282

IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells|evidence that IDH1 may regulate lipogenesis in hepatic cells

SIGNOR-253132

Q13263

O14757

0

phosphorylation

up-regulates activity

0.282

These data suggested that KAP1 Ser473 phosphorylation by Chk1 and Chk2 does not take place predominantly at sites of DNA damage, and are consistent with previous work indicating that, following their DNA-damage-localized phosphorylation and activation by ATR and ATM, Chk1 and Chk2 dissociate from chromatin to phosphorylate their substrates , ].|These results therefore indicated that both Chk1 and Chk2 can target KAP1 Ser473, and are in agreement with IR triggering both the ATM and Chk2 and ATR and Chk1 pathways .

SIGNOR-280226

P63096

P34969

0

binding

up-regulates activity

0.281

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-257055

P46527

Q06124

0

dephosphorylation

up-regulates activity

0.281

Moreover, SHP-2 was strongly activated on G-CSF stimulation and specifically dephosphorylated p27(Kip1) in vitro.|Most importantly, we could illustrate that SHP-2 modulates p27 (Kip1) stability and contributes to p27 (Kip1)-mediated cell cycle progression.

SIGNOR-277168

P19793

P24468

0

binding

up-regulates

0.281

Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site

SIGNOR-79446

O94953

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.281

KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter.

SIGNOR-263729

Q9HAW9

P20823

0

transcriptional regulation

up-regulates quantity by expression

0.281

Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.

SIGNOR-253972

O60674

P54764

0

phosphorylation

up-regulates activity

0.281

EphA4 phosphorylates JAK2.|These findings suggest that EphA4 activates not only growth hormone receptor, as shown above, but also JAK2 by direct phosphorylation.

SIGNOR-279040

O43474

P15941

0

binding

up-regulates activity

0.281

Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. Our results show that MUC1-C binds constitutively to KLF4, occupies PE21 with KLF4, and enhances the KLF4 occupancy of PE21.

SIGNOR-270543

Q9Y4X5

Q13619

0

binding

up-regulates activity

0.281

Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin.

SIGNOR-268847

Q9UQD0

Q13557

0

phosphorylation

up-regulates activity

0.281

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275792

P05091

Q02156

0

phosphorylation

up-regulates activity

0.281

Post-translational enhancement of ALDH2 activity can be achieved by serine/threonine phosphorylation by epsilon protein kinase C (epsilonPKC). |e identified S279 as a critical εPKC phosphorylation site in the activation of ALDH2. The critical catalytic site, cysteine 302 (C302) of ALDH2 is susceptible to adduct formation by reactive aldehyde, 4HNE, which readily renders the enzyme inactive. We show that phosphomimetic mutations of T185E, S279E and T412E confer protection of ALDH2 against 4HNE-induced inactivation, indicating that phosphorylation on these three sites by εPKC likely also protects the enzyme against reactive aldehydes.

SIGNOR-271864

P37173

P12931

0

phosphorylation

up-regulates

0.281

Tbetarii can also be phosphorylated by src, a non-rtk, on y284, which can serve as a docking site for the recruitment of grb2 and shc, thereby bridging tbetarii to mapk activation.

SIGNOR-182963

P46531

P41240

0

binding

up-regulates

0.281

We found that the notch-1-furin interaction is regulated by the non-receptor tyrosine kinase, c-src. c-src and notch-1 are physically associated, and this association is responsible for notch-1 processing and activation

SIGNOR-196824

Q96PG8

P04626

0

phosphorylation

down-regulates activity

0.281

These results show for the first time that PUMA can be phosphorylated at tyrosine residues directly by HER2.|Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein.

SIGNOR-278224

Q03164

Q13535

0

phosphorylation

up-regulates

0.281

Mll is phosphorylated at serine 516 by atr in response to genotoxic stress in the s phase, which disrupts its interaction with, and hence its degradation by, the scf(skp2) e3 ligase, leading to its accumulation.

SIGNOR-25151

Q6UUV9

Q96EB6

0

deacetylation

up-regulates

0.281

Sirt1 deacetylates and activates torc1

SIGNOR-191568

Q9BXH1

P04626

0

phosphorylation

down-regulates quantity by destabilization

0.281

HER2 phosphorylates and destabilizes pro-apoptotic PUMA. Using an intracellular assay, we found PUMA to be phosphorylated in breast cancer cells with activated HER2. Via cell-free HER2 kinase assay, we observed that PUMA was directly phosphorylated by HER2. Activation of HER2 decreased PUMA protein half-life.

SIGNOR-276474

O75676

P68400

0

phosphorylation

up-regulates activity

0.281

Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.

SIGNOR-276268

P55265

P31749

0

phosphorylation

down-regulates activity

0.281

AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively

SIGNOR-276193

P08754

P34969

0

binding

up-regulates activity

0.281

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-257168

O00443

P06493

0

phosphorylation

down-regulates activity

0.281

Mitotic and stress-induced phosphorylation of HsPI3K-C2alpha targets the protein for degradation. Stress-dependent and mitotic phosphorylation of hspik3-c2alpha occurs on the same serine residue (ser259) within a recognition motif for proline-directed kinases. Mitotic phosphorylation of hspik3-c2alpha can be attributed to cdc2 activity, and stress-induced phosphorylation of hspik3-c2alpha is mediated by jnk/sapk

SIGNOR-100903

P49279

P12931

0

phosphorylation

up-regulates activity

0.281

In this study, we provide evidence that SLC11A1 is phosphorylated by Src family kinases at tyrosine 15 present in a conserved tyrosine-based motif (YGSI) among all species.

SIGNOR-278500

Q92769

P67775

0

dephosphorylation

down-regulates activity

0.281

In contrast, in the present work, PPP2CA reduced HDAC2 S394 phosphorylation.|We postulated that PPP2CA would negatively regulate phospho dependent HDAC2 activity.

SIGNOR-277049

P45984

P14778

0

phosphorylation

up-regulates activity

0.281

Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab

SIGNOR-249514

Q00653

P62877

0

ubiquitination

up-regulates

0.281

Mechanism of processing of the nf-kappa b2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of nedd8-modification on the scf(beta-trcp) ubiquitin ligase.

SIGNOR-120342

P05231

P11831

0

null

up-regulates

0.281

Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.

SIGNOR-255966

Q99618

O60729

0

dephosphorylation

up-regulates

0.281

The phosphatase cdc14b translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase apc/ccdh1

SIGNOR-179664

Q9UKX5

P14921

0

null

up-regulates quantity by expression

0.281

We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.

SIGNOR-253352

P54132

Q86YT6

0

ubiquitination

down-regulates quantity by destabilization

0.281

BLM is Ubiquitinated by E3 Ligase MIB1.|Moreover, MIB1 mediated BLM degradation in G1 phase appears to be important for DNA double-strand break repair.

SIGNOR-278548

Q9Y4K3

Q15654

0

binding

up-regulates activity

0.28

Our results revealed that TRIP6 could enhance TRAF6 oligomerization and TRAF6 autoubiquitination through its interaction

SIGNOR-280455

P17480

Q8IWS0

0

binding

down-regulates

0.28

We demonstrate that phf6 is a nucleolus, ribosomal rna promoter-associated protein. Phf6 directly interacts with upstream binding factor (ubf) through its phd1 domain and suppresses ribosomal rna (rrna) transcription by affecting the protein level of ubf

SIGNOR-200133

P08567

P17252

0

phosphorylation

up-regulates

0.28

To determine the role of pkc-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in cos cells. Phosphorylation was found to occur almost exclusively on ser-113 and ser-117. Replacing all these sites with glycine decreased phosphorylation by > 90% and reduced pleckstrin's ability to inhibit phosphoinositide hydrolysis by as much as 80%.

SIGNOR-40048

P09471

P35346

0

binding

up-regulates activity

0.28

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-256969

Q9BYG3

P06493

0

phosphorylation

up-regulates activity

0.28

The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.

SIGNOR-262696

Q14289

P08581

0

phosphorylation

up-regulates activity

0.28

In this study, using a protein array approach, we found that c-Met phosphorylates FAK and Pyk2 in medulloblastoma cells.|Our study shows for the first time that c-Met activates FAK and Pyk2 and that FAK and Pyk2 mediate the effects of c-Met in medulloblastoma.

SIGNOR-280040

Q99933

Q8NI51

0

transcriptional regulation

up-regulates quantity by expression

0.28

DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation

SIGNOR-254107

P51170

P27361

0

phosphorylation

down-regulates quantity by destabilization

0.28

Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.

SIGNOR-249449

O00763

Q9NPA3

0

binding

up-regulates activity

0.28

Recently, we reported the discovery that MIG12, a 183 amino acid protein, binds to ACC1 and ACC2, which induces polymerization and subsequently increases the enzymatic activity of the protein

SIGNOR-267112

P08754

P28335

0

binding

up-regulates activity

0.28

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-256877

P19883

Q9UJU2

0

transcriptional regulation

up-regulates quantity by expression

0.28

We further demonstrate that Fst is a direct target of the WNT/β-catenin pathway. Activation and inactivation of β-catenin induced and inhibited Fst expression, respectively, in both C2C12 cells and mouse embryos. Specific TCF/LEF1 binding sites within the promoter and intron 1 region of the Fst gene were required for RSPO2 and WNT/β-catenin-induced Fst expression.

SIGNOR-251722

P42772

Q9HCX3

0

transcriptional regulation

down-regulates quantity by repression

0.28

Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.

SIGNOR-266099

P63000

P36897

0

null

up-regulates activity

0.28

Thus, TGF-_1 rapidly stimulates activity of both RhoA and Rac1 and this activation requires ALK5/T_RI kinase activity.

SIGNOR-227496

Q9NWB1

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.28

MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.

SIGNOR-264681

Q9H4B6

O00506

0

phosphorylation

down-regulates activity

0.28

STK25 inhibits the ability of SAV1 to counteract STRIPAK.|Using this antibody, we confirmed that SAV1 WT was indeed phosphorylated by STK25 at T26 in human cells (XREF_FIG).

SIGNOR-278369

O60341

Q99814

0

transcriptional regulation

down-regulates quantity by repression

0.28

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271588

Q12888

Q16539

0

phosphorylation

down-regulates activity

0.28

Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |phosphorylation of T1609 is likely to be mediated by p38 MAPK

SIGNOR-264446

P09471

P43115

0

binding

up-regulates activity

0.28

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-256995

O95551

P36896

0

phosphorylation

up-regulates activity

0.28

ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.

SIGNOR-262612

Q14814

P11802

0

binding

down-regulates

0.28

In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

SIGNOR-176524

P17676

Q8N2I9

0

binding

down-regulates quantity by destabilization

0.28

The COP1-interacting protein STK40 (Durzynska et al., 2017), which was detected in c/EBPβ complexes from BMDMs (Figure 1B), also appeared to contribute to the suppression of c/EBPβ in microglia. Specifically, deletion of the STK40 pseudokinase increased the amount of c/EBPβ protein without increasing the amount of Cebpb mRNA

SIGNOR-261925

Q99683

P11309

0

phosphorylation

down-regulates

0.28

Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation

SIGNOR-187905

P21580

Q96J02

0

binding

up-regulates activity

0.28

Here we demonstrate that the regulatory molecule tax1bp1 recruited the e3 ligase itch to a20 via two 'ppxy' motifs. Itch was essential for the termination of tumor necrosis factor receptor signaling by controlling a20-mediated recruitment and inactivation of rip1. (abstract)

SIGNOR-160621

P37231

P03372

0

transcriptional regulation

down-regulates quantity by repression

0.28

Our data show for the first time that eralpha binds to ppar response element and represses its transactivation

SIGNOR-140233

P60709

O95631

0

post transcriptional regulation

up-regulates quantity

0.28

Netrin-1 induces β-actin translation driven by its 3’UTR.

SIGNOR-268161

Q16637

Q93008

0

deubiquitination

up-regulates quantity by stabilization

0.28

Ubiquitin-specific Protease 9x Deubiquitinates and Stabilizes the Spinal Muscular Atrophy Protein-Survival Motor Neuron

SIGNOR-253113

P31749

Q9P0U3

0

desumoylation

down-regulates quantity by destabilization

0.28

Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity.

SIGNOR-252736

Q9BXW4

Q96A56

0

binding

up-regulates

0.28

These data indicate that cell death observed after tp53inp1-lc3 interaction depends on both autophagy and caspase activity. We conclude that tp53inp1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy.

SIGNOR-196676

P35354

Q12968

0

transcriptional regulation

up-regulates quantity by expression

0.279

NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration

SIGNOR-264028

P35499

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.279

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253460

Q13308

P12931

0

phosphorylation

up-regulates activity

0.279

Because Ptk7 lacks intrinsic kinase activitiy, we suggest a positive feedback model in which pre-existing active Src phosphorylates PTK7 enabling it to interact with the SH2 domain of additional Src molecules to result in further activation.

SIGNOR-279123

Q93008

P06493

0

phosphorylation

up-regulates activity

0.279

Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.

SIGNOR-275608

Q13422

P62136

0

dephosphorylation

up-regulates

0.279

Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway

SIGNOR-174859

Q14164

P35813

0

dephosphorylation

down-regulates activity

0.279

PPM1A directly dephosphorylates both MAVS and TBK1 and IKKepsilon.|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

SIGNOR-277072

Q9UQD0

Q9UQM7

0

phosphorylation

up-regulates activity

0.279

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275785

P62745

P52306

0

binding

up-regulates

0.279

Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob

SIGNOR-171615

P14618

P24666

0

dephosphorylation

up-regulates activity

0.279

Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm

SIGNOR-277134

P17987

P52747

0

transcriptional regulation

up-regulates quantity by expression

0.279

The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.

SIGNOR-266220

P18669

Q8IXJ6

0

deacetylation

up-regulates activity

0.279

Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.

SIGNOR-266517

Q00987

Q01130

0

transcriptional regulation

up-regulates quantity by expression

0.279

Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2.

SIGNOR-260076

P04839

P15976

0

transcriptional regulation

up-regulates quantity

0.279

These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils.

SIGNOR-259947

Q13043

Q9UL54

0

phosphorylation

up-regulates

0.279

In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2

SIGNOR-201330

P04406

Q13043

0

phosphorylation

up-regulates activity

0.279

Interestingly, GAPDH is phosphorylated by Mst1 to a comparable extent as its known substrate MBP, suggesting that GAPDH is a good substrate of Mst1 at least in vitro.|Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells.

SIGNOR-279295

P08754

P29275

0

binding

up-regulates activity

0.279

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-257152

Q99607

O15550

0

transcriptional regulation

down-regulates quantity by repression

0.279

Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase

SIGNOR-260031

P00519

P33981

0

phosphorylation

down-regulates

0.279

Ttk phosphorylation of thr735 was associated with partial inhibition of nuclear targeting of c-abl.

SIGNOR-181064

Q14353

P51608

0

post transcriptional regulation

up-regulates quantity by expression

0.279

MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.

SIGNOR-264678

P38405

P28336

0

binding

up-regulates activity

0.278

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-256918