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
Q6PCD5	P04637	1	ubiquitination	up-regulates quantity by stabilization	0.361	RFWD3 is a positive regulator of p53 abundance and regulates the G1 checkpoint in response to IR. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage.	SIGNOR-271944
P23771	P49715	1	binding	down-regulates	0.361	Whereas others, such as GATA2/3 and SMAD3, physically interact with C/EBPα to inhibit its transcriptional activity on the Pparg2 promoter.	SIGNOR-250569
O00141	Q9HBA0	1	phosphorylation	up-regulates activity	0.361	Recently, we identified that TRPV4 is also one of SGK1 substrate proteins (Fig. . , and the phosphorylation on serine 824 by SGK1 regulates the binding affinity to actin or tubulin [31].\|Therefore, we propose the hypothesis that the SGK1 phosphorylation may enhance TRPV4 channel density in the plasma membrane through the dissociation from STIM1, similar with the regulation mechanism of GLUT4 or AQP2 by insulin or vasopressin, respectively , ].	SIGNOR-279386
P08575	Q86WV1	1	dephosphorylation	up-regulates activity	0.361	Mutational analysis demonstrated the pivotal role of Tyr-232 in SKAP55 in the association with CD45. In Jurkat cells, anti-CD3 antibody stimulation promoted SKAP55 tyrosine phosphorylation and translocation from the cytoplasm to the membrane. Overexpression of SKAP55 in these cells induced transcriptional activation of the IL-2 promoter, while mutant SKAP55-Y232F totally suppressed the promoter activity. Furthermore, overexpression of SKAP55-Y232F also caused the tyrosine hyperphosphorylation of Fyn with a decreased kinase activity. Thus, SKAP55 is an essential adapter to couple CD45 with the Src family kinases for dephosphorylation and, thus, positively regulates TCR signaling.	SIGNOR-248360
P11309	Q9UNQ0	1	phosphorylation	up-regulates activity	0.36	Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells\|This is further corroborated by our finding that the plasma membrane localization and drug-resistant activity of BCRP were compromised by T362A mutation.	SIGNOR-264420
Q13315	Q9UQR1	1	phosphorylation	up-regulates	0.36	Here we found that zbp-89 is phosphorylated by atm kinase in vitro and in vivo. Disruption of the atm phosphorylation motif (202)sq within the zinc finger domain of zbp-89 attenuated its ability to enhance p21(waf1) activation by butyrate. Moreover, disruption of the atm phosphorylation site abrogated the ability of zbp-89 to potentiate butyrate induction of endogenous p21(waf1) expression.	SIGNOR-155634
O76039	P49418	1	phosphorylation	down-regulates activity	0.36	This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293.\| The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis	SIGNOR-245881
P17612	P11137	1	phosphorylation	down-regulates activity	0.36	CAMP-dependent protein kinase activity disrupts the MAP2-microtubule interaction in living HeLa cells. S319, S350, and S382 were thus identified as preferred targets of PKA	SIGNOR-250003
Q12972	Q15910	1	binding	up-regulates activity	0.36	Recruited NIPP1 enables the net phosphorylation of EZH2 by inhibiting its dephosphorylation by PP1.	SIGNOR-255665
P28482	P15923	1	phosphorylation	down-regulates quantity by destabilization	0.36	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-249451
P49137	P53667	1	phosphorylation	up-regulates	0.36	Mk2 activated limk1 by phosphorylation at ser-323.	SIGNOR-144333
Q6UUV7	P20749	1	binding	up-regulates	0.36	The ankyrin repeat domain of bcl3 interacted with torc3 / we determined that bcl3 inhibited transcription from the htlv-1 ltr in a manner dependent on torc3	SIGNOR-156950
O14757	Q96GD4	1	phosphorylation	up-regulates	0.36	Chk1 phosphorylates aurora-b and enhances its catalytic activity in vitro.	SIGNOR-152926
Q58EX7	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.36	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-260564
P28482	P51170	1	phosphorylation	down-regulates quantity by destabilization	0.36	Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.	SIGNOR-249448
P11802	Q92830	1	phosphorylation	up-regulates activity	0.36	Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5\|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)	SIGNOR-275494
Q9NRC8	Q13315	1	deacetylation	down-regulates activity	0.36	Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. \|Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016	SIGNOR-275890
Q969Q1	P19237	1	polyubiquitination	down-regulates quantity by destabilization	0.36	We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.	SIGNOR-272736
P04150	Q9Y616	1	transcriptional regulation	up-regulates quantity	0.36	We show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter	SIGNOR-259287
P04049	Q13188	1	binding	down-regulates	0.36	Raf-1 prevents dimerization and phosphorylation of the activation loop of mst2 independently of its protein kinase activity.Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (mst2)	SIGNOR-132824
Q05195	P17480	1	transcriptional regulation	down-regulates quantity by repression	0.36	MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation\|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.	SIGNOR-269646
P43405	P30307	1	phosphorylation	down-regulates activity	0.36	SYK Phosphorylates CDC25C on Serine 216.\|We now provide new genetic and biochemical evidence that SYK is an inhibitor of CDC25C in B-lineage lymphoid cells as well as non lymphohematopoietic cells, that prevents premature entry into mitosis by phosphorylating CDC25C at S216 when G 2 checkpoint responses are activated.	SIGNOR-278328
Q15772	Q9BR39	1	phosphorylation	up-regulates activity	0.36	Studies in HEK293 cells confirmed that SPEG overexpression increases JPH2 phosphorylation .	SIGNOR-279759
Q16566	P46531	1	phosphorylation	up-regulates quantity by stabilization	0.36	In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ).	SIGNOR-279596
Q13131	P36956	1	phosphorylation	down-regulates activity	0.36	Ampk was recently found to phosphorylate a conserved serine near the cleavage site within srebp1, suppressing its activation	SIGNOR-176497
P05129	P11388	1	phosphorylation	up-regulates activity	0.359	Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. \| Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.	SIGNOR-249196
Q13976	Q14847	1	phosphorylation	down-regulates activity	0.359	Studies with human lasp mutants identified serine 146 as a specific phosphorylation site for cgk and cak in vivo. Lasp is an actin-binding protein, and the phospho-lasp-mimicking mutant s146d showed reduced binding affinity for f-actin in cosedimentation experiments.	SIGNOR-97946
P60953	P35125	1	relocalization	up-regulates	0.359	In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.	SIGNOR-98935
P28482	P29590	1	phosphorylation	up-regulates	0.359	We report here that as(2)o(3) treatment induces phosphorylation of the pml protein through a mitogen-activated protein (map) kinase pathway. Increased pml phosphorylation is associated with increased sumoylation of pml and increased pml-mediated apoptosis.	SIGNOR-124248
Q16650	Q8WXX7	1	transcriptional regulation	up-regulates quantity by expression	0.359	Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism.	SIGNOR-266836
P40337	P48200	1	ubiquitination	down-regulates quantity by destabilization	0.359	We show here that IRP2 can interact with pVHL in co-transfection/co-immunoprecipitation assays. Furthermore, pVHL is able to promote the ubiquitination and the decay of transfected IRP2.	SIGNOR-271421
P17252	P27987	1	null	down-regulates activity	0.359	However, when assayed in the presence of calcium/calmodulin, the activity of the B isoform was decreased following phosphorylation by either protein kinase.	SIGNOR-248990
P45984	P01106	1	phosphorylation	up-regulates	0.359	The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71.	SIGNOR-72108
Q03112	P23769	1	transcriptional regulation	up-regulates quantity by expression	0.359	Evi1 directly binds to the promoter region of GATA-2 and thus enhances the GATA-2 transcription.	SIGNOR-266062
Q7Z419	P38936	1	ubiquitination	down-regulates quantity by destabilization	0.359	P53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1. Here we report the isolation of a novel transcriptional target of p53, designated p53RFP (p53-inducible RING-finger protein), whose product has E3 ubiquitin ligase activity. Its expression was negatively correlated to that of p21(WAF1) protein; p53RFP is likely to play a role in the regulation of this protein, probably through interaction with, and ubiquitination of, p21(WAF1).	SIGNOR-271478
P29350	P06213	2	dephosphorylation	down-regulates	0.359	Finally, we have tested the set of ptps for their ability to dephosphorylate a phosphopeptide corresponding to the irk autophosphorylation site. tc-ptp, sap-1, and ptp-1b all tested positive, but ptp-? Showed no activity, although the same gst-ptp preparation could efficiently convert pnpp (tablei). Interestingly, many other ptps showed activity, namely dep-1, glepp-1, lar, ptp-?, -?, -?, And shp-1.	SIGNOR-75938
Q969H0	Q71F56	1	ubiquitination	down-regulates quantity by destabilization	0.359	The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association.	SIGNOR-266688
P62913	O15350	1	binding	up-regulates	0.359	We report that rpl5 and rpl11 can also enhance the transcriptional activity of a p53 homolog tap73	SIGNOR-205514
Q13627	O43524	1	phosphorylation	down-regulates	0.359	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity phosphorylation of foxos by akt, ikk, erk, ck1, cdk2, and dyrk1a universally leads to foxo's inhibition.	SIGNOR-183674
O95628	Q96T37	1	ubiquitination	down-regulates quantity by destabilization	0.359	We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4).	SIGNOR-271466
P06213	P29350	2	phosphorylation	up-regulates	0.359	Insulin stimulates the phosphorylation of tyr538 and the catalytic activity of ptp1c, a protein tyrosine phosphatase with src homology-2 domains. these results suggest that ptp1c is a target protein for the insulin receptor tyrosine kinase	SIGNOR-26870
Q15418	P49841	1	phosphorylation	down-regulates	0.359	S6k then phosphorylates the same serine residue on gsk3 that is targeted by pkb/akt (fig. 1), thereby inhibiting its activity.	SIGNOR-110917
P43657	Q03113	1	binding	up-regulates activity	0.359	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-257286
P09619	Q07912	1	phosphorylation	up-regulates activity	0.359	Mutational analysis suggested that Y635 of ACK1 is a PDGFR-β phosphorylation site and that the ACK1 Y635F mutant abrogated the sequential activation of AKT.	SIGNOR-276854
P53350	P43487	1	phosphorylation	up-regulates activity	0.359	Here, we demonstrated in vitro and in vivo phosphorylation of RanBP1 by Plk1 as well as the importance of phosphorylation of RanBP1 in the interaction between Plk1 and Ran during early mitosis.	SIGNOR-279751
P29350	Q14289	1	dephosphorylation	down-regulates	0.359	Raftk binds constitutively to the protein tyrosine phosphatase shptp1.SHPTP1 Plays a negative role in pyk2/raftk signaling by dephosphorylating raftk on tyr-402, thereby inhibiting the interaction of the sh2 domain of c-src with raftk	SIGNOR-71414
P05771	P11388	1	phosphorylation	up-regulates activity	0.359	Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. \| Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.	SIGNOR-249195
Q13177	Q70Z35	1	phosphorylation	down-regulates activity	0.359	P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.	SIGNOR-277182
Q5S007	Q9NPP4	1	phosphorylation	up-regulates activity	0.359	LRRK2 phosphorylates NLRC4 at Ser533 upon inflammasome activation.\|These data suggest that LRRK2 promotes NLRC4 inflammasome activation through its kinase activity.	SIGNOR-279338
Q99496	Q9C0C7	1	ubiquitination	down-regulates quantity by destabilization	0.359	RNF2 ubiquitinates AMBRA1 at lysine 45.\|These data indicate that RNF2 directly accelerates the degradation of AMBRA1.	SIGNOR-278596
Q13315	P18846	1	phosphorylation	up-regulates activity	0.359	Exposure to DNA damage further induced ATF1 phosphorylation on Ser-51 by ATM in a manner that required prior phosphorylation of the upstream CK residues.	SIGNOR-278909
P15884	P30874	1	transcriptional regulation	up-regulates quantity by expression	0.358	Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.	SIGNOR-261618
O96017	Q9NY61	1	phosphorylation	up-regulates quantity by stabilization	0.358	Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.\| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.	SIGNOR-264416
Q15208	Q9Y5J3	1	phosphorylation	up-regulates activity	0.358	We have identified two related kinases, STK38 (serine/threonine kinase 38) and STK38L (serine/threonine kinase 38 like), which interact with and phosphorylate HEY1 at Ser-68.	SIGNOR-279489
Q9BY78	Q13501	1	ubiquitination	up-regulates activity	0.358	SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors.	SIGNOR-269830
A6NNM3	Q9UQ26	1	binding	down-regulates activity	0.358	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264369
P28482	Q92974	1	phosphorylation	up-regulates	0.358	Importantly tnf-alpha enhanced the erk pathway-dependent phosphorylation of thr-678 of gef-h1 that was key for activation.	SIGNOR-184469
P45983	Q13363	1	phosphorylation	down-regulates	0.358	In this study, we found that c-jun nh2-terminal kinase 1 activation triggered ctbp phosphorylation on ser-422 and subsequent degradation,	SIGNOR-149721
P06493	O94901	1	phosphorylation	down-regulates activity	0.358	Here, we show that SUN1, located in the INM, undergoes mitosis-specific phosphorylation on at least 3 sites within its nucleoplasmic N-terminus. We further identify Cdk1 as the kinase responsible for serine 48 and 333 phosphorylation, while serine 138 is phosphorylated by Plk1. Together, these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions.	SIGNOR-263099
P60510	Q13263	1	dephosphorylation	down-regulates activity	0.358	PP4 dephosphorylated pKAP1 in vitro.	SIGNOR-277163
Q14416	P63092	1	binding	up-regulates activity	0.358	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264079
Q9BXM7	O95202	1	phosphorylation	up-regulates activity	0.358	Here we demonstrate that PINK1 directly interacts with and phosphorylates LETM1 at Thr192 in vitro.\|Phosphorylated LETM1 or the phospho-mimetic LETM1-T192E increase calcium release in artificial liposomes and facilitates calcium transport in intact mitochondria.	SIGNOR-262540
P42345	O60516	1	phosphorylation	up-regulates	0.358	While promoting initiation of protein translation through mtor, eukaryoticinitiation factor 4e, and the ribosomal p70-s6 kinase.	SIGNOR-122035
P31749	Q9H9Q4	1	phosphorylation	down-regulates quantity by destabilization	0.358	Akt1 phosphorylates XLF at T181 Here, we report that Akt phosphorylates XLF at Thr181 to trigger its dissociation from the DNA ligase IV/XRCC4 complex, and promotes its interaction with 14-3-3β leading to XLF cytoplasmic retention, where cytosolic XLF is subsequently degraded by SCF(β-TRCP) in a CKI-dependent manner.	SIGNOR-276881
P21554	Q03113	1	binding	up-regulates activity	0.358	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-257285
Q9GZV5	O14640	1	binding	down-regulates	0.358	Taz binds to dvl proteins, thereby inhibiting dvl phosphorylation by casein kinase 1-delta and -epsilon kinases (ck1d/e), thus promoting beta-catenin degradation.	SIGNOR-195212
Q13153	Q12778	1	phosphorylation	down-regulates activity	0.358	Pak1 efficiently phosphorylated GST-FKHR.	SIGNOR-279242
P68400	Q9NQB0	1	phosphorylation	up-regulates activity	0.358	We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. \| Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4.	SIGNOR-250963
P31751	O00327	1	phosphorylation	down-regulates activity	0.358	Consistent with mass spectrometry results, constitutive active Akt2 (Akt2-CA) induced wild-type (WT) Bmal1 protein phosphorylation, which was abolished by a serine to alanine mutation at Ser42 residue (S42A) but not a S422A/S513A double mutation, as shown by immunoblot assay with phospho-Akt substrate antiserum ( xref ).\|In line with the in vivo results, overexpression of Akt2-CA strikingly lowered Bmal1 protein abundance in the nucleus in primary hepatocytes (XREF_FIG and XREF_SUPPLEMENTARY).	SIGNOR-280177
Q15418	P35568	1	phosphorylation	down-regulates quantity by destabilization	0.358	Negative feedback involves s6k, which inactivates irs by phosphorylation at multiple sites, thus inducing its degradation and altered cell localization.	SIGNOR-175687
P12931	O75365	1	phosphorylation	down-regulates activity	0.358	Our results show that Src kinase activity leads to the tyrosine phosphorylation of PRL-3, primarily on Y53.\|Collectively these results support a model in which Src causes phosphorylation of PRL-3 on Y53 to promote its pro-invasion functions, and suggest for the first time that the metastasis-associated tyrosine phosphatase PRL-3 may itself be regulated by post-translational modification.	SIGNOR-278262
P28482	Q12772	1	phosphorylation	up-regulates	0.358	Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.	SIGNOR-123045
Q13557	P56524	1	phosphorylation	up-regulates	0.358	These results demonstrate that camkiideltab preferentially targets hdac4, and this involves serine 210overexpression of camkiideltab in primary neonatal cardiomyocytes increases the activity of the mef2 transcription factor and completely rescues hdac4-mediated repression of mef2	SIGNOR-151418
Q00535	P26358	1	phosphorylation	up-regulates	0.358	We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5	SIGNOR-173685
Q9UFD9	Q9UQ26	1	binding	down-regulates activity	0.358	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264365
P24941	P09874	1	phosphorylation	up-regulates activity	0.358	CDK2 dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells.\|Hormone dependent phosphorylation of PARP-1 by CDK2, within the catalytic domain, enhances its enzymatic capabilities.	SIGNOR-279146
Q9UQ26	O14795	1	relocalization	up-regulates activity	0.358	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264383
P23193	O95071	1	binding	up-regulates	0.358	We show that the e3 ubiquitin ligase ubr5 associates with the cdk9 subunit of positive transcription elongation factor b to mediate its polyubiquitination in human cells. Tfiis also binds ubr5 to stimulate cdk9 polyubiquitination.	SIGNOR-170258
Q15915	P10071	1	relocalization	up-regulates	0.358	Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels	SIGNOR-105497
Q6IMN6	O75581	1	binding	up-regulates	0.358	A cytoplasmic protein in vertebrates, referred to as caprin-2, binds to lrp6 and facilitates lrp6 phosphorylation by gsk3	SIGNOR-187177
Q9NZJ0	Q13569	1	binding	down-regulates quantity by destabilization	0.358	TDG Is Polyubiquitinated by CRL4Cdt2 E3 Ubiquitin Ligase in a PIP Degron-dependent Manner	SIGNOR-272847
O15226	P01574	1	transcriptional regulation	down-regulates quantity by repression	0.358	Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB	SIGNOR-266227
P06241	Q9Y6K9	1	phosphorylation	down-regulates activity	0.357	Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation.	SIGNOR-276371
Q8WXH4	P04843	1	polyubiquitination	down-regulates quantity by destabilization	0.357	We also demonstrated that ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. Moreover, expression of ASB11 can increase Ribophorin 1 protein turnover in vivo.	SIGNOR-272057
Q13535	P09874	1	phosphorylation	down-regulates	0.357	Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.\|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity.	SIGNOR-278506
P00519	P17844	1	phosphorylation	up-regulates	0.357	These results suggested that p68 was phosphorylated by c-abl in ht-29 cells under stimulation of pdgf. we demonstrated that tyrosine phosphorylation of p68 at y593 mediated pdgf-stimulated epithelial-mesenchymal transition (emt). We showed that pdgf treatment led to phosphorylation of p68 at y593 in the cell nucleus. The y593-phosphorylated p68 (referred to as phosphor-p68) promotes beta-catenin nuclear translocation via a wnt-independent pathway.	SIGNOR-149988
P67775	Q13153	1	dephosphorylation	down-regulates activity	0.357	Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation.	SIGNOR-248641
P17252	Q05682	1	phosphorylation	down-regulates	0.357	Phosphorylation of both intact caldesmon and of its c-terminal fragment (658c), containing residues 658-756, significantly decreased their ability to inhibit acto-heavy meromyosin atpase.	SIGNOR-36792
Q16566	P29475	1	phosphorylation	down-regulates activity	0.357	It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.	SIGNOR-250713
P06493	P39880	1	phosphorylation	down-regulates	0.357	Phosphorylation of serines 1237 and 1270 caused inhibition of dna binding in vitro. In cotransfection studies, cyclin a-cdk1 inhibited cdp/cux stable dna binding and prevented repression of the p21(waf1) reporter.	SIGNOR-110912
Q07912	P42224	1	phosphorylation	up-regulates activity	0.357	Hence, ACK1 activates STAT1 through its kinase activity.\|We found that wild-type ACK1 and to a larger extent constitutively active ACK1 increased the phosphorylation of cytoplasmic STAT1 at Y701.	SIGNOR-278348
P27361	P17542	1	phosphorylation	down-regulates	0.357	We report here that the important proangiogenic stimulus hypoxia stimulates phosphorylation, ubiquitination, and proteasomal breakdown of tal1 in endothelial cells. A specific serine in the putative transactivation domain of the protein, ser122, is preferentially phosphorylated by mapk in vitro.	SIGNOR-116153
P41594	P63092	1	binding	up-regulates activity	0.357	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264078
P49841	Q04206	1	phosphorylation	up-regulates	0.357	Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) .	SIGNOR-151422
Q00535	Q8NEB9	1	phosphorylation	down-regulates	0.357	Thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy cdk5/p25, a neuronal cdk shown to play a role in alzheimer's disease, can also phosphorylate thr159 of vps34.	SIGNOR-165772
Q9NRC8	Q16531	1	deacetylation	down-regulates activity	0.357	Here, we show that DDB1 is acetylated and acetylation promotes DDB1 binding to CUL4. We also identify nucleolar sirtuin 7 (SIRT7) as a major deacetylase that negatively regulates DDB1-CUL4 interaction.	SIGNOR-275900
O14965	P03372	1	phosphorylation	up-regulates activity	0.357	Based on these findings, we conclude that ER\u03b1-Ser167 and -Ser305 are phosphorylated by Aurora-A in vitro and in vivo .\|These data suggest that Aurora-A not only activates ER\u03b1 activity but also enhances E2 action and that Aurora-A-induced ER\u03b1 activation could not be inhibited by tamoxifen.	SIGNOR-278508
Q13882	Q12929	1	phosphorylation	up-regulates activity	0.357	Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells. Mouse Eps8 expressed in HEK293 cells is phosphorylated by Myr-PTK6 at residues Tyr497, Tyr524, and Tyr534. These results indicate that plasma-membrane-associated PTK6 phosphorylates Eps8, which promotes cell proliferation, adhesion, and migration and, thus, tumorigenesis.	SIGNOR-263191
Q14831	P63092	1	binding	up-regulates activity	0.357	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264080
P60510	Q12888	1	dephosphorylation	up-regulates activity	0.357	Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.\|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks \|Depletion of PP4C, or PP4R3beta, causes persistence of phospho-T1609 and phospho-S1618	SIGNOR-264450

Q6PCD5

P04637

1

ubiquitination

up-regulates quantity by stabilization

0.361

RFWD3 is a positive regulator of p53 abundance and regulates the G1 checkpoint in response to IR. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage.

SIGNOR-271944

P23771

P49715

1

binding

down-regulates

0.361

Whereas others, such as GATA2/3 and SMAD3, physically interact with C/EBPα to inhibit its transcriptional activity on the Pparg2 promoter.

SIGNOR-250569

O00141

Q9HBA0

1

phosphorylation

up-regulates activity

0.361

Recently, we identified that TRPV4 is also one of SGK1 substrate proteins (Fig. . , and the phosphorylation on serine 824 by SGK1 regulates the binding affinity to actin or tubulin [31].|Therefore, we propose the hypothesis that the SGK1 phosphorylation may enhance TRPV4 channel density in the plasma membrane through the dissociation from STIM1, similar with the regulation mechanism of GLUT4 or AQP2 by insulin or vasopressin, respectively , ].

SIGNOR-279386

P08575

Q86WV1

1

dephosphorylation

up-regulates activity

0.361

Mutational analysis demonstrated the pivotal role of Tyr-232 in SKAP55 in the association with CD45. In Jurkat cells, anti-CD3 antibody stimulation promoted SKAP55 tyrosine phosphorylation and translocation from the cytoplasm to the membrane. Overexpression of SKAP55 in these cells induced transcriptional activation of the IL-2 promoter, while mutant SKAP55-Y232F totally suppressed the promoter activity. Furthermore, overexpression of SKAP55-Y232F also caused the tyrosine hyperphosphorylation of Fyn with a decreased kinase activity. Thus, SKAP55 is an essential adapter to couple CD45 with the Src family kinases for dephosphorylation and, thus, positively regulates TCR signaling.

SIGNOR-248360

P11309

Q9UNQ0

1

phosphorylation

up-regulates activity

0.36

Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells|This is further corroborated by our finding that the plasma membrane localization and drug-resistant activity of BCRP were compromised by T362A mutation.

SIGNOR-264420

Q13315

Q9UQR1

1

phosphorylation

up-regulates

0.36

Here we found that zbp-89 is phosphorylated by atm kinase in vitro and in vivo. Disruption of the atm phosphorylation motif (202)sq within the zinc finger domain of zbp-89 attenuated its ability to enhance p21(waf1) activation by butyrate. Moreover, disruption of the atm phosphorylation site abrogated the ability of zbp-89 to potentiate butyrate induction of endogenous p21(waf1) expression.

SIGNOR-155634

O76039

P49418

1

phosphorylation

down-regulates activity

0.36

This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293.| The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis

SIGNOR-245881

P17612

P11137

1

phosphorylation

down-regulates activity

0.36

CAMP-dependent protein kinase activity disrupts the MAP2-microtubule interaction in living HeLa cells. S319, S350, and S382 were thus identified as preferred targets of PKA

SIGNOR-250003

Q12972

Q15910

1

binding

up-regulates activity

0.36

Recruited NIPP1 enables the net phosphorylation of EZH2 by inhibiting its dephosphorylation by PP1.

SIGNOR-255665

P28482

P15923

1

phosphorylation

down-regulates quantity by destabilization

0.36

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-249451

P49137

P53667

1

phosphorylation

up-regulates

0.36

Mk2 activated limk1 by phosphorylation at ser-323.

SIGNOR-144333

Q6UUV7

P20749

1

binding

up-regulates

0.36

The ankyrin repeat domain of bcl3 interacted with torc3 / we determined that bcl3 inhibited transcription from the htlv-1 ltr in a manner dependent on torc3

SIGNOR-156950

O14757

Q96GD4

1

phosphorylation

up-regulates

0.36

Chk1 phosphorylates aurora-b and enhances its catalytic activity in vitro.

SIGNOR-152926

Q58EX7

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.36

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-260564

P28482

P51170

1

phosphorylation

down-regulates quantity by destabilization

0.36

Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.

SIGNOR-249448

P11802

Q92830

1

phosphorylation

up-regulates activity

0.36

Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)

SIGNOR-275494

Q9NRC8

Q13315

1

deacetylation

down-regulates activity

0.36

Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. |Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016

SIGNOR-275890

Q969Q1

P19237

1

polyubiquitination

down-regulates quantity by destabilization

0.36

We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.

SIGNOR-272736

P04150

Q9Y616

1

transcriptional regulation

up-regulates quantity

0.36

We show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter

SIGNOR-259287

P04049

Q13188

1

binding

down-regulates

0.36

Raf-1 prevents dimerization and phosphorylation of the activation loop of mst2 independently of its protein kinase activity.Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (mst2)

SIGNOR-132824

Q05195

P17480

1

transcriptional regulation

down-regulates quantity by repression

0.36

MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.

SIGNOR-269646

P43405

P30307

1

phosphorylation

down-regulates activity

0.36

SYK Phosphorylates CDC25C on Serine 216.|We now provide new genetic and biochemical evidence that SYK is an inhibitor of CDC25C in B-lineage lymphoid cells as well as non lymphohematopoietic cells, that prevents premature entry into mitosis by phosphorylating CDC25C at S216 when G 2 checkpoint responses are activated.

SIGNOR-278328

Q15772

Q9BR39

1

phosphorylation

up-regulates activity

0.36

Studies in HEK293 cells confirmed that SPEG overexpression increases JPH2 phosphorylation .

SIGNOR-279759

Q16566

P46531

1

phosphorylation

up-regulates quantity by stabilization

0.36

In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ).

SIGNOR-279596

Q13131

P36956

1

phosphorylation

down-regulates activity

0.36

Ampk was recently found to phosphorylate a conserved serine near the cleavage site within srebp1, suppressing its activation

SIGNOR-176497

P05129

P11388

1

phosphorylation

up-regulates activity

0.359

Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. | Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.

SIGNOR-249196

Q13976

Q14847

1

phosphorylation

down-regulates activity

0.359

Studies with human lasp mutants identified serine 146 as a specific phosphorylation site for cgk and cak in vivo. Lasp is an actin-binding protein, and the phospho-lasp-mimicking mutant s146d showed reduced binding affinity for f-actin in cosedimentation experiments.

SIGNOR-97946

P60953

P35125

1

relocalization

up-regulates

0.359

In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.

SIGNOR-98935

P28482

P29590

1

phosphorylation

up-regulates

0.359

We report here that as(2)o(3) treatment induces phosphorylation of the pml protein through a mitogen-activated protein (map) kinase pathway. Increased pml phosphorylation is associated with increased sumoylation of pml and increased pml-mediated apoptosis.

SIGNOR-124248

Q16650

Q8WXX7

1

transcriptional regulation

up-regulates quantity by expression

0.359

Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism.

SIGNOR-266836

P40337

P48200

1

ubiquitination

down-regulates quantity by destabilization

0.359

We show here that IRP2 can interact with pVHL in co-transfection/co-immunoprecipitation assays. Furthermore, pVHL is able to promote the ubiquitination and the decay of transfected IRP2.

SIGNOR-271421

P17252

P27987

1

null

down-regulates activity

0.359

However, when assayed in the presence of calcium/calmodulin, the activity of the B isoform was decreased following phosphorylation by either protein kinase.

SIGNOR-248990

P45984

P01106

1

phosphorylation

up-regulates

0.359

The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71.

SIGNOR-72108

Q03112

P23769

1

transcriptional regulation

up-regulates quantity by expression

0.359

Evi1 directly binds to the promoter region of GATA-2 and thus enhances the GATA-2 transcription.

SIGNOR-266062

Q7Z419

P38936

1

ubiquitination

down-regulates quantity by destabilization

0.359

P53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1. Here we report the isolation of a novel transcriptional target of p53, designated p53RFP (p53-inducible RING-finger protein), whose product has E3 ubiquitin ligase activity. Its expression was negatively correlated to that of p21(WAF1) protein; p53RFP is likely to play a role in the regulation of this protein, probably through interaction with, and ubiquitination of, p21(WAF1).

SIGNOR-271478

P29350

P06213

2

dephosphorylation

down-regulates

0.359

Finally, we have tested the set of ptps for their ability to dephosphorylate a phosphopeptide corresponding to the irk autophosphorylation site. tc-ptp, sap-1, and ptp-1b all tested positive, but ptp-? Showed no activity, although the same gst-ptp preparation could efficiently convert pnpp (tablei). Interestingly, many other ptps showed activity, namely dep-1, glepp-1, lar, ptp-?, -?, -?, And shp-1.

SIGNOR-75938

Q969H0

Q71F56

1

ubiquitination

down-regulates quantity by destabilization

0.359

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

SIGNOR-266688

P62913

O15350

1

binding

up-regulates

0.359

We report that rpl5 and rpl11 can also enhance the transcriptional activity of a p53 homolog tap73

SIGNOR-205514

Q13627

O43524

1

phosphorylation

down-regulates

0.359

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity phosphorylation of foxos by akt, ikk, erk, ck1, cdk2, and dyrk1a universally leads to foxo's inhibition.

SIGNOR-183674

O95628

Q96T37

1

ubiquitination

down-regulates quantity by destabilization

0.359

We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4).

SIGNOR-271466

P06213

P29350

2

phosphorylation

up-regulates

0.359

Insulin stimulates the phosphorylation of tyr538 and the catalytic activity of ptp1c, a protein tyrosine phosphatase with src homology-2 domains. these results suggest that ptp1c is a target protein for the insulin receptor tyrosine kinase

SIGNOR-26870

Q15418

P49841

1

phosphorylation

down-regulates

0.359

S6k then phosphorylates the same serine residue on gsk3 that is targeted by pkb/akt (fig. 1), thereby inhibiting its activity.

SIGNOR-110917

P43657

Q03113

1

binding

up-regulates activity

0.359

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-257286

P09619

Q07912

1

phosphorylation

up-regulates activity

0.359

Mutational analysis suggested that Y635 of ACK1 is a PDGFR-β phosphorylation site and that the ACK1 Y635F mutant abrogated the sequential activation of AKT.

SIGNOR-276854

P53350

P43487

1

phosphorylation

up-regulates activity

0.359

Here, we demonstrated in vitro and in vivo phosphorylation of RanBP1 by Plk1 as well as the importance of phosphorylation of RanBP1 in the interaction between Plk1 and Ran during early mitosis.

SIGNOR-279751

P29350

Q14289

1

dephosphorylation

down-regulates

0.359

Raftk binds constitutively to the protein tyrosine phosphatase shptp1.SHPTP1 Plays a negative role in pyk2/raftk signaling by dephosphorylating raftk on tyr-402, thereby inhibiting the interaction of the sh2 domain of c-src with raftk

SIGNOR-71414

P05771

P11388

1

phosphorylation

up-regulates activity

0.359

Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. | Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.

SIGNOR-249195

Q13177

Q70Z35

1

phosphorylation

down-regulates activity

0.359

P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.

SIGNOR-277182

Q5S007

Q9NPP4

1

phosphorylation

up-regulates activity

0.359

LRRK2 phosphorylates NLRC4 at Ser533 upon inflammasome activation.|These data suggest that LRRK2 promotes NLRC4 inflammasome activation through its kinase activity.

SIGNOR-279338

Q99496

Q9C0C7

1

ubiquitination

down-regulates quantity by destabilization

0.359

RNF2 ubiquitinates AMBRA1 at lysine 45.|These data indicate that RNF2 directly accelerates the degradation of AMBRA1.

SIGNOR-278596

Q13315

P18846

1

phosphorylation

up-regulates activity

0.359

Exposure to DNA damage further induced ATF1 phosphorylation on Ser-51 by ATM in a manner that required prior phosphorylation of the upstream CK residues.

SIGNOR-278909

P15884

P30874

1

transcriptional regulation

up-regulates quantity by expression

0.358

Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.

SIGNOR-261618

O96017

Q9NY61

1

phosphorylation

up-regulates quantity by stabilization

0.358

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

SIGNOR-264416

Q15208

Q9Y5J3

1

phosphorylation

up-regulates activity

0.358

We have identified two related kinases, STK38 (serine/threonine kinase 38) and STK38L (serine/threonine kinase 38 like), which interact with and phosphorylate HEY1 at Ser-68.

SIGNOR-279489

Q9BY78

Q13501

1

ubiquitination

up-regulates activity

0.358

SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors.

SIGNOR-269830

A6NNM3

Q9UQ26

1

binding

down-regulates activity

0.358

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264369

P28482

Q92974

1

phosphorylation

up-regulates

0.358

Importantly tnf-alpha enhanced the erk pathway-dependent phosphorylation of thr-678 of gef-h1 that was key for activation.

SIGNOR-184469

P45983

Q13363

1

phosphorylation

down-regulates

0.358

In this study, we found that c-jun nh2-terminal kinase 1 activation triggered ctbp phosphorylation on ser-422 and subsequent degradation,

SIGNOR-149721

P06493

O94901

1

phosphorylation

down-regulates activity

0.358

Here, we show that SUN1, located in the INM, undergoes mitosis-specific phosphorylation on at least 3 sites within its nucleoplasmic N-terminus. We further identify Cdk1 as the kinase responsible for serine 48 and 333 phosphorylation, while serine 138 is phosphorylated by Plk1. Together, these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions.

SIGNOR-263099

P60510

Q13263

1

dephosphorylation

down-regulates activity

0.358

PP4 dephosphorylated pKAP1 in vitro.

SIGNOR-277163

Q14416

P63092

1

binding

up-regulates activity

0.358

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264079

Q9BXM7

O95202

1

phosphorylation

up-regulates activity

0.358

Here we demonstrate that PINK1 directly interacts with and phosphorylates LETM1 at Thr192 in vitro.|Phosphorylated LETM1 or the phospho-mimetic LETM1-T192E increase calcium release in artificial liposomes and facilitates calcium transport in intact mitochondria.

SIGNOR-262540

P42345

O60516

1

phosphorylation

up-regulates

0.358

While promoting initiation of protein translation through mtor, eukaryoticinitiation factor 4e, and the ribosomal p70-s6 kinase.

SIGNOR-122035

P31749

Q9H9Q4

1

phosphorylation

down-regulates quantity by destabilization

0.358

Akt1 phosphorylates XLF at T181 Here, we report that Akt phosphorylates XLF at Thr181 to trigger its dissociation from the DNA ligase IV/XRCC4 complex, and promotes its interaction with 14-3-3β leading to XLF cytoplasmic retention, where cytosolic XLF is subsequently degraded by SCF(β-TRCP) in a CKI-dependent manner.

SIGNOR-276881

P21554

Q03113

1

binding

up-regulates activity

0.358

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-257285

Q9GZV5

O14640

1

binding

down-regulates

0.358

Taz binds to dvl proteins, thereby inhibiting dvl phosphorylation by casein kinase 1-delta and -epsilon kinases (ck1d/e), thus promoting beta-catenin degradation.

SIGNOR-195212

Q13153

Q12778

1

phosphorylation

down-regulates activity

0.358

Pak1 efficiently phosphorylated GST-FKHR.

SIGNOR-279242

P68400

Q9NQB0

1

phosphorylation

up-regulates activity

0.358

We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. | Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4.

SIGNOR-250963

P31751

O00327

1

phosphorylation

down-regulates activity

0.358

Consistent with mass spectrometry results, constitutive active Akt2 (Akt2-CA) induced wild-type (WT) Bmal1 protein phosphorylation, which was abolished by a serine to alanine mutation at Ser42 residue (S42A) but not a S422A/S513A double mutation, as shown by immunoblot assay with phospho-Akt substrate antiserum ( xref ).|In line with the in vivo results, overexpression of Akt2-CA strikingly lowered Bmal1 protein abundance in the nucleus in primary hepatocytes (XREF_FIG and XREF_SUPPLEMENTARY).

SIGNOR-280177

Q15418

P35568

1

phosphorylation

down-regulates quantity by destabilization

0.358

Negative feedback involves s6k, which inactivates irs by phosphorylation at multiple sites, thus inducing its degradation and altered cell localization.

SIGNOR-175687

P12931

O75365

1

phosphorylation

down-regulates activity

0.358

Our results show that Src kinase activity leads to the tyrosine phosphorylation of PRL-3, primarily on Y53.|Collectively these results support a model in which Src causes phosphorylation of PRL-3 on Y53 to promote its pro-invasion functions, and suggest for the first time that the metastasis-associated tyrosine phosphatase PRL-3 may itself be regulated by post-translational modification.

SIGNOR-278262

P28482

Q12772

1

phosphorylation

up-regulates

0.358

Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.

SIGNOR-123045

Q13557

P56524

1

phosphorylation

up-regulates

0.358

These results demonstrate that camkiideltab preferentially targets hdac4, and this involves serine 210overexpression of camkiideltab in primary neonatal cardiomyocytes increases the activity of the mef2 transcription factor and completely rescues hdac4-mediated repression of mef2

SIGNOR-151418

Q00535

P26358

1

phosphorylation

up-regulates

0.358

We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5

SIGNOR-173685

Q9UFD9

Q9UQ26

1

binding

down-regulates activity

0.358

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264365

P24941

P09874

1

phosphorylation

up-regulates activity

0.358

CDK2 dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells.|Hormone dependent phosphorylation of PARP-1 by CDK2, within the catalytic domain, enhances its enzymatic capabilities.

SIGNOR-279146

Q9UQ26

O14795

1

relocalization

up-regulates activity

0.358

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264383

P23193

O95071

1

binding

up-regulates

0.358

We show that the e3 ubiquitin ligase ubr5 associates with the cdk9 subunit of positive transcription elongation factor b to mediate its polyubiquitination in human cells. Tfiis also binds ubr5 to stimulate cdk9 polyubiquitination.

SIGNOR-170258

Q15915

P10071

1

relocalization

up-regulates

0.358

Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels

SIGNOR-105497

Q6IMN6

O75581

1

binding

up-regulates

0.358

A cytoplasmic protein in vertebrates, referred to as caprin-2, binds to lrp6 and facilitates lrp6 phosphorylation by gsk3

SIGNOR-187177

Q9NZJ0

Q13569

1

binding

down-regulates quantity by destabilization

0.358

TDG Is Polyubiquitinated by CRL4Cdt2 E3 Ubiquitin Ligase in a PIP Degron-dependent Manner

SIGNOR-272847

O15226

P01574

1

transcriptional regulation

down-regulates quantity by repression

0.358

Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB

SIGNOR-266227

P06241

Q9Y6K9

1

phosphorylation

down-regulates activity

0.357

Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation.

SIGNOR-276371

Q8WXH4

P04843

1

polyubiquitination

down-regulates quantity by destabilization

0.357

We also demonstrated that ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. Moreover, expression of ASB11 can increase Ribophorin 1 protein turnover in vivo.

SIGNOR-272057

Q13535

P09874

1

phosphorylation

down-regulates

0.357

Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity.

SIGNOR-278506

P00519

P17844

1

phosphorylation

up-regulates

0.357

These results suggested that p68 was phosphorylated by c-abl in ht-29 cells under stimulation of pdgf. we demonstrated that tyrosine phosphorylation of p68 at y593 mediated pdgf-stimulated epithelial-mesenchymal transition (emt). We showed that pdgf treatment led to phosphorylation of p68 at y593 in the cell nucleus. The y593-phosphorylated p68 (referred to as phosphor-p68) promotes beta-catenin nuclear translocation via a wnt-independent pathway.

SIGNOR-149988

P67775

Q13153

1

dephosphorylation

down-regulates activity

0.357

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

SIGNOR-248641

P17252

Q05682

1

phosphorylation

down-regulates

0.357

Phosphorylation of both intact caldesmon and of its c-terminal fragment (658c), containing residues 658-756, significantly decreased their ability to inhibit acto-heavy meromyosin atpase.

SIGNOR-36792

Q16566

P29475

1

phosphorylation

down-regulates activity

0.357

It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.

SIGNOR-250713

P06493

P39880

1

phosphorylation

down-regulates

0.357

Phosphorylation of serines 1237 and 1270 caused inhibition of dna binding in vitro. In cotransfection studies, cyclin a-cdk1 inhibited cdp/cux stable dna binding and prevented repression of the p21(waf1) reporter.

SIGNOR-110912

Q07912

P42224

1

phosphorylation

up-regulates activity

0.357

Hence, ACK1 activates STAT1 through its kinase activity.|We found that wild-type ACK1 and to a larger extent constitutively active ACK1 increased the phosphorylation of cytoplasmic STAT1 at Y701.

SIGNOR-278348

P27361

P17542

1

phosphorylation

down-regulates

0.357

We report here that the important proangiogenic stimulus hypoxia stimulates phosphorylation, ubiquitination, and proteasomal breakdown of tal1 in endothelial cells. A specific serine in the putative transactivation domain of the protein, ser122, is preferentially phosphorylated by mapk in vitro.

SIGNOR-116153

P41594

P63092

1

binding

up-regulates activity

0.357

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264078

P49841

Q04206

1

phosphorylation

up-regulates

0.357

Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) .

SIGNOR-151422

Q00535

Q8NEB9

1

phosphorylation

down-regulates

0.357

Thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy cdk5/p25, a neuronal cdk shown to play a role in alzheimer's disease, can also phosphorylate thr159 of vps34.

SIGNOR-165772

Q9NRC8

Q16531

1

deacetylation

down-regulates activity

0.357

Here, we show that DDB1 is acetylated and acetylation promotes DDB1 binding to CUL4. We also identify nucleolar sirtuin 7 (SIRT7) as a major deacetylase that negatively regulates DDB1-CUL4 interaction.

SIGNOR-275900

O14965

P03372

1

phosphorylation

up-regulates activity

0.357

Based on these findings, we conclude that ER\u03b1-Ser167 and -Ser305 are phosphorylated by Aurora-A in vitro and in vivo .|These data suggest that Aurora-A not only activates ER\u03b1 activity but also enhances E2 action and that Aurora-A-induced ER\u03b1 activation could not be inhibited by tamoxifen.

SIGNOR-278508

Q13882

Q12929

1

phosphorylation

up-regulates activity

0.357

Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells. Mouse Eps8 expressed in HEK293 cells is phosphorylated by Myr-PTK6 at residues Tyr497, Tyr524, and Tyr534. These results indicate that plasma-membrane-associated PTK6 phosphorylates Eps8, which promotes cell proliferation, adhesion, and migration and, thus, tumorigenesis.

SIGNOR-263191

Q14831

P63092

1

binding

up-regulates activity

0.357

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264080

P60510

Q12888

1

dephosphorylation

up-regulates activity

0.357

Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |Depletion of PP4C, or PP4R3beta, causes persistence of phospho-T1609 and phospho-S1618

SIGNOR-264450