GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 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
Q92847	P08754	1	binding	up-regulates activity	0.373	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-257167
O43318	Q15797	1	phosphorylation	up-regulates activity	0.373	This analysis showed that phosphorylation of Smad1 at the C-terminal serines S463 and S465 was increased by co-expression of constitutively active TAK1.	SIGNOR-279419
P04626	P00519	1	phosphorylation	up-regulates activity	0.373	In this study, we show that Abl kinase SH2 domains bind directly to Her-2, and like PDGFR-beta, Her-2 directly phosphorylates c-Abl.	SIGNOR-279407
Q12986	Q96ST3	1	binding	up-regulates activity	0.373	we investigated the mechanism of NFX1-91 repression of the hTERT promoter and demonstrated that NFX1-91 interacts with the corepressor mSin3A/HDAC to maintain the deacetylated status at the hTERT promoter, thus providing a mechanism by which NFX1-91 represses hTERT expression.	SIGNOR-226360
P53350	P54274	1	phosphorylation	up-regulates	0.373	Plk1 phosphorylation of trf1 is essential for its binding to telomeres	SIGNOR-179461
Q15744	P53567	1	binding	up-regulates activity	0.373	C/EBP-epsilon interacts with C/EBP-gamma through the leucine-zipper containing domain. C/EBP-epsilon and C/EBP-gamma synergistically activate transcription of lactoferrin promoter	SIGNOR-224900
P68400	Q9Y5B0	1	phosphorylation	down-regulates activity	0.373	We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.\| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. \| Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified	SIGNOR-250844
Q08345	Q06124	1	relocalization	up-regulates activity	0.373	Overexpression of DDR1a/b increased the interaction of DDR1 with SHP-2 and up-regulated the tyrosine phosphatase activity of SHP-2.	SIGNOR-272403
P43088	P63092	1	binding	up-regulates activity	0.373	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-256810
Q99576	Q04206	1	binding	down-regulates activity	0.373	GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits.	SIGNOR-253297
Q15233	P11387	1	binding	up-regulates	0.373	We show that the psf/p54 dimer has pronounced stimulatory effect on dna catalysis by topoisomerase i	SIGNOR-60557
P18089	Q03113	1	binding	up-regulates activity	0.373	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-257201
P12931	P55211	1	phosphorylation	up-regulates activity	0.373	As a result, we established that Src was able to directly phosphorylate caspase-9 at tyrosine 251, leading to elevated caspase-9 activity.	SIGNOR-272998
P46934	P10523	1	polyubiquitination	down-regulates quantity by destabilization	0.373	Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.	SIGNOR-272843
Q8IV08	P05067	1	binding	up-regulates quantity	0.373	Furthermore, PLD3 can be co-immunoprecipitated with APP in cultured cells (Extended Data Figure 4). Together, these studies demonstrate that PLD3 plays a role in APP processing. Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing.	SIGNOR-261200
Q16539	O15519	1	phosphorylation	up-regulates	0.373	Here we demonstrate that m. tuberculosis?induced Tnf triggered reactive oxygen species?dependent Activation of ask1 and the tyrosine kinase c-abl (a000161) in mouse macrophages and that flips was phosphorylated on tyr211 and ser4 by c-abl and p38, respectively.	SIGNOR-187001
O75487	P41221	1	binding	up-regulates	0.373	Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways	SIGNOR-195752
Q13546	Q9UHD2	2	phosphorylation	up-regulates activity	0.373	Additionally, RIPK1-dependent hyper-phosphorylation of TBK1 in Casp8 Ripk3 cells occurred during MNV-1 infection (Figure 4F).\|RIPK1 and its kinase activity were required to promote increased TBK1 phosphorylation in the absence of caspase-8 (Figure 3E), suggesting that RIPK1 may promote TBK1 activation.	SIGNOR-279278
Q96GD4	P01106	1	phosphorylation	up-regulates quantity by stabilization	0.373	AURKB directly phosphorylates MYC at serine 67, counteracting GSK3\u03b2-directed threonine 58 phosphorylation and subsequent FBXW7- mediated proteasomal degradation.	SIGNOR-279439
P35680	P16220	1	binding	up-regulates activity	0.373	The mammalian two-hybrid system showed that the region aa 393 to 476 of LFB3 is involved in the interaction with CREB or ATF1. The importance of this region for mediating cAMP induction was confirmed in transient transfection assays.	SIGNOR-241323
Q8NFU7	P60484	1	transcriptional regulation	up-regulates quantity by expression	0.373	We also found that TET1 directly binds to the promoter region of PTEN and activates its transcription through demethylation of CpG islands	SIGNOR-259096
Q07021	P04264	1	binding	up-regulates activity	0.373	Cytokeratin 1 binds to both gC1qR and u-PAR. Our data suggest that formation of HK (and Factor XII) binding sites along endothelial cell membranes consists of bimolecular com-plexes of gC1qR-cytokeratin 1 and u-PAR-cytokeratin 1, with gC1qR binding being favored.	SIGNOR-251881
Q96EP1	Q96EB6	1	ubiquitination	down-regulates quantity	0.372	CHFR binds to and ubiquitylates SIRT1, leading to its proteasomal degradation.\|CHFR ubiquitylates and promotes the proteasomal degradation of SIRT1.	SIGNOR-278691
Q9UPW6	Q9H3D4	1	binding	down-regulates activity	0.372	SATB2 attenuates p63-mediated gene expression of perp (p53 apoptosis effector related to PMP-22), a critical downstream target gene during development, and specifically decreases p63 perp promoter binding.	SIGNOR-255149
P68400	P31749	1	phosphorylation	up-regulates	0.372	CK2 hyperactivates AKT by phosphorylation at Ser129	SIGNOR-252595
Q16539	Q15910	1	phosphorylation	down-regulates quantity by destabilization	0.372	Here, we show that p38α kinase promotes EZH2 degradation in differentiating muscle cells through phosphorylation of threonine 372	SIGNOR-255663
O00308	P11161	1	ubiquitination	down-regulates quantity	0.372	The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination\|AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death.	SIGNOR-268849
P68400	Q93009	1	phosphorylation	up-regulates quantity by stabilization	0.372	We find that stabilization of Mdm2, and correspondingly p53 downregulation in unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by the protein kinase CK2. Phosphorylation stabilizes USP7S and thus contributes to Mdm2 stabilization and downregulation of p53.	SIGNOR-276530
P12931	Q13002	1	phosphorylation	up-regulates activity	0.372	GluK2 binds to Src, and the tyrosine residue at position 590 (Y590) on GluK2 is a major site of phosphorylation by Src kinases. GluK2 phosphorylation at Y590 is responsible for increases in whole-cell currents and calcium influx in response to transient kainate stimulation.	SIGNOR-276850
P06493	Q01167	1	phosphorylation	up-regulates	0.372	We have mapped two cdk phosphorylation sites, serines 368 and 423, which play a role in defining foxk2 function through regulating its stability and its activity as a transcriptional repressor protein. These two cdk sites appear vital for foxk2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis.	SIGNOR-167826
P24941	P17480	1	phosphorylation	up-regulates activity	0.372	Phosphorylation of ubf at serine 388 is required for interaction with rna polymerase i and activation of rdna transcription. After g(1) progression ubf is phosphorylated at serine 388 by cdk2/cyclin e and cdk2/cyclin a. Conversion of serine 388 to glycine abolishes ubf activity	SIGNOR-235419
P04637	Q8IUQ4	1	transcriptional regulation	up-regulates quantity by expression	0.372	P53 directly induces the expression of Siah-1 and in turn formation of a unique SCF-like complex (SCF(TBL1)) comprised of Siah-1, Siah-1-interacting protein (SIP), Skp1, transducin β-like 1 (TBL1), and APC	SIGNOR-271953
O14672	P35070	1	cleavage	up-regulates activity	0.372	Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin	SIGNOR-259839
P45983	P61978	1	phosphorylation	up-regulates	0.372	The current studies demonstrate the identification of hnrnp-k as a jnk and erk substrate. The phosphoacceptor sites for jnk and erk on the k protein are different, and indeed, erk phosphorylation results in biological consequences different from those of phosphorylation by jnk (49). Whereas erk phosphorylation on aa 284 and 353 contributes to k protein nuclear export and concomitant inhibition of rna translation (49), phosphorylation by k protein on aa 216 and 353 increases the transcriptional effects of the k protein.	SIGNOR-105770
P24941	O75469	1	phosphorylation	down-regulates quantity by destabilization	0.372	PXR Phosphorylation at S350 by CDK2 Triggers PXR Degradation via the Ubiquitin-Proteasome Pathway.	SIGNOR-279397
O95714	Q9Y2K6	1	ubiquitination	down-regulates quantity	0.372	HERC2 promotes USP20 degradation.\|Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase.	SIGNOR-278692
Q96MT8	P24941	1	relocalization	up-regulates activity	0.372	Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.	SIGNOR-271725
P24941	P12272	1	phosphorylation	down-regulates	0.372	Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization	SIGNOR-68548
Q9UKA4	P49841	2	binding	down-regulates activity	0.372	A-kinase anchoring protein 220 (AKAP220) is a multivalent anchoring protein that can sequester a variety of signal transduction enzymes. These include protein kinase A (PKA) and glycogen synthase kinase 3beta (GSK3beta). Using a combination of molecular and cellular approaches we show that GSK3beta phosphorylation of Thr-1132 on AKAP220 initiates recruitment of this kinase into the enzyme scaffold. We also find that AKAP220 anchors GSK3beta and its substrate beta-catenin in membrane ruffles.	SIGNOR-264817
P55212	P49768	1	cleavage	up-regulates activity	0.372	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261753
O75688	P37231	1	dephosphorylation	up-regulates activity	0.372	Furthermore we show that PPM1B can directly dephosphorylate PPARgamma, both in intact cells and in vitro.\|In addition PPM1B increases PPARγ-mediated transcription via dephosphorylation of Ser(112).\|The serine/threonine phosphatase PPM1B (PP2Cbeta) selectively modulates PPARgamma activity.	SIGNOR-277073
Q5VUA4	P10275	1	binding	down-regulates activity	0.372	Using different promoters and cells, we confirmed that AR-mediated transactivation was repressed by TZF in a dose-dependent manner (Fig. 1A and B). Endogenous ARmediated transactivation was also inhibited by expression of TZF; These results indicate that amino acid residues 512–663 are essential for the repressive effect of TZF on AR-mediated transactivation.	SIGNOR-261187
P49841	Q9UKA4	2	phosphorylation	down-regulates activity	0.372	A-kinase anchoring protein 220 (AKAP220) is a multivalent anchoring protein that can sequester a variety of signal transduction enzymes. These include protein kinase A (PKA) and glycogen synthase kinase 3beta (GSK3beta). Using a combination of molecular and cellular approaches we show that GSK3beta phosphorylation of Thr-1132 on AKAP220 initiates recruitment of this kinase into the enzyme scaffold. We also find that AKAP220 anchors GSK3beta and its substrate beta-catenin in membrane ruffles.	SIGNOR-264816
P46934	P37840	1	ubiquitination	down-regulates quantity by destabilization	0.372	Here we show that the ubiquitin ligase Nedd4, which functions in the endosomal-lysosomal pathway, robustly ubiquitinates alpha-synuclein, unlike ligases previously implicated in its degradation.	SIGNOR-278611
Q96GD4	Q8NEM2	1	phosphorylation	up-regulates activity	0.372	AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing.	SIGNOR-273552
P31751	P18031	1	phosphorylation	down-regulates activity	0.372	We conclude that ptp1b is a novel substrate for akt and that phosphorylation of ptp1b by akt at ser(50) may negatively modulate its phosphatase activity creating a positive feedback mechanism forinsulin signaling	SIGNOR-235491
O00743	O43318	1	dephosphorylation	down-regulates activity	0.372	Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway\|From proteomic analysis of TAK1-binding proteins, we identified protein phosphatase 6 (PP6), a type-2A phosphatase, and demonstrated that PP6 associated with and inactivated TAK1 by dephosphorylation of Thr-187.	SIGNOR-248292
O14965	P00352	1	phosphorylation	up-regulates activity	0.372	AURKA phosphorylates ALDH1A1 at three critical residues which exert a multifaceted regulation over its level, enzymatic activity, and quaternary structure. While all three phosphorylation sites contribute to its increased stability, T267 phosphorylation primarily regulates ALDH1A1 activity. AURKA-mediated phosphorylation rapidly dissociates tetrameric ALDH1A1 into a highly active monomeric species.	SIGNOR-276748
P20340	Q7Z7G8	1	binding	down-regulates activity	0.372	Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. COH1 Golgi Localization Is Mediated by Active RAB6 . COH1 Interacts with All Three Mammalian RAB6 Homologues	SIGNOR-269203
O00141	P42858	1	phosphorylation	down-regulates	0.372	The serum- and glucocorticoid-induced kinase sgk inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin.	SIGNOR-121349
O15111	P46527	1	phosphorylation	down-regulates activity	0.372	Reduced nuclear p27 was also found in MCF7 human breast cancer cells that were transiently transfected with an IKKalpha expression vector; increased IKKalpha expression resulted in a dose dependent decrease in nuclear p27 and increased cytoplasmic p27 (XREF_FIG).\|We found that IKKalpha phosphorylates p27 at S183 to cause its nuclear export.	SIGNOR-278438
P12931	Q8IW41	1	phosphorylation	up-regulates quantity	0.372	These data strongly suggest that PRAK phosphorylation by Src on Y188 and Y216 drives the relocalization of PRAK to focal adhesion structures during cell adhesion.	SIGNOR-279762
P67775	Q99759	1	dephosphorylation	down-regulates	0.372	Pp2ac binds to the phosphorylated mekk3 and subsequently dephosphorylate mekk3 at thr-516, ser-520, and ser-526 residues to terminate mekk3-mediated ikkbeta/Nf-kappaB Activation	SIGNOR-165233
P07766	P16333	1	relocalization	up-regulates activity	0.372	We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ϵ and results in recruitment of the adaptor protein Nck.	SIGNOR-259934
P23443	P27708	1	phosphorylation	up-regulates activity	0.372	CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.	SIGNOR-267443
Q9Y463	Q9UQL6	1	phosphorylation	down-regulates activity	0.372	Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent mannermirk phosphorylates hdac5 at ser-279	SIGNOR-235809
P23246	P11387	1	binding	up-regulates	0.372	We show that the psf/p54 dimer has pronounced stimulatory effect on dna catalysis by topoisomerase i	SIGNOR-60563
P50542	Q13501	1	binding	up-regulates activity	0.372	Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.	SIGNOR-262793
O14543	Q9Y286	1	binding	down-regulates quantity by destabilization	0.372	SOCS proteins can act as E3 ligases by forming a complex with Elongin B/C and Cul5/Rbx1/2.SOCS3 targets Siglec 7 for degradation	SIGNOR-272642
Q9UQM7	P28329	1	phosphorylation	up-regulates	0.372	We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.	SIGNOR-96628
P27361	P15923	1	phosphorylation	down-regulates quantity by destabilization	0.372	Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. \|Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)\|anti_phospho_M2 peptide (SSPSpTPVGSPQG)	SIGNOR-249117
P54646	P06213	1	phosphorylation	up-regulates	0.372	Ampk phosphorylates and activates theinsulinreceptor, providing a direct link between ampk and theinsulin pathway.	SIGNOR-195324
P28482	Q96RK0	1	phosphorylation	down-regulates	0.372	Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3))[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3	SIGNOR-169875
P31749	Q96HP0	1	phosphorylation	up-regulates activity	0.372	Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons\|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). \| In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching	SIGNOR-275666
P17612	P49840	1	phosphorylation	down-regulates	0.372	Phosphorylation of ser21 and inactivation of glycogen synthase kinase 3 by protein kinase a.	SIGNOR-83221
Q969H0	Q9UHV7	1	ubiquitination	down-regulates quantity by destabilization	0.371	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-266690
P11309	Q92934	1	phosphorylation	down-regulates activity	0.371	Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.	SIGNOR-250390
Q13131	P98177	1	phosphorylation	up-regulates	0.371	The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt phosphorylation sites, resulting in foxo activation	SIGNOR-157947
P48729	P37840	1	phosphorylation	up-regulates	0.371	In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.	SIGNOR-73799
Q00535	P29474	1	phosphorylation	down-regulates	0.371	Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels.	SIGNOR-164080
Q9UQM7	P00533	1	phosphorylation	down-regulates activity	0.371	We show that serines 1046/1047 are sites for CaM kinase II phosphorylation, although there is a preference for serine 1047, which resides within the consensus -R-X-X-S-. In addition, we have identified major phosphorylation sites at serine 1142 and serine 1057, which lie within a novel -S-X-D- consensus. Mutation of serines 1046/1047 in full-length EGFR enhanced both fibroblast transformation and tyrosine autokinase activity that was significantly potentiated by additional mutation of serines 1057 and 1142. A single CaM kinase II site was also identified at serine 744 within sub-kinase domain III, and autokinase activity was significantly affected by mutation of this serine to an aspartic acid making this site appear constitutively phosphorylated. We have addressed the mechanism by which CaM kinase II phosphorylation of the EGFR might regulate receptor autokinase activity and show that this modification can hinder association of the cytoplasmic tail with the kinase domain to prevent an enzyme-substrate interaction.	SIGNOR-250621
Q8IZP0	P22681	1	binding	up-regulates	0.371	Here we uncover a novel interaction between abi-1 and the cbl ubiquitin ligase and show that abi-1 mediates cbl accumulation to the plasma membrane upon stimulation by egf.	SIGNOR-154162
Q15139	Q96QB1	1	phosphorylation	down-regulates	0.371	The tumor suppressor protein dlc1 is regulated by pkd-mediated gap domain phosphorylation.Our results thus show that pkd-mediated phosphorylation of dlc1 on serine 807 negatively regulates dlc1 cellular function.	SIGNOR-169994
P15884	P01106	1	transcriptional regulation	up-regulates quantity by expression	0.371	Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription.	SIGNOR-253324
Q01543	Q13351	2	binding	down-regulates activity	0.371	FLI-1 represses the transcriptional activity of EKLF.Our data indicate that the ETS domain of FLI-1 is absolutely required to inhibit EKLF activity. Since the FLI-1 ETS domain interacts with the DNA binding domain of EKLF, one possibility could be that FLI-1 inhibits the binding of EKLF to its DNA targets	SIGNOR-256044
Q13469	P35354	1	transcriptional regulation	up-regulates quantity by expression	0.371	NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration	SIGNOR-264025
P27361	P49715	1	phosphorylation	down-regulates	0.371	Ccaat/enhancer-binding protein alpha (c/ebpalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes.Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of c/ebpalpha. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (erk1/2), which interact with c/ebpalpha through an fxfp docking site and phosphorylate serine 21.	SIGNOR-120570
P45983	P14618	1	phosphorylation	up-regulates activity	0.371	Active JNK1 specifically activates PKM2 but not PKM1. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365.	SIGNOR-276933
P12931	Q9Y3Q4	1	phosphorylation	up-regulates	0.371	These results demonstrate that src tyrosine kinase enhances hcn4 currents by shifting their activation to more positive potentials and increasing the whole cell channel conductance as well as speeding the channel kinetics. The tyrosine residue that mediates most of src s actions on hcn4 channels is tyr531.	SIGNOR-158707
P06493	O94782	1	phosphorylation	up-regulates activity	0.371	In this study, we show that Ser313 phosphorylation in USP1 is required for its interaction with UAF1 and for the stimulation of USP1's activity. We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1.	SIGNOR-276423
Q8TDX7	Q15058	1	phosphorylation	up-regulates activity	0.371	Nek7 direct phosphorylation is required for the anaphase localization of Kif14. we generated an EGFP-Kif14-5A construct in which Ser56, Ser607, Ser1217, Ser1219, and Ser1220 were all mutated to Ala. When transfected into HeLa cells, EGFP-Kif14-5A was expressed to similar levels as WT Kif14 (Fig. S3 C), but its localization to the central spindle in anaphase cells was completely abolished (Fig. 6 C).	SIGNOR-266420
Q9BV47	P04629	1	dephosphorylation	down-regulates activity	0.371	NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.\|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells	SIGNOR-277105
P14174	P61073	1	binding	up-regulates activity	0.371	We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.	SIGNOR-252062
Q00535	P35222	1	phosphorylation	up-regulates activity	0.371	By combining multiple network relations with PTM proteoform specific functional information, we proposed a mechanism to explain the observation that the cyclin dependent kinase CDK5 positively regulates beta-catenin co-activator activity.\|CDK5 phosphorylates beta-catenin on Ser 191 and Ser 246 (PR :000037229)	SIGNOR-279516
Q15139	Q8NEB9	1	phosphorylation	up-regulates activity	0.371	PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate formation, and autophagosome formation.\|Therefore, PKD phosphorylates Vps34 on multiple sites, including Thr677 within the catalytic domain.	SIGNOR-278495
Q99986	P15336	1	phosphorylation	up-regulates	0.371	Vrk1 phosphorylates atf2 mainly on thr-73, stabilizing the atf2 protein and increasing its intracellular level.	SIGNOR-124330
Q86YT6	Q15154	1	ubiquitination	down-regulates	0.371	We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation.	SIGNOR-272878
P45983	P63104	1	phosphorylation	down-regulates	0.371	Jnk phosphorylated 14-3-3 at ser-184 and 14-3-3 at ser-186 both in vitro and in vivo, and such phosphorylation reduced the affinity of 14-3-3 proteins for bax	SIGNOR-124020
P45983	Q9NR28	1	phosphorylation	up-regulates activity	0.371	JNK1\u2011mediated phosphorylation of Smac/DIABLO at the serine 6 residue is functionally linked to its mitochondrial release during TNF\u2011\u03b1-\u2011induced apoptosis of HeLa cells.	SIGNOR-280029
O14757	Q08050	1	phosphorylation	up-regulates activity	0.371	In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.	SIGNOR-280224
A6NJ46	Q9NS71	1	transcriptional regulation	up-regulates quantity by expression	0.371	In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter.	SIGNOR-266096
P52926	Q66K89	1	binding	down-regulates	0.371	Here we show that hmga2 associates with the e1a-regulated transcriptional repressor p120(e4f), interfering with p120(e4f) binding to the cyclin a promoter	SIGNOR-119537
Q6P1N0	P08908	1	transcriptional regulation	down-regulates quantity by repression	0.371	Akt kinase-interacting protein 1 (Aki1)/Freud-1/CC2D1A is localized in the cytosol, nucleus, and centrosome. Aki1 plays distinct roles depending on its localization. In the cytosol, it acts as a scaffold protein in the phosphoinositide 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase 1 (PDK1)/Akt pathway. In the nucleus, it is a transcriptional repressor of the serotonin-1A (5-HT1A) receptor.	SIGNOR-268295
P48729	O15151	1	phosphorylation	up-regulates	0.371	Previous studies showed that casein kinase 1? (ck1?) Stably associates with mdmx, stimulates mdmx-p53 binding, and cooperates with mdmx to inactivate p53ck1? Binding to the mdmx central domain and phosphorylation of s289 disrupts the intramolecular interaction, allowing the n terminus to bind p53 with increased affinity. After dna damage, the mdmx-ck1? Complex is disrupted by chk2-mediated phosphorylation of mdmx at s367, leading to reduced mdmx-p53 binding.	SIGNOR-199015
Q05655	Q16236	1	phosphorylation	up-regulates activity	0.371	Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription.	SIGNOR-249161
P06213	Q8WU20	1	phosphorylation	up-regulates activity	0.371	We found that insulin receptor can directly phosphorylate FRS2.	SIGNOR-278945
Q05513	P29474	1	phosphorylation	down-regulates activity	0.371	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-251637
Q00535	P10275	1	phosphorylation	up-regulates	0.371	Cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins	SIGNOR-175696
Q69YH5	P36873	1	binding	up-regulates activity	0.371	This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.	SIGNOR-274003
Q7Z6J0	P45983	1	binding	up-regulates	0.371	Posh activates jnk1 in cos-1 cells.	SIGNOR-55759

Q92847

P08754

1

binding

up-regulates activity

0.373

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-257167

O43318

Q15797

1

phosphorylation

up-regulates activity

0.373

This analysis showed that phosphorylation of Smad1 at the C-terminal serines S463 and S465 was increased by co-expression of constitutively active TAK1.

SIGNOR-279419

P04626

P00519

1

phosphorylation

up-regulates activity

0.373

In this study, we show that Abl kinase SH2 domains bind directly to Her-2, and like PDGFR-beta, Her-2 directly phosphorylates c-Abl.

SIGNOR-279407

Q12986

Q96ST3

1

binding

up-regulates activity

0.373

we investigated the mechanism of NFX1-91 repression of the hTERT promoter and demonstrated that NFX1-91 interacts with the corepressor mSin3A/HDAC to maintain the deacetylated status at the hTERT promoter, thus providing a mechanism by which NFX1-91 represses hTERT expression.

SIGNOR-226360

P53350

P54274

1

phosphorylation

up-regulates

0.373

Plk1 phosphorylation of trf1 is essential for its binding to telomeres

SIGNOR-179461

Q15744

P53567

1

binding

up-regulates activity

0.373

C/EBP-epsilon interacts with C/EBP-gamma through the leucine-zipper containing domain. C/EBP-epsilon and C/EBP-gamma synergistically activate transcription of lactoferrin promoter

SIGNOR-224900

P68400

Q9Y5B0

1

phosphorylation

down-regulates activity

0.373

We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. | Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified

SIGNOR-250844

Q08345

Q06124

1

relocalization

up-regulates activity

0.373

Overexpression of DDR1a/b increased the interaction of DDR1 with SHP-2 and up-regulated the tyrosine phosphatase activity of SHP-2.

SIGNOR-272403

P43088

P63092

1

binding

up-regulates activity

0.373

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-256810

Q99576

Q04206

1

binding

down-regulates activity

0.373

GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits.

SIGNOR-253297

Q15233

P11387

1

binding

up-regulates

0.373

We show that the psf/p54 dimer has pronounced stimulatory effect on dna catalysis by topoisomerase i

SIGNOR-60557

P18089

Q03113

1

binding

up-regulates activity

0.373

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-257201

P12931

P55211

1

phosphorylation

up-regulates activity

0.373

As a result, we established that Src was able to directly phosphorylate caspase-9 at tyrosine 251, leading to elevated caspase-9 activity.

SIGNOR-272998

P46934

P10523

1

polyubiquitination

down-regulates quantity by destabilization

0.373

Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.

SIGNOR-272843

Q8IV08

P05067

1

binding

up-regulates quantity

0.373

Furthermore, PLD3 can be co-immunoprecipitated with APP in cultured cells (Extended Data Figure 4). Together, these studies demonstrate that PLD3 plays a role in APP processing. Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing.

SIGNOR-261200

Q16539

O15519

1

phosphorylation

up-regulates

0.373

Here we demonstrate that m. tuberculosis?induced Tnf triggered reactive oxygen species?dependent Activation of ask1 and the tyrosine kinase c-abl (a000161) in mouse macrophages and that flips was phosphorylated on tyr211 and ser4 by c-abl and p38, respectively.

SIGNOR-187001

O75487

P41221

1

binding

up-regulates

0.373

Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways

SIGNOR-195752

Q13546

Q9UHD2

2

phosphorylation

up-regulates activity

0.373

Additionally, RIPK1-dependent hyper-phosphorylation of TBK1 in Casp8 Ripk3 cells occurred during MNV-1 infection (Figure 4F).|RIPK1 and its kinase activity were required to promote increased TBK1 phosphorylation in the absence of caspase-8 (Figure 3E), suggesting that RIPK1 may promote TBK1 activation.

SIGNOR-279278

Q96GD4

P01106

1

phosphorylation

up-regulates quantity by stabilization

0.373

AURKB directly phosphorylates MYC at serine 67, counteracting GSK3\u03b2-directed threonine 58 phosphorylation and subsequent FBXW7- mediated proteasomal degradation.

SIGNOR-279439

P35680

P16220

1

binding

up-regulates activity

0.373

The mammalian two-hybrid system showed that the region aa 393 to 476 of LFB3 is involved in the interaction with CREB or ATF1. The importance of this region for mediating cAMP induction was confirmed in transient transfection assays.

SIGNOR-241323

Q8NFU7

P60484

1

transcriptional regulation

up-regulates quantity by expression

0.373

We also found that TET1 directly binds to the promoter region of PTEN and activates its transcription through demethylation of CpG islands

SIGNOR-259096

Q07021

P04264

1

binding

up-regulates activity

0.373

Cytokeratin 1 binds to both gC1qR and u-PAR. Our data suggest that formation of HK (and Factor XII) binding sites along endothelial cell membranes consists of bimolecular com-plexes of gC1qR-cytokeratin 1 and u-PAR-cytokeratin 1, with gC1qR binding being favored.

SIGNOR-251881

Q96EP1

Q96EB6

1

ubiquitination

down-regulates quantity

0.372

CHFR binds to and ubiquitylates SIRT1, leading to its proteasomal degradation.|CHFR ubiquitylates and promotes the proteasomal degradation of SIRT1.

SIGNOR-278691

Q9UPW6

Q9H3D4

1

binding

down-regulates activity

0.372

SATB2 attenuates p63-mediated gene expression of perp (p53 apoptosis effector related to PMP-22), a critical downstream target gene during development, and specifically decreases p63 perp promoter binding.

SIGNOR-255149

P68400

P31749

1

phosphorylation

up-regulates

0.372

CK2 hyperactivates AKT by phosphorylation at Ser129

SIGNOR-252595

Q16539

Q15910

1

phosphorylation

down-regulates quantity by destabilization

0.372

Here, we show that p38α kinase promotes EZH2 degradation in differentiating muscle cells through phosphorylation of threonine 372

SIGNOR-255663

O00308

P11161

1

ubiquitination

down-regulates quantity

0.372

The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination|AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death.

SIGNOR-268849

P68400

Q93009

1

phosphorylation

up-regulates quantity by stabilization

0.372

We find that stabilization of Mdm2, and correspondingly p53 downregulation in unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by the protein kinase CK2. Phosphorylation stabilizes USP7S and thus contributes to Mdm2 stabilization and downregulation of p53.

SIGNOR-276530

P12931

Q13002

1

phosphorylation

up-regulates activity

0.372

GluK2 binds to Src, and the tyrosine residue at position 590 (Y590) on GluK2 is a major site of phosphorylation by Src kinases. GluK2 phosphorylation at Y590 is responsible for increases in whole-cell currents and calcium influx in response to transient kainate stimulation.

SIGNOR-276850

P06493

Q01167

1

phosphorylation

up-regulates

0.372

We have mapped two cdk phosphorylation sites, serines 368 and 423, which play a role in defining foxk2 function through regulating its stability and its activity as a transcriptional repressor protein. These two cdk sites appear vital for foxk2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis.

SIGNOR-167826

P24941

P17480

1

phosphorylation

up-regulates activity

0.372

Phosphorylation of ubf at serine 388 is required for interaction with rna polymerase i and activation of rdna transcription. After g(1) progression ubf is phosphorylated at serine 388 by cdk2/cyclin e and cdk2/cyclin a. Conversion of serine 388 to glycine abolishes ubf activity

SIGNOR-235419

P04637

Q8IUQ4

1

transcriptional regulation

up-regulates quantity by expression

0.372

P53 directly induces the expression of Siah-1 and in turn formation of a unique SCF-like complex (SCF(TBL1)) comprised of Siah-1, Siah-1-interacting protein (SIP), Skp1, transducin β-like 1 (TBL1), and APC

SIGNOR-271953

O14672

P35070

1

cleavage

up-regulates activity

0.372

Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin

SIGNOR-259839

P45983

P61978

1

phosphorylation

up-regulates

0.372

The current studies demonstrate the identification of hnrnp-k as a jnk and erk substrate. The phosphoacceptor sites for jnk and erk on the k protein are different, and indeed, erk phosphorylation results in biological consequences different from those of phosphorylation by jnk (49). Whereas erk phosphorylation on aa 284 and 353 contributes to k protein nuclear export and concomitant inhibition of rna translation (49), phosphorylation by k protein on aa 216 and 353 increases the transcriptional effects of the k protein.

SIGNOR-105770

P24941

O75469

1

phosphorylation

down-regulates quantity by destabilization

0.372

PXR Phosphorylation at S350 by CDK2 Triggers PXR Degradation via the Ubiquitin-Proteasome Pathway.

SIGNOR-279397

O95714

Q9Y2K6

1

ubiquitination

down-regulates quantity

0.372

HERC2 promotes USP20 degradation.|Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase.

SIGNOR-278692

Q96MT8

P24941

1

relocalization

up-regulates activity

0.372

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.

SIGNOR-271725

P24941

P12272

1

phosphorylation

down-regulates

0.372

Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization

SIGNOR-68548

Q9UKA4

P49841

2

binding

down-regulates activity

0.372

A-kinase anchoring protein 220 (AKAP220) is a multivalent anchoring protein that can sequester a variety of signal transduction enzymes. These include protein kinase A (PKA) and glycogen synthase kinase 3beta (GSK3beta). Using a combination of molecular and cellular approaches we show that GSK3beta phosphorylation of Thr-1132 on AKAP220 initiates recruitment of this kinase into the enzyme scaffold. We also find that AKAP220 anchors GSK3beta and its substrate beta-catenin in membrane ruffles.

SIGNOR-264817

P55212

P49768

1

cleavage

up-regulates activity

0.372

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261753

O75688

P37231

1

dephosphorylation

up-regulates activity

0.372

Furthermore we show that PPM1B can directly dephosphorylate PPARgamma, both in intact cells and in vitro.|In addition PPM1B increases PPARγ-mediated transcription via dephosphorylation of Ser(112).|The serine/threonine phosphatase PPM1B (PP2Cbeta) selectively modulates PPARgamma activity.

SIGNOR-277073

Q5VUA4

P10275

1

binding

down-regulates activity

0.372

Using different promoters and cells, we confirmed that AR-mediated transactivation was repressed by TZF in a dose-dependent manner (Fig. 1A and B). Endogenous ARmediated transactivation was also inhibited by expression of TZF; These results indicate that amino acid residues 512–663 are essential for the repressive effect of TZF on AR-mediated transactivation.

SIGNOR-261187

P49841

Q9UKA4

2

phosphorylation

down-regulates activity

0.372

A-kinase anchoring protein 220 (AKAP220) is a multivalent anchoring protein that can sequester a variety of signal transduction enzymes. These include protein kinase A (PKA) and glycogen synthase kinase 3beta (GSK3beta). Using a combination of molecular and cellular approaches we show that GSK3beta phosphorylation of Thr-1132 on AKAP220 initiates recruitment of this kinase into the enzyme scaffold. We also find that AKAP220 anchors GSK3beta and its substrate beta-catenin in membrane ruffles.

SIGNOR-264816

P46934

P37840

1

ubiquitination

down-regulates quantity by destabilization

0.372

Here we show that the ubiquitin ligase Nedd4, which functions in the endosomal-lysosomal pathway, robustly ubiquitinates alpha-synuclein, unlike ligases previously implicated in its degradation.

SIGNOR-278611

Q96GD4

Q8NEM2

1

phosphorylation

up-regulates activity

0.372

AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing.

SIGNOR-273552

P31751

P18031

1

phosphorylation

down-regulates activity

0.372

We conclude that ptp1b is a novel substrate for akt and that phosphorylation of ptp1b by akt at ser(50) may negatively modulate its phosphatase activity creating a positive feedback mechanism forinsulin signaling

SIGNOR-235491

O00743

O43318

1

dephosphorylation

down-regulates activity

0.372

Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway|From proteomic analysis of TAK1-binding proteins, we identified protein phosphatase 6 (PP6), a type-2A phosphatase, and demonstrated that PP6 associated with and inactivated TAK1 by dephosphorylation of Thr-187.

SIGNOR-248292

O14965

P00352

1

phosphorylation

up-regulates activity

0.372

AURKA phosphorylates ALDH1A1 at three critical residues which exert a multifaceted regulation over its level, enzymatic activity, and quaternary structure. While all three phosphorylation sites contribute to its increased stability, T267 phosphorylation primarily regulates ALDH1A1 activity. AURKA-mediated phosphorylation rapidly dissociates tetrameric ALDH1A1 into a highly active monomeric species.

SIGNOR-276748

P20340

Q7Z7G8

1

binding

down-regulates activity

0.372

Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. COH1 Golgi Localization Is Mediated by Active RAB6 . COH1 Interacts with All Three Mammalian RAB6 Homologues

SIGNOR-269203

O00141

P42858

1

phosphorylation

down-regulates

0.372

The serum- and glucocorticoid-induced kinase sgk inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin.

SIGNOR-121349

O15111

P46527

1

phosphorylation

down-regulates activity

0.372

Reduced nuclear p27 was also found in MCF7 human breast cancer cells that were transiently transfected with an IKKalpha expression vector; increased IKKalpha expression resulted in a dose dependent decrease in nuclear p27 and increased cytoplasmic p27 (XREF_FIG).|We found that IKKalpha phosphorylates p27 at S183 to cause its nuclear export.

SIGNOR-278438

P12931

Q8IW41

1

phosphorylation

up-regulates quantity

0.372

These data strongly suggest that PRAK phosphorylation by Src on Y188 and Y216 drives the relocalization of PRAK to focal adhesion structures during cell adhesion.

SIGNOR-279762

P67775

Q99759

1

dephosphorylation

down-regulates

0.372

Pp2ac binds to the phosphorylated mekk3 and subsequently dephosphorylate mekk3 at thr-516, ser-520, and ser-526 residues to terminate mekk3-mediated ikkbeta/Nf-kappaB Activation

SIGNOR-165233

P07766

P16333

1

relocalization

up-regulates activity

0.372

We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ϵ and results in recruitment of the adaptor protein Nck.

SIGNOR-259934

P23443

P27708

1

phosphorylation

up-regulates activity

0.372

CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.

SIGNOR-267443

Q9Y463

Q9UQL6

1

phosphorylation

down-regulates activity

0.372

Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent mannermirk phosphorylates hdac5 at ser-279

SIGNOR-235809

P23246

P11387

1

binding

up-regulates

0.372

We show that the psf/p54 dimer has pronounced stimulatory effect on dna catalysis by topoisomerase i

SIGNOR-60563

P50542

Q13501

1

binding

up-regulates activity

0.372

Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.

SIGNOR-262793

O14543

Q9Y286

1

binding

down-regulates quantity by destabilization

0.372

SOCS proteins can act as E3 ligases by forming a complex with Elongin B/C and Cul5/Rbx1/2.SOCS3 targets Siglec 7 for degradation

SIGNOR-272642

Q9UQM7

P28329

1

phosphorylation

up-regulates

0.372

We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.

SIGNOR-96628

P27361

P15923

1

phosphorylation

down-regulates quantity by destabilization

0.372

Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. |Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)|anti_phospho_M2 peptide (SSPSpTPVGSPQG)

SIGNOR-249117

P54646

P06213

1

phosphorylation

up-regulates

0.372

Ampk phosphorylates and activates theinsulinreceptor, providing a direct link between ampk and theinsulin pathway.

SIGNOR-195324

P28482

Q96RK0

1

phosphorylation

down-regulates

0.372

Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3))[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3

SIGNOR-169875

P31749

Q96HP0

1

phosphorylation

up-regulates activity

0.372

Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). | In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching

SIGNOR-275666

P17612

P49840

1

phosphorylation

down-regulates

0.372

Phosphorylation of ser21 and inactivation of glycogen synthase kinase 3 by protein kinase a.

SIGNOR-83221

Q969H0

Q9UHV7

1

ubiquitination

down-regulates quantity by destabilization

0.371

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-266690

P11309

Q92934

1

phosphorylation

down-regulates activity

0.371

Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.

SIGNOR-250390

Q13131

P98177

1

phosphorylation

up-regulates

0.371

The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt phosphorylation sites, resulting in foxo activation

SIGNOR-157947

P48729

P37840

1

phosphorylation

up-regulates

0.371

In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.

SIGNOR-73799

Q00535

P29474

1

phosphorylation

down-regulates

0.371

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

SIGNOR-164080

Q9UQM7

P00533

1

phosphorylation

down-regulates activity

0.371

We show that serines 1046/1047 are sites for CaM kinase II phosphorylation, although there is a preference for serine 1047, which resides within the consensus -R-X-X-S-. In addition, we have identified major phosphorylation sites at serine 1142 and serine 1057, which lie within a novel -S-X-D- consensus. Mutation of serines 1046/1047 in full-length EGFR enhanced both fibroblast transformation and tyrosine autokinase activity that was significantly potentiated by additional mutation of serines 1057 and 1142. A single CaM kinase II site was also identified at serine 744 within sub-kinase domain III, and autokinase activity was significantly affected by mutation of this serine to an aspartic acid making this site appear constitutively phosphorylated. We have addressed the mechanism by which CaM kinase II phosphorylation of the EGFR might regulate receptor autokinase activity and show that this modification can hinder association of the cytoplasmic tail with the kinase domain to prevent an enzyme-substrate interaction.

SIGNOR-250621

Q8IZP0

P22681

1

binding

up-regulates

0.371

Here we uncover a novel interaction between abi-1 and the cbl ubiquitin ligase and show that abi-1 mediates cbl accumulation to the plasma membrane upon stimulation by egf.

SIGNOR-154162

Q15139

Q96QB1

1

phosphorylation

down-regulates

0.371

The tumor suppressor protein dlc1 is regulated by pkd-mediated gap domain phosphorylation.Our results thus show that pkd-mediated phosphorylation of dlc1 on serine 807 negatively regulates dlc1 cellular function.

SIGNOR-169994

P15884

P01106

1

transcriptional regulation

up-regulates quantity by expression

0.371

Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription.

SIGNOR-253324

Q01543

Q13351

2

binding

down-regulates activity

0.371

FLI-1 represses the transcriptional activity of EKLF.Our data indicate that the ETS domain of FLI-1 is absolutely required to inhibit EKLF activity. Since the FLI-1 ETS domain interacts with the DNA binding domain of EKLF, one possibility could be that FLI-1 inhibits the binding of EKLF to its DNA targets

SIGNOR-256044

Q13469

P35354

1

transcriptional regulation

up-regulates quantity by expression

0.371

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

SIGNOR-264025

P27361

P49715

1

phosphorylation

down-regulates

0.371

Ccaat/enhancer-binding protein alpha (c/ebpalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes.Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of c/ebpalpha. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (erk1/2), which interact with c/ebpalpha through an fxfp docking site and phosphorylate serine 21.

SIGNOR-120570

P45983

P14618

1

phosphorylation

up-regulates activity

0.371

Active JNK1 specifically activates PKM2 but not PKM1. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365.

SIGNOR-276933

P12931

Q9Y3Q4

1

phosphorylation

up-regulates

0.371

These results demonstrate that src tyrosine kinase enhances hcn4 currents by shifting their activation to more positive potentials and increasing the whole cell channel conductance as well as speeding the channel kinetics. The tyrosine residue that mediates most of src s actions on hcn4 channels is tyr531.

SIGNOR-158707

P06493

O94782

1

phosphorylation

up-regulates activity

0.371

In this study, we show that Ser313 phosphorylation in USP1 is required for its interaction with UAF1 and for the stimulation of USP1's activity. We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1.

SIGNOR-276423

Q8TDX7

Q15058

1

phosphorylation

up-regulates activity

0.371

Nek7 direct phosphorylation is required for the anaphase localization of Kif14. we generated an EGFP-Kif14-5A construct in which Ser56, Ser607, Ser1217, Ser1219, and Ser1220 were all mutated to Ala. When transfected into HeLa cells, EGFP-Kif14-5A was expressed to similar levels as WT Kif14 (Fig. S3 C), but its localization to the central spindle in anaphase cells was completely abolished (Fig. 6 C).

SIGNOR-266420

Q9BV47

P04629

1

dephosphorylation

down-regulates activity

0.371

NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells

SIGNOR-277105

P14174

P61073

1

binding

up-regulates activity

0.371

We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.

SIGNOR-252062

Q00535

P35222

1

phosphorylation

up-regulates activity

0.371

By combining multiple network relations with PTM proteoform specific functional information, we proposed a mechanism to explain the observation that the cyclin dependent kinase CDK5 positively regulates beta-catenin co-activator activity.|CDK5 phosphorylates beta-catenin on Ser 191 and Ser 246 (PR :000037229)

SIGNOR-279516

Q15139

Q8NEB9

1

phosphorylation

up-regulates activity

0.371

PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate formation, and autophagosome formation.|Therefore, PKD phosphorylates Vps34 on multiple sites, including Thr677 within the catalytic domain.

SIGNOR-278495

Q99986

P15336

1

phosphorylation

up-regulates

0.371

Vrk1 phosphorylates atf2 mainly on thr-73, stabilizing the atf2 protein and increasing its intracellular level.

SIGNOR-124330

Q86YT6

Q15154

1

ubiquitination

down-regulates

0.371

We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation.

SIGNOR-272878

P45983

P63104

1

phosphorylation

down-regulates

0.371

Jnk phosphorylated 14-3-3 at ser-184 and 14-3-3 at ser-186 both in vitro and in vivo, and such phosphorylation reduced the affinity of 14-3-3 proteins for bax

SIGNOR-124020

P45983

Q9NR28

1

phosphorylation

up-regulates activity

0.371

JNK1\u2011mediated phosphorylation of Smac/DIABLO at the serine 6 residue is functionally linked to its mitochondrial release during TNF\u2011\u03b1-\u2011induced apoptosis of HeLa cells.

SIGNOR-280029

O14757

Q08050

1

phosphorylation

up-regulates activity

0.371

In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.

SIGNOR-280224

A6NJ46

Q9NS71

1

transcriptional regulation

up-regulates quantity by expression

0.371

In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter.

SIGNOR-266096

P52926

Q66K89

1

binding

down-regulates

0.371

Here we show that hmga2 associates with the e1a-regulated transcriptional repressor p120(e4f), interfering with p120(e4f) binding to the cyclin a promoter

SIGNOR-119537

Q6P1N0

P08908

1

transcriptional regulation

down-regulates quantity by repression

0.371

Akt kinase-interacting protein 1 (Aki1)/Freud-1/CC2D1A is localized in the cytosol, nucleus, and centrosome. Aki1 plays distinct roles depending on its localization. In the cytosol, it acts as a scaffold protein in the phosphoinositide 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase 1 (PDK1)/Akt pathway. In the nucleus, it is a transcriptional repressor of the serotonin-1A (5-HT1A) receptor.

SIGNOR-268295

P48729

O15151

1

phosphorylation

up-regulates

0.371

Previous studies showed that casein kinase 1? (ck1?) Stably associates with mdmx, stimulates mdmx-p53 binding, and cooperates with mdmx to inactivate p53ck1? Binding to the mdmx central domain and phosphorylation of s289 disrupts the intramolecular interaction, allowing the n terminus to bind p53 with increased affinity. After dna damage, the mdmx-ck1? Complex is disrupted by chk2-mediated phosphorylation of mdmx at s367, leading to reduced mdmx-p53 binding.

SIGNOR-199015

Q05655

Q16236

1

phosphorylation

up-regulates activity

0.371

Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription.

SIGNOR-249161

P06213

Q8WU20

1

phosphorylation

up-regulates activity

0.371

We found that insulin receptor can directly phosphorylate FRS2.

SIGNOR-278945

Q05513

P29474

1

phosphorylation

down-regulates activity

0.371

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-251637

Q00535

P10275

1

phosphorylation

up-regulates

0.371

Cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins

SIGNOR-175696

Q69YH5

P36873

1

binding

up-regulates activity

0.371

This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.

SIGNOR-274003

Q7Z6J0

P45983

1

binding

up-regulates

0.371

Posh activates jnk1 in cos-1 cells.

SIGNOR-55759