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
P60484	P42685	0	phosphorylation	up-regulates quantity by stabilization	0.599	Rak phosphorylates PTEN on Tyr 336 to prevent its protein degradation. In this study, we demonstrate that the Rak tyrosine kinase physically interacts with PTEN and phosphorylates PTEN on Tyr336. Knockdown of Rak enhanced the binding of PTEN to its E3 ligase NEDD4-1 and promoted PTEN polyubiquitination, leading to PTEN protein degradation.	SIGNOR-275458
Q7Z570	O43451	1	transcriptional regulation	down-regulates quantity by repression	0.2	ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).	SIGNOR-269466
P30679	O43603	2	binding	up-regulates activity	0.288	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-257226
P17481	P62736	1	transcriptional regulation	down-regulates quantity by repression	0.2	Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively	SIGNOR-261641
Q00535	P49768	1	phosphorylation	up-regulates	0.51	Cyclin-dependent kinase-5/p35 phosphorylates presenilin 1 to regulate carboxy-terminal fragment stabilityhere we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates ps1 on threonine(354) within c-ps1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize c-ps1.	SIGNOR-89145
P27361	Q13480	1	phosphorylation	up-regulates activity	0.633	Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. \|serine and threonine phosphorylation are capable of modulating the initial signal	SIGNOR-249464
Q9Y243	P56278	2	binding	up-regulates	0.364	Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation	SIGNOR-81677
P49407	Q99835	2	binding	up-regulates	0.635	Grk2-mediated phosphorylation of vertebrate smo allows smo to bind to beta-arrestins 1 or 2	SIGNOR-132678
Q13418	Q13765	1	phosphorylation	up-regulates	0.426	Ilk phosphorylated alpha-nac on residue ser-43. Ilk-dependent phosphorylation of alpha-nac induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-nac by ilk is required for the potentiation of c-jun-mediated responses by the kinase.	SIGNOR-127694
Q96KG9	Q9BV73	1	relocalization	down-regulates activity	0.2	Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting.	SIGNOR-265497
P29474	Q00535	0	phosphorylation	down-regulates	0.371	Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels.	SIGNOR-164080
O00744	O75197	2	binding	up-regulates	0.585	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131628
P06239	P27361	2	phosphorylation	up-regulates	0.566	The sh3 domain of lck modulates t-cell receptor-dependent activation of extracellular signal-regulated kinase through activation of raf-1.	SIGNOR-159168
P36894	O15169	0	ubiquitination	down-regulates	0.331	Other proteins, such as the serine/threonine kinase fused (fu), can function in concert with the e3 ligase smurf to regulate ubiquitination and proteolysis of the bmp receptor	SIGNOR-195552
P48730	P27707	1	phosphorylation	up-regulates activity	0.339	Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.\|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.	SIGNOR-280233
Q96S44	P04637	1	phosphorylation	up-regulates	0.76	The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of prpk to cos-7 cells. Prpk was shown to bind to p53 and to phosphorylate p53 at ser-15.	SIGNOR-157471
P06241	P43403	1	phosphorylation	up-regulates activity	0.574	Subsequently, Lck and Fyn phosphorylate and activate the Syk family kinase ZAP-70 when it is recruited to the phosphorylated ITAM motifs xref .	SIGNOR-279043
Q5S007	O95295	1	phosphorylation	down-regulates	0.514	Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2	SIGNOR-202436
P56704	P34925	2	binding	up-regulates	0.763	Here, we report that ryk directly binds wnt-1 and wnt-3a via its wif domain and is required for the tcf.	SIGNOR-129580
P27361	P09917	1	phosphorylation	up-regulates activity	0.328	Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.	SIGNOR-264440
P0DP25	Q9UQD0	2	binding	down-regulates activity	0.45	Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias.	SIGNOR-266346
P06493	Q9BXS6	1	phosphorylation	down-regulates	0.431	We report here that cdk1 phosphorylates nusap at threonine 300 and 338 in early mitosis. Phosphorylation of nusap inhibits its microtubule-binding activity in vitro and in vivo.	SIGNOR-177549
Q9Y243	O43524	1	phosphorylation	down-regulates quantity by destabilization	0.708	AKT phosphorylates FOXO3a at three conserved sites (Thr32, Ser253 and Ser315), therefore creating binding sites for the 14-3-3 chaperone proteins and leading to the active export of FOXO3a to the cytoplasm where it is targeted for proteasomal degradation.	SIGNOR-249644
Q13586	Q13153	0	phosphorylation	up-regulates activity	0.354	Taken together, our data demonstrate that PAK1 interacts with STIM1 and phosphorylates specific STIM1 cytosolic domains.	SIGNOR-279244
P84022	Q09472	0	acetylation	up-regulates quantity by stabilization	0.736	Smad proteins are crucial for the intracellular signaling of transforming growth factor-beta (TGF-beta). Upon their receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate the transcription of a select set of target genes. Here, we show that the co-activator p300/CBP bound and acetylated Smad3 as well as Smad2 in vivo, and that the acetylation was stimulated by TGF-beta.A major acetylation site of Smad3 by p300/CBP is Lys-378 in the MH2 domain (Smad3C) known to be critical for the regulation of transcriptional activity.	SIGNOR-260431
P17948	Q04760	1	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276190
Q93008	P42566	1	deubiquitination	down-regulates activity	0.271	We identify the endocytic protein Eps15 as one of the critical substrates of USP9X	SIGNOR-245052
Q96NG3	Q96M91	2	binding	up-regulates activity	0.2	CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).	SIGNOR-265543
Q7Z6J0	O14964	1	ubiquitination	down-regulates quantity	0.246	Importantly, ubiquitination of Hrs mediated by POSH caused the reduction of Hrs level via the ubiquitin-proteasome pathway.	SIGNOR-278575
Q86Y13	P0C0S8	1	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271749
P51668	Q6PJ69	1	ubiquitination	up-regulates activity	0.298	Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria.	SIGNOR-272175
P12931	Q96J92	1	phosphorylation	down-regulates activity	0.2	Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.	SIGNOR-276897
P61328	Q9UQD0	2	binding	down-regulates activity	0.317	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253412
Q9GZV5	Q15361	2	binding	up-regulates	0.313	Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.	SIGNOR-182296
Q96E17	Q9UQ26	0	relocalization	up-regulates activity	0.558	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-264378
Q13480	P62993	2	binding	up-regulates	0.873	The gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of gab1 occurs indirectly, via the adapter protein grb2	SIGNOR-235917
Q9H211	O75496	2	binding	down-regulates activity	0.972	Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading.	SIGNOR-261680
O14763	Q13158	2	binding	up-regulates	0.849	Fadd binds to ligated trailr1 or trail-r2	SIGNOR-98565
Q05655	P63104	1	phosphorylation	down-regulates activity	0.446	We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. \| Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1.	SIGNOR-249222
P61077	P29372	2	binding	up-regulates activity	0.2	Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. We observed that PP2Ac was ubiquitinated in the presence of UbcH5a-c and UbcH6, similar to results obtained with MID1-catalyzed ubiquitination of alpha4 (Figure 2E)	SIGNOR-271928
P14672	P04637	0	transcriptional regulation	down-regulates quantity by repression	0.335	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267465
P17612	P04626	1	phosphorylation	up-regulates	0.405	Pka directly phosphorylated erbb2 on thr-686, a highly conserved intracellular regulatory site that was required for the pka-mediated synergistic enhancement of neuregulin-induced erbb2-erbb3 activation and proliferation in scs.	SIGNOR-181191
Q13177	P60953	2	binding	up-regulates activity	0.885	A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.	SIGNOR-248253
P06239	Q9BZS1	1	phosphorylation	down-regulates	0.401	Lck phosphorylated tyr-342 of foxp3 by immunoprecipitation and in vitro kinase assay, and the replacement of tyr-342 with phenylalanine (y342f) abolished the ability to suppress mmp9 expression.	SIGNOR-203089
Q92913	Q14524	2	binding	down-regulates activity	0.41	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253415
Q9Y6W5	P00519	0	phosphorylation	up-regulates activity	0.698	Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2 deficient cells rescued with a Y150F mutant fail to regain their ability to ruffle and form microspikes, unlike cells rescued with wild-type WAVE2.\|Together, these data show that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo and that Abi-1 forms the crucial link between these two factors.	SIGNOR-279390
O14965	Q99661	1	phosphorylation	down-regulates activity	0.584	In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation.	SIGNOR-279139
Q9H0B6	Q13131	0	phosphorylation	up-regulates	0.2	Consistent with phosphorylation of both ser545 and ser582 of klc2 contributing to its 14-3-3 binding, a ser545ala mutant of klc2 could be phosphorylated in vitro by ampk on ser582	SIGNOR-174681
P51677	P13501	2	binding	up-regulates	0.768	In addition to the CCR1 receptor, RANTES activates several members of the CC subfamily of chemokine receptors including CCR3, CCR4, and CCR5	SIGNOR-254370
Q92585	Q09472	2	binding	up-regulates	0.651	Maml-1 is preassociated with other components of the transcriptional machinery, such as p300	SIGNOR-145057
P45984	P01106	1	phosphorylation	up-regulates	0.359	The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71.	SIGNOR-72108
P06239	P60484	1	phosphorylation	up-regulates	0.374	Thus, y240a and y315a are involved in the ability of mmac/pten to dephosphorylate ptdins and regulate tumor cell growth in vitro and in vivo.	SIGNOR-116499
Q8IV63	Q00535	0	phosphorylation	up-regulates activity	0.356	Vaccinia-related kinase 3 (VRK3), a member of the VRK family, is widely expressed in human tissues and increases VHR phosphatase activity through a direct binding\|Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation\|	SIGNOR-275544
Q13363	P12830	1	transcriptional regulation	down-regulates quantity by repression	0.6	Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells.	SIGNOR-259197
P19484	Q8IVH8	0	phosphorylation	down-regulates activity	0.25	However, although our results indicate that MAP4K3 initiates TFEB repression, MAP4K3 also promotes robust mTORC1 activation upon amino acid stimulation - ; hence, MAP4K3 and mTORC1 must ultimately work together to achieve robust suppression of autophagy.\|Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration.	SIGNOR-278282
P31749	P54253	1	phosphorylation	up-regulates quantity by stabilization	0.411	Interaction of Ataxin-1 and 14-3-3 Requires Akt Phosphorylation at S776. 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation.	SIGNOR-252561
Q9Y653	P61586	2	binding	up-regulates activity	0.2	Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); \| We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation.	SIGNOR-253981
O00533	Q01484	1	relocalization	up-regulates quantity	0.409	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266722
Q9UL54	Q13043	1	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
P30530	P04626	1	phosphorylation	down-regulates activity	0.316	Blockade of Axl function abrogated phosphorylation of ERBB2 (Her-2 and neu) at the Tyr877 residue, indicative of receptor crosstalk.\|We have demonstrated that either pharmacological or genetic inhibition of Axl function abrogates phosphorylation of ERBB2 at the critical Tyr877 residue and sensitizes OE33 cells to lapatinib in vitro.	SIGNOR-280193
Q13363	C9JLW8	2	binding	down-regulates activity	0.2	CtBP is recruited to promoter elements of target genes by interacting with the DNA-binding transcriptional repressor ZEB1. We found that MCRIP1 binds to CtBP, thereby competitively inhibiting CtBP-ZEB1 interaction. When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.	SIGNOR-264776
P04150	O15055	1	transcriptional regulation	up-regulates quantity by expression	0.5	GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription	SIGNOR-268049
Q9BYX4	Q96EQ8	0	polyubiquitination	down-regulates quantity by destabilization	0.657	Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.	SIGNOR-271646
P00519	Q70E73	1	phosphorylation	up-regulates activity	0.284	Here we show that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. This analysis revealed that, in vitro, four Lpd peptides harboring tyrosines (Y426, Y456, Y513, Y1226) are highly phosphorylated, and eight additional peptides are phosphorylated to a lesser extent (Figure 1C).	SIGNOR-262606
P49674	O15055	1	phosphorylation	down-regulates quantity by destabilization	0.902	Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2	SIGNOR-277419
P04275	P02679	2	binding	down-regulates activity	0.499	Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a).	SIGNOR-251968
O15169	Q5JTC6	0	relocalization	up-regulates activity	0.789	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171886
P08754	P41145	2	binding	up-regulates activity	0.459	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-256853
Q96S59	P08581	2	binding	up-regulates	0.557	Our data suggest that ranbpm, functioning as an adaptor protein for the met tyrosine kinase domain, can augment the hgf-met signaling pathway.	SIGNOR-91028
P12931	A1X283	1	phosphorylation	up-regulates activity	0.521	C-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells\|Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.	SIGNOR-264705
P16591	Q05397	1	phosphorylation	up-regulates activity	0.251	The Fer mediated phosphorylation of specific tyrosine residues of FAK was abolished by cotransfection of shRNA against Fer (i.e., shFer), but not by control shRNA, indicating that the phosphorylation of Tyr577, 861, or 925 of FAK in suspended cells was indeed caused by Fer.	SIGNOR-279409
Q14680	Q99683	1	phosphorylation	up-regulates activity	0.271	MELK, as an upstream kinase of ASK1, phosphorylates threonine 838 in an activation loop of human ASK1, thereby stimulating ASK1 kinase activity.	SIGNOR-280039
Q9NYV4	P24928	1	phosphorylation	up-regulates activity	0.784	Cyck/cdk12 can activate transcription and phosphorylate ser2 in the ctd of rnapii / phosphorylation of serine at position 2 (ser2) is thought to be responsible for productive transcriptional elongation and synthesis of full-length mature mrna	SIGNOR-176805
P23769	P37231	1	null	down-regulates activity	0.369	GATA2 interacts directly with PPARG and C/EBP a , which may deplete PPARG involved in the promotion of adipogenesis	SIGNOR-132949
P78352	Q13224	1	relocalization	up-regulates activity	0.823	The PDZ domains of PSD-95 and related proteins interact with the COOH-terminal sequences of K+channels and NMDA2 receptors (3). By these interactions, PSD-95 may mediate the clustering of K+ channels and NMDA receptors at synapses.	SIGNOR-264195
P62136	Q9GZV5	1	dephosphorylation	up-regulates activity	0.542	PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting the binding to the SCF E3 ubiquitin ligase.	SIGNOR-277116
P29466	Q9NRA0	2	binding	up-regulates activity	0.248	Our data so far indicated colocalization of SphK2 with caspase-1 at the plasma membrane after induction of apoptosis.These observations supported caspase-1–dependent cleavage of SphK2 at its N-terminus as a prerequisite for its release.	SIGNOR-268831
P15336	Q9H4B4	0	phosphorylation	up-regulates	0.2	Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.	SIGNOR-163274
Q13882	Q05397	1	phosphorylation	up-regulates activity	0.264	B. PTK6 phosphorylates FAK at tyrosine residue 861.\|Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis, which can be rescued by exogenous expression of FAK.	SIGNOR-278428
P63096	O43603	2	binding	up-regulates activity	0.45	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-256741
P29475	Q92769	1	s-nitrosylation	down-regulates activity	0.265	we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation	SIGNOR-236919
O76064	P61088	2	binding	up-regulates	0.75	The rnf8 ring domain signals ubc13 to sites of damage, which is sufficient for dna damage signal transduction.	SIGNOR-179823
Q5T5U3	P61586	1	gtpase-activating protein	down-regulates activity	0.628	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260475
P04626	O95243	1	phosphorylation	up-regulates activity	0.2	Importantly, we found that overexpression of HER2 alone is sufficient to induce MED1 phosphorylation at Thr (1032), a key site that is known to be critical for its functions, whereas blockage of HER2 or its downstream MAP kinase diminishes its phosphor ylation levels in these cells.	SIGNOR-279408
O75688	O43318	1	dephosphorylation	down-regulates activity	0.551	In vitro, PP2Cbeta-1 dephosphorylated and inactivated TAK1.	SIGNOR-277154
O00329	Q15303	2	binding	up-regulates	0.395	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146885
P10070	Q9Y297	0	ubiquitination	down-regulates quantity by destabilization	0.651	The phosphorylated gli2 protein interacts with beta-trcp, and is ubiquitinated and degraded by the proteasome	SIGNOR-146109
P53350	P01106	1	phosphorylation	up-regulates activity	0.533	Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency	SIGNOR-243522
P29374	P24941	0	phosphorylation	down-regulates	0.426	In the present study we identified rbp1 as a novel cdk substrate. Rbp1 is phosphorylated by cdk2 on serines 864 and 1007, which are n- and c-terminal to the lxcxe motif, respectively. Cdk2-mediated phosphorylation of rbp1 or prb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation	SIGNOR-170455
P07203	P00519	0	phosphorylation	up-regulates activity	0.459	GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress.	SIGNOR-104324
P60484	P06213	0	phosphorylation	down-regulates activity	0.442	Our results show that the kinase region of IRβ subunit physically binds to PTEN and phosphorylates on Y27 and Y174. In the current study, we discovered that IR also downregulates PTEN through tyrosine phosphorylation and suggest that Y27 and 174 are the two key tyrosines.	SIGNOR-276470
P06730	P42345	0	phosphorylation	down-regulates activity	0.801	Mechanistic target of rapamycin complex 1 (mTORC1) phosphorylates and inhibits eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1).	SIGNOR-278963
Q9HAZ1	P00519	1	phosphorylation	down-regulates	0.272	Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3	SIGNOR-181052
P36873	Q00987	1	dephosphorylation	up-regulates quantity by stabilization	0.2	Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.	SIGNOR-248504
Q70YC5	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.29	Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability\| Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy	SIGNOR-272476
P50613	P06493	1	phosphorylation	up-regulates	0.581	The mo15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (cdks) through phosphorylation of thr161 and its homologues	SIGNOR-38307
P03952	P00748	2	cleavage	up-regulates activity	0.606	FXIIa converts PK to the active protease PKa, which reciprocally activates more FXII\|In addition, PKa can initiate a further proteolysis of FXIIa into a ~30 kDa light chain fragment, termed β-FXIIa. The cleavage takes place at the peptide bond Arg353–Val354 and consequently, the active site released from the heavy chain and thus from surfaces.	SIGNOR-263520
P01116	O00329	2	binding	up-regulates	0.633	Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k	SIGNOR-175210
P54259	P53779	0	phosphorylation	down-regulates activity	0.2	Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,	SIGNOR-102394
Q9Y4K3	Q9NQC7	0	deubiquitination	down-regulates	0.789	The nf-kappab activation by cyld is mediated, at least in part, by the deubiquitination and inactivation of tnfr-associated factor 2 (traf2) and, to a lesser extent, traf6.	SIGNOR-117856

P60484

P42685

0

phosphorylation

up-regulates quantity by stabilization

0.599

Rak phosphorylates PTEN on Tyr 336 to prevent its protein degradation. In this study, we demonstrate that the Rak tyrosine kinase physically interacts with PTEN and phosphorylates PTEN on Tyr336. Knockdown of Rak enhanced the binding of PTEN to its E3 ligase NEDD4-1 and promoted PTEN polyubiquitination, leading to PTEN protein degradation.

SIGNOR-275458

Q7Z570

O43451

1

transcriptional regulation

down-regulates quantity by repression

0.2

ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).

SIGNOR-269466

P30679

O43603

2

binding

up-regulates activity

0.288

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-257226

P17481

P62736

1

transcriptional regulation

down-regulates quantity by repression

0.2

Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively

SIGNOR-261641

Q00535

P49768

1

phosphorylation

up-regulates

0.51

Cyclin-dependent kinase-5/p35 phosphorylates presenilin 1 to regulate carboxy-terminal fragment stabilityhere we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates ps1 on threonine(354) within c-ps1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize c-ps1.

SIGNOR-89145

P27361

Q13480

1

phosphorylation

up-regulates activity

0.633

Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal

SIGNOR-249464

Q9Y243

P56278

2

binding

up-regulates

0.364

Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation

SIGNOR-81677

P49407

Q99835

2

binding

up-regulates

0.635

Grk2-mediated phosphorylation of vertebrate smo allows smo to bind to beta-arrestins 1 or 2

SIGNOR-132678

Q13418

Q13765

1

phosphorylation

up-regulates

0.426

Ilk phosphorylated alpha-nac on residue ser-43. Ilk-dependent phosphorylation of alpha-nac induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-nac by ilk is required for the potentiation of c-jun-mediated responses by the kinase.

SIGNOR-127694

Q96KG9

Q9BV73

1

relocalization

down-regulates activity

0.2

Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting.

SIGNOR-265497

P29474

Q00535

0

phosphorylation

down-regulates

0.371

Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels.

SIGNOR-164080

O00744

O75197

2

binding

up-regulates

0.585

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131628

P06239

P27361

2

phosphorylation

up-regulates

0.566

The sh3 domain of lck modulates t-cell receptor-dependent activation of extracellular signal-regulated kinase through activation of raf-1.

SIGNOR-159168

P36894

O15169

0

ubiquitination

down-regulates

0.331

Other proteins, such as the serine/threonine kinase fused (fu), can function in concert with the e3 ligase smurf to regulate ubiquitination and proteolysis of the bmp receptor

SIGNOR-195552

P48730

P27707

1

phosphorylation

up-regulates activity

0.339

Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.

SIGNOR-280233

Q96S44

P04637

1

phosphorylation

up-regulates

0.76

The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of prpk to cos-7 cells. Prpk was shown to bind to p53 and to phosphorylate p53 at ser-15.

SIGNOR-157471

P06241

P43403

1

phosphorylation

up-regulates activity

0.574

Subsequently, Lck and Fyn phosphorylate and activate the Syk family kinase ZAP-70 when it is recruited to the phosphorylated ITAM motifs xref .

SIGNOR-279043

Q5S007

O95295

1

phosphorylation

down-regulates

0.514

Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2

SIGNOR-202436

P56704

P34925

2

binding

up-regulates

0.763

Here, we report that ryk directly binds wnt-1 and wnt-3a via its wif domain and is required for the tcf.

SIGNOR-129580

P27361

P09917

1

phosphorylation

up-regulates activity

0.328

Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.

SIGNOR-264440

P0DP25

Q9UQD0

2

binding

down-regulates activity

0.45

Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias.

SIGNOR-266346

P06493

Q9BXS6

1

phosphorylation

down-regulates

0.431

We report here that cdk1 phosphorylates nusap at threonine 300 and 338 in early mitosis. Phosphorylation of nusap inhibits its microtubule-binding activity in vitro and in vivo.

SIGNOR-177549

Q9Y243

O43524

1

phosphorylation

down-regulates quantity by destabilization

0.708

AKT phosphorylates FOXO3a at three conserved sites (Thr32, Ser253 and Ser315), therefore creating binding sites for the 14-3-3 chaperone proteins and leading to the active export of FOXO3a to the cytoplasm where it is targeted for proteasomal degradation.

SIGNOR-249644

Q13586

Q13153

0

phosphorylation

up-regulates activity

0.354

Taken together, our data demonstrate that PAK1 interacts with STIM1 and phosphorylates specific STIM1 cytosolic domains.

SIGNOR-279244

P84022

Q09472

0

acetylation

up-regulates quantity by stabilization

0.736

Smad proteins are crucial for the intracellular signaling of transforming growth factor-beta (TGF-beta). Upon their receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate the transcription of a select set of target genes. Here, we show that the co-activator p300/CBP bound and acetylated Smad3 as well as Smad2 in vivo, and that the acetylation was stimulated by TGF-beta.A major acetylation site of Smad3 by p300/CBP is Lys-378 in the MH2 domain (Smad3C) known to be critical for the regulation of transcriptional activity.

SIGNOR-260431

P17948

Q04760

1

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276190

Q93008

P42566

1

deubiquitination

down-regulates activity

0.271

We identify the endocytic protein Eps15 as one of the critical substrates of USP9X

SIGNOR-245052

Q96NG3

Q96M91

2

binding

up-regulates activity

0.2

CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).

SIGNOR-265543

Q7Z6J0

O14964

1

ubiquitination

down-regulates quantity

0.246

Importantly, ubiquitination of Hrs mediated by POSH caused the reduction of Hrs level via the ubiquitin-proteasome pathway.

SIGNOR-278575

Q86Y13

P0C0S8

1

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271749

P51668

Q6PJ69

1

ubiquitination

up-regulates activity

0.298

Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria.

SIGNOR-272175

P12931

Q96J92

1

phosphorylation

down-regulates activity

0.2

Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.

SIGNOR-276897

P61328

Q9UQD0

2

binding

down-regulates activity

0.317

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253412

Q9GZV5

Q15361

2

binding

up-regulates

0.313

Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.

SIGNOR-182296

Q96E17

Q9UQ26

0

relocalization

up-regulates activity

0.558

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-264378

Q13480

P62993

2

binding

up-regulates

0.873

The gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of gab1 occurs indirectly, via the adapter protein grb2

SIGNOR-235917

Q9H211

O75496

2

binding

down-regulates activity

0.972

Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading.

SIGNOR-261680

O14763

Q13158

2

binding

up-regulates

0.849

Fadd binds to ligated trailr1 or trail-r2

SIGNOR-98565

Q05655

P63104

1

phosphorylation

down-regulates activity

0.446

We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. | Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1.

SIGNOR-249222

P61077

P29372

2

binding

up-regulates activity

0.2

Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. We observed that PP2Ac was ubiquitinated in the presence of UbcH5a-c and UbcH6, similar to results obtained with MID1-catalyzed ubiquitination of alpha4 (Figure 2E)

SIGNOR-271928

P14672

P04637

0

transcriptional regulation

down-regulates quantity by repression

0.335

P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.

SIGNOR-267465

P17612

P04626

1

phosphorylation

up-regulates

0.405

Pka directly phosphorylated erbb2 on thr-686, a highly conserved intracellular regulatory site that was required for the pka-mediated synergistic enhancement of neuregulin-induced erbb2-erbb3 activation and proliferation in scs.

SIGNOR-181191

Q13177

P60953

2

binding

up-regulates activity

0.885

A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.

SIGNOR-248253

P06239

Q9BZS1

1

phosphorylation

down-regulates

0.401

Lck phosphorylated tyr-342 of foxp3 by immunoprecipitation and in vitro kinase assay, and the replacement of tyr-342 with phenylalanine (y342f) abolished the ability to suppress mmp9 expression.

SIGNOR-203089

Q92913

Q14524

2

binding

down-regulates activity

0.41

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253415

Q9Y6W5

P00519

0

phosphorylation

up-regulates activity

0.698

Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2 deficient cells rescued with a Y150F mutant fail to regain their ability to ruffle and form microspikes, unlike cells rescued with wild-type WAVE2.|Together, these data show that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo and that Abi-1 forms the crucial link between these two factors.

SIGNOR-279390

O14965

Q99661

1

phosphorylation

down-regulates activity

0.584

In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation.

SIGNOR-279139

Q9H0B6

Q13131

0

phosphorylation

up-regulates

0.2

Consistent with phosphorylation of both ser545 and ser582 of klc2 contributing to its 14-3-3 binding, a ser545ala mutant of klc2 could be phosphorylated in vitro by ampk on ser582

SIGNOR-174681

P51677

P13501

2

binding

up-regulates

0.768

In addition to the CCR1 receptor, RANTES activates several members of the CC subfamily of chemokine receptors including CCR3, CCR4, and CCR5

SIGNOR-254370

Q92585

Q09472

2

binding

up-regulates

0.651

Maml-1 is preassociated with other components of the transcriptional machinery, such as p300

SIGNOR-145057

P45984

P01106

1

phosphorylation

up-regulates

0.359

The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71.

SIGNOR-72108

P06239

P60484

1

phosphorylation

up-regulates

0.374

Thus, y240a and y315a are involved in the ability of mmac/pten to dephosphorylate ptdins and regulate tumor cell growth in vitro and in vivo.

SIGNOR-116499

Q8IV63

Q00535

0

phosphorylation

up-regulates activity

0.356

Vaccinia-related kinase 3 (VRK3), a member of the VRK family, is widely expressed in human tissues and increases VHR phosphatase activity through a direct binding|Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation|

SIGNOR-275544

Q13363

P12830

1

transcriptional regulation

down-regulates quantity by repression

0.6

Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells.

SIGNOR-259197

P19484

Q8IVH8

0

phosphorylation

down-regulates activity

0.25

However, although our results indicate that MAP4K3 initiates TFEB repression, MAP4K3 also promotes robust mTORC1 activation upon amino acid stimulation - ; hence, MAP4K3 and mTORC1 must ultimately work together to achieve robust suppression of autophagy.|Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration.

SIGNOR-278282

P31749

P54253

1

phosphorylation

up-regulates quantity by stabilization

0.411

Interaction of Ataxin-1 and 14-3-3 Requires Akt Phosphorylation at S776. 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation.

SIGNOR-252561

Q9Y653

P61586

2

binding

up-regulates activity

0.2

Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); | We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation.

SIGNOR-253981

O00533

Q01484

1

relocalization

up-regulates quantity

0.409

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266722

Q9UL54

Q13043

1

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

P30530

P04626

1

phosphorylation

down-regulates activity

0.316

Blockade of Axl function abrogated phosphorylation of ERBB2 (Her-2 and neu) at the Tyr877 residue, indicative of receptor crosstalk.|We have demonstrated that either pharmacological or genetic inhibition of Axl function abrogates phosphorylation of ERBB2 at the critical Tyr877 residue and sensitizes OE33 cells to lapatinib in vitro.

SIGNOR-280193

Q13363

C9JLW8

2

binding

down-regulates activity

0.2

CtBP is recruited to promoter elements of target genes by interacting with the DNA-binding transcriptional repressor ZEB1. We found that MCRIP1 binds to CtBP, thereby competitively inhibiting CtBP-ZEB1 interaction. When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.

SIGNOR-264776

P04150

O15055

1

transcriptional regulation

up-regulates quantity by expression

0.5

GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription

SIGNOR-268049

Q9BYX4

Q96EQ8

0

polyubiquitination

down-regulates quantity by destabilization

0.657

Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.

SIGNOR-271646

P00519

Q70E73

1

phosphorylation

up-regulates activity

0.284

Here we show that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. This analysis revealed that, in vitro, four Lpd peptides harboring tyrosines (Y426, Y456, Y513, Y1226) are highly phosphorylated, and eight additional peptides are phosphorylated to a lesser extent (Figure 1C).

SIGNOR-262606

P49674

O15055

1

phosphorylation

down-regulates quantity by destabilization

0.902

Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2

SIGNOR-277419

P04275

P02679

2

binding

down-regulates activity

0.499

Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a).

SIGNOR-251968

O15169

Q5JTC6

0

relocalization

up-regulates activity

0.789

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171886

P08754

P41145

2

binding

up-regulates activity

0.459

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-256853

Q96S59

P08581

2

binding

up-regulates

0.557

Our data suggest that ranbpm, functioning as an adaptor protein for the met tyrosine kinase domain, can augment the hgf-met signaling pathway.

SIGNOR-91028

P12931

A1X283

1

phosphorylation

up-regulates activity

0.521

C-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells|Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.

SIGNOR-264705

P16591

Q05397

1

phosphorylation

up-regulates activity

0.251

The Fer mediated phosphorylation of specific tyrosine residues of FAK was abolished by cotransfection of shRNA against Fer (i.e., shFer), but not by control shRNA, indicating that the phosphorylation of Tyr577, 861, or 925 of FAK in suspended cells was indeed caused by Fer.

SIGNOR-279409

Q14680

Q99683

1

phosphorylation

up-regulates activity

0.271

MELK, as an upstream kinase of ASK1, phosphorylates threonine 838 in an activation loop of human ASK1, thereby stimulating ASK1 kinase activity.

SIGNOR-280039

Q9NYV4

P24928

1

phosphorylation

up-regulates activity

0.784

Cyck/cdk12 can activate transcription and phosphorylate ser2 in the ctd of rnapii / phosphorylation of serine at position 2 (ser2) is thought to be responsible for productive transcriptional elongation and synthesis of full-length mature mrna

SIGNOR-176805

P23769

P37231

1

null

down-regulates activity

0.369

GATA2 interacts directly with PPARG and C/EBP a , which may deplete PPARG involved in the promotion of adipogenesis

SIGNOR-132949

P78352

Q13224

1

relocalization

up-regulates activity

0.823

The PDZ domains of PSD-95 and related proteins interact with the COOH-terminal sequences of K+channels and NMDA2 receptors (3). By these interactions, PSD-95 may mediate the clustering of K+ channels and NMDA receptors at synapses.

SIGNOR-264195

P62136

Q9GZV5

1

dephosphorylation

up-regulates activity

0.542

PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting the binding to the SCF E3 ubiquitin ligase.

SIGNOR-277116

P29466

Q9NRA0

2

binding

up-regulates activity

0.248

Our data so far indicated colocalization of SphK2 with caspase-1 at the plasma membrane after induction of apoptosis.These observations supported caspase-1–dependent cleavage of SphK2 at its N-terminus as a prerequisite for its release.

SIGNOR-268831

P15336

Q9H4B4

0

phosphorylation

up-regulates

0.2

Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.

SIGNOR-163274

Q13882

Q05397

1

phosphorylation

up-regulates activity

0.264

B. PTK6 phosphorylates FAK at tyrosine residue 861.|Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis, which can be rescued by exogenous expression of FAK.

SIGNOR-278428

P63096

O43603

2

binding

up-regulates activity

0.45

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-256741

P29475

Q92769

1

s-nitrosylation

down-regulates activity

0.265

we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation

SIGNOR-236919

O76064

P61088

2

binding

up-regulates

0.75

The rnf8 ring domain signals ubc13 to sites of damage, which is sufficient for dna damage signal transduction.

SIGNOR-179823

Q5T5U3

P61586

1

gtpase-activating protein

down-regulates activity

0.628

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260475

P04626

O95243

1

phosphorylation

up-regulates activity

0.2

Importantly, we found that overexpression of HER2 alone is sufficient to induce MED1 phosphorylation at Thr (1032), a key site that is known to be critical for its functions, whereas blockage of HER2 or its downstream MAP kinase diminishes its phosphor ylation levels in these cells.

SIGNOR-279408

O75688

O43318

1

dephosphorylation

down-regulates activity

0.551

In vitro, PP2Cbeta-1 dephosphorylated and inactivated TAK1.

SIGNOR-277154

O00329

Q15303

2

binding

up-regulates

0.395

Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.

SIGNOR-146885

P10070

Q9Y297

0

ubiquitination

down-regulates quantity by destabilization

0.651

The phosphorylated gli2 protein interacts with beta-trcp, and is ubiquitinated and degraded by the proteasome

SIGNOR-146109

P53350

P01106

1

phosphorylation

up-regulates activity

0.533

Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency

SIGNOR-243522

P29374

P24941

0

phosphorylation

down-regulates

0.426

In the present study we identified rbp1 as a novel cdk substrate. Rbp1 is phosphorylated by cdk2 on serines 864 and 1007, which are n- and c-terminal to the lxcxe motif, respectively. Cdk2-mediated phosphorylation of rbp1 or prb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation

SIGNOR-170455

P07203

P00519

0

phosphorylation

up-regulates activity

0.459

GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress.

SIGNOR-104324

P60484

P06213

0

phosphorylation

down-regulates activity

0.442

Our results show that the kinase region of IRβ subunit physically binds to PTEN and phosphorylates on Y27 and Y174. In the current study, we discovered that IR also downregulates PTEN through tyrosine phosphorylation and suggest that Y27 and 174 are the two key tyrosines.

SIGNOR-276470

P06730

P42345

0

phosphorylation

down-regulates activity

0.801

Mechanistic target of rapamycin complex 1 (mTORC1) phosphorylates and inhibits eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1).

SIGNOR-278963

Q9HAZ1

P00519

1

phosphorylation

down-regulates

0.272

Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3

SIGNOR-181052

P36873

Q00987

1

dephosphorylation

up-regulates quantity by stabilization

0.2

Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.

SIGNOR-248504

Q70YC5

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.29

Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability| Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy

SIGNOR-272476

P50613

P06493

1

phosphorylation

up-regulates

0.581

The mo15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (cdks) through phosphorylation of thr161 and its homologues

SIGNOR-38307

P03952

P00748

2

cleavage

up-regulates activity

0.606

FXIIa converts PK to the active protease PKa, which reciprocally activates more FXII|In addition, PKa can initiate a further proteolysis of FXIIa into a ~30 kDa light chain fragment, termed β-FXIIa. The cleavage takes place at the peptide bond Arg353–Val354 and consequently, the active site released from the heavy chain and thus from surfaces.

SIGNOR-263520

P01116

O00329

2

binding

up-regulates

0.633

Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k

SIGNOR-175210

P54259

P53779

0

phosphorylation

down-regulates activity

0.2

Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,

SIGNOR-102394

Q9Y4K3

Q9NQC7

0

deubiquitination

down-regulates

0.789

The nf-kappab activation by cyld is mediated, at least in part, by the deubiquitination and inactivation of tnfr-associated factor 2 (traf2) and, to a lesser extent, traf6.

SIGNOR-117856