GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
A2RUS2	O75385	0	phosphorylation	up-regulates activity	0.435	ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.	SIGNOR-264731
P27361	Q05682	1	phosphorylation	down-regulates	0.478	The actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759. This phosphorylation leads to markedly diminished actin affinity.	SIGNOR-86741
Q03112	P62136	0	dephosphorylation	down-regulates activity	0.2	We also identified EVI1 phosphorylation sites by MS analysis and showed that Ser538 and Ser858 can be phosphorylated and dephosphorylated by two EVI1 interactome proteins, casein kinase II and protein phosphatase-1α. Finally, mutations that impair EVI1 phosphorylation at these sites reduced EVI1 DNA binding through its C-terminal zinc finger domain and induced cancer cell proliferation.	SIGNOR-273430
P23469	P06213	1	dephosphorylation	down-regulates activity	0.285	In this study, we showed that receptor-type PTPepsilon (PTP epsilonM) dephosphorylated IR in rat primary hepatocytes and tyrosines 972, 1158, 1162 and 1163\| These results suggest that PTPepsilonM is a negative regulator of IR signaling and involved in insulin-induced glucose metabolism mainly through direct dephosphorylation and inactivation of IR in hepatocytes and liver.	SIGNOR-248444
P17612	Q9HC16	1	phosphorylation	up-regulates	0.324	Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.	SIGNOR-181526
Q9HAU4	P51668	1	ubiquitination	up-regulates activity	0.702	Our data further show that SMURF2 monoubiquitinates UBCH5 at lysine 144 to form an active complex required for efficient degradation of a RAS family E3, beta transducing repeat containing protein 1 (beta-TrCP1).	SIGNOR-278718
P06493	P04637	1	phosphorylation	up-regulates activity	0.579	The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A	SIGNOR-167779
Q03135	P17096	1	relocalization	up-regulates activity	0.265	CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.	SIGNOR-254428
P20810	P68400	0	phosphorylation	up-regulates activity	0.2	We also showed that casein kinase 2, a pro-survival kinase overexpressed in many cancer types, phosphorylated calpastatin at Ser-633. Our results indicate that calpastatin phosphorylation promotes radiation resistance in GBM cells by increasing the activity of calpain proteases, which are known to promote survival and invasion in cancer.	SIGNOR-277388
O00712	O75093	1	transcriptional regulation	up-regulates quantity	0.249	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268899
Q13153	P21333	1	phosphorylation	up-regulates	0.789	In flna, the pak1-binding site involves tandem repeat 23 in the carboxyl terminus and phosphorylation takes place on serine 2152.	SIGNOR-92065
Q16539	P41970	1	phosphorylation	up-regulates	0.379	Tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387. Mutation of these sites to alanine severely reduces c-fos sre-dependent transcription mediated by sap-1a and p38 map kinase.	SIGNOR-47685
P15498	P29350	0	dephosphorylation	down-regulates activity	0.576	SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.	SIGNOR-277171
Q13131	P14859	1	phosphorylation	down-regulates	0.2	Mitosis-specific phosphorylation site in the homeodomain of oct-1 was phosphorylated in vitro by protein kinase a. Pka-mediated phosphorylation event was identified in the cns-specific pou domain protein brn-2/n-oct-3/pou3f2 (nieto et al. 2007). In this case, the modification, at a position homologous to oct1 s385, was found to alter binding specificity for complex dimeric sites.	SIGNOR-53254
P48729	P10071	1	phosphorylation	down-regulates	0.6	In principle, pka, ck-1 and gsk3 can phosphorylate as many as 19 serine residues in gli3: fourpkasites, three primarygsk3sites, four primary ck-1 sites and eight secondary gsk3 and ck-1 sites	SIGNOR-116512
O76061	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.297	With the ChIP assay, we demonstrated the direct binding of HIF-1alpha to STC2 promoter. These findings support the notion that HIF-1 is a potent stimulator of STC2 expression. Collectively, this is the first report to show that STC2 was aberrantly hypermethylated in human cancer cells. The findings demonstrated that STC2 epigenetic inactivation may interfere with HIF-1 mediated activation of STC2 expression.	SIGNOR-260389
P54868	Q9NXA8	0	post translational modification	up-regulates activity	0.343	We demonstrate that SIRT5 regu-lates succinylation of the rate-limiting ketogenicenzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2) both in vivo and in vitro.\|Succinylation of Lysine Residues within the SubstrateBinding Pocket Inhibits HMGCS2 Activity\|Here, we use a label-freequantitative proteomic approach to characterizethe lysine succinylome in liver mitochondria and itsregulation by the desuccinylase SIRT5	SIGNOR-267641
P31749	P07949	0	phosphorylation	up-regulates	0.323	The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity	SIGNOR-252619
P55283	P07737	0	null	up-regulates activity	0.335	Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation.	SIGNOR-253111
Q14680	O15530	1	phosphorylation	down-regulates activity	0.267	The results showed that MPK38 interacted with and inhibited PDK1 activity via Thr(354) phosphorylation.	SIGNOR-276414
Q92529	Q15303	0	relocalization	up-regulates	0.497	Like erbb1, erbb4 recruits grb2, shc and stat5.	SIGNOR-147850
Q06124	Q13224	1	dephosphorylation	down-regulates activity	0.469	In addition, surface expression of GluN2B was not reduced in mutant mice and it remains to be investigated how the direct dephosphorylation of GluN2B Y1252 by Shp2 reduces GluN2B function.\|The increased GluN2B Y1472 phosphorylation was reversed by a Src family kinase inhibitor, suggesting that Shp2 may negatively regulate GluN2B Y1472 phosphorylation through suppressing Src activity .	SIGNOR-276950
P45984	P45983	0	phosphorylation	up-regulates	0.593	Our studies revealed a novel mechanism in which phosphorylation of jnk2 is mediated by jnk1 before phosphorylation of p53, and then p53 is directly phosphorylated by jnk2 at ser6.	SIGNOR-155205
Q92934	P23443	0	phosphorylation	down-regulates activity	0.295	P70S6K, the downstream target of mTORC1, can phosphorylate and inactivate pro apoptotic BAD by producing a reaction that disrupts BAD 's binding to other pro apoptotic molecules thereby allowing cell survival.\|p70S6K, the downstream target of mTORC1, can phosphorylate and inactivate pro-apoptotic BAD by producing a reaction that disrupts BAD\u2019s binding to other pro-apoptotic molecules thereby allowing cell survival. xref , xref On the other hand, in a recent study, Li et al showed that increased expression of anti-apoptotic BCL2 was induced in myeloid progenitor cells upon activation of p76S6K, thereby promoting cell survival. xref Further studies are needed to better understand the effect of rapamycin and its derivatives on apoptosis in various cancer cells.	SIGNOR-280016
P01106	P38936	1	transcriptional regulation	down-regulates quantity by repression	0.779	C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a	SIGNOR-102740
Q13526	P45983	0	phosphorylation	up-regulates quantity by stabilization	0.272	Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.	SIGNOR-277562
Q9BPZ3	O95071	0	polyubiquitination	down-regulates quantity by destabilization	0.445	We demonstrate a mechanism for this co-regulation that involves an E3 ubiquitin ligase, EDD, which targets Paip2 for degradation. PABP depletion by RNA interference (RNAi) causes co-depletion of Paip2 protein without affecting Paip2 mRNA levels. Upon PABP knockdown, Paip2 interacts with EDD, which leads to Paip2 ubiquitination.	SIGNOR-272648
O75116	Q96A00	1	phosphorylation	up-regulates activity	0.413	A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.\| CPI-17 can be also directly phosphorylated at Thr38 residue by MYPT1-associated kinase [222], by PAK, which is downstream of Rac and/or Cdc42 cascade [223], by Rho-associated coiled-coil kinase (ROCK) [224] and by PKN [225].	SIGNOR-96696
P40429	O43293	0	phosphorylation	up-regulates	0.402	Zipk phosphorylates l13a in vitro / l13a is phosphorylated on ser77 in vitro	SIGNOR-182117
Q16539	O95382	0	phosphorylation	up-regulates activity	0.2	These data indicate that MKK6 phosphorylates p38 MAP kinase on Thr-180 and Tyr-182, the sites of phosphorylation that activate p38 MAP kinase	SIGNOR-260916
P10275	O75592	0	ubiquitination	down-regulates quantity by destabilization	0.2	We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.	SIGNOR-267149
Q14118	Q12955	0	relocalization	up-regulates quantity	0.259	We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.	SIGNOR-266714
Q96EP5	P28482	0	phosphorylation	down-regulates activity	0.2	Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 (extracellular-signal-regulated protein kinase 2) at two Thr-Pro sequences (Thr269 and Thr315), and that both sites became phosphorylated in HEK-293 (human embryonic kidney 293) cells in response to PMA or EGF (epidermal growth factor), or RAW 264.7 macrophages in response to LPS. Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ	SIGNOR-262970
O14522	P40763	1	dephosphorylation	down-regulates activity	0.516	Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T\|Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.	SIGNOR-263981
Q99684	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.2	GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation.	SIGNOR-277465
Q06124	P12235	1	dephosphorylation	down-regulates activity	0.271	Specifically, SHP2-mediated dephosphorylation of ANT1 at Tyr 191 is essential for mitochondrial homeostasis and mitigation of NLRP3 inflammasome activation.\|The interaction between SHP2 and ANT1 (Fig.\u00a0 xref ), and the opposite effects of SHP2 and ANT1 shRNAs in the activation of NLRP3 inflammasome (Figs.\u00a0 xref and xref ) raised the possibility that the SHP2 may inhibit ANT1 to suppress NLRP3 inflammasome activation.\|To further determine which tyrosine phosphorylation site of ANT1 is dephosphorylated by SHP2, we created the dephosphorylated mutant of ANT1, in which tyrosine was replaced with phenylalanine (Y to F mutation).	SIGNOR-277124
Q969H0	O00141	0	phosphorylation	up-regulates	0.291	Here, we report that the serum- and glucocorticoid-inducible protein kinase sgk1 remarkably reduced the protein stability of the active form of notch1 through fbw7activated sgk1 phosphorylated fbw7 at serine 227	SIGNOR-170404
P49841	Q6NZ36	1	phosphorylation	down-regulates quantity	0.2	Furthermore, GSK3beta was able to decrease the cellular FAAP20 levels when overexpressed in wild-type, but not in FBW7 -/- HCT116 cells, indicating that GSK3beta requires downstream FBW7 to regulate the FAAP20 stability.\|GSK3\u03b2 phosphorylates FAAP20 at Ser113.	SIGNOR-279048
Q03393	Q13976	0	phosphorylation	up-regulates	0.257	Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps	SIGNOR-71680
O75807	P35638	0	transcriptional regulation	up-regulates quantity by expression	0.454	ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.	SIGNOR-260173
P68400	Q6ZMG9	1	phosphorylation	up-regulates activity	0.2	Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.	SIGNOR-273992
Q9UQL6	P34947	0	phosphorylation	down-regulates activity	0.356	GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5.	SIGNOR-279045
Q96NY9	P68400	0	phosphorylation	up-regulates activity	0.2	Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex.	SIGNOR-273626
Q6NXT2	Q92831	0	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269617
P46019	P17612	0	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267410
P43405	P37840	1	phosphorylation	down-regulates	0.532	Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (syk), which phosphorylates three tyrosyl residues in its c-terminal domain (y-125, y-133, and y-136), here, we show that _-syn is an outstanding substrate for syk and that once it is tyrosine phosphorylated, it loses the ability to form oligomers.	SIGNOR-113065
O00571	Q9UHD2	0	phosphorylation	up-regulates activity	0.721	Coexpression of TBK1 strongly increased the activity of DDX3X.\|This suggests that DDX3X is rather specifically phosphorylated by TBK1 and IKK-i.	SIGNOR-278997
Q6ZNA4	P61956	1	polyubiquitination	down-regulates quantity by destabilization	0.626	Arkadia ubiquitinates poly-SUMO2 chains in a SIM- and RING-dependent manner.	SIGNOR-272882
Q15418	Q07352	1	phosphorylation	down-regulates activity	0.2	These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the Messenger RNA destabilization activity of ZFP36L1.\|These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the mRNA destabilization activity of ZFP36L1.	SIGNOR-279280
P18031	P09619	1	dephosphorylation	down-regulates	0.691	Ptp1b blocked pdgf-induced tyr716 and tyr751 phosphorylation of the pdgfr.	SIGNOR-179064
P51955	Q15154	0	relocalization	up-regulates	0.425	Recruitment of nek2 and c-nap1 to the centrosome is dependent on pcm-1	SIGNOR-133337
Q05655	P45983	1	phosphorylation	up-regulates	0.501	By contrast, after uv stimulation, rela directly induces the expression of pkcdelta, which in turn activates jnk.	SIGNOR-151428
Q15417	Q06187	0	phosphorylation	up-regulates quantity	0.2	Co-expression of calponin-3 with various kinases in S2 Schneider cells promoted a phosphorylation of calponin-3 by Syk, but also by the Tec family kinase Btk.	SIGNOR-280196
P08575	P19784	0	phosphorylation	up-regulates activity	0.434	Mutational analysis of CK2 consensus sites showed that the target for CK2 was in an acidic insert of 19 amino acids in the D2 domain, and Ser to Ala mutations at amino acids 965, 968, 969, and 973 abrogated CK2 phosphorylation of CD45. CK2 phosphorylation increased CD45 activity 3-fold toward phosphorylated myelin basic protein, and this increase was reversible by PP2A treatment.	SIGNOR-251031
O00141	Q96J92	1	phosphorylation	up-regulates activity	0.415	In addition, we identified a novel SGK1 phosphorylation site (S1201) in WNK4, and phosphorylation at this site is reduced by Ca(2+)/CaM.	SIGNOR-276421
P49841	P24864	1	phosphorylation	down-regulates	0.445	Our experiments suggest that gsk3 is the kinase primarily responsible for phosphorylation of cyclin e on t380	SIGNOR-118563
P53539	P59595	0	transcriptional regulation	up-regulates quantity by expression	0.2	The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well	SIGNOR-260728
Q14258	Q969H0	1	ubiquitination	down-regulates activity	0.264	This newly stabilized TRIM25 then directly ubiquitinates Lys412 of FBXW7α, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex involved in Myc ubiquitination, thereby stabilizing Myc.	SIGNOR-277457
Q14164	P35813	0	dephosphorylation	down-regulates activity	0.279	PPM1A directly dephosphorylates both MAVS and TBK1 and IKKepsilon.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.	SIGNOR-277072
P18848	O95750	1	transcriptional regulation	up-regulates quantity by expression	0.2	Reporter gene analyses using the 5'-promoter region of FGF19 revealed that a functional AARE (amino-acid-response element) was localized in this region, and this site was responsible for inducing its transcription through ATF4 (activating transcription factor 4), which is activated in response to ER stress	SIGNOR-253727
P35568	Q9H0K1	0	phosphorylation	down-regulates quantity	0.567	SIK2 is known to attenuate insulin signaling by phosphorylating IRS-1/Ser789	SIGNOR-265745
Q13131	Q9UQL6	1	phosphorylation	down-regulates	0.341	Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs)	SIGNOR-176479
P17612	P32245	1	phosphorylation	down-regulates activity	0.308	Activation of MC4R by agonist is associated with protein kinase A (PKA) and GRK phosphorylation of serine/threonine residues in the C-terminal tail of MC4R, followed by -arrestin and dynamin-dependent internalization of the receptor. Thr312 and Ser329/330 in the C-terminal tail of MC4R are potential sites for PKA	SIGNOR-250016
P35226	P16104	1	ubiquitination	up-regulates activity	0.2	In this process, BMI1 ubiquitinates histone H2A and \u03b3H2AX, thereby facilitating the repair of double-stranded DNA breaks through stimulating homologous recombination and non-homologous end joining.	SIGNOR-278744
Q13131	P08559	1	phosphorylation	up-regulates activity	0.2	AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex	SIGNOR-276837
O00303	P21127	0	phosphorylation	up-regulates activity	0.515	EIF3f is phosphorylated by CDK11p46 at Ser46 during apoptosis.\|Phosphorylation of eIF3f plays an important role in regulating its function in translation and apoptosis. Phosphorylation of eIF3f enhances the association of eIF3f with the core eIF3 subunits during apoptosis.	SIGNOR-273133
Q9H3R0	Q99814	0	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271585
P08581	P49841	1	phosphorylation	up-regulates activity	0.308	MET phosphorylated and activated GSK3B at tyrosine 56, which decreased the expression of PDL1 by liver cancer cells.	SIGNOR-277428
P51151	Q7Z6M1	1	null	up-regulates activity	0.581	P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking.	SIGNOR-253088
O60674	O14744	1	phosphorylation	down-regulates	0.693	Oncogenic jak2 kinases phosphorylate prmt5 in_vivo phosphorylation of prmt5 by jak2v617f greatly impairs its methyltransferase activity	SIGNOR-171994
Q03112	Q15389	1	transcriptional regulation	up-regulates quantity by expression	0.2	We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2	SIGNOR-266059
O14950	Q13464	0	phosphorylation	up-regulates	0.624	Here we found that rho-kinase has an activity for mrlc diphosphorylation at both threonine 18 and serine 19 in nonmuscle cells using sequential column chromatographies.	SIGNOR-91542
Q15058	Q8TDX7	0	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
O43683	Q96GD4	0	phosphorylation	up-regulates activity	0.749	Although our analysis identified only one of the 15 sites implicated in Bub1-Mad1 interaction, it suggests that following its rapamycin-induced dimerization, Ipl1 phosphorylates Bub1, and potentially Mad1, to drive eSAC signaling.	SIGNOR-279010
P03951	P00740	1	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
P09493	P53355	0	phosphorylation	up-regulates activity	0.277	We identified, for the first time, death-associated protein kinase 1 (DAP kinase 1) as the kinase that phosphorylates tropomyosin-1 in response to ERK activation by hydrogen peroxide (H(2)O(2)). We also report that the phosphorylation of tropomyosin-1 mediated by DAP kinase occurs on Ser283. Our finding that tropomyosin-1 is phosphorylated downstream of ERK and DAP kinase and that it helps regulate the formation of stress fibers will aid understanding the role of this protein in regulating the endothelial functions associated with cytoskeletal remodeling.	SIGNOR-262845
P01111	Q8TEU7	0	guanine nucleotide exchange factor	up-regulates	0.331	Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.	SIGNOR-183799
P43405	Q9GZY6	1	phosphorylation	up-regulates activity	0.592	Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.The dramatic reduction in phosphorylation of the LAB Y233F mutant suggested that Tyr233 is a primary target of the Syk family kinases.	SIGNOR-273576
O75962	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.692	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-260579
P11362	Q96QU1	1	phosphorylation	up-regulates activity	0.2	FGFR1 mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.\|We find that on activation, FGFR1 binds and phosphorylates Pcdh15.	SIGNOR-280014
P00533	P40763	1	phosphorylation	up-regulates activity	0.879	The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation.	SIGNOR-121965
Q14114	Q05519	0	post transcriptional regulation	up-regulates quantity by stabilization	0.2	We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling.	SIGNOR-269670
Q13153	Q7Z628	1	phosphorylation	down-regulates activity	0.249	In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner.	SIGNOR-263018
P27361	P23467	0	dephosphorylation	up-regulates	0.432	When cells are stimulated with various ligands such as growth factors, hormones, neurotransmitters, or tumor promoters, erk1/2 is activated through dualphosphorylation at the -ptepy-motif. Subsequently, p-erk1/2 translocates into the nucleus and phosphorylates elk-1, thereby acting as a transcription factor for cell proliferationthese data indicate that sa-p-erk1/2 might not only be regulated by mkp such as rvhr, but also by pp1 and ptp as well	SIGNOR-103165
Q9Y2K7	Q99814	0	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271581
Q05513	P49841	1	phosphorylation	down-regulates	0.597	Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent.	SIGNOR-119889
P11802	P07947	0	phosphorylation	down-regulates	0.254	We purified tyrosine 17 kinases from hela cells and found that the src family non-receptor tyrosine kinase c-yes contributes a large fraction of the tyrosine 17 kinase activity in hela lysatesthis site is equivalent to tyrosine 15 of cyclin dependent kinase 1, which undergoes inhibitory phosphorylation by wee1 and myt1	SIGNOR-178624
Q7L5N7	P49137	0	phosphorylation	up-regulates activity	0.2	Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2).	SIGNOR-263077
P25098	Q13304	1	phosphorylation	down-regulates activity	0.2	As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.\|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17.	SIGNOR-279999
P53990	Q9UBP0	1	relocalization	up-regulates activity	0.519	Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery.	SIGNOR-269047
P17612	O76054	1	phosphorylation	up-regulates activity	0.2	These results suggest that phosphorylation of SPF by PKA is a dynamic process and that, in the absence of PKA activity, SPF is rapidly inactivated.Thus, phosphorylation of SPF at Ser-289 appears necessary for maximal stimulation of squalene monooxygenase activity in vitro and absolutely required for the stimulation of cholesterol synthesis in cell culture.	SIGNOR-276027
Q09472	P15172	1	acetylation	up-regulates	0.681	Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo.	SIGNOR-81053
P12931	Q8IXH7	1	phosphorylation	down-regulates activity	0.336	Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1.	SIGNOR-276402
Q04912	P00519	1	phosphorylation	up-regulates activity	0.272	This suggests that by interacting with Sdc4, either directly or indirectly, RON is activated via transphosphorylation when clustered, engages the ABL1 SH2 domain, and activates ABL1 by phosphorylation.	SIGNOR-272999
P19419	P45984	0	phosphorylation	up-regulates activity	0.49	However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.	SIGNOR-247062
Q16539	Q14814	1	phosphorylation	up-regulates activity	0.612	Targeting of ash2l to specific genes is mediated by the transcriptional regulator mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 mapk signaling pathway via phosphorylation of mef2d.	SIGNOR-159331
Q15910	Q9C0B5	0	palmitoylation	down-regulates activity	0.2	Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2.	SIGNOR-261144
Q05397	P51813	0	phosphorylation	up-regulates	0.551	Bmx phosphorylated focal adhesion kinase (fak) at tyr577 subsequent to its src-mediated phosphorylation at tyr576. Loss of bmx by rna interference or by genetic deletion in mouse embryonic fibroblasts (mefs) markedly impaired fak activity.	SIGNOR-202139
Q13233	O14733	1	phosphorylation	up-regulates	0.723	Here we show that jnkk2, a novel member of the map kinase kinase family, was phosphorylated and activated by mekk1	SIGNOR-51207
P10721	Q5JUK2	0	transcriptional regulation	up-regulates quantity by expression	0.346	Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression.	SIGNOR-266205

A2RUS2

O75385

0

phosphorylation

up-regulates activity

0.435

ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.

SIGNOR-264731

P27361

Q05682

1

phosphorylation

down-regulates

0.478

The actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759. This phosphorylation leads to markedly diminished actin affinity.

SIGNOR-86741

Q03112

P62136

0

dephosphorylation

down-regulates activity

0.2

We also identified EVI1 phosphorylation sites by MS analysis and showed that Ser538 and Ser858 can be phosphorylated and dephosphorylated by two EVI1 interactome proteins, casein kinase II and protein phosphatase-1α. Finally, mutations that impair EVI1 phosphorylation at these sites reduced EVI1 DNA binding through its C-terminal zinc finger domain and induced cancer cell proliferation.

SIGNOR-273430

P23469

P06213

1

dephosphorylation

down-regulates activity

0.285

In this study, we showed that receptor-type PTPepsilon (PTP epsilonM) dephosphorylated IR in rat primary hepatocytes and tyrosines 972, 1158, 1162 and 1163| These results suggest that PTPepsilonM is a negative regulator of IR signaling and involved in insulin-induced glucose metabolism mainly through direct dephosphorylation and inactivation of IR in hepatocytes and liver.

SIGNOR-248444

P17612

Q9HC16

1

phosphorylation

up-regulates

0.324

Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.

SIGNOR-181526

Q9HAU4

P51668

1

ubiquitination

up-regulates activity

0.702

Our data further show that SMURF2 monoubiquitinates UBCH5 at lysine 144 to form an active complex required for efficient degradation of a RAS family E3, beta transducing repeat containing protein 1 (beta-TrCP1).

SIGNOR-278718

P06493

P04637

1

phosphorylation

up-regulates activity

0.579

The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A

SIGNOR-167779

Q03135

P17096

1

relocalization

up-regulates activity

0.265

CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.

SIGNOR-254428

P20810

P68400

0

phosphorylation

up-regulates activity

0.2

We also showed that casein kinase 2, a pro-survival kinase overexpressed in many cancer types, phosphorylated calpastatin at Ser-633. Our results indicate that calpastatin phosphorylation promotes radiation resistance in GBM cells by increasing the activity of calpain proteases, which are known to promote survival and invasion in cancer.

SIGNOR-277388

O00712

O75093

1

transcriptional regulation

up-regulates quantity

0.249

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

SIGNOR-268899

Q13153

P21333

1

phosphorylation

up-regulates

0.789

In flna, the pak1-binding site involves tandem repeat 23 in the carboxyl terminus and phosphorylation takes place on serine 2152.

SIGNOR-92065

Q16539

P41970

1

phosphorylation

up-regulates

0.379

Tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387. Mutation of these sites to alanine severely reduces c-fos sre-dependent transcription mediated by sap-1a and p38 map kinase.

SIGNOR-47685

P15498

P29350

0

dephosphorylation

down-regulates activity

0.576

SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.

SIGNOR-277171

Q13131

P14859

1

phosphorylation

down-regulates

0.2

Mitosis-specific phosphorylation site in the homeodomain of oct-1 was phosphorylated in vitro by protein kinase a. Pka-mediated phosphorylation event was identified in the cns-specific pou domain protein brn-2/n-oct-3/pou3f2 (nieto et al. 2007). In this case, the modification, at a position homologous to oct1 s385, was found to alter binding specificity for complex dimeric sites.

SIGNOR-53254

P48729

P10071

1

phosphorylation

down-regulates

0.6

In principle, pka, ck-1 and gsk3 can phosphorylate as many as 19 serine residues in gli3: fourpkasites, three primarygsk3sites, four primary ck-1 sites and eight secondary gsk3 and ck-1 sites

SIGNOR-116512

O76061

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.297

With the ChIP assay, we demonstrated the direct binding of HIF-1alpha to STC2 promoter. These findings support the notion that HIF-1 is a potent stimulator of STC2 expression. Collectively, this is the first report to show that STC2 was aberrantly hypermethylated in human cancer cells. The findings demonstrated that STC2 epigenetic inactivation may interfere with HIF-1 mediated activation of STC2 expression.

SIGNOR-260389

P54868

Q9NXA8

0

post translational modification

up-regulates activity

0.343

We demonstrate that SIRT5 regu-lates succinylation of the rate-limiting ketogenicenzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2) both in vivo and in vitro.|Succinylation of Lysine Residues within the SubstrateBinding Pocket Inhibits HMGCS2 Activity|Here, we use a label-freequantitative proteomic approach to characterizethe lysine succinylome in liver mitochondria and itsregulation by the desuccinylase SIRT5

SIGNOR-267641

P31749

P07949

0

phosphorylation

up-regulates

0.323

The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity

SIGNOR-252619

P55283

P07737

0

null

up-regulates activity

0.335

Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation.

SIGNOR-253111

Q14680

O15530

1

phosphorylation

down-regulates activity

0.267

The results showed that MPK38 interacted with and inhibited PDK1 activity via Thr(354) phosphorylation.

SIGNOR-276414

Q92529

Q15303

0

relocalization

up-regulates

0.497

Like erbb1, erbb4 recruits grb2, shc and stat5.

SIGNOR-147850

Q06124

Q13224

1

dephosphorylation

down-regulates activity

0.469

In addition, surface expression of GluN2B was not reduced in mutant mice and it remains to be investigated how the direct dephosphorylation of GluN2B Y1252 by Shp2 reduces GluN2B function.|The increased GluN2B Y1472 phosphorylation was reversed by a Src family kinase inhibitor, suggesting that Shp2 may negatively regulate GluN2B Y1472 phosphorylation through suppressing Src activity .

SIGNOR-276950

P45984

P45983

0

phosphorylation

up-regulates

0.593

Our studies revealed a novel mechanism in which phosphorylation of jnk2 is mediated by jnk1 before phosphorylation of p53, and then p53 is directly phosphorylated by jnk2 at ser6.

SIGNOR-155205

Q92934

P23443

0

phosphorylation

down-regulates activity

0.295

P70S6K, the downstream target of mTORC1, can phosphorylate and inactivate pro apoptotic BAD by producing a reaction that disrupts BAD 's binding to other pro apoptotic molecules thereby allowing cell survival.|p70S6K, the downstream target of mTORC1, can phosphorylate and inactivate pro-apoptotic BAD by producing a reaction that disrupts BAD\u2019s binding to other pro-apoptotic molecules thereby allowing cell survival. xref , xref On the other hand, in a recent study, Li et al showed that increased expression of anti-apoptotic BCL2 was induced in myeloid progenitor cells upon activation of p76S6K, thereby promoting cell survival. xref Further studies are needed to better understand the effect of rapamycin and its derivatives on apoptosis in various cancer cells.

SIGNOR-280016

P01106

P38936

1

transcriptional regulation

down-regulates quantity by repression

0.779

C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a

SIGNOR-102740

Q13526

P45983

0

phosphorylation

up-regulates quantity by stabilization

0.272

Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.

SIGNOR-277562

Q9BPZ3

O95071

0

polyubiquitination

down-regulates quantity by destabilization

0.445

We demonstrate a mechanism for this co-regulation that involves an E3 ubiquitin ligase, EDD, which targets Paip2 for degradation. PABP depletion by RNA interference (RNAi) causes co-depletion of Paip2 protein without affecting Paip2 mRNA levels. Upon PABP knockdown, Paip2 interacts with EDD, which leads to Paip2 ubiquitination.

SIGNOR-272648

O75116

Q96A00

1

phosphorylation

up-regulates activity

0.413

A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.| CPI-17 can be also directly phosphorylated at Thr38 residue by MYPT1-associated kinase [222], by PAK, which is downstream of Rac and/or Cdc42 cascade [223], by Rho-associated coiled-coil kinase (ROCK) [224] and by PKN [225].

SIGNOR-96696

P40429

O43293

0

phosphorylation

up-regulates

0.402

Zipk phosphorylates l13a in vitro / l13a is phosphorylated on ser77 in vitro

SIGNOR-182117

Q16539

O95382

0

phosphorylation

up-regulates activity

0.2

These data indicate that MKK6 phosphorylates p38 MAP kinase on Thr-180 and Tyr-182, the sites of phosphorylation that activate p38 MAP kinase

SIGNOR-260916

P10275

O75592

0

ubiquitination

down-regulates quantity by destabilization

0.2

We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.

SIGNOR-267149

Q14118

Q12955

0

relocalization

up-regulates quantity

0.259

We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.

SIGNOR-266714

Q96EP5

P28482

0

phosphorylation

down-regulates activity

0.2

Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 (extracellular-signal-regulated protein kinase 2) at two Thr-Pro sequences (Thr269 and Thr315), and that both sites became phosphorylated in HEK-293 (human embryonic kidney 293) cells in response to PMA or EGF (epidermal growth factor), or RAW 264.7 macrophages in response to LPS. Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ

SIGNOR-262970

O14522

P40763

1

dephosphorylation

down-regulates activity

0.516

Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T|Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.

SIGNOR-263981

Q99684

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation.

SIGNOR-277465

Q06124

P12235

1

dephosphorylation

down-regulates activity

0.271

Specifically, SHP2-mediated dephosphorylation of ANT1 at Tyr 191 is essential for mitochondrial homeostasis and mitigation of NLRP3 inflammasome activation.|The interaction between SHP2 and ANT1 (Fig.\u00a0 xref ), and the opposite effects of SHP2 and ANT1 shRNAs in the activation of NLRP3 inflammasome (Figs.\u00a0 xref and xref ) raised the possibility that the SHP2 may inhibit ANT1 to suppress NLRP3 inflammasome activation.|To further determine which tyrosine phosphorylation site of ANT1 is dephosphorylated by SHP2, we created the dephosphorylated mutant of ANT1, in which tyrosine was replaced with phenylalanine (Y to F mutation).

SIGNOR-277124

Q969H0

O00141

0

phosphorylation

up-regulates

0.291

Here, we report that the serum- and glucocorticoid-inducible protein kinase sgk1 remarkably reduced the protein stability of the active form of notch1 through fbw7activated sgk1 phosphorylated fbw7 at serine 227

SIGNOR-170404

P49841

Q6NZ36

1

phosphorylation

down-regulates quantity

0.2

Furthermore, GSK3beta was able to decrease the cellular FAAP20 levels when overexpressed in wild-type, but not in FBW7 -/- HCT116 cells, indicating that GSK3beta requires downstream FBW7 to regulate the FAAP20 stability.|GSK3\u03b2 phosphorylates FAAP20 at Ser113.

SIGNOR-279048

Q03393

Q13976

0

phosphorylation

up-regulates

0.257

Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps

SIGNOR-71680

O75807

P35638

0

transcriptional regulation

up-regulates quantity by expression

0.454

ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.

SIGNOR-260173

P68400

Q6ZMG9

1

phosphorylation

up-regulates activity

0.2

Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.

SIGNOR-273992

Q9UQL6

P34947

0

phosphorylation

down-regulates activity

0.356

GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5.

SIGNOR-279045

Q96NY9

P68400

0

phosphorylation

up-regulates activity

0.2

Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex.

SIGNOR-273626

Q6NXT2

Q92831

0

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269617

P46019

P17612

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267410

P43405

P37840

1

phosphorylation

down-regulates

0.532

Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (syk), which phosphorylates three tyrosyl residues in its c-terminal domain (y-125, y-133, and y-136), here, we show that _-syn is an outstanding substrate for syk and that once it is tyrosine phosphorylated, it loses the ability to form oligomers.

SIGNOR-113065

O00571

Q9UHD2

0

phosphorylation

up-regulates activity

0.721

Coexpression of TBK1 strongly increased the activity of DDX3X.|This suggests that DDX3X is rather specifically phosphorylated by TBK1 and IKK-i.

SIGNOR-278997

Q6ZNA4

P61956

1

polyubiquitination

down-regulates quantity by destabilization

0.626

Arkadia ubiquitinates poly-SUMO2 chains in a SIM- and RING-dependent manner.

SIGNOR-272882

Q15418

Q07352

1

phosphorylation

down-regulates activity

0.2

These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the Messenger RNA destabilization activity of ZFP36L1.|These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the mRNA destabilization activity of ZFP36L1.

SIGNOR-279280

P18031

P09619

1

dephosphorylation

down-regulates

0.691

Ptp1b blocked pdgf-induced tyr716 and tyr751 phosphorylation of the pdgfr.

SIGNOR-179064

P51955

Q15154

0

relocalization

up-regulates

0.425

Recruitment of nek2 and c-nap1 to the centrosome is dependent on pcm-1

SIGNOR-133337

Q05655

P45983

1

phosphorylation

up-regulates

0.501

By contrast, after uv stimulation, rela directly induces the expression of pkcdelta, which in turn activates jnk.

SIGNOR-151428

Q15417

Q06187

0

phosphorylation

up-regulates quantity

0.2

Co-expression of calponin-3 with various kinases in S2 Schneider cells promoted a phosphorylation of calponin-3 by Syk, but also by the Tec family kinase Btk.

SIGNOR-280196

P08575

P19784

0

phosphorylation

up-regulates activity

0.434

Mutational analysis of CK2 consensus sites showed that the target for CK2 was in an acidic insert of 19 amino acids in the D2 domain, and Ser to Ala mutations at amino acids 965, 968, 969, and 973 abrogated CK2 phosphorylation of CD45. CK2 phosphorylation increased CD45 activity 3-fold toward phosphorylated myelin basic protein, and this increase was reversible by PP2A treatment.

SIGNOR-251031

O00141

Q96J92

1

phosphorylation

up-regulates activity

0.415

In addition, we identified a novel SGK1 phosphorylation site (S1201) in WNK4, and phosphorylation at this site is reduced by Ca(2+)/CaM.

SIGNOR-276421

P49841

P24864

1

phosphorylation

down-regulates

0.445

Our experiments suggest that gsk3 is the kinase primarily responsible for phosphorylation of cyclin e on t380

SIGNOR-118563

P53539

P59595

0

transcriptional regulation

up-regulates quantity by expression

0.2

The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well

SIGNOR-260728

Q14258

Q969H0

1

ubiquitination

down-regulates activity

0.264

This newly stabilized TRIM25 then directly ubiquitinates Lys412 of FBXW7α, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex involved in Myc ubiquitination, thereby stabilizing Myc.

SIGNOR-277457

Q14164

P35813

0

dephosphorylation

down-regulates activity

0.279

PPM1A directly dephosphorylates both MAVS and TBK1 and IKKepsilon.|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

SIGNOR-277072

P18848

O95750

1

transcriptional regulation

up-regulates quantity by expression

0.2

Reporter gene analyses using the 5'-promoter region of FGF19 revealed that a functional AARE (amino-acid-response element) was localized in this region, and this site was responsible for inducing its transcription through ATF4 (activating transcription factor 4), which is activated in response to ER stress

SIGNOR-253727

P35568

Q9H0K1

0

phosphorylation

down-regulates quantity

0.567

SIK2 is known to attenuate insulin signaling by phosphorylating IRS-1/Ser789

SIGNOR-265745

Q13131

Q9UQL6

1

phosphorylation

down-regulates

0.341

Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs)

SIGNOR-176479

P17612

P32245

1

phosphorylation

down-regulates activity

0.308

Activation of MC4R by agonist is associated with protein kinase A (PKA) and GRK phosphorylation of serine/threonine residues in the C-terminal tail of MC4R, followed by -arrestin and dynamin-dependent internalization of the receptor. Thr312 and Ser329/330 in the C-terminal tail of MC4R are potential sites for PKA

SIGNOR-250016

P35226

P16104

1

ubiquitination

up-regulates activity

0.2

In this process, BMI1 ubiquitinates histone H2A and \u03b3H2AX, thereby facilitating the repair of double-stranded DNA breaks through stimulating homologous recombination and non-homologous end joining.

SIGNOR-278744

Q13131

P08559

1

phosphorylation

up-regulates activity

0.2

AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex

SIGNOR-276837

O00303

P21127

0

phosphorylation

up-regulates activity

0.515

EIF3f is phosphorylated by CDK11p46 at Ser46 during apoptosis.|Phosphorylation of eIF3f plays an important role in regulating its function in translation and apoptosis. Phosphorylation of eIF3f enhances the association of eIF3f with the core eIF3 subunits during apoptosis.

SIGNOR-273133

Q9H3R0

Q99814

0

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271585

P08581

P49841

1

phosphorylation

up-regulates activity

0.308

MET phosphorylated and activated GSK3B at tyrosine 56, which decreased the expression of PDL1 by liver cancer cells.

SIGNOR-277428

P51151

Q7Z6M1

1

null

up-regulates activity

0.581

P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking.

SIGNOR-253088

O60674

O14744

1

phosphorylation

down-regulates

0.693

Oncogenic jak2 kinases phosphorylate prmt5 in_vivo phosphorylation of prmt5 by jak2v617f greatly impairs its methyltransferase activity

SIGNOR-171994

Q03112

Q15389

1

transcriptional regulation

up-regulates quantity by expression

0.2

We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2

SIGNOR-266059

O14950

Q13464

0

phosphorylation

up-regulates

0.624

Here we found that rho-kinase has an activity for mrlc diphosphorylation at both threonine 18 and serine 19 in nonmuscle cells using sequential column chromatographies.

SIGNOR-91542

Q15058

Q8TDX7

0

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

O43683

Q96GD4

0

phosphorylation

up-regulates activity

0.749

Although our analysis identified only one of the 15 sites implicated in Bub1-Mad1 interaction, it suggests that following its rapamycin-induced dimerization, Ipl1 phosphorylates Bub1, and potentially Mad1, to drive eSAC signaling.

SIGNOR-279010

P03951

P00740

1

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

P09493

P53355

0

phosphorylation

up-regulates activity

0.277

We identified, for the first time, death-associated protein kinase 1 (DAP kinase 1) as the kinase that phosphorylates tropomyosin-1 in response to ERK activation by hydrogen peroxide (H(2)O(2)). We also report that the phosphorylation of tropomyosin-1 mediated by DAP kinase occurs on Ser283. Our finding that tropomyosin-1 is phosphorylated downstream of ERK and DAP kinase and that it helps regulate the formation of stress fibers will aid understanding the role of this protein in regulating the endothelial functions associated with cytoskeletal remodeling.

SIGNOR-262845

P01111

Q8TEU7

0

guanine nucleotide exchange factor

up-regulates

0.331

Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.

SIGNOR-183799

P43405

Q9GZY6

1

phosphorylation

up-regulates activity

0.592

Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.The dramatic reduction in phosphorylation of the LAB Y233F mutant suggested that Tyr233 is a primary target of the Syk family kinases.

SIGNOR-273576

O75962

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.692

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-260579

P11362

Q96QU1

1

phosphorylation

up-regulates activity

0.2

FGFR1 mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.|We find that on activation, FGFR1 binds and phosphorylates Pcdh15.

SIGNOR-280014

P00533

P40763

1

phosphorylation

up-regulates activity

0.879

The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation.

SIGNOR-121965

Q14114

Q05519

0

post transcriptional regulation

up-regulates quantity by stabilization

0.2

We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling.

SIGNOR-269670

Q13153

Q7Z628

1

phosphorylation

down-regulates activity

0.249

In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner.

SIGNOR-263018

P27361

P23467

0

dephosphorylation

up-regulates

0.432

When cells are stimulated with various ligands such as growth factors, hormones, neurotransmitters, or tumor promoters, erk1/2 is activated through dualphosphorylation at the -ptepy-motif. Subsequently, p-erk1/2 translocates into the nucleus and phosphorylates elk-1, thereby acting as a transcription factor for cell proliferationthese data indicate that sa-p-erk1/2 might not only be regulated by mkp such as rvhr, but also by pp1 and ptp as well

SIGNOR-103165

Q9Y2K7

Q99814

0

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271581

Q05513

P49841

1

phosphorylation

down-regulates

0.597

Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent.

SIGNOR-119889

P11802

P07947

0

phosphorylation

down-regulates

0.254

We purified tyrosine 17 kinases from hela cells and found that the src family non-receptor tyrosine kinase c-yes contributes a large fraction of the tyrosine 17 kinase activity in hela lysatesthis site is equivalent to tyrosine 15 of cyclin dependent kinase 1, which undergoes inhibitory phosphorylation by wee1 and myt1

SIGNOR-178624

Q7L5N7

P49137

0

phosphorylation

up-regulates activity

0.2

Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2).

SIGNOR-263077

P25098

Q13304

1

phosphorylation

down-regulates activity

0.2

As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17.

SIGNOR-279999

P53990

Q9UBP0

1

relocalization

up-regulates activity

0.519

Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery.

SIGNOR-269047

P17612

O76054

1

phosphorylation

up-regulates activity

0.2

These results suggest that phosphorylation of SPF by PKA is a dynamic process and that, in the absence of PKA activity, SPF is rapidly inactivated.Thus, phosphorylation of SPF at Ser-289 appears necessary for maximal stimulation of squalene monooxygenase activity in vitro and absolutely required for the stimulation of cholesterol synthesis in cell culture.

SIGNOR-276027

Q09472

P15172

1

acetylation

up-regulates

0.681

Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo.

SIGNOR-81053

P12931

Q8IXH7

1

phosphorylation

down-regulates activity

0.336

Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1.

SIGNOR-276402

Q04912

P00519

1

phosphorylation

up-regulates activity

0.272

This suggests that by interacting with Sdc4, either directly or indirectly, RON is activated via transphosphorylation when clustered, engages the ABL1 SH2 domain, and activates ABL1 by phosphorylation.

SIGNOR-272999

P19419

P45984

0

phosphorylation

up-regulates activity

0.49

However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.

SIGNOR-247062

Q16539

Q14814

1

phosphorylation

up-regulates activity

0.612

Targeting of ash2l to specific genes is mediated by the transcriptional regulator mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 mapk signaling pathway via phosphorylation of mef2d.

SIGNOR-159331

Q15910

Q9C0B5

0

palmitoylation

down-regulates activity

0.2

Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2.

SIGNOR-261144

Q05397

P51813

0

phosphorylation

up-regulates

0.551

Bmx phosphorylated focal adhesion kinase (fak) at tyr577 subsequent to its src-mediated phosphorylation at tyr576. Loss of bmx by rna interference or by genetic deletion in mouse embryonic fibroblasts (mefs) markedly impaired fak activity.

SIGNOR-202139

Q13233

O14733

1

phosphorylation

up-regulates

0.723

Here we show that jnkk2, a novel member of the map kinase kinase family, was phosphorylated and activated by mekk1

SIGNOR-51207

P10721

Q5JUK2

0

transcriptional regulation

up-regulates quantity by expression

0.346

Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression.

SIGNOR-266205