GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q8TBJ5	Q16650	transcriptional regulation	down-regulates quantity by repression	0.486	We found that TBR1 promotes the identity of corticothalamic neurons and represses subcerebral fates through reducing expression of Fezf2 and CTIP2.\|(3) Chromatin immunoprecipitation analysis using TBR1 antibodies showed that TBR1 bound to a conserved region in the Fezf2 gene.	SIGNOR-268967
P43243	P35637	relocalization	up-regulates activity	0.486	Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates.	SIGNOR-262822
Q07812	P31749	phosphorylation	down-regulates activity	0.486	Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophilsWe suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members	SIGNOR-252538
P23458	Q9UHF4	binding	up-regulates	0.486	Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain.	SIGNOR-124486
P03372	P17612	phosphorylation	down-regulates	0.486	Phosphorylation of human estrogen receptor alpha by protein kinase a regulates dimerizationeralpha is phosphorylated by protein kinase a (pka) on serine-236 within the dna binding domain. Mutation of serine-236 to glutamic acid prevents dna binding by inhibiting dimerization by eralpha	SIGNOR-63984
P12931	P63096	binding	up-regulates activity	0.486	Here we demonstrate that Galphas and Galphai, but neither Galphaq, Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c-Src	SIGNOR-256526
Q9Y2T1	P53350	phosphorylation	up-regulates activity	0.486	Plk1 phosphorylates axin2 at Ser311.	SIGNOR-277180
Q13191	O43597	binding	down-regulates	0.486	One function of hspry2 in signaling processes downstream of rtks may be to modulate c-cbl physiological function such as that seen with receptor-mediated endocytosis.	SIGNOR-83507
P04150	P31749	phosphorylation	down-regulates	0.486	Akt1 impairs glucocorticoid-induced gene expression by direct phosphorylation of nr3c1 at position s134 and blocking glucocorticoid-induced nr3c1 translocation to the nucleus	SIGNOR-252543
P13569	P17612	phosphorylation	up-regulates	0.485	Cftr, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to camp agonists. Serines 660, 737, 795, and 813 were identified as in vivo targets for phosphorylation by protein kinase a.mutagenesis of all four sites abolished the response.	SIGNOR-21312
P29474	Q9Y243	phosphorylation	up-regulates activity	0.485	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-251626
Q99453	Q96F44	ubiquitination	down-regulates	0.485	The e3 ubiquitin ligasetrim11mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expandedphox2b.	SIGNOR-195878
P36956	P49841	phosphorylation	down-regulates quantity by destabilization	0.485	Importantly, we demonstrate that the mature form of endogenous SREBP1 is phosphorylated on Ser-434. Glycogen synthase kinase-3 phosphorylates Ser-434, and the phosphorylation of this residue is attenuated in response to insulin signaling. Interestingly, phosphorylation of Ser-434 promotes the glycogen synthase kinase-3-dependent phosphorylation of Thr-426 and Ser-430 and destabilizes SREBP1.	SIGNOR-236667
Q15121	O43464	binding	down-regulates	0.485	Htra2 promotes cell death by binding and degrading the anti-apoptotic protein pea15	SIGNOR-126966
P35637	Q99873	methylation	down-regulates activity	0.485	PRMT1 catalyzes the arginine methylation of Fused in Sarcoma (FUS), an RNA-binding protein that interacts with RALY. We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels, thus reducing FUS methylation. It is known that mutations in the FUS nuclear localization signal (NLS) retain the protein to the cytosol, promote aggregate formation, and are associated with amyotrophic lateral sclerosis.	SIGNOR-262274
Q03113	Q96RI0	binding	up-regulates	0.485	Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).	SIGNOR-196012
P30307	P27448	phosphorylation	down-regulates activity	0.485	C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. Phosphorylation of serine 21 6 promotes 1 4-3-3 binding to Cdc25C and is inhibitory to Cdc25C function.	SIGNOR-250176
P35222	O15111	phosphorylation	up-regulates quantity	0.485	Interestingly, while IKK2 negatively regulates beta-catenin stability similar to GSK3beta, IKK1 seems to increase beta-catenin protein level and downstream signal, such as cyclin D1 transcription.\|These results suggested IKK1 may phosphorylate beta-catenin at different residues and protect it from ubiquitination mediated degradation.	SIGNOR-280230
P63000	P52306	binding	up-regulates	0.485	Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob	SIGNOR-171418
Q99623	P31749	binding	down-regulates	0.485	Akt binds prohibitin 2 and relieves its repression of myod and muscle differentiation	SIGNOR-252541
P27695	P68400	phosphorylation	up-regulates activity	0.485	Here we demonstrate that APE/Ref-1 is phosphorylated by casein kinase II (CKII). This was shown for both the recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting DNA binding activity of AP-1.	SIGNOR-250825
Q8TDC3	Q15831	phosphorylation	up-regulates	0.485	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122413
P29992	P34981	binding	up-regulates activity	0.485	Binding of TRH to TRH-R1 receptor, which is coupled to Gq/11 protein, activates phospholipase C, mobilizes calcium and activates protein kinase C.	SIGNOR-267201
P42338	Q15303	binding	up-regulates	0.485	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146882
O94989	P29323	phosphorylation	down-regulates quantity by destabilization	0.485	We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. EphB2 mediates phosphorylation of Ephexin5 at tyrosine-361	SIGNOR-262864
P02452	P01137	transcriptional regulation	up-regulates quantity by expression	0.485	COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity	SIGNOR-277678
P62841	Q5S007	phosphorylation	up-regulates activity	0.485	Taken together, these results suggest that phosphorylation of s15 on T136 by LRRK2 mediates enhanced cap-dependent and cap-independent reporter translation and that a stimulatory effect of LRRK2 on mRNA translation contributes to LRRK2 toxicity.	SIGNOR-279058
Q02750	P00540	phosphorylation	up-regulates activity	0.485	Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222.	SIGNOR-260920
Q96P48	Q13882	phosphorylation	up-regulates activity	0.485	ARAP1 associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner. In addition, the SH2 domain of PTK6, particularly the Arg(105) residue that contacts the phosphate group of the tyrosine residue, was essential for the association. Moreover, PTK6 phosphorylated residue Tyr(231) in the N-terminal domain of ARAP1. Expression of ARAP1, but not of the Y231F mutant, inhibited the down-regulation of EGFR in HEK293 cells expressing PTK6. These results demonstrate that PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells.	SIGNOR-263188
P30679	P32238	binding	up-regulates activity	0.485	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-257410
Q12972	P17612	phosphorylation	down-regulates activity	0.484	NIPP-1 is the RNA-binding subunit of a major species of protein phosphatase-1 in the nucleus. The purified recombinant protein was a potent (Ki = 9.9 +/- 0.3 pM) and specific inhibitor of protein phosphatase-1 and was stoichiometrically phosphorylated by protein kinases A and CK2. At physiological ionic strength, phosphorylation by these protein kinases drastically decreased the inhibitory potency of free NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A	SIGNOR-250033
P08047	Q05513	phosphorylation	up-regulates	0.484	Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 binding to the platelet-derived growth factor-d promoter.	SIGNOR-160774
P25963	Q14164	phosphorylation	down-regulates quantity by destabilization	0.484	The activated ikk complex then phosphorylates ikbalfa (an inhibitor of nf-kb) thereby targeting it for ubiquitination and proteasomal degradation.	SIGNOR-167524
O95747	Q9H4A3	phosphorylation	up-regulates	0.484	Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1)	SIGNOR-151659
Q8NEB9	P51149	guanine nucleotide exchange factor	up-regulates activity	0.484	The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7	SIGNOR-261302
P55017	Q9UEW8	phosphorylation	down-regulates activity	0.484	SPAK directly phosphorylates NCC and its effects on NCC are universally associated with phosphorylation\|This adds to the evidence that SPAK-mediated phosphorylation acts primarily to increase activity of individual cotransporters without affecting the amount of NCC on the surface\| the kinase (SPAK) that phosphorylates NCC at T53	SIGNOR-264623
O95837	Q9HBW0	binding	up-regulates activity	0.484	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-257431
P00740	P03951	cleavage	up-regulates activity	0.484	Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX.\|The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets.	SIGNOR-263537
O14950	Q13153	phosphorylation	up-regulates activity	0.484	It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ].	SIGNOR-280053
P31749	P63151	binding	down-regulates activity	0.484	Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt.\|Phosphorylation of Akt at regulatory residues Thr-308 and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity. The PP2A holoenzyme consists of the structural \|Here we report the identification of the specific B regulatory subunit that targets the PP2A holoenzyme to Akt. We found endogenous association of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro-lymphoid FL5.12 cells.subunit (A), catalytic subunit (C), and a variable regulatory subunit (B).	SIGNOR-252637
P04899	P61073	binding	up-regulates activity	0.484	Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner	SIGNOR-278103
Q16659	P06493	phosphorylation	up-regulates	0.484	Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3. All four sites are followed by a proline residue. We have shown that purified cyclin b-cdk1 (cyclindependent kinase 1) phosphorylates these sitesalanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.	SIGNOR-164499
P14923	Q9UI47	relocalization	up-regulates quantity	0.484	Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14	SIGNOR-265494
P63027	Q9Y4I1	binding	up-regulates activity	0.484	Another potential role of myosin Va in LDCV exocytosis lies in facilitating the formation of the SNARE complex, which is needed for fusion of the vesicle with the plasma membrane. Notably, myosin Va binds to at least two SNARE proteins in a Ca2+-dependent manner: at micromolar Ca2+-levels, it binds to VAMP2 located in the membrane of the cargo vesicle via its globular tail domain	SIGNOR-269281
P53805	P49841	phosphorylation	up-regulates activity	0.484	Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively \|Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.	SIGNOR-249359
P40426	P17481	binding	up-regulates activity	0.484	the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.	SIGNOR-223149
Q9H1J5	Q92765	binding	down-regulates	0.484	We and others demonstrated that fzb-1 blocks wnt-1 and xwnt-8 signaling in xenopus embryos,	SIGNOR-51798
Q9BY44	Q9P2K8	phosphorylation	down-regulates activity	0.484	Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ).	SIGNOR-280005
Q99759	Q6Q0C0	binding	up-regulates	0.484	Traf7 specifically interacts with and activates mekk3.	SIGNOR-123221
Q9NQ66	P30679	binding	up-regulates activity	0.484	This suggests that both Gal4 and Gal6 can activate PLC b1.	SIGNOR-278120
P30281	Q9UKC9	binding	down-regulates quantity by destabilization	0.484	Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF (FBXL2) , impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation.	SIGNOR-271887
P04637	O43683	phosphorylation	up-regulates activity	0.484	In addition, purified Bub1 directly phosphorylates p53 on Ser-37 in vitro , possibly inducing cellular senescence [ xref ].\|Studies have shown that depletion and inhibition of Aurora A, Aurora B, Plk1, or Bub1 induces cellular senescence or cell death in a p53 dependent or -independent but p73 dependent manner in many different cell types , - ].	SIGNOR-280199
O14640	P34925	binding	up-regulates	0.483	Ryk also binds to dishevelled, through which it activates the canonical wnt, providing a link between wnt and dishevelled.	SIGNOR-129568
P55212	O60285	phosphorylation	down-regulates activity	0.483	ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system.	SIGNOR-250209
P54253	Q86Y13	polyubiquitination	down-regulates quantity by destabilization	0.483	HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation.	SIGNOR-272078
P50148	Q9UBY5	binding	up-regulates activity	0.483	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-257297
P63096	P14416	binding	up-regulates activity	0.483	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-256701
Q01094	P49336	phosphorylation	down-regulates	0.483	E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1.	SIGNOR-181078
Q96BY2	Q9HCM9	binding	up-regulates quantity by stabilization	0.483	TRIM39 stabilizes MOAP-1 by inhibiting the poly-ubiquitination process of MOAP-1.In this study, we report the identification and characterization of TRIM39 as a binding partner of MOAP-1. TRIM39 is the first regulator of MOAP-1 protein stability identified.	SIGNOR-272911
P60953	Q7Z6J4	guanine nucleotide exchange factor	up-regulates activity	0.483	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-260552
Q9NQ66	P62873	binding	down-regulates	0.483	These results indicate that g-protein beta gamma subunits constitute a mechanism by which g-protein mediate a rapid and transient plc- beta 1.	SIGNOR-44369
P28907	P16284	binding	up-regulates activity	0.483	As a receptor, CD38 interacts with its ligand CD31 [15,16]. CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a 130 kDa type I transmembrane glycoprotein that consists of six extracellular immunoglobulin-like homology domains, a 19-residue transmembrane domain, and a 118-residue cytoplasmic tail	SIGNOR-264254
P30307	Q8TDC3	phosphorylation	down-regulates	0.483	Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3	SIGNOR-56473
Q96GD4	Q9UKC9	binding	down-regulates quantity by destabilization	0.483	The SCF complex contains a catalytic core consisting of Skp1, Cullin1, and the E2 ubiquitin-conjugating (Ubc) enzyme and a F box component that acts as a receptor targeting numerous substrates via phosphodegron elicited interactions. our screening studies suggested that FBXL2 also targets Aurora B protein for ubiquitination and degradation.	SIGNOR-272097
P55771	Q9UGL1	binding	up-regulates activity	0.483	Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression	SIGNOR-223875
Q92934	P27361	phosphorylation	down-regulates	0.483	Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.	SIGNOR-188172
Q9UER7	O43791	ubiquitination	down-regulates quantity	0.483	These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis.	SIGNOR-268858
Q13363	P31749	phosphorylation	down-regulates quantity	0.483	Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.\|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.	SIGNOR-278304
Q04206	P67775	dephosphorylation	down-regulates	0.483	Rela was dephosphorylated by a purified pp2a core enzyme, a heterodimer formed by the catalytic subunit of pp2a (pp2ac) and pr65, in a concentration-dependent manner.These data suggest that the constitutive activation of rela in melanoma cells could be due, at least in part, to the deficiency of pp2a, which exhibits decreased dephosphorylation of nf-kappa b/rela.	SIGNOR-110959
Q13616	P01106	transcriptional regulation	up-regulates quantity by expression	0.483	Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2	SIGNOR-102749
Q969H0	Q9NYY3	phosphorylation	down-regulates	0.483	Plk2 regulates centriole duplication through phosphorylation-mediated degradation of fbxw7 (human cdc4).Plk2 phosphorylates fbxw7 on serine 176	SIGNOR-196448
Q12798	O43303	binding	up-regulates activity	0.483	We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.	SIGNOR-265966
O14672	Q86UF1	binding	up-regulates activity	0.483	Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11.	SIGNOR-261251
Q14527	Q96EP1	polyubiquitination	down-regulates quantity by destabilization	0.482	CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.	SIGNOR-271460
Q15797	P12757	binding	down-regulates	0.482	Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7	SIGNOR-195636
Q14582	P61244	binding	up-regulates activity	0.482	the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.	SIGNOR-240224
Q8TD19	P06493	phosphorylation	up-regulates activity	0.482	We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1.	SIGNOR-273889
Q6JBY9	Q16644	phosphorylation	down-regulates activity	0.482	Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263082
Q08211	P35637	relocalization	down-regulates activity	0.482	We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.\|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. \| We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons	SIGNOR-262810
Q969H0	P06748	binding	up-regulates quantity	0.482	We report here that NPM regulates turnover of the c-Myc oncoprotein by acting on the F-box protein Fbw7 , a component of the E3 ligase complex involved in the ubiquitination and proteasome degradation of c-Myc. NPM was required for nucleolar localization and stabili- zation of Fbw7	SIGNOR-245084
Q13887	Q14258	polyubiquitination	down-regulates quantity by destabilization	0.482	The oestrogen-inducible E3 ligase EFP (oestrogen-responsive finger protein) was identified as a key player in oestrogen-mediated degradation of KLF5, as knockdown and overexpression of EFP increased and decreased KLF5 protein levels respectively, and the decrease continued even when protein synthesis was blocked.	SIGNOR-271908
O95863	Q13315	phosphorylation	up-regulates activity	0.482	ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity.	SIGNOR-279587
P63092	P21918	binding	up-regulates activity	0.482	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 ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256771
P40763	P45984	phosphorylation	up-regulates	0.482	Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.	SIGNOR-179275
P07101	P27361	phosphorylation	up-regulates	0.482	In this paper we have studied the phosphorylation and activation of alternatively spliced forms of human th by mapkap kinase-1 , mapkap kinase-2, map kinase, and cam kinase-11	SIGNOR-34678
Q13702	Q9P2G9	binding	down-regulates quantity by destabilization	0.482	We found that rapsyn was polyubiquitinated by KLHL8-containing E3 ligase, but not by KEAP1-containing E3 ligase, clearly indicating that rapsyn is a direct substrate of KLHL8-containing E3 ligase in mammals. We next examined the effect of KLHL-8 depletion on the ubiquitination of rapsyn by performing RNAi experiments in mammalian cells. We found that knockdown of KLHL8 in 3T3 cells reduced the level of rapsyn ubiquitination (Fig. 5C), again indicating that the maintenance mechanism for rapsyn stability is conserved in mammals.The in vitro ubiquitination of mammalian rapsyn by CUL3-containing E3 ligase and the effect of KLHL8 knockdown on the ubiquitination of rapsyn.	SIGNOR-271781
P11388	P53350	phosphorylation	up-regulates	0.481	Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin	SIGNOR-182844
Q01970	P17252	phosphorylation	down-regulates	0.481	These data establish that direct phosphorylation by pka of ser1105 in the putative g-box of plcbeta3 inhibits galphaq-stimulated plcbeta3 activity.	SIGNOR-58859
P00533	P23470	dephosphorylation	down-regulates activity	0.481	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254699
Q04721	P49841	phosphorylation	down-regulates activity	0.481	We show that gsk-3beta directly binds at c-terminal of the notch2 ankyrin repeats and phosphorylates thr-2068 and/or ser-2070, thr-2074, and thr-2093.	SIGNOR-101570
Q96T58	P35548	binding	up-regulates	0.481	Furthermore, in addition to msx2, both tlx1 and nkx2-5 proteins interacted with notch-pathway repressors, spen/mint/sharp and tle1/grg1, representing a potential mechanism for (de)regulation.	SIGNOR-188572
Q96N96	Q96SB3	binding	up-regulates activity	0.481	Here we show that Asef2, but not Asef, interacts with Neurabin2/Spinophilin, a scaffold protein that binds to Filamentous actin (F-actin). Neurabin2 is required for Asef2-induced filopodia formation. RNA interference experiments showed that Asef2, Neurabin2 and APC are involved in HGF-induced cell migration. Furthermore, knockdown of Neurabin2 resulted in the suppression of Asef2-induced filopodia formation.	SIGNOR-269174
P04150	Q00535	phosphorylation	down-regulates activity	0.481	Cdk5 phosphorylated gr at multiple serines, including ser203 and ser211 of its n-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to dna.\| the effect of CDK5 on GR-induced transcriptional activity is specific to gene promoter, and possibly, to tissue	SIGNOR-154405
P49711	Q00341	binding	up-regulates activity	0.481	Vigilin interacts with CCCTC-binding factor (CTCF) and is involved in CTCF-dependent regulation of the imprinted genes Igf2 and H19. vigilin is present at several known CTCF target sites, such as the promoter regions of c-myc and BRCA1, the locus control region of β-globin, and several regions within the Igf2/H19 locus. These results reveal the functional relevance of vigilin and CTCF, and show that the CTCF-vigilin complex contributes to regulation of Igf2/H19.	SIGNOR-266693
P10243	Q92793	binding	up-regulates activity	0.481	CBP co-operates functionally with A-Myb	SIGNOR-240984
Q9H0K1	Q15831	phosphorylation	up-regulates	0.481	A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.	SIGNOR-122788
P31751	P62714	dephosphorylation	down-regulates	0.481	These results confirm that the activity changes observed are achieved by a reversible phosphorylation mechanism, and also argue that pp2a may negatively regulate rac-pk activity in vivo. Dephosphorylation of the activated rac-pk in itro by pp2ac resulted in an 87% reduction of kinase activity	SIGNOR-42123
P60568	Q03060	transcriptional regulation	down-regulates quantity by repression	0.481	In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production.	SIGNOR-261576
P38936	P11309	phosphorylation	up-regulates quantity by stabilization	0.481	Pim-2 phosphorylation of p21(cip1/waf1) enhances its stability and inhibits cell proliferation in hct116 cellshere we demonstrate that like pim-1, pim-2 also phosphorylates the cell cycle inhibitor p21(cip1/waf1) (p21) on thr145 in vitro and in vivo	SIGNOR-164642
P04275	P09958	cleavage	up-regulates activity	0.481	Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine	SIGNOR-260368

Q8TBJ5

Q16650

0

transcriptional regulation

down-regulates quantity by repression

0.486

We found that TBR1 promotes the identity of corticothalamic neurons and represses subcerebral fates through reducing expression of Fezf2 and CTIP2.|(3) Chromatin immunoprecipitation analysis using TBR1 antibodies showed that TBR1 bound to a conserved region in the Fezf2 gene.

SIGNOR-268967

P43243

P35637

0

relocalization

up-regulates activity

0.486

Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates.

SIGNOR-262822

Q07812

P31749

0

phosphorylation

down-regulates activity

0.486

Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophilsWe suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members

SIGNOR-252538

P23458

Q9UHF4

0

binding

up-regulates

0.486

Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain.

SIGNOR-124486

P03372

P17612

0

phosphorylation

down-regulates

0.486

Phosphorylation of human estrogen receptor alpha by protein kinase a regulates dimerizationeralpha is phosphorylated by protein kinase a (pka) on serine-236 within the dna binding domain. Mutation of serine-236 to glutamic acid prevents dna binding by inhibiting dimerization by eralpha

SIGNOR-63984

P12931

P63096

0

binding

up-regulates activity

0.486

Here we demonstrate that Galphas and Galphai, but neither Galphaq, Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c-Src

SIGNOR-256526

Q9Y2T1

P53350

0

phosphorylation

up-regulates activity

0.486

Plk1 phosphorylates axin2 at Ser311.

SIGNOR-277180

Q13191

O43597

0

binding

down-regulates

0.486

One function of hspry2 in signaling processes downstream of rtks may be to modulate c-cbl physiological function such as that seen with receptor-mediated endocytosis.

SIGNOR-83507

P04150

P31749

0

phosphorylation

down-regulates

0.486

Akt1 impairs glucocorticoid-induced gene expression by direct phosphorylation of nr3c1 at position s134 and blocking glucocorticoid-induced nr3c1 translocation to the nucleus

SIGNOR-252543

P13569

P17612

0

phosphorylation

up-regulates

0.485

Cftr, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to camp agonists. Serines 660, 737, 795, and 813 were identified as in vivo targets for phosphorylation by protein kinase a.mutagenesis of all four sites abolished the response.

SIGNOR-21312

P29474

Q9Y243

0

phosphorylation

up-regulates activity

0.485

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-251626

Q99453

Q96F44

0

ubiquitination

down-regulates

0.485

The e3 ubiquitin ligasetrim11mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expandedphox2b.

SIGNOR-195878

P36956

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.485

Importantly, we demonstrate that the mature form of endogenous SREBP1 is phosphorylated on Ser-434. Glycogen synthase kinase-3 phosphorylates Ser-434, and the phosphorylation of this residue is attenuated in response to insulin signaling. Interestingly, phosphorylation of Ser-434 promotes the glycogen synthase kinase-3-dependent phosphorylation of Thr-426 and Ser-430 and destabilizes SREBP1.

SIGNOR-236667

Q15121

O43464

0

binding

down-regulates

0.485

Htra2 promotes cell death by binding and degrading the anti-apoptotic protein pea15

SIGNOR-126966

P35637

Q99873

0

methylation

down-regulates activity

0.485

PRMT1 catalyzes the arginine methylation of Fused in Sarcoma (FUS), an RNA-binding protein that interacts with RALY. We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels, thus reducing FUS methylation. It is known that mutations in the FUS nuclear localization signal (NLS) retain the protein to the cytosol, promote aggregate formation, and are associated with amyotrophic lateral sclerosis.

SIGNOR-262274

Q03113

Q96RI0

0

binding

up-regulates

0.485

Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).

SIGNOR-196012

P30307

P27448

0

phosphorylation

down-regulates activity

0.485

C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. Phosphorylation of serine 21 6 promotes 1 4-3-3 binding to Cdc25C and is inhibitory to Cdc25C function.

SIGNOR-250176

P35222

O15111

0

phosphorylation

up-regulates quantity

0.485

Interestingly, while IKK2 negatively regulates beta-catenin stability similar to GSK3beta, IKK1 seems to increase beta-catenin protein level and downstream signal, such as cyclin D1 transcription.|These results suggested IKK1 may phosphorylate beta-catenin at different residues and protect it from ubiquitination mediated degradation.

SIGNOR-280230

P63000

P52306

0

binding

up-regulates

0.485

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

SIGNOR-171418

Q99623

P31749

0

binding

down-regulates

0.485

Akt binds prohibitin 2 and relieves its repression of myod and muscle differentiation

SIGNOR-252541

P27695

P68400

0

phosphorylation

up-regulates activity

0.485

Here we demonstrate that APE/Ref-1 is phosphorylated by casein kinase II (CKII). This was shown for both the recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting DNA binding activity of AP-1.

SIGNOR-250825

Q8TDC3

Q15831

0

phosphorylation

up-regulates

0.485

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122413

P29992

P34981

0

binding

up-regulates activity

0.485

Binding of TRH to TRH-R1 receptor, which is coupled to Gq/11 protein, activates phospholipase C, mobilizes calcium and activates protein kinase C.

SIGNOR-267201

P42338

Q15303

0

binding

up-regulates

0.485

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

SIGNOR-146882

O94989

P29323

0

phosphorylation

down-regulates quantity by destabilization

0.485

We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. EphB2 mediates phosphorylation of Ephexin5 at tyrosine-361

SIGNOR-262864

P02452

P01137

0

transcriptional regulation

up-regulates quantity by expression

0.485

COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity

SIGNOR-277678

P62841

Q5S007

0

phosphorylation

up-regulates activity

0.485

Taken together, these results suggest that phosphorylation of s15 on T136 by LRRK2 mediates enhanced cap-dependent and cap-independent reporter translation and that a stimulatory effect of LRRK2 on mRNA translation contributes to LRRK2 toxicity.

SIGNOR-279058

Q02750

P00540

0

phosphorylation

up-regulates activity

0.485

Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222.

SIGNOR-260920

Q96P48

Q13882

0

phosphorylation

up-regulates activity

0.485

ARAP1 associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner. In addition, the SH2 domain of PTK6, particularly the Arg(105) residue that contacts the phosphate group of the tyrosine residue, was essential for the association. Moreover, PTK6 phosphorylated residue Tyr(231) in the N-terminal domain of ARAP1. Expression of ARAP1, but not of the Y231F mutant, inhibited the down-regulation of EGFR in HEK293 cells expressing PTK6. These results demonstrate that PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells.

SIGNOR-263188

P30679

P32238

0

binding

up-regulates activity

0.485

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-257410

Q12972

P17612

0

phosphorylation

down-regulates activity

0.484

NIPP-1 is the RNA-binding subunit of a major species of protein phosphatase-1 in the nucleus. The purified recombinant protein was a potent (Ki = 9.9 +/- 0.3 pM) and specific inhibitor of protein phosphatase-1 and was stoichiometrically phosphorylated by protein kinases A and CK2. At physiological ionic strength, phosphorylation by these protein kinases drastically decreased the inhibitory potency of free NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A

SIGNOR-250033

P08047

Q05513

0

phosphorylation

up-regulates

0.484

Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 binding to the platelet-derived growth factor-d promoter.

SIGNOR-160774

P25963

Q14164

0

phosphorylation

down-regulates quantity by destabilization

0.484

The activated ikk complex then phosphorylates ikbalfa (an inhibitor of nf-kb) thereby targeting it for ubiquitination and proteasomal degradation.

SIGNOR-167524

O95747

Q9H4A3

0

phosphorylation

up-regulates

0.484

Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1)

SIGNOR-151659

Q8NEB9

P51149

0

guanine nucleotide exchange factor

up-regulates activity

0.484

The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7

SIGNOR-261302

P55017

Q9UEW8

0

phosphorylation

down-regulates activity

0.484

SPAK directly phosphorylates NCC and its effects on NCC are universally associated with phosphorylation|This adds to the evidence that SPAK-mediated phosphorylation acts primarily to increase activity of individual cotransporters without affecting the amount of NCC on the surface| the kinase (SPAK) that phosphorylates NCC at T53

SIGNOR-264623

O95837

Q9HBW0

0

binding

up-regulates activity

0.484

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-257431

P00740

P03951

0

cleavage

up-regulates activity

0.484

Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX.|The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets.

SIGNOR-263537

O14950

Q13153

0

phosphorylation

up-regulates activity

0.484

It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ].

SIGNOR-280053

P31749

P63151

0

binding

down-regulates activity

0.484

Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt.|Phosphorylation of Akt at regulatory residues Thr-308 and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity. The PP2A holoenzyme consists of the structural |Here we report the identification of the specific B regulatory subunit that targets the PP2A holoenzyme to Akt. We found endogenous association of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro-lymphoid FL5.12 cells.subunit (A), catalytic subunit (C), and a variable regulatory subunit (B).

SIGNOR-252637

P04899

P61073

0

binding

up-regulates activity

0.484

Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner

SIGNOR-278103

Q16659

P06493

0

phosphorylation

up-regulates

0.484

Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3. All four sites are followed by a proline residue. We have shown that purified cyclin b-cdk1 (cyclindependent kinase 1) phosphorylates these sitesalanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.

SIGNOR-164499

P14923

Q9UI47

0

relocalization

up-regulates quantity

0.484

Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14

SIGNOR-265494

P63027

Q9Y4I1

0

binding

up-regulates activity

0.484

Another potential role of myosin Va in LDCV exocytosis lies in facilitating the formation of the SNARE complex, which is needed for fusion of the vesicle with the plasma membrane. Notably, myosin Va binds to at least two SNARE proteins in a Ca2+-dependent manner: at micromolar Ca2+-levels, it binds to VAMP2 located in the membrane of the cargo vesicle via its globular tail domain

SIGNOR-269281

P53805

P49841

0

phosphorylation

up-regulates activity

0.484

Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.

SIGNOR-249359

P40426

P17481

0

binding

up-regulates activity

0.484

the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.

SIGNOR-223149

Q9H1J5

Q92765

0

binding

down-regulates

0.484

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

SIGNOR-51798

Q9BY44

Q9P2K8

0

phosphorylation

down-regulates activity

0.484

Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ).

SIGNOR-280005

Q99759

Q6Q0C0

0

binding

up-regulates

0.484

Traf7 specifically interacts with and activates mekk3.

SIGNOR-123221

Q9NQ66

P30679

0

binding

up-regulates activity

0.484

This suggests that both Gal4 and Gal6 can activate PLC b1.

SIGNOR-278120

P30281

Q9UKC9

0

binding

down-regulates quantity by destabilization

0.484

Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF (FBXL2) , impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation.

SIGNOR-271887

P04637

O43683

0

phosphorylation

up-regulates activity

0.484

In addition, purified Bub1 directly phosphorylates p53 on Ser-37 in vitro , possibly inducing cellular senescence [ xref ].|Studies have shown that depletion and inhibition of Aurora A, Aurora B, Plk1, or Bub1 induces cellular senescence or cell death in a p53 dependent or -independent but p73 dependent manner in many different cell types , - ].

SIGNOR-280199

O14640

P34925

0

binding

up-regulates

0.483

Ryk also binds to dishevelled, through which it activates the canonical wnt, providing a link between wnt and dishevelled.

SIGNOR-129568

P55212

O60285

0

phosphorylation

down-regulates activity

0.483

ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system.

SIGNOR-250209

P54253

Q86Y13

0

polyubiquitination

down-regulates quantity by destabilization

0.483

HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation.

SIGNOR-272078

P50148

Q9UBY5

0

binding

up-regulates activity

0.483

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-257297

P63096

P14416

0

binding

up-regulates activity

0.483

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-256701

Q01094

P49336

0

phosphorylation

down-regulates

0.483

E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1.

SIGNOR-181078

Q96BY2

Q9HCM9

0

binding

up-regulates quantity by stabilization

0.483

TRIM39 stabilizes MOAP-1 by inhibiting the poly-ubiquitination process of MOAP-1.In this study, we report the identification and characterization of TRIM39 as a binding partner of MOAP-1. TRIM39 is the first regulator of MOAP-1 protein stability identified.

SIGNOR-272911

P60953

Q7Z6J4

0

guanine nucleotide exchange factor

up-regulates activity

0.483

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-260552

Q9NQ66

P62873

0

binding

down-regulates

0.483

These results indicate that g-protein beta gamma subunits constitute a mechanism by which g-protein mediate a rapid and transient plc- beta 1.

SIGNOR-44369

P28907

P16284

0

binding

up-regulates activity

0.483

As a receptor, CD38 interacts with its ligand CD31 [15,16]. CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a 130 kDa type I transmembrane glycoprotein that consists of six extracellular immunoglobulin-like homology domains, a 19-residue transmembrane domain, and a 118-residue cytoplasmic tail

SIGNOR-264254

P30307

Q8TDC3

0

phosphorylation

down-regulates

0.483

Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3

SIGNOR-56473

Q96GD4

Q9UKC9

0

binding

down-regulates quantity by destabilization

0.483

The SCF complex contains a catalytic core consisting of Skp1, Cullin1, and the E2 ubiquitin-conjugating (Ubc) enzyme and a F box component that acts as a receptor targeting numerous substrates via phosphodegron elicited interactions. our screening studies suggested that FBXL2 also targets Aurora B protein for ubiquitination and degradation.

SIGNOR-272097

P55771

Q9UGL1

0

binding

up-regulates activity

0.483

Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression

SIGNOR-223875

Q92934

P27361

0

phosphorylation

down-regulates

0.483

Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.

SIGNOR-188172

Q9UER7

O43791

0

ubiquitination

down-regulates quantity

0.483

These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis.

SIGNOR-268858

Q13363

P31749

0

phosphorylation

down-regulates quantity

0.483

Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.

SIGNOR-278304

Q04206

P67775

0

dephosphorylation

down-regulates

0.483

Rela was dephosphorylated by a purified pp2a core enzyme, a heterodimer formed by the catalytic subunit of pp2a (pp2ac) and pr65, in a concentration-dependent manner.These data suggest that the constitutive activation of rela in melanoma cells could be due, at least in part, to the deficiency of pp2a, which exhibits decreased dephosphorylation of nf-kappa b/rela.

SIGNOR-110959

Q13616

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.483

Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2

SIGNOR-102749

Q969H0

Q9NYY3

0

phosphorylation

down-regulates

0.483

Plk2 regulates centriole duplication through phosphorylation-mediated degradation of fbxw7 (human cdc4).Plk2 phosphorylates fbxw7 on serine 176

SIGNOR-196448

Q12798

O43303

0

binding

up-regulates activity

0.483

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

SIGNOR-265966

O14672

Q86UF1

0

binding

up-regulates activity

0.483

Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11.

SIGNOR-261251

Q14527

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.482

CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.

SIGNOR-271460

Q15797

P12757

0

binding

down-regulates

0.482

Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7

SIGNOR-195636

Q14582

P61244

0

binding

up-regulates activity

0.482

the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.

SIGNOR-240224

Q8TD19

P06493

0

phosphorylation

up-regulates activity

0.482

We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1.

SIGNOR-273889

Q6JBY9

Q16644

0

phosphorylation

down-regulates activity

0.482

Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263082

Q08211

P35637

0

relocalization

down-regulates activity

0.482

We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons

SIGNOR-262810

Q969H0

P06748

0

binding

up-regulates quantity

0.482

We report here that NPM regulates turnover of the c-Myc oncoprotein by acting on the F-box protein Fbw7 , a component of the E3 ligase complex involved in the ubiquitination and proteasome degradation of c-Myc. NPM was required for nucleolar localization and stabili- zation of Fbw7

SIGNOR-245084

Q13887

Q14258

0

polyubiquitination

down-regulates quantity by destabilization

0.482

The oestrogen-inducible E3 ligase EFP (oestrogen-responsive finger protein) was identified as a key player in oestrogen-mediated degradation of KLF5, as knockdown and overexpression of EFP increased and decreased KLF5 protein levels respectively, and the decrease continued even when protein synthesis was blocked.

SIGNOR-271908

O95863

Q13315

0

phosphorylation

up-regulates activity

0.482

ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity.

SIGNOR-279587

P63092

P21918

0

binding

up-regulates activity

0.482

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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256771

P40763

P45984

0

phosphorylation

up-regulates

0.482

Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

SIGNOR-179275

P07101

P27361

0

phosphorylation

up-regulates

0.482

In this paper we have studied the phosphorylation and activation of alternatively spliced forms of human th by mapkap kinase-1 , mapkap kinase-2, map kinase, and cam kinase-11

SIGNOR-34678

Q13702

Q9P2G9

0

binding

down-regulates quantity by destabilization

0.482

We found that rapsyn was polyubiquitinated by KLHL8-containing E3 ligase, but not by KEAP1-containing E3 ligase, clearly indicating that rapsyn is a direct substrate of KLHL8-containing E3 ligase in mammals. We next examined the effect of KLHL-8 depletion on the ubiquitination of rapsyn by performing RNAi experiments in mammalian cells. We found that knockdown of KLHL8 in 3T3 cells reduced the level of rapsyn ubiquitination (Fig. 5C), again indicating that the maintenance mechanism for rapsyn stability is conserved in mammals.The in vitro ubiquitination of mammalian rapsyn by CUL3-containing E3 ligase and the effect of KLHL8 knockdown on the ubiquitination of rapsyn.

SIGNOR-271781

P11388

P53350

0

phosphorylation

up-regulates

0.481

Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin

SIGNOR-182844

Q01970

P17252

0

phosphorylation

down-regulates

0.481

These data establish that direct phosphorylation by pka of ser1105 in the putative g-box of plcbeta3 inhibits galphaq-stimulated plcbeta3 activity.

SIGNOR-58859

P00533

P23470

0

dephosphorylation

down-regulates activity

0.481

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254699

Q04721

P49841

0

phosphorylation

down-regulates activity

0.481

We show that gsk-3beta directly binds at c-terminal of the notch2 ankyrin repeats and phosphorylates thr-2068 and/or ser-2070, thr-2074, and thr-2093.

SIGNOR-101570

Q96T58

P35548

0

binding

up-regulates

0.481

Furthermore, in addition to msx2, both tlx1 and nkx2-5 proteins interacted with notch-pathway repressors, spen/mint/sharp and tle1/grg1, representing a potential mechanism for (de)regulation.

SIGNOR-188572

Q96N96

Q96SB3

0

binding

up-regulates activity

0.481

Here we show that Asef2, but not Asef, interacts with Neurabin2/Spinophilin, a scaffold protein that binds to Filamentous actin (F-actin). Neurabin2 is required for Asef2-induced filopodia formation. RNA interference experiments showed that Asef2, Neurabin2 and APC are involved in HGF-induced cell migration. Furthermore, knockdown of Neurabin2 resulted in the suppression of Asef2-induced filopodia formation.

SIGNOR-269174

P04150

Q00535

0

phosphorylation

down-regulates activity

0.481

Cdk5 phosphorylated gr at multiple serines, including ser203 and ser211 of its n-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to dna.| the effect of CDK5 on GR-induced transcriptional activity is specific to gene promoter, and possibly, to tissue

SIGNOR-154405

P49711

Q00341

0

binding

up-regulates activity

0.481

Vigilin interacts with CCCTC-binding factor (CTCF) and is involved in CTCF-dependent regulation of the imprinted genes Igf2 and H19. vigilin is present at several known CTCF target sites, such as the promoter regions of c-myc and BRCA1, the locus control region of β-globin, and several regions within the Igf2/H19 locus. These results reveal the functional relevance of vigilin and CTCF, and show that the CTCF-vigilin complex contributes to regulation of Igf2/H19.

SIGNOR-266693

P10243

Q92793

0

binding

up-regulates activity

0.481

CBP co-operates functionally with A-Myb

SIGNOR-240984

Q9H0K1

Q15831

0

phosphorylation

up-regulates

0.481

A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.

SIGNOR-122788

P31751

P62714

0

dephosphorylation

down-regulates

0.481

These results confirm that the activity changes observed are achieved by a reversible phosphorylation mechanism, and also argue that pp2a may negatively regulate rac-pk activity in vivo. Dephosphorylation of the activated rac-pk in itro by pp2ac resulted in an 87% reduction of kinase activity

SIGNOR-42123

P60568

Q03060

0

transcriptional regulation

down-regulates quantity by repression

0.481

In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production.

SIGNOR-261576

P38936

P11309

0

phosphorylation

up-regulates quantity by stabilization

0.481

Pim-2 phosphorylation of p21(cip1/waf1) enhances its stability and inhibits cell proliferation in hct116 cellshere we demonstrate that like pim-1, pim-2 also phosphorylates the cell cycle inhibitor p21(cip1/waf1) (p21) on thr145 in vitro and in vivo

SIGNOR-164642

P04275

P09958

0

cleavage

up-regulates activity

0.481

Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine

SIGNOR-260368