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
P48736	Q6ZUJ8	2	binding	up-regulates	0.244	This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.	SIGNOR-191670
O75582	Q13541	1	phosphorylation	down-regulates activity	0.671	In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E	SIGNOR-262992
P06241	P29350	1	phosphorylation	up-regulates activity	0.551	By contrast, receptor multivalent aggregation induced a Fyn-dependent SHP-1 S591 phosphorylation (Fig.\u00a0 xref ).\|Fyn simultaneously activates the PI3K-PKC\u03b1 pathway, leading to SHP-1 phosphorylation on serine 591.	SIGNOR-279716
O75581	P49674	0	phosphorylation	up-regulates	0.262	We find that ckiepsilon binds to lrp5 and lrp6 in vitro and in vivo and identify three ckiepsilon-specific phosphorylation sites in lrp6. Two of the identified phosphorylation sites, ser1420 and ser1430, influence wnt signaling in vivo,	SIGNOR-145049
Q96RG2	P13807	1	phosphorylation	down-regulates activity	0.508	Recombinant human PASK (hPASK) phosphorylates purified muscle glycogen synthase, causing robust inactivation. Furthermore, hPASK interacts directly with glycogen synthase when expressed in cultured cells and this interaction and the phosphorylation of glycogen synthase by human PASK (hPASK) are inhibited by glycogen.	SIGNOR-245866
P07900	O95433	2	binding	up-regulates activity	0.742	The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity	SIGNOR-252211
Q9C0C7	O75385	0	phosphorylation	up-regulates	0.695	When autophagy is induced, ulk1 phosphorylates ambra1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Ambra1-dlc1 dissociates from the dynein complex upon ulk1-dependent ambra1 phosphorylation.	SIGNOR-168292
Q9UJM3	O14757	0	phosphorylation	down-regulates activity	0.326	Our results suggest that Chk1 phosphorylates Mig-6 on Ser 251, resulting in the inhibition of Mig-6, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1.	SIGNOR-276411
Q13563	Q15139	0	phosphorylation	up-regulates activity	0.458	Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. Phosphorylation at this site was significantly increased in response to serum and epidermal growth factor stimulation.We confirmed previous studies showing that PC2 mediated Ca2+ release from the ER can be stimulated by ATP.Phosphorylation at Ser801 seems to be permissive for this activity without altering the subcellular localization nor homophilic and heterophilic (with PC1) interactions of wild-type PC2.	SIGNOR-259829
Q6IE81	Q8IUQ4	0	polyubiquitination	down-regulates quantity by destabilization	0.291	Siah-1 decreases Jade-1 abundance and enhances Jade-1 ubiquitination	SIGNOR-272915
P55795	Q15554	1	post transcriptional regulation	down-regulates quantity	0.332	During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.	SIGNOR-266806
Q15208	Q9UBF8	1	phosphorylation	up-regulates activity	0.267	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.	SIGNOR-263033
P12931	Q9Y446	1	phosphorylation	up-regulates activity	0.306	We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.	SIGNOR-273807
P12931	Q12879	1	phosphorylation	up-regulates activity	0.567	To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.	SIGNOR-247167
P54756	P20827	2	binding	up-regulates	0.811	Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm. ephrin-a1 interacts with all the other epha subclass receptors as well, although with different affinity	SIGNOR-56910
Q9UPZ9	Q8IZL9	0	phosphorylation	up-regulates	0.2	Recombinant cak1p phosphorylates thr-157 in the tdy motif of recombinant ick and activates its activity in vitro.	SIGNOR-138420
P12931	P42224	1	phosphorylation	up-regulates activity	0.559	The tyr701 phosphorylation of signal transducer and activator of transcription 1 (stat1) induced by interferon-gamma (ifn-gamma) and 12-o-tetradecanoylphorbol 13-acetate (tpa) was inhibited by the protein kinase c (pkc) inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin, or the src kinase inhibitor pp2. An association between c-src and stat1 was increased by ifn-gamma and tpa, indicating the direct phosphorylation of stat1 by pkc-dependent c-src activation.	SIGNOR-235696
P21730	P01031	2	binding	up-regulates activity	0.757	The chemotactic receptor for human C5a anaphylatoxin\|The human C5a receptor was cloned from U937 and HL-60 cells and identified by high affinity binding when expressed in COS-7 cells.	SIGNOR-263457
P23025	P54727	2	binding	up-regulates activity	0.769	GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo	SIGNOR-275697
Q9HAU4	P25490	1	ubiquitination	down-regulates quantity by destabilization	0.364	In addition, Smurf2 decreased the protein half-life and transcriptional activity of YY1.\|Wild type Smurf2, but not the E3 ubiquitin ligase defective mutant, increased the poly-ubiquitination of YY1.	SIGNOR-278544
O43734	Q14164	0	phosphorylation	up-regulates activity	0.416	IKKi was required for IL-17-induced phosphorylation of Act1 on Ser311, adjacent to a putative TRAF-binding motif. Substitution of the serine at position 311 with alanine impaired the IL-17-mediated Act1-TRAF2-TRAF5 interaction and gene expression. Thus, IKKi is a kinase newly identified as modulating IL-17 signaling through its effect on Act1 phosphorylation and consequent function.	SIGNOR-262883
Q96JK9	Q9UM47	2	binding	up-regulates	0.881	We report here the cloning and characterization of two new genes, maml2 and maml3, that also function as transcriptional coactivators for notch receptors.	SIGNOR-94100
Q9UKI8	Q8IW41	1	phosphorylation	up-regulates activity	0.2	We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.	SIGNOR-276747
Q9UK05	P37023	2	binding	up-regulates	0.907	Finally, we demonstrate that bmp9 and bmp10 potently inhibit endothelial cell migration and growth, and stimulate endothelial expression of a panel of genes that was previously reported to be activated by the constitutively active form of alk1. Taken together, our results suggest that bmp9 and bmp10 are two specific alk1 ligands that may physiologically trigger the effects of alk1 on angiogenesis.	SIGNOR-150260
Q14765	O43504	2	binding	up-regulates activity	0.327	It suggests that HBXIP is able to activate S100A4 promoter via interacting with STAT4 in breast cancer cells, leading to the up-regulation of S100A4. here we first report that the transcription factor STAT4 plays a role in regulating S100A4 mediated by HBXIP in breast cancer.	SIGNOR-255247
Q14106	P24941	0	phosphorylation	up-regulates activity	0.246	Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.	SIGNOR-273601
P41182	Q9BZL6	0	phosphorylation	down-regulates activity	0.2	Prkd2 directly binds to Bcl6 and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development.	SIGNOR-279651
O14649	Q02156	0	phosphorylation	down-regulates activity	0.2	We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel.	SIGNOR-276431
Q13188	P67775	0	dephosphorylation	down-regulates	0.693	Rassf1a apparently protects mst1/2 against inactivation by pp2a, the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.	SIGNOR-201266
Q9Y5X5	P19086	2	binding	up-regulates activity	0.252	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-257104
O00311	P33993	1	phosphorylation	up-regulates	0.942	We propose that phosphorylation of mcm4/6 s/tp sites, which are already phosphorylated in g1, allows initial mcm2-7 phosphorylation by ddk and initiation from the first origins of replication ( fig. 7ai ).	SIGNOR-169506
O96017	Q9NY61	1	phosphorylation	up-regulates quantity by stabilization	0.358	Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.\| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.	SIGNOR-264416
P61586	Q9P227	0	gtpase-activating protein	down-regulates activity	0.548	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-260479
P62136	P04049	1	dephosphorylation	up-regulates activity	0.271	We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins	SIGNOR-251649
P40763	P19525	0	phosphorylation	up-regulates activity	0.612	Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).\|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.	SIGNOR-279613
O15304	P42684	0	phosphorylation	up-regulates	0.334	Our results also demonstrate that mutation of the siva-1 tyr48 site abrogates the apoptotic function of siva-1 and that apoptosis induced by siva-1 is dependent on expression of kinase-active arg.	SIGNOR-104992
P08754	P30542	2	binding	up-regulates activity	0.461	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-256840
P42226	O60674	0	phosphorylation	up-regulates activity	0.67	Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6.	SIGNOR-249532
O15234	Q9H2K2	0	ADP-ribosylation	down-regulates quantity by destabilization	0.2	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263382
Q09472	Q9H2X6	0	phosphorylation	up-regulates activity	0.611	Furthermore, HIPK2 forms a complex with the coactivator p300 and AML1, phosphorylates p300 at multiple Serine/Threonine sites and activates p300 HAT activity and coactivator function.	SIGNOR-278943
P26678	Q09013	0	phosphorylation	up-regulates	0.54	Coimmunoprecipitation studies showed that dmpk and pln can physically associate. Furthermore, purified wild-type dmpk, but not a kinase-deficient mutant (k110a dmpk), phosphorylates pln in vitro	SIGNOR-131371
P55211	P39687	2	binding	up-regulates activity	0.277	PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation.	SIGNOR-259082
P58401	Q8NFZ4	2	binding	up-regulates activity	0.829	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265455
Q8IW41	P28482	0	phosphorylation	up-regulates	0.48	Activated following phosphorylation at thr-182 by p38-alpha/mapk14, p38-beta/mapk11, erk2/mapk1, erk3/mapk6, and erk4/mapk4.	SIGNOR-58127
Q5VT25	Q5VT25	2	phosphorylation	up-regulates activity	0.2	N terminus-mediated dimerization and transautophosphorylation are essential for MRCKα catalytic activity. Three mutations, S234A, T240A, and T403A, strongly affected the in vitro autophosphorylation activity of FLAG-MRCKα-CAT1–473 (Fig. (Fig.5D).5D).	SIGNOR-275974
P48729	Q04206	1	phosphorylation	up-regulates activity	0.2	These data strongly suggested that CKI phosphorylated Ser-316 of p65. Our data suggested that phosphorylation of p65 on Ser-316 controls the activity and function of NF-κB. Importantly, we found that phosphorylation at the novel Ser-316 site and other two known phosphorylation sites, Ser-529 and Ser-536, either individually or cooperatively, regulated distinct groups of NF-κB-dependent genes, suggesting the unique role of each individual phosphorylation site on NF-κB-dependent gene regulation.	SIGNOR-276916
Q02556	P17947	2	binding	up-regulates activity	0.594	We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP.	SIGNOR-222880
Q15842	Q96P20	2	binding	down-regulates activity	0.2	We further show that Kir6.1 physically associates with NLRP3 and thus inhibits the interactions between the NLRP3 inflammasome subunits. Our results reveal a previously unrecognized function of Kir6.1 as a negative regulator of the NLRP3 inflammasome	SIGNOR-262034
P11308	P56704	1	transcriptional regulation	up-regulates quantity by expression	0.2	Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.	SIGNOR-261598
P00519	Q96PD2	1	phosphorylation	up-regulates activity	0.2	SFKs and Abl differentially phosphorylate DCBLD1 and DCBLD2 at distinct tyrosine phosphorylation sites.\|We report that Src family kinases and Abl differentially promote the interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while Src family kinases and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of Abl is more pronounced for DCBLD1. 45999997={Domain=45999998 LikeProtein=1399} 45999998="sh2 domain" 45999999="sh2 domain"}	SIGNOR-280167
P63096	O00155	2	binding	up-regulates activity	0.25	GPR25 is expressed in human memory T-cells and NK-cells and identified as a primary causal gene associated with autoimmune \|Within the class A GPCR family, GPR25 shares a relatively high degree of amino acid sequence identity (29e34%) with vertebrate Apelin receptor (APLNR) diseases revealed by cis-eQTL mapping based on a genome-wide association study (GWAS).	SIGNOR-272501
P37231	Q96EB6	0	transcriptional regulation	down-regulates quantity by repression	0.695	Interestingly, SIRT1 suppresses PPARγ but activates PGC-1α , and thus affects the clock network through multiple mechanisms.	SIGNOR-268032
Q00535	P49023	1	phosphorylation	up-regulates activity	0.377	Thus, phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization.\|cdk5 and p38MAPK phosphorylates Ser 85 on paxillin in vitro.	SIGNOR-278921
P35222	Q13882	0	phosphorylation	down-regulates quantity	0.305	PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.\|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo.	SIGNOR-278289
O14490	P78352	2	binding	up-regulates activity	0.932	SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.	SIGNOR-264209
Q92913	Q9UI33	2	binding	down-regulates activity	0.2	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-253435
O00141	P19634	1	phosphorylation	up-regulates activity	0.304	Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].\|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment.	SIGNOR-280123
Q12913	P06213	1	dephosphorylation	down-regulates	0.304	Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta.	SIGNOR-21295
Q2TAL8	P23381	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269410
P06730	O14965	0	phosphorylation	up-regulates activity	0.278	In this study, we demonstrated for the first time that AURKA can phosphorylate and activate EIF4E.	SIGNOR-279495
Q92765	P04628	2	binding	down-regulates	0.517	We and others demonstrated that fzb-1 blocks wnt-1 and xwnt-8 signaling in xenopus embryos,	SIGNOR-51762
P0DP24	Q96RR4	2	binding	up-regulates	0.541	The ca2+-calmodulin-dependent protein kinase (cam kinase) cascade includes three kinases: cam-kinase kinase (camkk);and the cam kinases camki and camkiv, which are phosphorylated and activated by camkk.	SIGNOR-266329
P68400	P55087	1	phosphorylation	down-regulates activity	0.416	We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. \| To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.	SIGNOR-250827
O75688	Q6WCQ1	1	dephosphorylation	down-regulates activity	0.2	Ppm1b prevents Rip3 auto-activation in resting cells.\|Together, these data demonstrate that Ppm1b dephosphorylates Rip3 and thus negatively regulates TNF induced necroptosis in L929 cells.	SIGNOR-277019
Q8IYM9	P62837	2	binding	up-regulates activity	0.3	It was found that TRIM22 underwent self-ubiquitylation in vitro in combination with the E2 enzyme UbcH5B and the ubiquitylation was dependent on its RING finger domain. Further evidences showed that TRIM22 could also be self-ubiquitylated in vivo. Importantly, TRIM22 was conjugated with poly-ubiquitin chains and stabilized by the proteasome inhibitor in 293T cells, suggesting that TRIM22 targeted itself for proteasomal degradation through the poly-ubiquitylation. We also found that TRIM22 was located in the nucleus, indicating that TRIM22 might function as a nuclear E3 ubiquitin ligase.	SIGNOR-271779
P41182	Q86XK2	2	binding	down-regulates	0.49	Fbxo11 targets bcl6 for degradation	SIGNOR-177652
Q96P68	P63096	2	binding	up-regulates activity	0.385	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-257042
P56817	Q9UNE7	0	ubiquitination	down-regulates quantity	0.378	This result establishes that CHIP negatively regulates BACE1 stability.\|Thus, both deletion mutants of CHIP could not enhance the ubiquitination of BACE1, suggesting that both domains of CHIP were essential for ubiquitination and degradation of BACE1.	SIGNOR-278719
P63000	Q12979	0	gtpase-activating protein	down-regulates activity	0.504	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-260525
Q15678	P56945	1	dephosphorylation	down-regulates	0.394	We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation	SIGNOR-197923
P07437	Q14980	2	binding	up-regulates	0.404	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-116900
Q05655	P61073	1	phosphorylation	down-regulates activity	0.2	Therefore, internalization of CXCR4 in response to PMA appears to be mediated by activation of protein kinase C \| However, mutation of the dileucine motif or the serines at positions 324, 325, 338, and 339 profoundly decreased internalization.	SIGNOR-260898
P05230	P22455	2	binding	up-regulates	0.827	Our results establish an fgf binding profile for fgfr-4 with afgf having the highest affinity, followed by k-fgf/hst-1 and bfgf. In addition, fgf-6 was found to bind to fgfr-4 in ligand competition experiments. Ligands binding to fgfr-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides.	SIGNOR-18454
P29474	P05129	0	phosphorylation	down-regulates activity	0.2	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251633
P09471	Q99705	2	binding	up-regulates activity	0.273	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-257235
P62714	Q13153	1	dephosphorylation	down-regulates activity	0.2	Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation.	SIGNOR-248600
Q8NFG4	P0DMV8	2	binding	up-regulates quantity by stabilization	0.2	These data suggest that inhibition of Hsp70 does not lead to an increase in misfolded FLCN but instead to its degradation.	SIGNOR-256506
O95622	P19086	2	binding	down-regulates activity	0.52	Activated a z inhibits the activity of type I and type V adenylyl cyclases.	SIGNOR-278045
O60282	O60296	2	binding	up-regulates activity	0.549	Trafficking kinesin proteins (TRAKs) are kinesin adaptors. They bind the cargo binding domain of kinesin-1 motor proteins forming a link between the motor and their cargoes. This supports the idea that the KIF5A–TRAK2 interaction is multivalent and could act to ensure stable motor-cargo interaction during intracellular trafficking; dimerization of both motor and adaptor molecules further enhances this stability (Fig. 6). A similar multivalent profile was found for the TRAK2 binding site within the kinesin-1 isoform, KIF5C.	SIGNOR-264064
P12931	Q9UHR4	1	phosphorylation	up-regulates activity	0.389	Here, we report that overexpression of IRTKS increases the speed of wound closure of HT1080 cells in a Src-dependent manner. Active Src phosphorylates IRTKS in vivo and in vitro. Deletion mapping and mutation analysis revealed that six tyrosine residues (Y37, Y156, Y163, Y274, Y293 and Y439) were Src-stimulated phosphorylation sites on IRTKS. Disruption of Src-stimulated IRTKS phosphorylation abolished the effect of IRTKS on wound closure. Collectively, these data suggest Src-stimulated IRTKS phosphorylation is essential for its function in cell motility.	SIGNOR-263041
Q96PV0	P78352	2	binding	up-regulates activity	0.596	The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95.	SIGNOR-264229
Q15120	P29803	1	phosphorylation	down-regulates	0.563	Pdh2 was found to be very similar to pdh1 / in the mechanism of inactivation by phosphorylation of three sites;and (iv) in the phosphorylation of sites 1 and 2 by pdk3 / (ser-264 (site 1), ser-271 (site 2), and ser-203 (site 3)	SIGNOR-143974
Q07820	Q9Y577	0	polyubiquitination	down-regulates quantity by destabilization	0.444	Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons.	SIGNOR-272032
P63000	O43312	2	binding	up-regulates	0.2	Mim-b binds and activates rac via its irsp53/mim domain	SIGNOR-141573
Q16539	P35638	1	phosphorylation	up-regulates activity	0.61	CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. It accumulates under conditions of stress and undergoes inducible phosphorylation on two adjacent serine residues (78 and 81). In vitro, CHOP is phosphorylated on these residues by p38 mitogen-activated protein kinase (MAP kinase).	SIGNOR-250096
Q9Y468	Q8NHG7	2	binding	down-regulates activity	0.2	In response to DNA damage, VCP/p97, an ATPase which unfolds proteins, removes L3MBTL1 from H4K20me2, creating free H4K20me2 for 53BP1 to bind to (Fig. 3b).	SIGNOR-262060
P51587	Q7Z589	2	binding	down-regulates activity	0.2	The EMSY protein interacts precisely with a highly conserved transactivating region at the N terminus of the breast cancer protein BRCA2, and has endogenous transcriptional repressor activity when recruited to a high basal promoter. We have suggested that the independent activation domain of BRCA2 within exon 3 might have some role in transcription (Milner et al., 1997). The identification of the repressor protein EMSY, which binds and silences this domain, is consistent with such a function.	SIGNOR-263915
P37231	Q13164	2	binding	up-regulates activity	0.377	In endothelial cells, flow-mediated activation of ERK5 has been shown to lead to activation of PPAR gamma by direct binding to the hinge-helix region of PPAR gamma	SIGNOR-278108
P43403	Q15669	2	binding	up-regulates activity	0.458	These findings suggest that RhoH is a critical regulator of thymocyte development and TCR signaling by mediating recruitment and activation of Zap70.	SIGNOR-259084
P24941	Q5MJ70	0	relocalization	up-regulates activity	0.791	Speedy/RINGO A, a noncanonical activator of CDK2, was recently identified as a key regulator for CDK2 recruitment to meiotic telomeres	SIGNOR-263310
P06241	Q04759	1	phosphorylation	up-regulates	0.344	Further indications of direct interaction are that p59fyn potentiates ?PKC Catalytic activity and that ?PKC Is a substrate for tyrosine phosphorylation by p59fyn.	SIGNOR-68798
O00631	P16157	2	binding	down-regulates activity	0.257	These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN's inhibitory effect on SERCA1 activity.	SIGNOR-265930
P49913	P25090	2	binding	up-regulates	0.533	Ll-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and t cells to sites of microbial invasion by interacting with fprl1.	SIGNOR-82701
Q8N3U4	O60216	2	binding	up-regulates quantity by stabilization	0.965	Cohesin is an evolutionarily conserved complex composed of four core proteins (SMC1A, SMC3, RAD21 and either STAG2 or STAG1) that form a ring-shaped structure able to encircle chromatin	SIGNOR-261511
P98177	Q96EB6	0	deacetylation	up-regulates	0.744	Deacetylation of foxos involves binding of the nad-dependent deacetylase hsir2(sirt1). Accordingly, hsir2(sirt1)-mediated deacetylation precludes foxo inhibition through acetylation and thereby prolongs foxo-dependent transcription of stress-regulating genes.	SIGNOR-124714
Q9NRM7	P60891	1	phosphorylation	down-regulates quantity by destabilization	0.2	Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.	SIGNOR-276504
O15550	P09017	1	transcriptional regulation	up-regulates quantity by expression	0.467	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260030
P36894	O15198	1	phosphorylation	up-regulates activity	0.706	To ascertain whether overexpression of BMPr1A can initiate adipocyte lineage commitment in the absence of its BMP ligand, constitutively active (CA)-BMPr1A and CA-BMPr1B were expressed in C3H10T1/2 stem cells using a mouse stem cell virus (MSCV) retroviral system. […]Thus, their overexpression provoked a substantial rise in the phosphorylation of Smad1/5/8 and p38 MAPK, known downstream phosphorylated intermediates in the BMP signaling pathway.	SIGNOR-255772
Q15796	Q13705	0	phosphorylation	up-regulates activity	0.776	It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains	SIGNOR-254984
P16403	Q96J02	0	polyubiquitination	up-regulates activity	0.2	ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. The results indicated that ITCH-mediated K46-Ubn is essential for the binding of histone H1.2 to chromatin.	SIGNOR-272926

P48736

Q6ZUJ8

2

binding

up-regulates

0.244

This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.

SIGNOR-191670

O75582

Q13541

1

phosphorylation

down-regulates activity

0.671

In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E

SIGNOR-262992

P06241

P29350

1

phosphorylation

up-regulates activity

0.551

By contrast, receptor multivalent aggregation induced a Fyn-dependent SHP-1 S591 phosphorylation (Fig.\u00a0 xref ).|Fyn simultaneously activates the PI3K-PKC\u03b1 pathway, leading to SHP-1 phosphorylation on serine 591.

SIGNOR-279716

O75581

P49674

0

phosphorylation

up-regulates

0.262

We find that ckiepsilon binds to lrp5 and lrp6 in vitro and in vivo and identify three ckiepsilon-specific phosphorylation sites in lrp6. Two of the identified phosphorylation sites, ser1420 and ser1430, influence wnt signaling in vivo,

SIGNOR-145049

Q96RG2

P13807

1

phosphorylation

down-regulates activity

0.508

Recombinant human PASK (hPASK) phosphorylates purified muscle glycogen synthase, causing robust inactivation. Furthermore, hPASK interacts directly with glycogen synthase when expressed in cultured cells and this interaction and the phosphorylation of glycogen synthase by human PASK (hPASK) are inhibited by glycogen.

SIGNOR-245866

P07900

O95433

2

binding

up-regulates activity

0.742

The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity

SIGNOR-252211

Q9C0C7

O75385

0

phosphorylation

up-regulates

0.695

When autophagy is induced, ulk1 phosphorylates ambra1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Ambra1-dlc1 dissociates from the dynein complex upon ulk1-dependent ambra1 phosphorylation.

SIGNOR-168292

Q9UJM3

O14757

0

phosphorylation

down-regulates activity

0.326

Our results suggest that Chk1 phosphorylates Mig-6 on Ser 251, resulting in the inhibition of Mig-6, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1.

SIGNOR-276411

Q13563

Q15139

0

phosphorylation

up-regulates activity

0.458

Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. Phosphorylation at this site was significantly increased in response to serum and epidermal growth factor stimulation.We confirmed previous studies showing that PC2 mediated Ca2+ release from the ER can be stimulated by ATP.Phosphorylation at Ser801 seems to be permissive for this activity without altering the subcellular localization nor homophilic and heterophilic (with PC1) interactions of wild-type PC2.

SIGNOR-259829

Q6IE81

Q8IUQ4

0

polyubiquitination

down-regulates quantity by destabilization

0.291

Siah-1 decreases Jade-1 abundance and enhances Jade-1 ubiquitination

SIGNOR-272915

P55795

Q15554

1

post transcriptional regulation

down-regulates quantity

0.332

During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.

SIGNOR-266806

Q15208

Q9UBF8

1

phosphorylation

up-regulates activity

0.267

We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.

SIGNOR-263033

P12931

Q9Y446

1

phosphorylation

up-regulates activity

0.306

We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.

SIGNOR-273807

P12931

Q12879

1

phosphorylation

up-regulates activity

0.567

To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.

SIGNOR-247167

P54756

P20827

2

binding

up-regulates

0.811

Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm. ephrin-a1 interacts with all the other epha subclass receptors as well, although with different affinity

SIGNOR-56910

Q9UPZ9

Q8IZL9

0

phosphorylation

up-regulates

0.2

Recombinant cak1p phosphorylates thr-157 in the tdy motif of recombinant ick and activates its activity in vitro.

SIGNOR-138420

P12931

P42224

1

phosphorylation

up-regulates activity

0.559

The tyr701 phosphorylation of signal transducer and activator of transcription 1 (stat1) induced by interferon-gamma (ifn-gamma) and 12-o-tetradecanoylphorbol 13-acetate (tpa) was inhibited by the protein kinase c (pkc) inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin, or the src kinase inhibitor pp2. An association between c-src and stat1 was increased by ifn-gamma and tpa, indicating the direct phosphorylation of stat1 by pkc-dependent c-src activation.

SIGNOR-235696

P21730

P01031

2

binding

up-regulates activity

0.757

The chemotactic receptor for human C5a anaphylatoxin|The human C5a receptor was cloned from U937 and HL-60 cells and identified by high affinity binding when expressed in COS-7 cells.

SIGNOR-263457

P23025

P54727

2

binding

up-regulates activity

0.769

GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo

SIGNOR-275697

Q9HAU4

P25490

1

ubiquitination

down-regulates quantity by destabilization

0.364

In addition, Smurf2 decreased the protein half-life and transcriptional activity of YY1.|Wild type Smurf2, but not the E3 ubiquitin ligase defective mutant, increased the poly-ubiquitination of YY1.

SIGNOR-278544

O43734

Q14164

0

phosphorylation

up-regulates activity

0.416

IKKi was required for IL-17-induced phosphorylation of Act1 on Ser311, adjacent to a putative TRAF-binding motif. Substitution of the serine at position 311 with alanine impaired the IL-17-mediated Act1-TRAF2-TRAF5 interaction and gene expression. Thus, IKKi is a kinase newly identified as modulating IL-17 signaling through its effect on Act1 phosphorylation and consequent function.

SIGNOR-262883

Q96JK9

Q9UM47

2

binding

up-regulates

0.881

We report here the cloning and characterization of two new genes, maml2 and maml3, that also function as transcriptional coactivators for notch receptors.

SIGNOR-94100

Q9UKI8

Q8IW41

1

phosphorylation

up-regulates activity

0.2

We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.

SIGNOR-276747

Q9UK05

P37023

2

binding

up-regulates

0.907

Finally, we demonstrate that bmp9 and bmp10 potently inhibit endothelial cell migration and growth, and stimulate endothelial expression of a panel of genes that was previously reported to be activated by the constitutively active form of alk1. Taken together, our results suggest that bmp9 and bmp10 are two specific alk1 ligands that may physiologically trigger the effects of alk1 on angiogenesis.

SIGNOR-150260

Q14765

O43504

2

binding

up-regulates activity

0.327

It suggests that HBXIP is able to activate S100A4 promoter via interacting with STAT4 in breast cancer cells, leading to the up-regulation of S100A4. here we first report that the transcription factor STAT4 plays a role in regulating S100A4 mediated by HBXIP in breast cancer.

SIGNOR-255247

Q14106

P24941

0

phosphorylation

up-regulates activity

0.246

Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.

SIGNOR-273601

P41182

Q9BZL6

0

phosphorylation

down-regulates activity

0.2

Prkd2 directly binds to Bcl6 and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development.

SIGNOR-279651

O14649

Q02156

0

phosphorylation

down-regulates activity

0.2

We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel.

SIGNOR-276431

Q13188

P67775

0

dephosphorylation

down-regulates

0.693

Rassf1a apparently protects mst1/2 against inactivation by pp2a, the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.

SIGNOR-201266

Q9Y5X5

P19086

2

binding

up-regulates activity

0.252

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-257104

O00311

P33993

1

phosphorylation

up-regulates

0.942

We propose that phosphorylation of mcm4/6 s/tp sites, which are already phosphorylated in g1, allows initial mcm2-7 phosphorylation by ddk and initiation from the first origins of replication ( fig. 7ai ).

SIGNOR-169506

O96017

Q9NY61

1

phosphorylation

up-regulates quantity by stabilization

0.358

Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.

SIGNOR-264416

P61586

Q9P227

0

gtpase-activating protein

down-regulates activity

0.548

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-260479

P62136

P04049

1

dephosphorylation

up-regulates activity

0.271

We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins

SIGNOR-251649

P40763

P19525

0

phosphorylation

up-regulates activity

0.612

Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.

SIGNOR-279613

O15304

P42684

0

phosphorylation

up-regulates

0.334

Our results also demonstrate that mutation of the siva-1 tyr48 site abrogates the apoptotic function of siva-1 and that apoptosis induced by siva-1 is dependent on expression of kinase-active arg.

SIGNOR-104992

P08754

P30542

2

binding

up-regulates activity

0.461

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-256840

P42226

O60674

0

phosphorylation

up-regulates activity

0.67

Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6.

SIGNOR-249532

O15234

Q9H2K2

0

ADP-ribosylation

down-regulates quantity by destabilization

0.2

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263382

Q09472

Q9H2X6

0

phosphorylation

up-regulates activity

0.611

Furthermore, HIPK2 forms a complex with the coactivator p300 and AML1, phosphorylates p300 at multiple Serine/Threonine sites and activates p300 HAT activity and coactivator function.

SIGNOR-278943

P26678

Q09013

0

phosphorylation

up-regulates

0.54

Coimmunoprecipitation studies showed that dmpk and pln can physically associate. Furthermore, purified wild-type dmpk, but not a kinase-deficient mutant (k110a dmpk), phosphorylates pln in vitro

SIGNOR-131371

P55211

P39687

2

binding

up-regulates activity

0.277

PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation.

SIGNOR-259082

P58401

Q8NFZ4

2

binding

up-regulates activity

0.829

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265455

Q8IW41

P28482

0

phosphorylation

up-regulates

0.48

Activated following phosphorylation at thr-182 by p38-alpha/mapk14, p38-beta/mapk11, erk2/mapk1, erk3/mapk6, and erk4/mapk4.

SIGNOR-58127

Q5VT25

2

phosphorylation

up-regulates activity

0.2

N terminus-mediated dimerization and transautophosphorylation are essential for MRCKα catalytic activity. Three mutations, S234A, T240A, and T403A, strongly affected the in vitro autophosphorylation activity of FLAG-MRCKα-CAT1–473 (Fig. (Fig.5D).5D).

SIGNOR-275974

P48729

Q04206

1

phosphorylation

up-regulates activity

0.2

These data strongly suggested that CKI phosphorylated Ser-316 of p65. Our data suggested that phosphorylation of p65 on Ser-316 controls the activity and function of NF-κB. Importantly, we found that phosphorylation at the novel Ser-316 site and other two known phosphorylation sites, Ser-529 and Ser-536, either individually or cooperatively, regulated distinct groups of NF-κB-dependent genes, suggesting the unique role of each individual phosphorylation site on NF-κB-dependent gene regulation.

SIGNOR-276916

Q02556

P17947

2

binding

up-regulates activity

0.594

We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP.

SIGNOR-222880

Q15842

Q96P20

2

binding

down-regulates activity

0.2

We further show that Kir6.1 physically associates with NLRP3 and thus inhibits the interactions between the NLRP3 inflammasome subunits. Our results reveal a previously unrecognized function of Kir6.1 as a negative regulator of the NLRP3 inflammasome

SIGNOR-262034

P11308

P56704

1

transcriptional regulation

up-regulates quantity by expression

0.2

Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.

SIGNOR-261598

P00519

Q96PD2

1

phosphorylation

up-regulates activity

0.2

SFKs and Abl differentially phosphorylate DCBLD1 and DCBLD2 at distinct tyrosine phosphorylation sites.|We report that Src family kinases and Abl differentially promote the interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while Src family kinases and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of Abl is more pronounced for DCBLD1. 45999997={Domain=45999998 LikeProtein=1399} 45999998="sh2 domain" 45999999="sh2 domain"}

SIGNOR-280167

P63096

O00155

2

binding

up-regulates activity

0.25

GPR25 is expressed in human memory T-cells and NK-cells and identified as a primary causal gene associated with autoimmune |Within the class A GPCR family, GPR25 shares a relatively high degree of amino acid sequence identity (29e34%) with vertebrate Apelin receptor (APLNR) diseases revealed by cis-eQTL mapping based on a genome-wide association study (GWAS).

SIGNOR-272501

P37231

Q96EB6

0

transcriptional regulation

down-regulates quantity by repression

0.695

Interestingly, SIRT1 suppresses PPARγ but activates PGC-1α , and thus affects the clock network through multiple mechanisms.

SIGNOR-268032

Q00535

P49023

1

phosphorylation

up-regulates activity

0.377

Thus, phosphorylation of paxillin is involved in NGF-induced neurite extension of PC-12 cells, probably through regulating focal adhesion organization.|cdk5 and p38MAPK phosphorylates Ser 85 on paxillin in vitro.

SIGNOR-278921

P35222

Q13882

0

phosphorylation

down-regulates quantity

0.305

PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo.

SIGNOR-278289

O14490

P78352

2

binding

up-regulates activity

0.932

SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.

SIGNOR-264209

Q92913

Q9UI33

2

binding

down-regulates activity

0.2

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-253435

O00141

P19634

1

phosphorylation

up-regulates activity

0.304

Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment.

SIGNOR-280123

Q12913

P06213

1

dephosphorylation

down-regulates

0.304

Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta.

SIGNOR-21295

Q2TAL8

P23381

1

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-269410

P06730

O14965

0

phosphorylation

up-regulates activity

0.278

In this study, we demonstrated for the first time that AURKA can phosphorylate and activate EIF4E.

SIGNOR-279495

Q92765

P04628

2

binding

down-regulates

0.517

We and others demonstrated that fzb-1 blocks wnt-1 and xwnt-8 signaling in xenopus embryos,

SIGNOR-51762

P0DP24

Q96RR4

2

binding

up-regulates

0.541

The ca2+-calmodulin-dependent protein kinase (cam kinase) cascade includes three kinases: cam-kinase kinase (camkk);and the cam kinases camki and camkiv, which are phosphorylated and activated by camkk.

SIGNOR-266329

P68400

P55087

1

phosphorylation

down-regulates activity

0.416

We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. | To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.

SIGNOR-250827

O75688

Q6WCQ1

1

dephosphorylation

down-regulates activity

0.2

Ppm1b prevents Rip3 auto-activation in resting cells.|Together, these data demonstrate that Ppm1b dephosphorylates Rip3 and thus negatively regulates TNF induced necroptosis in L929 cells.

SIGNOR-277019

Q8IYM9

P62837

2

binding

up-regulates activity

0.3

It was found that TRIM22 underwent self-ubiquitylation in vitro in combination with the E2 enzyme UbcH5B and the ubiquitylation was dependent on its RING finger domain. Further evidences showed that TRIM22 could also be self-ubiquitylated in vivo. Importantly, TRIM22 was conjugated with poly-ubiquitin chains and stabilized by the proteasome inhibitor in 293T cells, suggesting that TRIM22 targeted itself for proteasomal degradation through the poly-ubiquitylation. We also found that TRIM22 was located in the nucleus, indicating that TRIM22 might function as a nuclear E3 ubiquitin ligase.

SIGNOR-271779

P41182

Q86XK2

2

binding

down-regulates

0.49

Fbxo11 targets bcl6 for degradation

SIGNOR-177652

Q96P68

P63096

2

binding

up-regulates activity

0.385

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-257042

P56817

Q9UNE7

0

ubiquitination

down-regulates quantity

0.378

This result establishes that CHIP negatively regulates BACE1 stability.|Thus, both deletion mutants of CHIP could not enhance the ubiquitination of BACE1, suggesting that both domains of CHIP were essential for ubiquitination and degradation of BACE1.

SIGNOR-278719

P63000

Q12979

0

gtpase-activating protein

down-regulates activity

0.504

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-260525

Q15678

P56945

1

dephosphorylation

down-regulates

0.394

We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation

SIGNOR-197923

P07437

Q14980

2

binding

up-regulates

0.404

Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.

SIGNOR-116900

Q05655

P61073

1

phosphorylation

down-regulates activity

0.2

Therefore, internalization of CXCR4 in response to PMA appears to be mediated by activation of protein kinase C | However, mutation of the dileucine motif or the serines at positions 324, 325, 338, and 339 profoundly decreased internalization.

SIGNOR-260898

P05230

P22455

2

binding

up-regulates

0.827

Our results establish an fgf binding profile for fgfr-4 with afgf having the highest affinity, followed by k-fgf/hst-1 and bfgf. In addition, fgf-6 was found to bind to fgfr-4 in ligand competition experiments. Ligands binding to fgfr-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides.

SIGNOR-18454

P29474

P05129

0

phosphorylation

down-regulates activity

0.2

The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites

SIGNOR-251633

P09471

Q99705

2

binding

up-regulates activity

0.273

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-257235

P62714

Q13153

1

dephosphorylation

down-regulates activity

0.2

Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation.

SIGNOR-248600

Q8NFG4

P0DMV8

2

binding

up-regulates quantity by stabilization

0.2

These data suggest that inhibition of Hsp70 does not lead to an increase in misfolded FLCN but instead to its degradation.

SIGNOR-256506

O95622

P19086

2

binding

down-regulates activity

0.52

Activated a z inhibits the activity of type I and type V adenylyl cyclases.

SIGNOR-278045

O60282

O60296

2

binding

up-regulates activity

0.549

Trafficking kinesin proteins (TRAKs) are kinesin adaptors. They bind the cargo binding domain of kinesin-1 motor proteins forming a link between the motor and their cargoes. This supports the idea that the KIF5A–TRAK2 interaction is multivalent and could act to ensure stable motor-cargo interaction during intracellular trafficking; dimerization of both motor and adaptor molecules further enhances this stability (Fig. 6). A similar multivalent profile was found for the TRAK2 binding site within the kinesin-1 isoform, KIF5C.

SIGNOR-264064

P12931

Q9UHR4

1

phosphorylation

up-regulates activity

0.389

Here, we report that overexpression of IRTKS increases the speed of wound closure of HT1080 cells in a Src-dependent manner. Active Src phosphorylates IRTKS in vivo and in vitro. Deletion mapping and mutation analysis revealed that six tyrosine residues (Y37, Y156, Y163, Y274, Y293 and Y439) were Src-stimulated phosphorylation sites on IRTKS. Disruption of Src-stimulated IRTKS phosphorylation abolished the effect of IRTKS on wound closure. Collectively, these data suggest Src-stimulated IRTKS phosphorylation is essential for its function in cell motility.

SIGNOR-263041

Q96PV0

P78352

2

binding

up-regulates activity

0.596

The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95.

SIGNOR-264229

Q15120

P29803

1

phosphorylation

down-regulates

0.563

Pdh2 was found to be very similar to pdh1 / in the mechanism of inactivation by phosphorylation of three sites;and (iv) in the phosphorylation of sites 1 and 2 by pdk3 / (ser-264 (site 1), ser-271 (site 2), and ser-203 (site 3)

SIGNOR-143974

Q07820

Q9Y577

0

polyubiquitination

down-regulates quantity by destabilization

0.444

Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons.

SIGNOR-272032

P63000

O43312

2

binding

up-regulates

0.2

Mim-b binds and activates rac via its irsp53/mim domain

SIGNOR-141573

Q16539

P35638

1

phosphorylation

up-regulates activity

0.61

CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. It accumulates under conditions of stress and undergoes inducible phosphorylation on two adjacent serine residues (78 and 81). In vitro, CHOP is phosphorylated on these residues by p38 mitogen-activated protein kinase (MAP kinase).

SIGNOR-250096

Q9Y468

Q8NHG7

2

binding

down-regulates activity

0.2

In response to DNA damage, VCP/p97, an ATPase which unfolds proteins, removes L3MBTL1 from H4K20me2, creating free H4K20me2 for 53BP1 to bind to (Fig. 3b).

SIGNOR-262060

P51587

Q7Z589

2

binding

down-regulates activity

0.2

The EMSY protein interacts precisely with a highly conserved transactivating region at the N terminus of the breast cancer protein BRCA2, and has endogenous transcriptional repressor activity when recruited to a high basal promoter. We have suggested that the independent activation domain of BRCA2 within exon 3 might have some role in transcription (Milner et al., 1997). The identification of the repressor protein EMSY, which binds and silences this domain, is consistent with such a function.

SIGNOR-263915

P37231

Q13164

2

binding

up-regulates activity

0.377

In endothelial cells, flow-mediated activation of ERK5 has been shown to lead to activation of PPAR gamma by direct binding to the hinge-helix region of PPAR gamma

SIGNOR-278108

P43403

Q15669

2

binding

up-regulates activity

0.458

These findings suggest that RhoH is a critical regulator of thymocyte development and TCR signaling by mediating recruitment and activation of Zap70.

SIGNOR-259084

P24941

Q5MJ70

0

relocalization

up-regulates activity

0.791

Speedy/RINGO A, a noncanonical activator of CDK2, was recently identified as a key regulator for CDK2 recruitment to meiotic telomeres

SIGNOR-263310

P06241

Q04759

1

phosphorylation

up-regulates

0.344

Further indications of direct interaction are that p59fyn potentiates ?PKC Catalytic activity and that ?PKC Is a substrate for tyrosine phosphorylation by p59fyn.

SIGNOR-68798

O00631

P16157

2

binding

down-regulates activity

0.257

These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN's inhibitory effect on SERCA1 activity.

SIGNOR-265930

P49913

P25090

2

binding

up-regulates

0.533

Ll-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and t cells to sites of microbial invasion by interacting with fprl1.

SIGNOR-82701

Q8N3U4

O60216

2

binding

up-regulates quantity by stabilization

0.965

Cohesin is an evolutionarily conserved complex composed of four core proteins (SMC1A, SMC3, RAD21 and either STAG2 or STAG1) that form a ring-shaped structure able to encircle chromatin

SIGNOR-261511

P98177

Q96EB6

0

deacetylation

up-regulates

0.744

Deacetylation of foxos involves binding of the nad-dependent deacetylase hsir2(sirt1). Accordingly, hsir2(sirt1)-mediated deacetylation precludes foxo inhibition through acetylation and thereby prolongs foxo-dependent transcription of stress-regulating genes.

SIGNOR-124714

Q9NRM7

P60891

1

phosphorylation

down-regulates quantity by destabilization

0.2

Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.

SIGNOR-276504

O15550

P09017

1

transcriptional regulation

up-regulates quantity by expression

0.467

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260030

P36894

O15198

1

phosphorylation

up-regulates activity

0.706

To ascertain whether overexpression of BMPr1A can initiate adipocyte lineage commitment in the absence of its BMP ligand, constitutively active (CA)-BMPr1A and CA-BMPr1B were expressed in C3H10T1/2 stem cells using a mouse stem cell virus (MSCV) retroviral system. […]Thus, their overexpression provoked a substantial rise in the phosphorylation of Smad1/5/8 and p38 MAPK, known downstream phosphorylated intermediates in the BMP signaling pathway.

SIGNOR-255772

Q15796

Q13705

0

phosphorylation

up-regulates activity

0.776

It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains

SIGNOR-254984

P16403

Q96J02

0

polyubiquitination

up-regulates activity

0.2

ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. The results indicated that ITCH-mediated K46-Ubn is essential for the binding of histone H1.2 to chromatin.

SIGNOR-272926