GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P18846	Q14012	0	phosphorylation	up-regulates activity	0.512	Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.	SIGNOR-250611
P31749	Q96J02	1	phosphorylation	up-regulates quantity	0.319	AKT1-mediated phosphorylation of ITCH at Ser257 drives its nuclear translocation	SIGNOR-272922
Q14872	O95835	0	phosphorylation	down-regulates activity	0.2	The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1\|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1\|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression	SIGNOR-275473
Q00987	P33981	0	phosphorylation	up-regulates activity	0.264	(D and E) MDM2 was phosphorylated by hMps1 at Thr4, Thr306 and Ser307 in vitro.\|In support, the MDM2 Ser307 to Ala mutant was less stable than the wild-type protein when coexpressed with hMps1 (Supplementary Figure S2B and C). hMps1 promotes MDM2-mediated H2B ubiquitination. (A) wild-type but not kinase-dead mutant hMps1 promotes MDM2-mediated H2B ubiquitination. 293T cells were transfected with the indicated plasmids and lysates were prepared for the Ni-NTA bead pulldown assay. 46999999="S307A"}	SIGNOR-279315
Q13535	Q14566	1	phosphorylation	up-regulates	0.562	Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.	SIGNOR-169450
P27361	P05412	1	phosphorylation	up-regulates	0.781	Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein.	SIGNOR-91379
Q12852	O14733	1	phosphorylation	up-regulates activity	0.556	Collectively, these data suggest the hypothesis that ApoE activates DLK by increasing its levels	SIGNOR-279630
P17252	O15519	1	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins	SIGNOR-276147
P19525	P05198	1	phosphorylation	down-regulates activity	0.728	Besides PERK, eIF2Î± can also be phosphorylated by three other kinases: heme-regulated inhibitor kinase (HRI), general control nonderepressible 2 (GCN2), and PKR. PKR is an interferon-stimulated gene (ISG) activated by binding of double-stranded RNA (dsRNA), a common intermediate during the replication of DNA and RNA viruses. Together, these four eIF2Î± kinases and their convergent downstream signaling pathways are known as the integrated stress response (ISR)	SIGNOR-260168
P68400	P00736	1	phosphorylation	down-regulates activity	0.307	We provide evidence that this kinase phosphorylates Clr at the level of Ser189. \| Accessibility of Ser189 was low in intact C1r, due in part to the presence of one of the oligosaccharides borne by the alpha region, further reduced in the presence of calcium, and abolished when C1r was incorporated into the C1s-C1r-C1r-C1s tetramer or the C1 complex.	SIGNOR-250833
P23443	P07814	1	phosphorylation	up-regulates activity	0.2	Our studies reveal an unexpected adipogenic pathway resulting from mTORC1-S6K1 activation of EPRS ( xref ).\|These results establish the requirement for mTORC1-activated S6K1 to phosphorylate EPRS at Ser 999 ( xref ).	SIGNOR-279483
O15393	P14210	1	transcriptional regulation	up-regulates quantity by expression	0.2	we identified pro-hepatocyte growth factor (HGF) as a TMPRSS2 substrate and confirmed that HGF and it’s cognate receptor c-Met are activated in prostate cancers expressing TMPRSS2, a finding that also associated with the acquisition of a pro-invasive mesenchymal gene expression program.	SIGNOR-263657
P49674	O15055	1	phosphorylation	down-regulates quantity by destabilization	0.902	Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2	SIGNOR-277419
P61978	P45983	0	phosphorylation	up-regulates	0.372	The current studies demonstrate the identification of hnrnp-k as a jnk and erk substrate. The phosphoacceptor sites for jnk and erk on the k protein are different, and indeed, erk phosphorylation results in biological consequences different from those of phosphorylation by jnk (49). Whereas erk phosphorylation on aa 284 and 353 contributes to k protein nuclear export and concomitant inhibition of rna translation (49), phosphorylation by k protein on aa 216 and 353 increases the transcriptional effects of the k protein.	SIGNOR-105770
P04150	P31749	0	phosphorylation	down-regulates	0.486	Akt1 impairs glucocorticoid-induced gene expression by direct phosphorylation of nr3c1 at position s134 and blocking glucocorticoid-induced nr3c1 translocation to the nucleus	SIGNOR-252543
Q99558	Q13114	0	ubiquitination	down-regulates quantity by destabilization	0.668	TRAF2 and TRAF3 mediate NIK ubiquitination by forming a complex with the E3 ligase cIAP (cIAP1 or cIAP2).\|We demonstrated further that TRAF3 mediates the degradation of NIK and thereby serves as a pivotal negative regulator of noncanonical NF-kappaB signaling.	SIGNOR-278673
O14744	O60674	0	phosphorylation	down-regulates	0.693	Oncogenic jak2 kinases phosphorylate prmt5 in_vivo phosphorylation of prmt5 by jak2v617f greatly impairs its methyltransferase activity	SIGNOR-171994
P84077	Q8N6T3	0	gtpase-activating protein	up-regulates activity	0.862	The ARFGAP molecule binds to switch 2 and helix α3 to orient ARF1 residues for catalysis, but it supplies neither arginine nor other amino acid side chains to the GTPase active site.	SIGNOR-261915
Q9NQA5	Q5T4S7	0	ubiquitination	down-regulates quantity by destabilization	0.246	Cytomix induced interaction between TRPV5 and UBR4 (Ubiquitin recoginition 4), an E3 ubiquitin ligase; knockdown of UBR4 with small interfering RNAs prevented cytomix-induced degradation of TRPV5. UBR4/p600 ubiquitin ligase is responsible for TRPV5 ubiquitination and proteasomal degradation in response to cytomix	SIGNOR-272117
Q01543	Q13547	0	deacetylation	up-regulates	0.2	Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380	SIGNOR-202689
P00519	Q15139	1	phosphorylation	up-regulates	0.339	By using a phospho-specific antibody, we show that abl directly phosphorylates pkd at tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of pkd	SIGNOR-99255
Q13554	Q9H6L5	1	phosphorylation	up-regulates activity	0.2	Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy.	SIGNOR-273554
P38398	P30307	1	ubiquitination	down-regulates quantity by destabilization	0.464	BRCA1 mediates cyclin B and Cdc25C ubiquitination.\|Thus, BRCA1 dependent proteasomal degradation of cyclin B and Cdc25C precede the subsequent BRCA1 dependent cell cycle arrest.	SIGNOR-278623
P68400	Q13428	1	phosphorylation	up-regulates activity	0.305	Phosphorylated Thr 210 in Treacle is the major interaction site for NBS1\|A purified GST fragment of this region was efficiently phosphorylated by CK2 in vitro (Supplementary Fig. 4; T-2) and this fragment pulled down the MRN complex from Hela nuclear extracts only when previously phosphorylated by CK2	SIGNOR-265086
P38432	Q99986	0	phosphorylation	up-regulates quantity by stabilization	0.361	The active murine VRK1, but not its kinase-dead mutant (K179E), also phosphorylates coilin in Ser184 ( xref ).	SIGNOR-279772
P08151	Q92831	0	acetylation	down-regulates activity	0.469	NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase	SIGNOR-269270
P00533	Q16512	0	phosphorylation	down-regulates activity	0.2	This identified thr654 in egfr as the pkn1 phosphorylation siteit has been shown that the phosphorylation of egfr at thr654 by pkc reduces the tyrosine kinase activity of the receptor	SIGNOR-174755
Q02156	Q9BZL6	1	phosphorylation	up-regulates	0.2	In cells transfected with pkc? Or pkc? The phosphorylation of ser876 was markedly more pronounced than the phosphorylation of ser706/ser710 / the phosphorylation of ser706/ser710 in pkd2 reflects the activation of the kinase.	SIGNOR-89415
Q9BXM7	Q8IXI2	1	phosphorylation	down-regulates quantity by destabilization	0.775	PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C).	SIGNOR-272728
Q9NRY4	Q6PJ69	0	polyubiquitination	down-regulates quantity by destabilization	0.2	Ubiquitin ligase TRIM65 promotes colorectal cancer metastasis by targeting ARHGAP35 for protein degradation	SIGNOR-272256
P15498	P12931	0	phosphorylation	up-regulates activity	0.368	These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.\|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ).	SIGNOR-279124
Q9UEW8	Q04759	0	phosphorylation	up-regulates activity	0.487	Recombinant SPAK was phosphorylated on Ser-311 in its kinase domain by PKCtheta, but not by PKCalpha. This synergistic activity, as well as the receptor-induced SPAK activation, required the PKCtheta-interacting region of SPAK, and Ser-311 mutation greatly reduced these activities of SPAK.	SIGNOR-276007
P33991	Q13535	0	phosphorylation	up-regulates	0.724	Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.	SIGNOR-169412
P27037	Q15796	1	phosphorylation	up-regulates activity	0.71	In ACVR2A/B dKO parental cells, only ACVR2A , but not ACVR2A , could rescue both pSMAD2 and pSMAD1/5 (Fig\u00a04B).\|In marked contrast, in ACVR2A/B dKO HOM1 cells, ACVR2A restored SMAD1/5 phosphorylation, but not SMAD2 phosphorylation (Fig\u00a04C).	SIGNOR-279786
Q8TDD2	Q16539	0	phosphorylation	up-regulates activity	0.408	We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes	SIGNOR-255791
P06850	P51608	0	transcriptional regulation	down-regulates quantity by repression	0.466	Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. \| Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice.	SIGNOR-264548
P15056	Q9Y243	0	phosphorylation	down-regulates	0.289	We show that phosphorylation of b-raf by akt occurs at multiple residues within its aminoterminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity.	SIGNOR-78693
Q14527	P12004	1	ubiquitination	up-regulates activity	0.78	HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability.	SIGNOR-278608
P19174	Q12913	0	dephosphorylation	down-regulates	0.369	Cd148 can dephosphorylate lat and plc?1 In vitro. / plc?1 Undergoes inducible tyrosine phosphorylation following tcr stimulation (46), and this phosphorylation is required to stimulate its catalytic activity	SIGNOR-105790
P51812	P03372	1	phosphorylation	up-regulates	0.403	S6k1 regulates estrogen receptor alpha (eralpha) by phosphorylating it on serine 167, leading to transcriptional activation of eralpha.	SIGNOR-182958
P60484	P52732	1	dephosphorylation	up-regulates activity	0.455	PTEN significantly reduces EG5 phosphorylation at Thr926 (XREF_FIG), suggesting PTEN may target this EG5 site for dephosphorylation.	SIGNOR-277000
O14965	Q9GZM8	1	phosphorylation	down-regulates quantity by destabilization	0.603	Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation.	SIGNOR-263159
Q8N726	Q00987	1	relocalization	down-regulates activity	0.765	We propose that p14(arf) increases the binding of p53-mdm2 complexes to chromatin, thereby limiting the access of protein deacetylases to p53.	SIGNOR-192697
Q5JXC2	Q02156	0	phosphorylation	up-regulates activity	0.2	Here, we show that EGF stimulation induces PKCε-dependent phosphorylation of migration and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes the interaction between MIIP and RelA in the nucleus, by which MIIP prevents histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances transcriptional activity of RelA and facilitates tumor metastasis.	SIGNOR-273828
Q96PU5	Q9Y5Y9	1	ubiquitination	down-regulates quantity by destabilization	0.32	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253463
P0C6X7-PRO_0000037310	P11362	0	chemical inhibition	down-regulates activity	0.2	Pyrimidine 13 showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140, and 146 nM, respectively.	SIGNOR-260150
P56945	P06241	0	phosphorylation	up-regulates activity	0.766	Taken together, these results suggest that p130Cas is directly phosphorylated by Fyn kinase in the cytoplasm of oligodendrocytes.	SIGNOR-279372
Q15051	Q9H992	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH7 induces K48 ubiquitination of NPHP5 and protein degradation, while BBS11 triggers K63 ubiquitination and protein delocalization.\|Unlike the catalytically inactive mutant , wild type MARCH7 was able to trigger NPHP5 ubiquitination (XREF_FIG).	SIGNOR-278585
Q92934	P04049	0	phosphorylation	down-regulates	0.66	The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins	SIGNOR-155293
P12931	P56945	1	phosphorylation	up-regulates activity	0.803	Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of CasBased on these data, 11 tyrosine residues (132, 169, 183, 196, 238, 253, 271, 291, 301, 391, and 414) were phosphorylated by Src\|the biological activity of Cas depends on its phosphorylation by Src (16–18). After phosphorylation, Cas associates with a number of proteins, including Crk, Src, phosphatidylinositol 3-kinase, Nck, and phospholipase Cgamma, via SH2 binding motifs	SIGNOR-246393
Q9UN19	P12931	0	phosphorylation	up-regulates activity	0.586	Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell linesyrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins.	SIGNOR-247119
Q969H0	P31749	0	phosphorylation	up-regulates activity	0.41	A reciprocal immunoprecipiation with anti-phospho-Akt substrate antibody followed by immunoblotting with anti-FLAG antibodies confirmed these findings (Fig. 1C). We concluded that Fbw7 is phosphorylated at S227 in vivo. Phosphorylation of Fbw7 is required for its biological activity.	SIGNOR-276328
O95477	P00533	0	phosphorylation	down-regulates quantity by destabilization	0.295	We further provide in vitro evidence that epidermal growth factor receptor (EGFR)-mediated phosphorylation regulated ABCA1 ubiquitination \|The EGFR selective inhibitor PD168393 blocked the EGFR-ABCA1 interaction and abolished ABCA1Ser2054 phosphorylation\|	SIGNOR-264419
Q9P055	Q99942	0	ubiquitination	down-regulates activity	0.509	RNF5 is a ubiquitin ligase anchored to the ER membrane implicated in ERAD via ubiquitination of misfolded proteins. This association results in Ubc13-dependent RNF5-mediated noncanonical ubiquitination of JAMP. This ubiquitination does not alter JAMP stability but rather inhibits its association with Rpt5 and p97.	SIGNOR-271483
P49841	Q9HB09	1	phosphorylation	up-regulates	0.338	Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s156a)	SIGNOR-195512
P21127	P50613	0	phosphorylation	up-regulates activity	0.335	We conclude that CDK7 phsphorylates Cdk11, dependent on the conserved Thr219 residue in the CDK11 T loop, and it is therefore likely to be a genuine Cdk11 activating kinase	SIGNOR-245871
P53350	Q71F23	1	phosphorylation	down-regulates	0.741	S77 and t78 of pbip1 are important for plk1-dependent pbip1 phosphorylation and degradation. Here, we demonstrate that a pbd-binding protein, pbip1, is crucial for recruiting plk1 to the interphase and mitotic kinetochores. Unprecedentedly, plk1 phosphorylated pbip1 at t78. Later in mitosis, plk1 also induced pbip1 degradation in a t78-dependent manner, thereby enabling itself to interact with other components critical for proper kinetochore functions	SIGNOR-150457
P25025	P43250	0	phosphorylation	down-regulates quantity	0.563	GRK2 mainly phosphorylates CXCR1, while GRK6 mediates CXCR2 phosphorylation .\|Overexpression of GRK6 or treatment with CXCR2 siRNA suppresses CXCR2 expression in dorsal root ganglion and significantly reduces pain in animal model of neuropathic pain , .	SIGNOR-279782
Q14493	Q99880	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265389
O14920	P08151	1	phosphorylation	up-regulates activity	0.356	Active IKKbeta promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.\|Herein, we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL.	SIGNOR-279194
P01189	P16220	0	transcriptional regulation	up-regulates quantity by expression	0.37	Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein\|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE.	SIGNOR-268620
P46527	Q13309	0	ubiquitination	down-regulates	0.766	Up-regulation of skp2 by notch signaling enhances proteasome-mediated degradation of the ckis, p27 kip1 and p21 cip1, and causes premature entry into s phase. ;the recognition of p27 by skp2/cks1 of the scfskp2 complex is dictated by cycline/cdk2, providing a high affinity binding site and the phosphorylation of p27 at t187, serving here we provide evidence suggesting that both cdk2/e and phosphorylation of thr(187) on p27 are essential for the recognition of p27 by the scf(skp2/cks1) complex, the ubiquitin-protein isopeptide ligase (e3).	SIGNOR-154194
Q05655	P21730	1	phosphorylation	down-regulates	0.2	Whole cell phosphorylation assays with specific inhibitors as well as in vitro phosphorylation assays with recombinant enzymes and peptide substrates revealed that phosphorylation of ser-334 is regulated by protein kinase c-beta this study is among the first to analyze in a detailed manner, using a non-mutational approach, modifications of a defined phosphorylation site in a g protein-coupled receptor and to correlate these findings with functional parameters of receptor deactivation.	SIGNOR-73967
P00533	P28482	0	phosphorylation	down-regulates activity	0.639	A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase	SIGNOR-20545
P07947	P40189	0	phosphorylation	up-regulates activity	0.2	Binding of LIF to the LIFR-gp130 receptor complex has been previously shown to activate YES and YAP/TAZ-TEAD -dependent transcription, which is required to maintain self-renewal in embryonic stem cells	SIGNOR-278033
P49840	Q9BYG3	1	phosphorylation	up-regulates activity	0.2	The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.	SIGNOR-262697
P35558	Q09472	0	acetylation	down-regulates quantity by destabilization	0.546	Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase\|P300 Acetylates and Destabilizes PEPCK1\|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1	SIGNOR-267603
Q92900	Q96Q15	0	phosphorylation	up-regulates	0.971	Smg-1 directly phosphorylates upf1 helicase, another key component of nmd, upon recognition of ptc on postspliced mrna during the initial round of translation. Phosphorylated-upf1 recruits the smg-5/smg-7 complex to induce ribosome dissociation and decapping-mediated decay. T28 and s1096 are responsible for phospho-specific recruitment of smg-6 to the n-terminal conserved region, and the smg-5/smg-7 heterodimer complex to the c-terminal sq-rich region of upf1, respectively	SIGNOR-200785
Q05655	Q5JVS0	1	phosphorylation	down-regulates activity	0.29	We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. \| This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. \| Ki-1/57 Exits the Nucleus upon PMA Activation	SIGNOR-249254
P30307	P27448	0	phosphorylation	down-regulates activity	0.485	C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. Phosphorylation of serine 21 6 promotes 1 4-3-3 binding to Cdc25C and is inhibitory to Cdc25C function.	SIGNOR-250176
P24752	P48735	1	acetylation	down-regulates activity	0.287	Mitochondrial acetyltransferase ACAT1 and deacetylase SIRT3 are responsible for acetylation and deacetylation, respectively, at K413 of mIDH2\|K413 acetylation inhibits mIDH2 by simultaneously attenuating dimer formation from monomers and destabilizing dimers for conversion to monomers	SIGNOR-267627
Q15139	P29475	1	phosphorylation	up-regulates activity	0.385	In addition, we demonstrate that protein kinase D1 activates nNOS by phosphorylating the activatory residue Ser1412, leading to increased \u00b7NO production, hence establishing a novel role of PKD in the regulation of \u00b7NO synthesis.\|PKD1 phosphorylates nNOS at activatory Ser 1412 in vitro and in live cells.	SIGNOR-278426
P06493	Q8TAP9	1	phosphorylation	up-regulates	0.341	Ttdn1 is phosphorylated by cdk1 in vitro and in vivo. Ttdn1 is phosphorylated at multiple residues, including ser93 and ser104. Mutation of thr120 of ttdn1 abolishes its interaction with plk1, suggesting phosphorylation of thr120 in the consensus plk1-binding motif is required for its interaction with plk1	SIGNOR-153308
Q8IXI2	Q9BXM7	0	phosphorylation	down-regulates quantity by destabilization	0.775	PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C).	SIGNOR-272728
Q86U44	Q92995	1	post transcriptional regulation	up-regulates quantity by stabilization	0.2	Furthermore, N6-methyladenosine methyltransferase-like 3 (METTL3) mediated stabilization of USP13 mRNA that required the m6A reader IGF2BP2.	SIGNOR-275839
P08559	Q15120	0	phosphorylation	down-regulates activity	0.871	Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes.	SIGNOR-109647
Q9NTG7	P06493	0	phosphorylation	up-regulates activity	0.315	Both SIRT3 T150 and S159 phosphorylated by CDK1 indicates that CDK1-SIRT3 pathway may play a role in the overall mitochondrial protein acetylation involved in mitochondrial homeostasis and apoptosis.	SIGNOR-279395
Q16620	P35398	0	transcriptional regulation	up-regulates quantity by expression	0.266	Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).	SIGNOR-265137
A7MCY6	Q9UHD2	1	relocalization	up-regulates activity	0.603	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272469
P33981	Q96PE2	1	phosphorylation	down-regulates activity	0.2	Because Mps1 also phosphorylates ARHGEF17, the Mps1\u2013ARHGEF17 complex is short lived and promotes its own dissociation, which in turn releases Mps1 and ARHGEF17 from the kinetochore.\|ARHGEF17 and Mps1 interact during mitosis and Mps1 phosphorylates ARHGEF17.	SIGNOR-279352
P16144	P17252	0	phosphorylation	down-regulates	0.531	Egf stimulates a pkc-?-Dependent pathway that results in the phosphorylation of the ?4 Integrin subunit on serine residues and its redistribution to actin-rich structures together, these results highlight the importance of serine phosphorylation in regulating type ii hemidesmosome disassembly, implicate a cluster of serine residues within the connecting segment of ?4, and argue for a key role for pkc-? In regulating these structures	SIGNOR-124494
Q92630	Q00613	1	phosphorylation	up-regulates activity	0.318	To test whether in a similar way DYRK2 phosphorylates and activates HSF1 in human cancer cells, we overexpressed DYRK2 and, by use of phosphospecific antibodies, we observed that the levels of endogenous HSF1 phosphorylated at S326 and S320 (two main phosphorylation events linked to HSF1 activation) were increased (Fig.\u00a0 xref ).\|Together, these results show that DYRK2 phosphorylates HSF1 in cells and in vitro at S320 and also at S326, which is critical for HSF1 activation.Next, to test whether endogenous DYRK2 plays a role in HSF1 activation by proteotoxic stress, we used the prototypical HSF1 inducer heat shock (HS), in the absence or in the presence of harmine, observing that the inhibitor clearly impaired the phosphorylation of HSF1 upon HS (Fig S1F).	SIGNOR-278355
P39900	P02671	1	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. \|Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.\|MMP-12 20ADSGEGD a-chain\| 540FVSETESRG a-chain\|433LVTSKGDK a-chain	SIGNOR-263622
P11279	Q9NR19	0	transcriptional regulation	up-regulates quantity by expression	0.2	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276556
P63244	P05412	0	null	up-regulates quantity by expression	0.2	In turn, c-Jun induces expression of RACK1, which is required for JNK activation by PKC, pointing to a c-Jun/RACK1/PKC/JNK feedback loop.	SIGNOR-278066
Q13261	P52333	1	null	up-regulates	0.501	Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated	SIGNOR-256226
Q00534	P05412	1	phosphorylation	up-regulates quantity	0.423	CDK6 additionally induced c-Jun phosphorylation, but did not activate JNK, as determined by examining JNK phosphorylation at various time-points.\|CDK6 upregulates c-Jun expression.	SIGNOR-280222
P08246	P01019	1	cleavage	up-regulates activity	0.275	Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.	SIGNOR-256313
P60568	Q9UL17	0	transcriptional regulation	down-regulates quantity by repression	0.473	T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells	SIGNOR-266233
O00311	Q5FWF5	1	phosphorylation	down-regulates	0.432	We show here that eco1 degradation requires the sequential actions of cdk1 and two additional kinases, cdc7-dbf4 and the gsk-3 homolog mck1.	SIGNOR-200397
Q9Y2I6	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.422	In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation.	SIGNOR-259831
Q05209	Q14161	1	dephosphorylation	down-regulates	0.344	Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest.	SIGNOR-142719
O43236	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Thus, Parkin degrades ARTS in a proteasome dependent manner.\|Together, these results suggest that Parkin specifically ubiquitinates and degrades ARTS, and that this degradation may be linked to the pro-apoptotic function of ARTS.	SIGNOR-278642
P63000	O94988	0	gtpase-activating protein	down-regulates activity	0.435	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-260502
P53350	Q9Y6K1	1	phosphorylation	down-regulates activity	0.269	2.11 Plk1 Directly Phosphorylates DNMT3a at S393.\|Elevated Plk1 further inhibited DNMT3a via phosphorylation at S393 in mitosis in accord with its mitotic role during cell cycle.	SIGNOR-279552
Q96FF9	Q96GD4	0	phosphorylation	down-regulates activity	0.629	Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.	SIGNOR-276116
Q15797	P27361	0	phosphorylation	down-regulates	0.528	Ras signaling was shown previously to induce the phosphorylation of the bmp mediator smad1 at four erk consensus sites in the linker domain (kretzschmar et al. 1997a). Phosphorylation of these four sites inhibits smad1 accumulation in the nucleus	SIGNOR-66755
Q99708	Q504Q3	0	deubiquitination	up-regulates activity	0.2	Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52.	SIGNOR-273509
Q92630	P43686	1	phosphorylation	down-regulates quantity by destabilization	0.284	Through a kinome-wide screen, we have identified dual-specificity tyrosine-regulated kinase 2 (DYRK2) as the primary kinase that phosphorylates Rpt3-Thr25, leading to enhanced substrate translocation and degradation.	SIGNOR-275845
Q96J92	O95747	1	phosphorylation	up-regulates activity	0.48	In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].\|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].	SIGNOR-278389

P18846

Q14012

0

phosphorylation

up-regulates activity

0.512

Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.

SIGNOR-250611

P31749

Q96J02

1

phosphorylation

up-regulates quantity

0.319

AKT1-mediated phosphorylation of ITCH at Ser257 drives its nuclear translocation

SIGNOR-272922

Q14872

O95835

0

phosphorylation

down-regulates activity

0.2

The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression

SIGNOR-275473

Q00987

P33981

0

phosphorylation

up-regulates activity

0.264

(D and E) MDM2 was phosphorylated by hMps1 at Thr4, Thr306 and Ser307 in vitro.|In support, the MDM2 Ser307 to Ala mutant was less stable than the wild-type protein when coexpressed with hMps1 (Supplementary Figure S2B and C). hMps1 promotes MDM2-mediated H2B ubiquitination. (A) wild-type but not kinase-dead mutant hMps1 promotes MDM2-mediated H2B ubiquitination. 293T cells were transfected with the indicated plasmids and lysates were prepared for the Ni-NTA bead pulldown assay. 46999999="S307A"}

SIGNOR-279315

Q13535

Q14566

1

phosphorylation

up-regulates

0.562

Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.

SIGNOR-169450

P27361

P05412

1

phosphorylation

up-regulates

0.781

Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein.

SIGNOR-91379

Q12852

O14733

1

phosphorylation

up-regulates activity

0.556

Collectively, these data suggest the hypothesis that ApoE activates DLK by increasing its levels

SIGNOR-279630

P17252

O15519

1

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins

SIGNOR-276147

P19525

P05198

1

phosphorylation

down-regulates activity

0.728

Besides PERK, eIF2Î± can also be phosphorylated by three other kinases: heme-regulated inhibitor kinase (HRI), general control nonderepressible 2 (GCN2), and PKR. PKR is an interferon-stimulated gene (ISG) activated by binding of double-stranded RNA (dsRNA), a common intermediate during the replication of DNA and RNA viruses. Together, these four eIF2Î± kinases and their convergent downstream signaling pathways are known as the integrated stress response (ISR)

SIGNOR-260168

P68400

P00736

1

phosphorylation

down-regulates activity

0.307

We provide evidence that this kinase phosphorylates Clr at the level of Ser189. | Accessibility of Ser189 was low in intact C1r, due in part to the presence of one of the oligosaccharides borne by the alpha region, further reduced in the presence of calcium, and abolished when C1r was incorporated into the C1s-C1r-C1r-C1s tetramer or the C1 complex.

SIGNOR-250833

P23443

P07814

1

phosphorylation

up-regulates activity

0.2

Our studies reveal an unexpected adipogenic pathway resulting from mTORC1-S6K1 activation of EPRS ( xref ).|These results establish the requirement for mTORC1-activated S6K1 to phosphorylate EPRS at Ser 999 ( xref ).

SIGNOR-279483

O15393

P14210

1

transcriptional regulation

up-regulates quantity by expression

0.2

we identified pro-hepatocyte growth factor (HGF) as a TMPRSS2 substrate and confirmed that HGF and it’s cognate receptor c-Met are activated in prostate cancers expressing TMPRSS2, a finding that also associated with the acquisition of a pro-invasive mesenchymal gene expression program.

SIGNOR-263657

P49674

O15055

1

phosphorylation

down-regulates quantity by destabilization

0.902

Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2

SIGNOR-277419

P61978

P45983

0

phosphorylation

up-regulates

0.372

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

SIGNOR-105770

P04150

P31749

0

phosphorylation

down-regulates

0.486

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

SIGNOR-252543

Q99558

Q13114

0

ubiquitination

down-regulates quantity by destabilization

0.668

TRAF2 and TRAF3 mediate NIK ubiquitination by forming a complex with the E3 ligase cIAP (cIAP1 or cIAP2).|We demonstrated further that TRAF3 mediates the degradation of NIK and thereby serves as a pivotal negative regulator of noncanonical NF-kappaB signaling.

SIGNOR-278673

O14744

O60674

0

phosphorylation

down-regulates

0.693

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

SIGNOR-171994

P84077

Q8N6T3

0

gtpase-activating protein

up-regulates activity

0.862

The ARFGAP molecule binds to switch 2 and helix α3 to orient ARF1 residues for catalysis, but it supplies neither arginine nor other amino acid side chains to the GTPase active site.

SIGNOR-261915

Q9NQA5

Q5T4S7

0

ubiquitination

down-regulates quantity by destabilization

0.246

Cytomix induced interaction between TRPV5 and UBR4 (Ubiquitin recoginition 4), an E3 ubiquitin ligase; knockdown of UBR4 with small interfering RNAs prevented cytomix-induced degradation of TRPV5. UBR4/p600 ubiquitin ligase is responsible for TRPV5 ubiquitination and proteasomal degradation in response to cytomix

SIGNOR-272117

Q01543

Q13547

0

deacetylation

up-regulates

0.2

Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380

SIGNOR-202689

P00519

Q15139

1

phosphorylation

up-regulates

0.339

By using a phospho-specific antibody, we show that abl directly phosphorylates pkd at tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of pkd

SIGNOR-99255

Q13554

Q9H6L5

1

phosphorylation

up-regulates activity

0.2

Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy.

SIGNOR-273554

P38398

P30307

1

ubiquitination

down-regulates quantity by destabilization

0.464

BRCA1 mediates cyclin B and Cdc25C ubiquitination.|Thus, BRCA1 dependent proteasomal degradation of cyclin B and Cdc25C precede the subsequent BRCA1 dependent cell cycle arrest.

SIGNOR-278623

P68400

Q13428

1

phosphorylation

up-regulates activity

0.305

Phosphorylated Thr 210 in Treacle is the major interaction site for NBS1|A purified GST fragment of this region was efficiently phosphorylated by CK2 in vitro (Supplementary Fig. 4; T-2) and this fragment pulled down the MRN complex from Hela nuclear extracts only when previously phosphorylated by CK2

SIGNOR-265086

P38432

Q99986

0

phosphorylation

up-regulates quantity by stabilization

0.361

The active murine VRK1, but not its kinase-dead mutant (K179E), also phosphorylates coilin in Ser184 ( xref ).

SIGNOR-279772

P08151

Q92831

0

acetylation

down-regulates activity

0.469

NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase

SIGNOR-269270

P00533

Q16512

0

phosphorylation

down-regulates activity

0.2

This identified thr654 in egfr as the pkn1 phosphorylation siteit has been shown that the phosphorylation of egfr at thr654 by pkc reduces the tyrosine kinase activity of the receptor

SIGNOR-174755

Q02156

Q9BZL6

1

phosphorylation

up-regulates

0.2

In cells transfected with pkc? Or pkc? The phosphorylation of ser876 was markedly more pronounced than the phosphorylation of ser706/ser710 / the phosphorylation of ser706/ser710 in pkd2 reflects the activation of the kinase.

SIGNOR-89415

Q9BXM7

Q8IXI2

1

phosphorylation

down-regulates quantity by destabilization

0.775

PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C).

SIGNOR-272728

Q9NRY4

Q6PJ69

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Ubiquitin ligase TRIM65 promotes colorectal cancer metastasis by targeting ARHGAP35 for protein degradation

SIGNOR-272256

P15498

P12931

0

phosphorylation

up-regulates activity

0.368

These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ).

SIGNOR-279124

Q9UEW8

Q04759

0

phosphorylation

up-regulates activity

0.487

Recombinant SPAK was phosphorylated on Ser-311 in its kinase domain by PKCtheta, but not by PKCalpha. This synergistic activity, as well as the receptor-induced SPAK activation, required the PKCtheta-interacting region of SPAK, and Ser-311 mutation greatly reduced these activities of SPAK.

SIGNOR-276007

P33991

Q13535

0

phosphorylation

up-regulates

0.724

Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.

SIGNOR-169412

P27037

Q15796

1

phosphorylation

up-regulates activity

0.71

In ACVR2A/B dKO parental cells, only ACVR2A , but not ACVR2A , could rescue both pSMAD2 and pSMAD1/5 (Fig\u00a04B).|In marked contrast, in ACVR2A/B dKO HOM1 cells, ACVR2A restored SMAD1/5 phosphorylation, but not SMAD2 phosphorylation (Fig\u00a04C).

SIGNOR-279786

Q8TDD2

Q16539

0

phosphorylation

up-regulates activity

0.408

We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes

SIGNOR-255791

P06850

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.466

Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. | Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice.

SIGNOR-264548

P15056

Q9Y243

0

phosphorylation

down-regulates

0.289

We show that phosphorylation of b-raf by akt occurs at multiple residues within its aminoterminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity.

SIGNOR-78693

Q14527

P12004

1

ubiquitination

up-regulates activity

0.78

HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability.

SIGNOR-278608

P19174

Q12913

0

dephosphorylation

down-regulates

0.369

Cd148 can dephosphorylate lat and plc?1 In vitro. / plc?1 Undergoes inducible tyrosine phosphorylation following tcr stimulation (46), and this phosphorylation is required to stimulate its catalytic activity

SIGNOR-105790

P51812

P03372

1

phosphorylation

up-regulates

0.403

S6k1 regulates estrogen receptor alpha (eralpha) by phosphorylating it on serine 167, leading to transcriptional activation of eralpha.

SIGNOR-182958

P60484

P52732

1

dephosphorylation

up-regulates activity

0.455

PTEN significantly reduces EG5 phosphorylation at Thr926 (XREF_FIG), suggesting PTEN may target this EG5 site for dephosphorylation.

SIGNOR-277000

O14965

Q9GZM8

1

phosphorylation

down-regulates quantity by destabilization

0.603

Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation.

SIGNOR-263159

Q8N726

Q00987

1

relocalization

down-regulates activity

0.765

We propose that p14(arf) increases the binding of p53-mdm2 complexes to chromatin, thereby limiting the access of protein deacetylases to p53.

SIGNOR-192697

Q5JXC2

Q02156

0

phosphorylation

up-regulates activity

0.2

Here, we show that EGF stimulation induces PKCε-dependent phosphorylation of migration and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes the interaction between MIIP and RelA in the nucleus, by which MIIP prevents histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances transcriptional activity of RelA and facilitates tumor metastasis.

SIGNOR-273828

Q96PU5

Q9Y5Y9

1

ubiquitination

down-regulates quantity by destabilization

0.32

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253463

P0C6X7-PRO_0000037310

P11362

0

chemical inhibition

down-regulates activity

0.2

Pyrimidine 13 showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140, and 146 nM, respectively.

SIGNOR-260150

P56945

P06241

0

phosphorylation

up-regulates activity

0.766

Taken together, these results suggest that p130Cas is directly phosphorylated by Fyn kinase in the cytoplasm of oligodendrocytes.

SIGNOR-279372

Q15051

Q9H992

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH7 induces K48 ubiquitination of NPHP5 and protein degradation, while BBS11 triggers K63 ubiquitination and protein delocalization.|Unlike the catalytically inactive mutant , wild type MARCH7 was able to trigger NPHP5 ubiquitination (XREF_FIG).

SIGNOR-278585

Q92934

P04049

0

phosphorylation

down-regulates

0.66

The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins

SIGNOR-155293

P12931

P56945

1

phosphorylation

up-regulates activity

0.803

Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of CasBased on these data, 11 tyrosine residues (132, 169, 183, 196, 238, 253, 271, 291, 301, 391, and 414) were phosphorylated by Src|the biological activity of Cas depends on its phosphorylation by Src (16–18). After phosphorylation, Cas associates with a number of proteins, including Crk, Src, phosphatidylinositol 3-kinase, Nck, and phospholipase Cgamma, via SH2 binding motifs

SIGNOR-246393

Q9UN19

P12931

0

phosphorylation

up-regulates activity

0.586

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

SIGNOR-247119

Q969H0

P31749

0

phosphorylation

up-regulates activity

0.41

A reciprocal immunoprecipiation with anti-phospho-Akt substrate antibody followed by immunoblotting with anti-FLAG antibodies confirmed these findings (Fig. 1C). We concluded that Fbw7 is phosphorylated at S227 in vivo. Phosphorylation of Fbw7 is required for its biological activity.

SIGNOR-276328

O95477

P00533

0

phosphorylation

down-regulates quantity by destabilization

0.295

We further provide in vitro evidence that epidermal growth factor receptor (EGFR)-mediated phosphorylation regulated ABCA1 ubiquitination |The EGFR selective inhibitor PD168393 blocked the EGFR-ABCA1 interaction and abolished ABCA1Ser2054 phosphorylation|

SIGNOR-264419

Q9P055

Q99942

0

ubiquitination

down-regulates activity

0.509

RNF5 is a ubiquitin ligase anchored to the ER membrane implicated in ERAD via ubiquitination of misfolded proteins. This association results in Ubc13-dependent RNF5-mediated noncanonical ubiquitination of JAMP. This ubiquitination does not alter JAMP stability but rather inhibits its association with Rpt5 and p97.

SIGNOR-271483

P49841

Q9HB09

1

phosphorylation

up-regulates

0.338

Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s156a)

SIGNOR-195512

P21127

P50613

0

phosphorylation

up-regulates activity

0.335

We conclude that CDK7 phsphorylates Cdk11, dependent on the conserved Thr219 residue in the CDK11 T loop, and it is therefore likely to be a genuine Cdk11 activating kinase

SIGNOR-245871

P53350

Q71F23

1

phosphorylation

down-regulates

0.741

S77 and t78 of pbip1 are important for plk1-dependent pbip1 phosphorylation and degradation. Here, we demonstrate that a pbd-binding protein, pbip1, is crucial for recruiting plk1 to the interphase and mitotic kinetochores. Unprecedentedly, plk1 phosphorylated pbip1 at t78. Later in mitosis, plk1 also induced pbip1 degradation in a t78-dependent manner, thereby enabling itself to interact with other components critical for proper kinetochore functions

SIGNOR-150457

P25025

P43250

0

phosphorylation

down-regulates quantity

0.563

GRK2 mainly phosphorylates CXCR1, while GRK6 mediates CXCR2 phosphorylation .|Overexpression of GRK6 or treatment with CXCR2 siRNA suppresses CXCR2 expression in dorsal root ganglion and significantly reduces pain in animal model of neuropathic pain , .

SIGNOR-279782

Q14493

Q99880

1

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265389

O14920

P08151

1

phosphorylation

up-regulates activity

0.356

Active IKKbeta promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.|Herein, we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL.

SIGNOR-279194

P01189

P16220

0

transcriptional regulation

up-regulates quantity by expression

0.37

Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE.

SIGNOR-268620

P46527

Q13309

0

ubiquitination

down-regulates

0.766

Up-regulation of skp2 by notch signaling enhances proteasome-mediated degradation of the ckis, p27 kip1 and p21 cip1, and causes premature entry into s phase. ;the recognition of p27 by skp2/cks1 of the scfskp2 complex is dictated by cycline/cdk2, providing a high affinity binding site and the phosphorylation of p27 at t187, serving here we provide evidence suggesting that both cdk2/e and phosphorylation of thr(187) on p27 are essential for the recognition of p27 by the scf(skp2/cks1) complex, the ubiquitin-protein isopeptide ligase (e3).

SIGNOR-154194

Q05655

P21730

1

phosphorylation

down-regulates

0.2

Whole cell phosphorylation assays with specific inhibitors as well as in vitro phosphorylation assays with recombinant enzymes and peptide substrates revealed that phosphorylation of ser-334 is regulated by protein kinase c-beta this study is among the first to analyze in a detailed manner, using a non-mutational approach, modifications of a defined phosphorylation site in a g protein-coupled receptor and to correlate these findings with functional parameters of receptor deactivation.

SIGNOR-73967

P00533

P28482

0

phosphorylation

down-regulates activity

0.639

A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase

SIGNOR-20545

P07947

P40189

0

phosphorylation

up-regulates activity

0.2

Binding of LIF to the LIFR-gp130 receptor complex has been previously shown to activate YES and YAP/TAZ-TEAD -dependent transcription, which is required to maintain self-renewal in embryonic stem cells

SIGNOR-278033

P49840

Q9BYG3

1

phosphorylation

up-regulates activity

0.2

The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.

SIGNOR-262697

P35558

Q09472

0

acetylation

down-regulates quantity by destabilization

0.546

Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase|P300 Acetylates and Destabilizes PEPCK1|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1

SIGNOR-267603

Q92900

Q96Q15

0

phosphorylation

up-regulates

0.971

Smg-1 directly phosphorylates upf1 helicase, another key component of nmd, upon recognition of ptc on postspliced mrna during the initial round of translation. Phosphorylated-upf1 recruits the smg-5/smg-7 complex to induce ribosome dissociation and decapping-mediated decay. T28 and s1096 are responsible for phospho-specific recruitment of smg-6 to the n-terminal conserved region, and the smg-5/smg-7 heterodimer complex to the c-terminal sq-rich region of upf1, respectively

SIGNOR-200785

Q05655

Q5JVS0

1

phosphorylation

down-regulates activity

0.29

We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation

SIGNOR-249254

P30307

P27448

0

phosphorylation

down-regulates activity

0.485

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

SIGNOR-250176

P24752

P48735

1

acetylation

down-regulates activity

0.287

Mitochondrial acetyltransferase ACAT1 and deacetylase SIRT3 are responsible for acetylation and deacetylation, respectively, at K413 of mIDH2|K413 acetylation inhibits mIDH2 by simultaneously attenuating dimer formation from monomers and destabilizing dimers for conversion to monomers

SIGNOR-267627

Q15139

P29475

1

phosphorylation

up-regulates activity

0.385

In addition, we demonstrate that protein kinase D1 activates nNOS by phosphorylating the activatory residue Ser1412, leading to increased \u00b7NO production, hence establishing a novel role of PKD in the regulation of \u00b7NO synthesis.|PKD1 phosphorylates nNOS at activatory Ser 1412 in vitro and in live cells.

SIGNOR-278426

P06493

Q8TAP9

1

phosphorylation

up-regulates

0.341

Ttdn1 is phosphorylated by cdk1 in vitro and in vivo. Ttdn1 is phosphorylated at multiple residues, including ser93 and ser104. Mutation of thr120 of ttdn1 abolishes its interaction with plk1, suggesting phosphorylation of thr120 in the consensus plk1-binding motif is required for its interaction with plk1

SIGNOR-153308

Q8IXI2

Q9BXM7

0

phosphorylation

down-regulates quantity by destabilization

0.775

PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C).

SIGNOR-272728

Q86U44

Q92995

1

post transcriptional regulation

up-regulates quantity by stabilization

0.2

Furthermore, N6-methyladenosine methyltransferase-like 3 (METTL3) mediated stabilization of USP13 mRNA that required the m6A reader IGF2BP2.

SIGNOR-275839

P08559

Q15120

0

phosphorylation

down-regulates activity

0.871

Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes.

SIGNOR-109647

Q9NTG7

P06493

0

phosphorylation

up-regulates activity

0.315

Both SIRT3 T150 and S159 phosphorylated by CDK1 indicates that CDK1-SIRT3 pathway may play a role in the overall mitochondrial protein acetylation involved in mitochondrial homeostasis and apoptosis.

SIGNOR-279395

Q16620

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.266

Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).

SIGNOR-265137

A7MCY6

Q9UHD2

1

relocalization

up-regulates activity

0.603

TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

SIGNOR-272469

P33981

Q96PE2

1

phosphorylation

down-regulates activity

0.2

Because Mps1 also phosphorylates ARHGEF17, the Mps1\u2013ARHGEF17 complex is short lived and promotes its own dissociation, which in turn releases Mps1 and ARHGEF17 from the kinetochore.|ARHGEF17 and Mps1 interact during mitosis and Mps1 phosphorylates ARHGEF17.

SIGNOR-279352

P16144

P17252

0

phosphorylation

down-regulates

0.531

Egf stimulates a pkc-?-Dependent pathway that results in the phosphorylation of the ?4 Integrin subunit on serine residues and its redistribution to actin-rich structures together, these results highlight the importance of serine phosphorylation in regulating type ii hemidesmosome disassembly, implicate a cluster of serine residues within the connecting segment of ?4, and argue for a key role for pkc-? In regulating these structures

SIGNOR-124494

Q92630

Q00613

1

phosphorylation

up-regulates activity

0.318

To test whether in a similar way DYRK2 phosphorylates and activates HSF1 in human cancer cells, we overexpressed DYRK2 and, by use of phosphospecific antibodies, we observed that the levels of endogenous HSF1 phosphorylated at S326 and S320 (two main phosphorylation events linked to HSF1 activation) were increased (Fig.\u00a0 xref ).|Together, these results show that DYRK2 phosphorylates HSF1 in cells and in vitro at S320 and also at S326, which is critical for HSF1 activation.Next, to test whether endogenous DYRK2 plays a role in HSF1 activation by proteotoxic stress, we used the prototypical HSF1 inducer heat shock (HS), in the absence or in the presence of harmine, observing that the inhibitor clearly impaired the phosphorylation of HSF1 upon HS (Fig S1F).

SIGNOR-278355

P39900

P02671

1

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. |Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.|MMP-12 20ADSGEGD a-chain| 540FVSETESRG a-chain|433LVTSKGDK a-chain

SIGNOR-263622

P11279

Q9NR19

0

transcriptional regulation

up-regulates quantity by expression

0.2

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276556

P63244

P05412

0

null

up-regulates quantity by expression

0.2

In turn, c-Jun induces expression of RACK1, which is required for JNK activation by PKC, pointing to a c-Jun/RACK1/PKC/JNK feedback loop.

SIGNOR-278066

Q13261

P52333

1

null

up-regulates

0.501

Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated

SIGNOR-256226

Q00534

P05412

1

phosphorylation

up-regulates quantity

0.423

CDK6 additionally induced c-Jun phosphorylation, but did not activate JNK, as determined by examining JNK phosphorylation at various time-points.|CDK6 upregulates c-Jun expression.

SIGNOR-280222

P08246

P01019

1

cleavage

up-regulates activity

0.275

Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.

SIGNOR-256313

P60568

Q9UL17

0

transcriptional regulation

down-regulates quantity by repression

0.473

T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells

SIGNOR-266233

O00311

Q5FWF5

1

phosphorylation

down-regulates

0.432

We show here that eco1 degradation requires the sequential actions of cdk1 and two additional kinases, cdc7-dbf4 and the gsk-3 homolog mck1.

SIGNOR-200397

Q9Y2I6

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.422

In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation.

SIGNOR-259831

Q05209

Q14161

1

dephosphorylation

down-regulates

0.344

Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest.

SIGNOR-142719

O43236

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Thus, Parkin degrades ARTS in a proteasome dependent manner.|Together, these results suggest that Parkin specifically ubiquitinates and degrades ARTS, and that this degradation may be linked to the pro-apoptotic function of ARTS.

SIGNOR-278642

P63000

O94988

0

gtpase-activating protein

down-regulates activity

0.435

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-260502

P53350

Q9Y6K1

1

phosphorylation

down-regulates activity

0.269

2.11 Plk1 Directly Phosphorylates DNMT3a at S393.|Elevated Plk1 further inhibited DNMT3a via phosphorylation at S393 in mitosis in accord with its mitotic role during cell cycle.

SIGNOR-279552

Q96FF9

Q96GD4

0

phosphorylation

down-regulates activity

0.629

Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.

SIGNOR-276116

Q15797

P27361

0

phosphorylation

down-regulates

0.528

Ras signaling was shown previously to induce the phosphorylation of the bmp mediator smad1 at four erk consensus sites in the linker domain (kretzschmar et al. 1997a). Phosphorylation of these four sites inhibits smad1 accumulation in the nucleus

SIGNOR-66755

Q99708

Q504Q3

0

deubiquitination

up-regulates activity

0.2

Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52.

SIGNOR-273509

Q92630

P43686

1

phosphorylation

down-regulates quantity by destabilization

0.284

Through a kinome-wide screen, we have identified dual-specificity tyrosine-regulated kinase 2 (DYRK2) as the primary kinase that phosphorylates Rpt3-Thr25, leading to enhanced substrate translocation and degradation.

SIGNOR-275845

Q96J92

O95747

1

phosphorylation

up-regulates activity

0.48

In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].

SIGNOR-278389