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
P46663	O95837	2	binding	up-regulates activity	0.435	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257362
Q6ZNA4	P12755	1	ubiquitination	down-regulates	0.595	On tgf-beta treatment, the e3 ubiquitin ligase arkadia mediates degradation of ski in a smad-dependent manner	SIGNOR-178598
Q13639	P08754	2	binding	up-regulates activity	0.25	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-257154
P27361	Q03060	1	phosphorylation	down-regulates quantity by destabilization	0.41	The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.	SIGNOR-275978
O76064	P54132	1	ubiquitination	up-regulates activity	0.337	Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of .	SIGNOR-272115
P17252	O60928	1	phosphorylation	down-regulates	0.2	After pharmacological pkc activation, kir7.1 currents were strongly inhibited. Co-application of pkc inhibitors attenuated this effect. Inactivation of pkc consensus sites also strongly attenuated the effect with a single site ((201)s) being essential for almost the total pkc sensitivity.	SIGNOR-181863
O00459	Q9UK22	2	binding	down-regulates quantity by destabilization	0.2	FBXL2 interacts with the pool of p85β that is free of p110 PI(3)K catalytic subunits and targets this pool for ubiquitylation and subsequent proteasomal degradation.	SIGNOR-271936
Q99683	P11309	0	phosphorylation	down-regulates	0.28	Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation	SIGNOR-187905
O14745	Q15418	0	phosphorylation	up-regulates activity	0.33	In summary, these results demonstrate that Ras-RSK1 signaling promotes nuclear localization of EBP50.\|Specifically, RSK1 phosphorylates EBP50 at threonine 156 (T156) residue in a cell cycle dependent manner, which is important for nuclear translocation of EBP50 to facilitate cellular proliferation and transformation.	SIGNOR-278290
Q8WXE1	P15927	2	binding	up-regulates	0.686	Ssdna lesions are then coated by replication protein a (rpa), recruiting atr/atrip (atr-interacting protein) complexes via recognition and association of rpa-ssdna by atrip.	SIGNOR-163176
Q99661	Q96GD4	0	phosphorylation	up-regulates	0.731	Here, we show that the binding of mcak to chromosome arms is also regulated by aurora b and that aurora b-dependent chromosome arm and centromere localization is regulated by distinct two-site phosphoregulatory mechanisms. Mcak association with chromosome arms is promoted by phosphorylation of t95 on mcak, whereas phosphorylation of s196 on mcak promotes dissociation from the arms. Although targeting of mcak to centromeres requires phosphorylation of s110 on mcak, dephosphorylation of t95 on mcak increases the binding of mcak to centromeres.	SIGNOR-155890
P10415	O00198	2	binding	down-regulates	0.472	Hrk, physically interacts with the death-repressor proteins bcl2 and bcl2l1. Hrk activates cell death at least in part by interacting with and inhibiting the protection afforded by bcl2 and bcl2l1.	SIGNOR-47794
O75364	Q13330	2	binding	up-regulates activity	0.325	we found that the MTA1/DJ1 complex is required for optimum stimulation of the TH expression by paired like homeodomain transcription factor (Pitx3) homeodomain transcription factor and that the MTA1/DJ1 complex is recruited to the TH gene chromatin via the direct interaction of MTA1 with Pitx3.	SIGNOR-239770
P22413	P0DMV8	0	post transcriptional regulation	up-regulates quantity	0.2	We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation.	SIGNOR-252197
O14965	Q96EP1	0	polyubiquitination	down-regulates quantity by destabilization	0.471	Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.	SIGNOR-271463
P27361	O43524	1	phosphorylation	down-regulates quantity by destabilization	0.595	Phosphorylation of foxo3a by erk1/2 at residues ser 294, ser 344 and ser 425 increases foxo3amdm2 interaction and enhances foxo3a degradation via an mdm2-dependent ubiquitin-proteasome pathway	SIGNOR-184569
P10916	Q15746	0	phosphorylation	up-regulates activity	0.72	MLCK directly phosphorylates MLC2 and is a substrate for ERK1/2 ( ), thus providing a direct link between the Raf-MEK1/2-ERK1/2 module and MLC2.\|These findings strongly suggest that the phosphorylation of MLC2 stimulated by MLCK and ROCK1/2 is an integral component of the biochemical signal transduction program that promotes noninvasive motility.	SIGNOR-279233
Q14938	Q14393	1	transcriptional regulation	down-regulates quantity	0.205	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268888
Q8TAS1	Q9BSJ6	1	phosphorylation	up-regulates	0.2	Cats is a substrate of kis and mapped the phosphorylation site to cats serine 131 (s131). Kis enhances the transcriptional repressor activity of cats	SIGNOR-192702
Q14980	Q9BQE3	2	binding	up-regulates	0.258	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-116677
Q71F56	Q969H0	0	ubiquitination	down-regulates quantity by destabilization	0.359	The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association.	SIGNOR-266688
O43791	P53671	0	phosphorylation	down-regulates activity	0.2	LIMK2 phosphorylates SPOP at S59, S171 and S226.\|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability.	SIGNOR-278338
P50281	P00748	1	cleavage	down-regulates quantity by destabilization	0.331	The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377\|However, no activity of Factor XII can be observed after MMPinduced cleavage.	SIGNOR-263610
Q13233	P40763	1	phosphorylation	up-regulates activity	0.291	Phosphorylation of s727 induces pin1 binding which increases transcription. Pin1 binding increases stat3 interaction with p300 and dna.	SIGNOR-236346
P46527	P24941	2	binding	down-regulates	0.95	P27, an important cell cycle regulator, blocks the g(1)/s transition in cells by binding and inhibiting cdk2/cyclin a and cdk2/cyclin e complexes (cdk2/e).	SIGNOR-154191
P12931	Q00610	1	phosphorylation	up-regulates	0.406	Egf-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of src kinase by egf receptor (egfr) signaling	SIGNOR-65714
Q15398	O14965	0	phosphorylation	up-regulates quantity by stabilization	0.751	Phosphorylation and stabilization of HURP by Aurora-A. Four phosphorylated residues were identified, namely, HURP-S627, -S725, -S757, and -S830, with 65% amino acid sequence coverage. we propose here that Aurora-A may phosphorylate HURP and this probably attenuates the negative impact of cdk1 phosphorylation and by inhibiting subsequent proteasome activity and this will generate a longer HURP half-life.	SIGNOR-262651
P62136	P04637	1	dephosphorylation	down-regulates activity	0.314	Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities\|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway.	SIGNOR-248557
P02458	P03956	0	cleavage	down-regulates quantity by destabilization	0.445	MMP-1 cleaves type II collagen at the peptide bond Gly906-Leu907 Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process.	SIGNOR-256341
P18887	P19784	0	phosphorylation	up-regulates activity	0.46	XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on S518, T519, and T523 largely determines aprataxin binding to XRCC1 though its FHA domain \| In addition, we present data to show that the acute loss of aprataxin by small interfering RNA (siRNA) renders HeLa cells sensitive to MMS through a mechanism that destabilizes XRCC1.	SIGNOR-251050
Q96CN5	Q9BV73	2	binding	up-regulates activity	0.408	Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin	SIGNOR-273703
Q13253	P12644	2	binding	down-regulates	0.814	Noggin acts by binding bmps, thus preventing them from binding to their receptors (180). Noggin binds with various degrees of affinity bmp-2, -4, -5, -6, and -7, gdf-5, gdf-6, and vg1, but not other members of the tgf- family of peptides	SIGNOR-100660
O75093	P35052	2	binding	up-regulates	0.382	Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis.	SIGNOR-68327
P13498	Q05655	0	phosphorylation	up-regulates	0.2	Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. \| Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro	SIGNOR-260892
P30260	P68400	0	phosphorylation	up-regulates	0.378	We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling.	SIGNOR-170872
P29590	P68400	0	phosphorylation	down-regulates	0.342	Here we show that ck2 regulates pml protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at ser517.	SIGNOR-148306
P29459	P29460	2	binding	up-regulates	0.848	However, a proper conformation required for high affinity binding is achieved only when p40 is associated with a p35 subunit or another p40 subunit. When p40 is associated with a p35 subunit, the heterodimer acts as an agonist mediating biologic activity. However, when p40 associates with another p40, the homodimer behaves as an antagonist in vitro	SIGNOR-27619
Q9H410	Q8IWV8	0	ubiquitination	down-regulates quantity	0.2	Mub1 and Ubr2 mediate Dsn1 ubiquitylation and degradation.\|The levels of WT Dsn1 were also increased in the mub1Delta and ubr2Delta strains, suggesting that Mub1 and Ubr2 mediate the degradation of WT Dsn1 protein.	SIGNOR-278795
Q13114	P0C6X7-PRO_0000037311	0	deubiquitination	down-regulates activity	0.2	Overexpressing PLPro of SARS-CoV or MERS-CoV significantly reduced the expression of IFN-Î² and proinflammatory cytokines in MDA5-stimulated 293T cells (83).Also, SARS-CoVPLPro catalyzed deubiquitination of TNF-receptor-associated factor3 (TRAF3) and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist (63). The deubiquitinating activity of SARS-CoV PLPro also suppressed a constitutively active phosphomimetic IRF3, suggesting its involvement in the postactivation signaling of IRF3	SIGNOR-260246
O75386	Q8N6U8	1	relocalization	up-regulates activity	0.608	Upon knockdown of Tulp3 using siRNA in IMCD3 cells, ciliary localization of Gpr161 was severely reduced	SIGNOR-259938
O15105	O75807	2	binding	up-regulates	0.679	We found smad7 interacts with growth arrest and dna damage protein, gadd34, a regulatory subunit of the protein phosphatase 1 (pp1) holoenzyme, which subsequently recruits catalytic subunit of pp1 (pp1c) to dephosphorylate t?RI.	SIGNOR-121280
P62714	Q13315	1	dephosphorylation	down-regulates activity	0.269	Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro.	SIGNOR-248601
Q9Y297	Q9UKB1	2	binding	down-regulates quantity by destabilization	0.591	Glucose deprivation activates AMPK kinase to phosphorylate β-TrCP1 and promotes the subsequent ubiquitination and degradation of β-TrCP1 by β-TrCP2, but does not promote β-TrCP2 degradation by β-TrCP1.	SIGNOR-277476
Q9NRC8	Q16695	1	deacetylation	up-regulates activity	0.2	Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37.	SIGNOR-275876
Q9NQU5	P04049	1	phosphorylation	up-regulates activity	0.2	PAK5 phosphorylates Raf-1 on serine 338 and stimulates Raf-1 activity.	SIGNOR-278971
Q02750	Q9Y2X7	2	binding	up-regulates activity	0.391	We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens.	SIGNOR-261245
Q9P0L9	Q9UQM7	0	phosphorylation	down-regulates activity	0.2	CaM inhibits the function of TRPP3 through promoting CaMK2's phosphorylation towards T591 on TRPP3.	SIGNOR-277812
Q9HCE7	Q15797	1	ubiquitination	down-regulates	0.708	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps	SIGNOR-195660
O60674	Q5VWQ8	2	binding	down-regulates activity	0.349	In vascular smooth muscle cells (VSMCs) treated with IFN-γ, DAB2IP directly binds to JAK2 and inhibits its kinase activity, limiting JAK-dependent STAT1/3 and PI3K–AKT phosphorylation and activation	SIGNOR-254760
Q8IZQ8	P49841	0	phosphorylation	down-regulates activity	0.397	In vitro and in vivo (HEK 293 cells) kinase assays with synthetic peptides and full-length myocardin demonstrated that myocardin was a primed GSK3beta substrate, with serines 455 to 467 and 624 to 636 being the major GSK3beta phosphorylation sites. GSK3β phosphorylation at the sites identified inhibits myocardin intrinsic transcriptional activity	SIGNOR-251247
Q969V1	P38405	2	binding	up-regulates activity	0.25	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-256938
O60716	P12830	2	binding	up-regulates quantity by stabilization	0.947	P120 regulates E-cadherin turnover at the cell membrane. Because direct binding of p120 to E-cadherin is required, it is possible that p120 binding blocks the interaction of an unknown binding partner (or event) that targets E-cadherin for degradation	SIGNOR-252123
P01112	Q7Z5G4	0	palmitoylation	up-regulates activity	0.349	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261351
Q07955	Q96SB4	0	phosphorylation	up-regulates	0.799	These results suggest that the formation of complexes between sf2/asf and srpks, which is influenced by the phosphorylation state of sf2/asf, may have regulatory roles in the assembly and localization of this splicing factor.	SIGNOR-66465
O14920	Q9UKB1	2	binding	down-regulates quantity by destabilization	0.443	We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo.	SIGNOR-272544
Q8WUP2	O75369	2	binding	up-regulates activity	0.721	Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.	SIGNOR-266106
P06239	Q9UN19	1	phosphorylation	up-regulates activity	0.646	Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines\|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins.	SIGNOR-249373
P63096	P32249	2	binding	up-regulates activity	0.418	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-256715
P41182	Q13153	0	phosphorylation	down-regulates activity	0.2	The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates genes involved in cell-cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase-activated protein kinase PAK1.	SIGNOR-253930
Q92529-2	P12931	0	phosphorylation	up-regulates activity	0.576	We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo.	SIGNOR-273921
Q6Q788	P06858	2	binding	up-regulates activity	0.718	Apo A5 binds to and enhances the activity of lipoprotein lipase (LPL) enzyme	SIGNOR-251845
P22415	Q16539	0	phosphorylation	up-regulates activity	0.552	Following uv irradiation, usf-1 is phosphorylated by the p38 stress-activated kinase on threonine 153 and directly up-regulates expression of the pomc, mc1r, tyr, tyrp-1 and dct genes	SIGNOR-185572
Q99677	P09471	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257258
Q6UWZ7	P38398	2	binding	up-regulates	0.2	Full length abraxas binds the brct-repeats of brca1the rap80-abraxas complex may help recruit brca1 to dna damage sites in part through recognition of ubiquitinated proteins	SIGNOR-155144
Q16539	O75676	1	phosphorylation	up-regulates	0.604	Rskb, a 90-kda ribosomal s6 protein kinase family (rsk) member with two complete catalytic domains connected by a linker, is activated through p38- and erk-mitogen-activated protein kinases. unlike other rsks, the activation loop phosphorylation sites of both catalytic domains of rskb, ser(196) and thr(568), were required for activity. Rskb activation depended on phosphorylation of linker ser(343) and ser(360) and associated with phosphorylation of nonconserved ser(347), but ser(347)-deficient rskb retained partial activity.	SIGNOR-77212
P12931	P11511	1	phosphorylation	up-regulates	0.35	Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.	SIGNOR-186284
Q9UKC9	O00459	2	binding	down-regulates quantity by destabilization	0.365	FBXL2 binds p85α and p85β. p85β is targeted for ubiquitylation and degradation by SCF FBXL2.	SIGNOR-272111
P49841	Q9UBK2	1	phosphorylation	down-regulates quantity	0.476	GSK3\u03b2 is an important serine/threonine kinase to regulate PPAR\u03b3 coactivator-1\u03b1 degradation. , GSK3\u03b2 reduces PPAR\u03b3 coactivator-1\u03b1 levels by phosphorylating PPAR\u03b3 coactivator-1\u03b1 and subsequently stimulating PPAR\u03b3 coactivator-1\u03b1 degradation by the ubiquitin-proteasomal system.\|Within them, GSK3beta, which can phosphorylate PGC-1alpha and promote its ubiquitin mediated degradation , , was upregulated significantly in mnd2 mouse brain and spinal cord compared with that in wide-type mice (XREF_FIG).	SIGNOR-279723
Q9Y4K3	P42336	1	ubiquitination	up-regulates activity	0.458	In contrast to NEDD4L, overexpression of TRAF6 increases the stability of PIK3CA protein and promotes PI3K activation.\|TRAF6 ubiquitinates PIK3CA in vivo.	SIGNOR-278727
P32249	Q03113	2	binding	up-regulates activity	0.26	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-257202
P06493	P35251	1	phosphorylation	down-regulates activity	0.245	Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr506 by cyclin-dependent kinases regulates binding to PCNA\|Replication factor C (RF-C) complex binds to DNA primers and loads PCNA onto DNA, thereby increasing the processivity of DNA polymerases. \|Phosphorylation of either RF-Cp145 as a part of the RF-C complex or RF-Cp145 domain B by cdk-cyclin kinases inhibits their ability to bind PCNA.	SIGNOR-265504
P49841	Q9UBN7	1	phosphorylation	up-regulates activity	0.381	GSK3beta was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3beta resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3beta phosphorylation site in HDAC6.\|This suggests that GSK3\u03b2 may directly phosphorylate HDAC6 at this site, although further work with purified proteins is needed to determine whether this is the case.\|The fact that HDAC6 is the predominant cytoplasmic deacetylase in neurons suggests that GSK3beta dependent phosphorylation may enhance HDAC6 activity, resulting in a decrease in acetylation of tubulin and an inhibition of both mitochondrial motility and the transport of other kinesin-1 dependent cargoes.	SIGNOR-278941
Q92993	P46531	1	acetylation	down-regulates	0.414	This result implies that the residues k2019, k2039, k2044, and k2068 of notch1-ic are the major targets of the acetyltransferase activity of tip60.	SIGNOR-156923
Q9Y625	Q15465	2	binding	up-regulates activity	0.451	Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.	SIGNOR-264029
P42229	P17706	0	dephosphorylation	down-regulates activity	0.733	Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.	SIGNOR-133547
Q5T447	Q9UDY8	1	polyubiquitination	up-regulates quantity by stabilization	0.366	HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.	SIGNOR-272096
P08754	P28336	2	binding	up-regulates activity	0.268	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-257160
P80370	P02751	2	binding	up-regulates	0.37	We show a direct interaction of pref-1 and fibronectin via the pref-1 juxtamembrane domain and fibronectin c-terminal domain	SIGNOR-165347
Q86TM6	Q9UBU6	2	binding	up-regulates activity	0.577	FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp	SIGNOR-261348
Q9UQD0	P0DP23	2	binding	down-regulates activity	0.451	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-253410
Q96LB1	P38405	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256930
P54756	O00712	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268902
Q9UD71	P19784	0	phosphorylation	up-regulates activity	0.375	Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. \| Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase	SIGNOR-251018
Q96JC9	P55199	2	binding	up-regulates	0.847	Positive regulation of ell elongation activity depends on stable binding of eaf1 to the ell n terminus	SIGNOR-138516
P23771	Q9UI32	1	transcriptional regulation	up-regulates quantity by expression	0.332	Thus, GATA3 contributes to the elevated expression of GLS2 in luminal-subtype breast cancers.	SIGNOR-268034
Q05655	Q13541	1	phosphorylation	down-regulates activity	0.2	As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation.\|Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1.	SIGNOR-279100
P19474	Q02556	1	ubiquitination	down-regulates quantity	0.638	From these results, we concluded that TRIM21 down-regulated IRF8 and enhanced the secretion of IL-12/23p40 in BD monocytes.\|IRF8 is ubiquitinated by TRIM21, which promotes secretion of IL-12/23p40 after TLR/IFN-\u03b3 stimulation xref .	SIGNOR-278791
Q13936	Q15139	0	phosphorylation	up-regulates	0.255	Both the expression of a dominant-negative mutant of pkd and the mutation of serine 1884 but not serine 1930, putative targets of pkd, strongly reduced l-type calcium currents and single channel activity without affecting the channel's expression at the plasma membrane. Our results suggest that serine 1884 is essential for the regulation of hcav1.2 by pkd.	SIGNOR-177481
P67775	P06400	1	dephosphorylation	up-regulates	0.505	This dephosphorylation returns prb to its active, growth suppressive state.	SIGNOR-75398
Q9HB75	Q13315	0	phosphorylation	up-regulates activity	0.636	ATM phosphorylates PIDD on Thr788 within the DD. This phosphorylation is necessary and sufficient for RAIDD binding and caspase-2 activation. Conversely, nonphosphorylatable PIDD fails to bind RAIDD or activate caspase-2, and engages prosurvival RIP1 instead. Thus, ATM phosphorylation of the PIDD DD enables a binary switch through which cells elect to survive or die upon DNA injury.	SIGNOR-262640
P45983	P05412	1	phosphorylation	up-regulates activity	0.907	JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain.	SIGNOR-250122
P26583	P09086	2	binding	up-regulates activity	0.32	HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins	SIGNOR-240108
P62805	Q58F21	1	relocalization	up-regulates activity	0.2	BRDT interacts with acetylated nucleosomes via its BD1 domain. Binding may be initiated through non-specific interactions with DNA, which allow BRDT to localize to chromatin. Specificity is generated through recognition of tandem acetylated lysine residues (K5ac/K8ac) on the histone H4 tail,	SIGNOR-262066
Q96JA1	P00533	2	binding	down-regulates	0.736	Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation	SIGNOR-127304
P50548	P28482	0	phosphorylation	up-regulates	0.596	The experiments presented here indicate that erf is regulated during nuclear import and/or export and that this process depends on its phosphorylation by erks our analysis indicates that in addition to t526 (position 7), s161 (position 2), s246 (position 3), and s251 (position 4) are also phosphorylated in vitro by erk2 and in vivo after mitogenic stimulation (fig. 3a).	SIGNOR-67524
P01574	Q13526	0	transcriptional regulation	down-regulates quantity by repression	0.2	To investigate the temporal regulation of IRF3-dependent transcription by Pin1, we used a rapid-response luciferase reporter gene. Real-time reporter gene assays showed that suppression of endogenous Pin1 expression substantially prolonged both IRF3-dependent transcription and IFN-beta promoter activation after poly(I)dotpoly(C) stimulation (Fig. 4c,d). Consistent with the inhibitory effects of Pin1 on the IFN-beta promoter	SIGNOR-252289
Q9NUX5	P15927	2	binding	down-regulates activity	0.407	The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA	SIGNOR-263324
P46527	Q13315	0	phosphorylation	up-regulates quantity by stabilization	0.419	We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its stabilization after induction of DNA double-strand breaks.	SIGNOR-279392
P18433	Q9H267	1	dephosphorylation	down-regulates activity	0.2	Here, we report that VPS33B, a host protein involved in vesicle trafficking, is dephosphorylated by PtpA leading to a block of phagosome maturation by M. tuberculosis.\|These data suggest that M. tuberculosis PtpA inhibits phagosome maturation.To assess the role of VPS33B in phagosome maturation, we attenuated the expression of endogenous VPS33B expression in THP-1 cells using a siRNA based approach.	SIGNOR-277015
P19793	Q03181	2	binding	up-regulates	0.582	Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology	SIGNOR-105442

P46663

O95837

2

binding

up-regulates activity

0.435

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257362

Q6ZNA4

P12755

1

ubiquitination

down-regulates

0.595

On tgf-beta treatment, the e3 ubiquitin ligase arkadia mediates degradation of ski in a smad-dependent manner

SIGNOR-178598

Q13639

P08754

2

binding

up-regulates activity

0.25

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-257154

P27361

Q03060

1

phosphorylation

down-regulates quantity by destabilization

0.41

The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.

SIGNOR-275978

O76064

P54132

1

ubiquitination

up-regulates activity

0.337

Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of .

SIGNOR-272115

P17252

O60928

1

phosphorylation

down-regulates

0.2

After pharmacological pkc activation, kir7.1 currents were strongly inhibited. Co-application of pkc inhibitors attenuated this effect. Inactivation of pkc consensus sites also strongly attenuated the effect with a single site ((201)s) being essential for almost the total pkc sensitivity.

SIGNOR-181863

O00459

Q9UK22

2

binding

down-regulates quantity by destabilization

0.2

FBXL2 interacts with the pool of p85β that is free of p110 PI(3)K catalytic subunits and targets this pool for ubiquitylation and subsequent proteasomal degradation.

SIGNOR-271936

Q99683

P11309

0

phosphorylation

down-regulates

0.28

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

SIGNOR-187905

O14745

Q15418

0

phosphorylation

up-regulates activity

0.33

In summary, these results demonstrate that Ras-RSK1 signaling promotes nuclear localization of EBP50.|Specifically, RSK1 phosphorylates EBP50 at threonine 156 (T156) residue in a cell cycle dependent manner, which is important for nuclear translocation of EBP50 to facilitate cellular proliferation and transformation.

SIGNOR-278290

Q8WXE1

P15927

2

binding

up-regulates

0.686

Ssdna lesions are then coated by replication protein a (rpa), recruiting atr/atrip (atr-interacting protein) complexes via recognition and association of rpa-ssdna by atrip.

SIGNOR-163176

Q99661

Q96GD4

0

phosphorylation

up-regulates

0.731

Here, we show that the binding of mcak to chromosome arms is also regulated by aurora b and that aurora b-dependent chromosome arm and centromere localization is regulated by distinct two-site phosphoregulatory mechanisms. Mcak association with chromosome arms is promoted by phosphorylation of t95 on mcak, whereas phosphorylation of s196 on mcak promotes dissociation from the arms. Although targeting of mcak to centromeres requires phosphorylation of s110 on mcak, dephosphorylation of t95 on mcak increases the binding of mcak to centromeres.

SIGNOR-155890

P10415

O00198

2

binding

down-regulates

0.472

Hrk, physically interacts with the death-repressor proteins bcl2 and bcl2l1. Hrk activates cell death at least in part by interacting with and inhibiting the protection afforded by bcl2 and bcl2l1.

SIGNOR-47794

O75364

Q13330

2

binding

up-regulates activity

0.325

we found that the MTA1/DJ1 complex is required for optimum stimulation of the TH expression by paired like homeodomain transcription factor (Pitx3) homeodomain transcription factor and that the MTA1/DJ1 complex is recruited to the TH gene chromatin via the direct interaction of MTA1 with Pitx3.

SIGNOR-239770

P22413

P0DMV8

0

post transcriptional regulation

up-regulates quantity

0.2

We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation.

SIGNOR-252197

O14965

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.471

Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.

SIGNOR-271463

P27361

O43524

1

phosphorylation

down-regulates quantity by destabilization

0.595

Phosphorylation of foxo3a by erk1/2 at residues ser 294, ser 344 and ser 425 increases foxo3amdm2 interaction and enhances foxo3a degradation via an mdm2-dependent ubiquitin-proteasome pathway

SIGNOR-184569

P10916

Q15746

0

phosphorylation

up-regulates activity

0.72

MLCK directly phosphorylates MLC2 and is a substrate for ERK1/2 ( ), thus providing a direct link between the Raf-MEK1/2-ERK1/2 module and MLC2.|These findings strongly suggest that the phosphorylation of MLC2 stimulated by MLCK and ROCK1/2 is an integral component of the biochemical signal transduction program that promotes noninvasive motility.

SIGNOR-279233

Q14938

Q14393

1

transcriptional regulation

down-regulates quantity

0.205

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268888

Q8TAS1

Q9BSJ6

1

phosphorylation

up-regulates

0.2

Cats is a substrate of kis and mapped the phosphorylation site to cats serine 131 (s131). Kis enhances the transcriptional repressor activity of cats

SIGNOR-192702

Q14980

Q9BQE3

2

binding

up-regulates

0.258

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

SIGNOR-116677

Q71F56

Q969H0

0

ubiquitination

down-regulates quantity by destabilization

0.359

The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association.

SIGNOR-266688

O43791

P53671

0

phosphorylation

down-regulates activity

0.2

LIMK2 phosphorylates SPOP at S59, S171 and S226.|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability.

SIGNOR-278338

P50281

P00748

1

cleavage

down-regulates quantity by destabilization

0.331

The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage.

SIGNOR-263610

Q13233

P40763

1

phosphorylation

up-regulates activity

0.291

Phosphorylation of s727 induces pin1 binding which increases transcription. Pin1 binding increases stat3 interaction with p300 and dna.

SIGNOR-236346

P46527

P24941

2

binding

down-regulates

0.95

P27, an important cell cycle regulator, blocks the g(1)/s transition in cells by binding and inhibiting cdk2/cyclin a and cdk2/cyclin e complexes (cdk2/e).

SIGNOR-154191

P12931

Q00610

1

phosphorylation

up-regulates

0.406

Egf-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of src kinase by egf receptor (egfr) signaling

SIGNOR-65714

Q15398

O14965

0

phosphorylation

up-regulates quantity by stabilization

0.751

Phosphorylation and stabilization of HURP by Aurora-A. Four phosphorylated residues were identified, namely, HURP-S627, -S725, -S757, and -S830, with 65% amino acid sequence coverage. we propose here that Aurora-A may phosphorylate HURP and this probably attenuates the negative impact of cdk1 phosphorylation and by inhibiting subsequent proteasome activity and this will generate a longer HURP half-life.

SIGNOR-262651

P62136

P04637

1

dephosphorylation

down-regulates activity

0.314

Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway.

SIGNOR-248557

P02458

P03956

0

cleavage

down-regulates quantity by destabilization

0.445

MMP-1 cleaves type II collagen at the peptide bond Gly906-Leu907 Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process.

SIGNOR-256341

P18887

P19784

0

phosphorylation

up-regulates activity

0.46

XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on S518, T519, and T523 largely determines aprataxin binding to XRCC1 though its FHA domain | In addition, we present data to show that the acute loss of aprataxin by small interfering RNA (siRNA) renders HeLa cells sensitive to MMS through a mechanism that destabilizes XRCC1.

SIGNOR-251050

Q96CN5

Q9BV73

2

binding

up-regulates activity

0.408

Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin

SIGNOR-273703

Q13253

P12644

2

binding

down-regulates

0.814

Noggin acts by binding bmps, thus preventing them from binding to their receptors (180). Noggin binds with various degrees of affinity bmp-2, -4, -5, -6, and -7, gdf-5, gdf-6, and vg1, but not other members of the tgf- family of peptides

SIGNOR-100660

O75093

P35052

2

binding

up-regulates

0.382

Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis.

SIGNOR-68327

P13498

Q05655

0

phosphorylation

up-regulates

0.2

Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro

SIGNOR-260892

P30260

P68400

0

phosphorylation

up-regulates

0.378

We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling.

SIGNOR-170872

P29590

P68400

0

phosphorylation

down-regulates

0.342

Here we show that ck2 regulates pml protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at ser517.

SIGNOR-148306

P29459

P29460

2

binding

up-regulates

0.848

However, a proper conformation required for high affinity binding is achieved only when p40 is associated with a p35 subunit or another p40 subunit. When p40 is associated with a p35 subunit, the heterodimer acts as an agonist mediating biologic activity. However, when p40 associates with another p40, the homodimer behaves as an antagonist in vitro

SIGNOR-27619

Q9H410

Q8IWV8

0

ubiquitination

down-regulates quantity

0.2

Mub1 and Ubr2 mediate Dsn1 ubiquitylation and degradation.|The levels of WT Dsn1 were also increased in the mub1Delta and ubr2Delta strains, suggesting that Mub1 and Ubr2 mediate the degradation of WT Dsn1 protein.

SIGNOR-278795

Q13114

P0C6X7-PRO_0000037311

0

deubiquitination

down-regulates activity

0.2

Overexpressing PLPro of SARS-CoV or MERS-CoV significantly reduced the expression of IFN-Î² and proinflammatory cytokines in MDA5-stimulated 293T cells (83).Also, SARS-CoVPLPro catalyzed deubiquitination of TNF-receptor-associated factor3 (TRAF3) and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist (63). The deubiquitinating activity of SARS-CoV PLPro also suppressed a constitutively active phosphomimetic IRF3, suggesting its involvement in the postactivation signaling of IRF3

SIGNOR-260246

O75386

Q8N6U8

1

relocalization

up-regulates activity

0.608

Upon knockdown of Tulp3 using siRNA in IMCD3 cells, ciliary localization of Gpr161 was severely reduced

SIGNOR-259938

O15105

O75807

2

binding

up-regulates

0.679

We found smad7 interacts with growth arrest and dna damage protein, gadd34, a regulatory subunit of the protein phosphatase 1 (pp1) holoenzyme, which subsequently recruits catalytic subunit of pp1 (pp1c) to dephosphorylate t?RI.

SIGNOR-121280

P62714

Q13315

1

dephosphorylation

down-regulates activity

0.269

Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro.

SIGNOR-248601

Q9Y297

Q9UKB1

2

binding

down-regulates quantity by destabilization

0.591

Glucose deprivation activates AMPK kinase to phosphorylate β-TrCP1 and promotes the subsequent ubiquitination and degradation of β-TrCP1 by β-TrCP2, but does not promote β-TrCP2 degradation by β-TrCP1.

SIGNOR-277476

Q9NRC8

Q16695

1

deacetylation

up-regulates activity

0.2

Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37.

SIGNOR-275876

Q9NQU5

P04049

1

phosphorylation

up-regulates activity

0.2

PAK5 phosphorylates Raf-1 on serine 338 and stimulates Raf-1 activity.

SIGNOR-278971

Q02750

Q9Y2X7

2

binding

up-regulates activity

0.391

We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens.

SIGNOR-261245

Q9P0L9

Q9UQM7

0

phosphorylation

down-regulates activity

0.2

CaM inhibits the function of TRPP3 through promoting CaMK2's phosphorylation towards T591 on TRPP3.

SIGNOR-277812

Q9HCE7

Q15797

1

ubiquitination

down-regulates

0.708

Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps

SIGNOR-195660

O60674

Q5VWQ8

2

binding

down-regulates activity

0.349

In vascular smooth muscle cells (VSMCs) treated with IFN-γ, DAB2IP directly binds to JAK2 and inhibits its kinase activity, limiting JAK-dependent STAT1/3 and PI3K–AKT phosphorylation and activation

SIGNOR-254760

Q8IZQ8

P49841

0

phosphorylation

down-regulates activity

0.397

In vitro and in vivo (HEK 293 cells) kinase assays with synthetic peptides and full-length myocardin demonstrated that myocardin was a primed GSK3beta substrate, with serines 455 to 467 and 624 to 636 being the major GSK3beta phosphorylation sites. GSK3β phosphorylation at the sites identified inhibits myocardin intrinsic transcriptional activity

SIGNOR-251247

Q969V1

P38405

2

binding

up-regulates activity

0.25

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-256938

O60716

P12830

2

binding

up-regulates quantity by stabilization

0.947

P120 regulates E-cadherin turnover at the cell membrane. Because direct binding of p120 to E-cadherin is required, it is possible that p120 binding blocks the interaction of an unknown binding partner (or event) that targets E-cadherin for degradation

SIGNOR-252123

P01112

Q7Z5G4

0

palmitoylation

up-regulates activity

0.349

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261351

Q07955

Q96SB4

0

phosphorylation

up-regulates

0.799

These results suggest that the formation of complexes between sf2/asf and srpks, which is influenced by the phosphorylation state of sf2/asf, may have regulatory roles in the assembly and localization of this splicing factor.

SIGNOR-66465

O14920

Q9UKB1

2

binding

down-regulates quantity by destabilization

0.443

We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo.

SIGNOR-272544

Q8WUP2

O75369

2

binding

up-regulates activity

0.721

Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.

SIGNOR-266106

P06239

Q9UN19

1

phosphorylation

up-regulates activity

0.646

Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins.

SIGNOR-249373

P63096

P32249

2

binding

up-regulates activity

0.418

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-256715

P41182

Q13153

0

phosphorylation

down-regulates activity

0.2

The transcriptional repressor B-cell lymphoma (BCL)-6 downregulates genes involved in cell-cycle progression and becomes inactivated following phosphorylation by the Rac1 GTPase-activated protein kinase PAK1.

SIGNOR-253930

Q92529-2

P12931

0

phosphorylation

up-regulates activity

0.576

We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo.

SIGNOR-273921

Q6Q788

P06858

2

binding

up-regulates activity

0.718

Apo A5 binds to and enhances the activity of lipoprotein lipase (LPL) enzyme

SIGNOR-251845

P22415

Q16539

0

phosphorylation

up-regulates activity

0.552

Following uv irradiation, usf-1 is phosphorylated by the p38 stress-activated kinase on threonine 153 and directly up-regulates expression of the pomc, mc1r, tyr, tyrp-1 and dct genes

SIGNOR-185572

Q99677

P09471

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257258

Q6UWZ7

P38398

2

binding

up-regulates

0.2

Full length abraxas binds the brct-repeats of brca1the rap80-abraxas complex may help recruit brca1 to dna damage sites in part through recognition of ubiquitinated proteins

SIGNOR-155144

Q16539

O75676

1

phosphorylation

up-regulates

0.604

Rskb, a 90-kda ribosomal s6 protein kinase family (rsk) member with two complete catalytic domains connected by a linker, is activated through p38- and erk-mitogen-activated protein kinases. unlike other rsks, the activation loop phosphorylation sites of both catalytic domains of rskb, ser(196) and thr(568), were required for activity. Rskb activation depended on phosphorylation of linker ser(343) and ser(360) and associated with phosphorylation of nonconserved ser(347), but ser(347)-deficient rskb retained partial activity.

SIGNOR-77212

P12931

P11511

1

phosphorylation

up-regulates

0.35

Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.

SIGNOR-186284

Q9UKC9

O00459

2

binding

down-regulates quantity by destabilization

0.365

FBXL2 binds p85α and p85β. p85β is targeted for ubiquitylation and degradation by SCF FBXL2.

SIGNOR-272111

P49841

Q9UBK2

1

phosphorylation

down-regulates quantity

0.476

GSK3\u03b2 is an important serine/threonine kinase to regulate PPAR\u03b3 coactivator-1\u03b1 degradation. , GSK3\u03b2 reduces PPAR\u03b3 coactivator-1\u03b1 levels by phosphorylating PPAR\u03b3 coactivator-1\u03b1 and subsequently stimulating PPAR\u03b3 coactivator-1\u03b1 degradation by the ubiquitin-proteasomal system.|Within them, GSK3beta, which can phosphorylate PGC-1alpha and promote its ubiquitin mediated degradation , , was upregulated significantly in mnd2 mouse brain and spinal cord compared with that in wide-type mice (XREF_FIG).

SIGNOR-279723

Q9Y4K3

P42336

1

ubiquitination

up-regulates activity

0.458

In contrast to NEDD4L, overexpression of TRAF6 increases the stability of PIK3CA protein and promotes PI3K activation.|TRAF6 ubiquitinates PIK3CA in vivo.

SIGNOR-278727

P32249

Q03113

2

binding

up-regulates activity

0.26

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-257202

P06493

P35251

1

phosphorylation

down-regulates activity

0.245

Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr506 by cyclin-dependent kinases regulates binding to PCNA|Replication factor C (RF-C) complex binds to DNA primers and loads PCNA onto DNA, thereby increasing the processivity of DNA polymerases. |Phosphorylation of either RF-Cp145 as a part of the RF-C complex or RF-Cp145 domain B by cdk-cyclin kinases inhibits their ability to bind PCNA.

SIGNOR-265504

P49841

Q9UBN7

1

phosphorylation

up-regulates activity

0.381

GSK3beta was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3beta resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3beta phosphorylation site in HDAC6.|This suggests that GSK3\u03b2 may directly phosphorylate HDAC6 at this site, although further work with purified proteins is needed to determine whether this is the case.|The fact that HDAC6 is the predominant cytoplasmic deacetylase in neurons suggests that GSK3beta dependent phosphorylation may enhance HDAC6 activity, resulting in a decrease in acetylation of tubulin and an inhibition of both mitochondrial motility and the transport of other kinesin-1 dependent cargoes.

SIGNOR-278941

Q92993

P46531

1

acetylation

down-regulates

0.414

This result implies that the residues k2019, k2039, k2044, and k2068 of notch1-ic are the major targets of the acetyltransferase activity of tip60.

SIGNOR-156923

Q9Y625

Q15465

2

binding

up-regulates activity

0.451

Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.

SIGNOR-264029

P42229

P17706

0

dephosphorylation

down-regulates activity

0.733

Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.

SIGNOR-133547

Q5T447

Q9UDY8

1

polyubiquitination

up-regulates quantity by stabilization

0.366

HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.

SIGNOR-272096

P08754

P28336

2

binding

up-regulates activity

0.268

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-257160

P80370

P02751

2

binding

up-regulates

0.37

We show a direct interaction of pref-1 and fibronectin via the pref-1 juxtamembrane domain and fibronectin c-terminal domain

SIGNOR-165347

Q86TM6

Q9UBU6

2

binding

up-regulates activity

0.577

FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp

SIGNOR-261348

Q9UQD0

P0DP23

2

binding

down-regulates activity

0.451

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-253410

Q96LB1

P38405

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256930

P54756

O00712

0

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268902

Q9UD71

P19784

0

phosphorylation

up-regulates activity

0.375

Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase

SIGNOR-251018

Q96JC9

P55199

2

binding

up-regulates

0.847

Positive regulation of ell elongation activity depends on stable binding of eaf1 to the ell n terminus

SIGNOR-138516

P23771

Q9UI32

1

transcriptional regulation

up-regulates quantity by expression

0.332

Thus, GATA3 contributes to the elevated expression of GLS2 in luminal-subtype breast cancers.

SIGNOR-268034

Q05655

Q13541

1

phosphorylation

down-regulates activity

0.2

As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation.|Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1.

SIGNOR-279100

P19474

Q02556

1

ubiquitination

down-regulates quantity

0.638

From these results, we concluded that TRIM21 down-regulated IRF8 and enhanced the secretion of IL-12/23p40 in BD monocytes.|IRF8 is ubiquitinated by TRIM21, which promotes secretion of IL-12/23p40 after TLR/IFN-\u03b3 stimulation xref .

SIGNOR-278791

Q13936

Q15139

0

phosphorylation

up-regulates

0.255

Both the expression of a dominant-negative mutant of pkd and the mutation of serine 1884 but not serine 1930, putative targets of pkd, strongly reduced l-type calcium currents and single channel activity without affecting the channel's expression at the plasma membrane. Our results suggest that serine 1884 is essential for the regulation of hcav1.2 by pkd.

SIGNOR-177481

P67775

P06400

1

dephosphorylation

up-regulates

0.505

This dephosphorylation returns prb to its active, growth suppressive state.

SIGNOR-75398

Q9HB75

Q13315

0

phosphorylation

up-regulates activity

0.636

ATM phosphorylates PIDD on Thr788 within the DD. This phosphorylation is necessary and sufficient for RAIDD binding and caspase-2 activation. Conversely, nonphosphorylatable PIDD fails to bind RAIDD or activate caspase-2, and engages prosurvival RIP1 instead. Thus, ATM phosphorylation of the PIDD DD enables a binary switch through which cells elect to survive or die upon DNA injury.

SIGNOR-262640

P45983

P05412

1

phosphorylation

up-regulates activity

0.907

JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain.

SIGNOR-250122

P26583

P09086

2

binding

up-regulates activity

0.32

HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins

SIGNOR-240108

P62805

Q58F21

1

relocalization

up-regulates activity

0.2

BRDT interacts with acetylated nucleosomes via its BD1 domain. Binding may be initiated through non-specific interactions with DNA, which allow BRDT to localize to chromatin. Specificity is generated through recognition of tandem acetylated lysine residues (K5ac/K8ac) on the histone H4 tail,

SIGNOR-262066

Q96JA1

P00533

2

binding

down-regulates

0.736

Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation

SIGNOR-127304

P50548

P28482

0

phosphorylation

up-regulates

0.596

The experiments presented here indicate that erf is regulated during nuclear import and/or export and that this process depends on its phosphorylation by erks our analysis indicates that in addition to t526 (position 7), s161 (position 2), s246 (position 3), and s251 (position 4) are also phosphorylated in vitro by erk2 and in vivo after mitogenic stimulation (fig. 3a).

SIGNOR-67524

P01574

Q13526

0

transcriptional regulation

down-regulates quantity by repression

0.2

To investigate the temporal regulation of IRF3-dependent transcription by Pin1, we used a rapid-response luciferase reporter gene. Real-time reporter gene assays showed that suppression of endogenous Pin1 expression substantially prolonged both IRF3-dependent transcription and IFN-beta promoter activation after poly(I)dotpoly(C) stimulation (Fig. 4c,d). Consistent with the inhibitory effects of Pin1 on the IFN-beta promoter

SIGNOR-252289

Q9NUX5

P15927

2

binding

down-regulates activity

0.407

The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA

SIGNOR-263324

P46527

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.419

We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its stabilization after induction of DNA double-strand breaks.

SIGNOR-279392

P18433

Q9H267

1

dephosphorylation

down-regulates activity

0.2

Here, we report that VPS33B, a host protein involved in vesicle trafficking, is dephosphorylated by PtpA leading to a block of phagosome maturation by M. tuberculosis.|These data suggest that M. tuberculosis PtpA inhibits phagosome maturation.To assess the role of VPS33B in phagosome maturation, we attenuated the expression of endogenous VPS33B expression in THP-1 cells using a siRNA based approach.

SIGNOR-277015

P19793

Q03181

2

binding

up-regulates

0.582

Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology

SIGNOR-105442