GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P0C6X7-PRO_0000037311	Q14653	1	deubiquitination	down-regulates activity	0.2	Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response.	SIGNOR-260249
P45985	Q16539	1	phosphorylation	up-regulates activity	0.591	Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase.	SIGNOR-34121
P53355	P37840	1	phosphorylation	up-regulates quantity	0.27	We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates.	SIGNOR-278440
P55957	P48729	0	phosphorylation	up-regulates activity	0.286	Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. \| These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid.	SIGNOR-250785
Q969H0	P17252	0	phosphorylation	down-regulates activity	0.345	Here, we report that Fbw7α, the only Fbw7 isoform detected in eggs, is phosphorylated by PKC (protein kinase C) at a key residue (S18) in a manner coincident with Fbw7α inactivation.	SIGNOR-277249
P46527	O00141	0	phosphorylation	down-regulates	0.469	Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.	SIGNOR-179117
Q9NYJ7	Q86YT6	0	ubiquitination	up-regulates activity	0.35	Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.	SIGNOR-209672
P17252	O60674	1	phosphorylation	up-regulates activity	0.26	These results suggest that PKC activates JAK2 and thereby STAT3 by directly phosphorylating T174 and S518.	SIGNOR-277262
Q96RG2	P61964	1	phosphorylation	up-regulates activity	0.307	Pask directly interacts with and phosphorylates Wdr5 at Ser49.\|We therefore believe that differentiation cues act, at least in part, to drive the myogenic transcriptional program via Pask activation and phosphorylation of Wdr5.	SIGNOR-278266
P02810	P48730	0	phosphorylation	up-regulates	0.2	Ser22 may be phosphorylated by a g-ck that recognizes an atypical substrate sequence or by a novel kinase. While prp1 secreted from salivary glands is fully phosphorylated at ser8 and 22	SIGNOR-75272
Q9P2Y5	Q9UGI0	0	deubiquitination	up-regulates activity	0.2	Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux.	SIGNOR-273651
Q08050	P12931	0	phosphorylation	up-regulates activity	0.324	Hence, c-Src-dependent phosphorylation of MPP2 could be part of a negative feedback loop within the circuitry that modulates c-Src activity by MPP2.	SIGNOR-279117
Q9BYU1	P55075	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265806
P17987	P52747	0	transcriptional regulation	up-regulates quantity by expression	0.279	The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.	SIGNOR-266220
Q9Y463	P46734	0	phosphorylation	up-regulates	0.348	Mkk3 enhanced mirk kinase activity. Mkk3 possibly activates mirk by phosphorylating it.	SIGNOR-86731
Q05397	Q14680	0	phosphorylation	up-regulates activity	0.2	As the aforementioned results showed that MELK promotes FAK phosphorylation, and it is well known that FAK is an important regulator of cell migration and invasion, we speculated that MELK could regulate cell migration and invasion via the FAK/Paxillin pathway.\|Finally, knockdown of MELK decreased the phosphorylation of the FAK and paxillin, and prevented gastrin stimulated FAK and paxillin phosphorylation.	SIGNOR-279230
Q9ULT8	P07900	1	ubiquitination	down-regulates quantity	0.2	We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Identification of Hsp90 in both proteomic screens suggested that members of the Hsp90 superfamily may be substrates of Hectd1. Myc-Hectd1ANK and HA-Hsp90bd (the fragment identified in the yeast two-hybrid screen) bind in an in vitro binding assay (Fig. 3 D) and when coexpressed in HEK293T cells. Hectd1 is required for K63-linked Ubn of Hsp90. Together, these results demonstrate that Hectd1-dependent Ubn of Hsp90 targets it away from the membrane and the secretory pathway.	SIGNOR-261199
Q99986	P04637	1	phosphorylation	up-regulates	0.523	Vrk1 phosphorylates murine p53 in threonine 18. This threonine is within the p53 hydrophobic loop (residues 13-23) required for the interaction of p53 with the cleft of its inhibitor mdm-2.	SIGNOR-81222
Q14493	Q8N257	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-265388
P00742	P00734	1	cleavage	up-regulates activity	0.459	The present data point to key roles of FVIII and FIX in FX activation at the site of a platelet thrombus by supporting: (i) thrombin generation, (ii) thrombus growth and platelet phosphatidylserine exposure, and (iii) fibrin formation at the platelet surface. The likely mechanism is that tenase activity via FVIIIa and FIXa, which is confined to the sites of platelet thrombi, generates FXa that directly catalyzes the conversion of prothrombin into thrombin.	SIGNOR-263539
Q12802	P17612	0	phosphorylation	up-regulates	0.332	Using a combination of biochemical, enzymatic, and immunofluorescence techniques, we show that the anchoring protein contributes to pkd activation in two ways: it recruits an upstream kinase pkceta and coordinates pka phosphorylation events that release activated protein kinase d. Thus, akap-lbc synchronizes pka and pkc activities in a manner that leads to the activation of a third kinase.	SIGNOR-129345
P50549	P17612	0	phosphorylation	up-regulates activity	0.292	The camp-dependent protein kinase a (pka) phosphorylates er81 on ser(191)/ser(216)ser(191) and ser(216), were identified, whose mutation to alanine reduces er81 activity upon erk-mapk stimulation.	SIGNOR-92447
P35568	Q15418	0	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
P49841	Q13950	1	phosphorylation	down-regulates activity	0.301	Collectively, these data demonstrate that the kinase activity of GSK-3beta suppresses the Runx2 transcriptional activity.\|In vitro kinase assay confirmed that the Runx2 phosphorylation by GSK-3\u03b2 was reduced by the S369-S373-S377 mutation ( xref ).	SIGNOR-279051
P27361	P06401	1	phosphorylation	down-regulates	0.561	Specifically, down-regulation of mature prs occurs by a mechanism in which ligand binding activates pr phosphorylation by mapks at a unique serine residue, which then targets the receptors for degradation.	SIGNOR-74716
Q15788	P28482	0	phosphorylation	up-regulates	0.364	Furthermore, erk-2 phosphorylated threonine 1179 and serine 1185 (and to a lesser extent, serine 395) in vitro, suggesting the importance of this pathway for src-1 regulation. Treatment of cells expressing src-1 with epidermal growth factor enhanced the ligand-dependent, progesterone receptor-mediated activation of a target reporter gene.	SIGNOR-74880
P49841	P04150	1	phosphorylation	down-regulates activity	0.54	We found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta [ ]Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB	SIGNOR-181541
Q13882	P49023	1	phosphorylation	up-regulates activity	0.63	It was also observed that the attenuation of BRK phosphorylation in turn inhibits BRK mediated activation of its direct targets, STAT3, SAM68, and Paxillin.\|The EGF pathway also stimulates BRK 's phosphorylation of paxillin to promote migratory and invasive characteristics in breast cancer cells.	SIGNOR-280102
P61586	Q6P4F7	0	gtpase-activating protein	down-regulates activity	0.549	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-260466
P45983	Q14451	1	phosphorylation	down-regulates quantity by destabilization	0.262	Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N-terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. I	SIGNOR-277280
P67775	P56524	1	dephosphorylation	up-regulates	0.35	Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a	SIGNOR-159492
Q9UNE7	O14654	1	polyubiquitination	down-regulates quantity by destabilization	0.2	IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).	SIGNOR-277616
P36776	P49675	1	cleavage	down-regulates quantity by destabilization	0.268	Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: the unexpected effect of proteasome inhibitors	SIGNOR-265726
P16112	O75173	0	cleavage	down-regulates quantity by destabilization	0.767	Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints\|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE373	SIGNOR-266984
P84022	Q14974	0	relocalization	up-regulates	0.524	Here we show that the isolated smad 3 mh1 domain displays significant specific binding to importin beta. we propose that activation of all of the pathway-specific smad proteins (smads 1, 2, 3, 5, 8, and 9) exposes the conserved nls motif, which then binds directly to importin beta and triggers nuclear translocation.	SIGNOR-78191
P12931	P23467	0	dephosphorylation	down-regulates activity	0.445	Collectively, these results suggest that PTPRB inhibits Src activation and down -- regulation of PTPRB activates Src signalling pathway required for cell invasion in A549 cells.\|Knockdown of PTPRB increased Src phosphorylation and cell invasion, which was reversed by Src inhibitor PP2.	SIGNOR-277132
P36888	Q13191	0	ubiquitination	down-regulates activity	0.326	Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.	SIGNOR-260106
Q8N4N8	P53350	0	phosphorylation	up-regulates activity	0.66	We show that Plk1 directly phosphorylates Kif2b at threonine 125 (T125) and serine 204 (S204), and that these two sites differentially regulate Kif2b function. Phosphorylation of S204 is required for the kinetochore localization and activity of Kif2b in prometaphase, and phosphorylation of T125 is required for Kif2b activity in the correction of k-MT attachment errors.	SIGNOR-252049
P41970	P45983	0	phosphorylation	down-regulates activity	0.323	JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export.	SIGNOR-250139
P19838	P17612	0	phosphorylation	up-regulates	0.509	In this study, we demonstrate that the phosphorylation of p50 and p65 by the catalytic subunit of protein kinase a (pkac) is essential for nf-kappab dna binding and transactivation activity. treatment with h89 and knockdown of pkac in cells led to the inhibition of phosphorylation at p50 ser(337) and p65 ser(276) and loss of dna binding by nf-kappab.	SIGNOR-158595
Q7Z5G4	P01112	1	palmitoylation	up-regulates activity	0.349	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261351
Q13546	Q13233	1	phosphorylation	up-regulates activity	0.455	These findings strongly suggest that rip phosphorylates mekk1 at ser-957 and ser-994.	SIGNOR-108257
Q9UM11	O00429	1	ubiquitination	down-regulates quantity	0.349	Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1 catalyzed by the APC/Ccdh1 (anaphase-promoting complex/cyclosome and its coactivator (Cdh1) E3 ubiquiting ligase complex	SIGNOR-274127
P24941	Q01167	1	phosphorylation	up-regulates	0.369	We have mapped two cdk phosphorylation sites, serines 368 and 423, which play a role in defining foxk2 function through regulating its stability and its activity as a transcriptional repressor protein. These two cdk sites appear vital for foxk2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis.	SIGNOR-167834
Q96G01	P49841	0	phosphorylation	up-regulates activity	0.331	Therefore, at least Ser585 and Thr597 in BICD1 are important phosphorylation sites for BICD1 to exert its functions, and GSK-3β-dependent phosphorylation is required for the interaction of BICD1 with dynein.	SIGNOR-262744
P12931	P05107	1	phosphorylation	down-regulates activity	0.449	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254740
P54762	P40763	1	phosphorylation	up-regulates activity	0.353	By integrating mouse in vivo and in vitro models with human iPSC derived astrocytes, we provide direct evidence that EphB1 can induce early astrocytic STAT3 activation via ephrin-B1 signalling.\|We confirmed that EphB1 activates astrocytes by inducing ephrin-B1 dependent STAT3 phosphorylation.	SIGNOR-279709
P49761	Q92995	1	phosphorylation	up-regulates activity	0.2	CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes.	SIGNOR-274122
Q9P2N2	P61586	1	gtpase-activating protein	down-regulates activity	0.504	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-260483
Q3KR16	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.583	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-260567
P13674	Q01581	1	transcriptional regulation	up-regulates quantity by expression	0.2	In this study, we found that the prolyl 4-hydroxylase (P4H) subunit P4HA1 protects NPC cells from erastin-induced ferroptosis by activating HMGCS1, a key enzyme in the mevalonate pathway. Our results show that HMGCS1 and HMGCR are regulated by P4HA subunits at the transcriptional level (Fig. S4).	SIGNOR-279853
Q9NR28	Q16611	0	relocalization	up-regulates	0.522	Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi	SIGNOR-118905
P19174	P09619	0	phosphorylation	up-regulates	0.859	Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.	SIGNOR-28179
P15056	Q02750	1	phosphorylation	up-regulates activity	0.789	Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.	SIGNOR-235475
Q12923	O00506	1	dephosphorylation	down-regulates activity	0.421	To investigate dephosphorylation of CCM3 by FAP-1, phosphorylated GST-CCM3 was incubated with cdFAP-1, and reactions were analyzed by autoradiography. Again, GST-STK25 phosphorylated GST-CCM3 and possessed autophosphorylation activity. cdFAP-1 of 0.005 U were sufficient to dephosphorylate GST-CCM3 as well as the kinase GST-STK25.\|More recently, the Golgi matrix protein GM130 was shown to function as a scaffold protein for STK25 and to activate STK25 through stimulation of autophosphorylation.	SIGNOR-248711
P43405	P17252	1	phosphorylation	up-regulates activity	0.391	We present evidence that Tyr-662 and Tyr-658 of PKCbetaI and PKCalpha, respectively, are phosphorylated by Syk in the membrane compartment of FcepsilonRI-stimulated mast cells. These phosphorylations require prior PKC autophosphorylation of the adjacent serine residues (Ser-661 and Ser-657, respectively) and generate a binding site for the SH2 domain of the adaptor protein Grb-2.	SIGNOR-246581
P01100	Q13536	0	transcriptional regulation	up-regulates quantity by expression	0.2	CROC-4: a novel brain specific transcriptional activator of c-fos expressed from proliferation through to maturation of multiple neuronal cell types.	SIGNOR-261569
O15360	Q13535	0	phosphorylation	up-regulates	0.598	The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site	SIGNOR-182953
Q9BY44	Q9P2K8	0	phosphorylation	down-regulates activity	0.484	Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ).	SIGNOR-280005
Q6PJ69	Q8NDV7	1	polyubiquitination	down-regulates quantity by destabilization	0.445	Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6.	SIGNOR-272174
O15198	Q9HAU4	0	ubiquitination	down-regulates	0.644	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps	SIGNOR-193390
P67775	Q13043	1	dephosphorylation	down-regulates	0.367	Rassf1a apparently protects mst1/2 against inactivation by pp2a , the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.	SIGNOR-201270
Q8TBB1	Q96BR9	1	polyubiquitination	down-regulates quantity by destabilization	0.2	LNX (ligand of Numb protein-X) is a RING finger and four PDZ domain-containing E3 ubiquitin ligase. Lnx-l induced K48-linked polyubiquitylation of Boz, leading to its proteasomal degradation in human 293T cells and in zebrafish embryos.	SIGNOR-272777
P12931	O00206	1	phosphorylation	up-regulates activity	0.588	Src dependent phosphorylation of TLR4 is significantly increased in Cftr-KO cholangiocytes.\|TLR4 can be activated through the phosphorylation of its TIR domains by Src, a non receptor tyrosine kinase 28.	SIGNOR-279658
P68400	O15379	1	phosphorylation	up-regulates activity	0.531	A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity.	SIGNOR-250889
Q92574	P53350	0	phosphorylation	down-regulates quantity by destabilization	0.467	The Hsp90 client Plk1 phosphorylates Sgt1, which had a positive impact on Sgt1 function, whereas phosphorylation of Tsc1 by Plk1 led to its ubiquitination and degradation.	SIGNOR-280072
P55795	Q15554	1	post transcriptional regulation	down-regulates quantity	0.332	During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.	SIGNOR-266806
P35712	P49715	1	transcriptional regulation	up-regulates quantity by expression	0.292	We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST	SIGNOR-255824
Q9H6E5	Q05655	0	phosphorylation	up-regulates activity	0.2	PKCdelta associates with and directly phosphorylates Star-PAP.	SIGNOR-279385
P08183	P11309	0	dephosphorylation	up-regulates activity	0.438	Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function\|P-gp is known to be phosphorylated at Ser667, Ser671, and Ser683 by PKA; at Ser661, Ser667, and Ser671 by PKC; and at Ser683 by Pim-1\|simultaneous expression of PP5 and PPP2R3C reduced the phosphorylation detected by the antibodies that specifically recognize serine/threonine phosphorylated by PKA or serine phosphorylated by PKC. These results suggest that the PP5/PPP2R3C complex dephosphorylates PKA- and PKC-phosphorylated serine residues on P-gp	SIGNOR-272511
Q9HAU4	P20333	1	ubiquitination	up-regulates activity	0.326	However, co-transfection of Smurf2, but not Smurf2-C/A, drastically increased the potential of TNF-R2 to induce JNK phosphorylation.\|In conclusion, these results indicate that Smurf2 is able to ubiquitinate TNF-R2, which is further enhanced by the TRAF2-mediated targeting of Smurf2 to TNF-R2.	SIGNOR-278716
Q06609	P24941	0	phosphorylation	down-regulates quantity by destabilization	0.595	Phosphorylation of the BRCA2 C-terminal RAD51 binding site by CDK2 promotes RAD51 filament disassembly, leading to nucleolitic cleavage of newly synthesized DNA and compromised fork integrity.	SIGNOR-280213
P35568	Q05655	0	phosphorylation	down-regulates activity	0.646	Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).	SIGNOR-249267
P15882	P63000	1	gtpase-activating protein	down-regulates activity	0.666	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-260499
Q9Y266	P53350	0	phosphorylation	up-regulates activity	0.73	Here, we characterize the interaction between plk1 and nudc, show that plk1 phosphorylates nudc at conserved s274 and s326 residues in vitro, and present evidence that nudc is also a substrate for plk1 in vivo. Downregulation of nudc by rna interference results in multiple mitotic defects, including multinucleation and cells arrested at the midbody stage, which are rescued by ectopic expression of wild-type nudc, but not by nudc with mutations in the plk1 phosphorylation sites.	SIGNOR-103403
Q05655	Q15717	1	phosphorylation	up-regulates	0.637	Tandem phosphorylation of serines 221 and 318 by protein kinase cdelta coordinates mrna binding and nucleocytoplasmic shuttling of hurstabilization of mrna by the ubiquitous rna binding protein human antigen r (hur), a member of the embryonic lethal abnormal vision (elav) protein family, requires canonical binding to au-rich element (are)-bearing target mrna and export of nuclear hur-mrna complexes to the cytoplasm. In human mesangial cells (hmc) both processes are induced by angiotensin ii (angii) via protein kinase cdelta (pkcdelta)-triggered serine phosphorylation of hur.	SIGNOR-163524
P40763	P18031	0	dephosphorylation	down-regulates activity	0.552	PTP1B was able to dephosphorylate activated JAK2 and STAT3 in vitro, whereas either no or a minimal effect was observed with cluster of differentiation 45 (CD45), PTPalpha and leukocyte antigen-related (LAR). By utilisation of a selective PTP1B inhibitor, the leptin-induced STAT3 activation was enhanced in cells. In conclusion, these results suggested that the negative regulatory role of PTP1B on leptin signalling is mediated through a direct and selective dephosphorylation of the two signalling molecules, JAK2 and STAT3.	SIGNOR-248427
P43405	Q8WV28	1	phosphorylation	up-regulates	0.806	The phosphorylation of multiple tyrosine residues not only amplifies plcgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex.	SIGNOR-96044
P49841	O15273	1	phosphorylation	down-regulates quantity by destabilization	0.2	GSK-3beta phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation.\|These results show direct GSK-3beta phosphorylation of TCAP S157 and FBXL21 T33 sites.	SIGNOR-264852
Q13144	P49840	0	phosphorylation	down-regulates activity	0.368	We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B	SIGNOR-251215
P18754	Q13188	0	phosphorylation	up-regulates	0.2	MST2 Phosphorylates RCC1 In Vitro and In Vivo. Using an antibody generated against phospho-S2/11 in RCC1 [18], we found that these two residues were also efficiently phosphorylated by MST1 and MST2 (Figure 2D), further supporting that S2 and/or S11 are genuine MST2 phosphorylation targets.	SIGNOR-263146
P49840	P13051	1	phosphorylation	down-regulates quantity by destabilization	0.2	Here we show that glycogen synthase kinase 3 (GSK-3) interacts with and phosphorylates UNG2 at Thr60 and that Thr60 phosphorylation requires a Ser64 priming phosphorylation event.\|phosphorylation of Thr60 and Ser64 creates a cyclin E/c-Myc-like phosphodegron that promotes polyubiquitylation and proteasome-mediated degradation	SIGNOR-264886
Q16236	P36969	1	transcriptional regulation	up-regulates quantity by expression	0.383	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis.	SIGNOR-279874
Q16512	P10275	1	phosphorylation	up-regulates	0.587	Rho can sensitize the ar to low levels of circulating androgens by promoting the nuclear translocation of a transcriptional co-activator, fhl2 (four and a half lim domains 2), which binds ar, and by stimulating protein kinase n (pkn), which phosphorylates ar directly.	SIGNOR-152762
O15033	Q9NR28	1	ubiquitination	down-regulates quantity by destabilization	0.377	AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 \|E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination.	SIGNOR-267672
P05129	P04049	1	phosphorylation	up-regulates	0.403	Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation.	SIGNOR-37545
Q99933	Q8NI51	0	transcriptional regulation	up-regulates quantity by expression	0.28	DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation	SIGNOR-254107
P51608	P41145	1	post transcriptional regulation	up-regulates quantity by expression	0.272	MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.	SIGNOR-264677
P18031	P35568	1	dephosphorylation	down-regulates	0.779	Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein.	SIGNOR-74852
P06493	Q9Y5B0	0	dephosphorylation	down-regulates activity	0.333	Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression.\|We can not exclude that, in addition to S90 and S453, other Cdk1 phosphorylation sites in Gwl are dephosphorylated by Fcp1; nevertheless, assaying S67-Ensa kinase activity of V5-GwlS90A and V5-GwlS453A mutant proteins, isolated from transfected and prometaphase arrested HeLa cells, revealed that both mutants had significantly reduced S67-Ensa kinase activity compared to V5-GwlWT (XREF_FIG).\|We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells.	SIGNOR-277141
P28482	O43353	0	phosphorylation	up-regulates activity	0.295	RIP2 directly phosphorylates and activates ERK2 in vivo and in vitro.	SIGNOR-279106
O60566	P53350	0	phosphorylation	up-regulates	0.84	We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions.	SIGNOR-157646
P04637	Q9UI32	1	transcriptional regulation	up-regulates quantity by expression	0.631	Glutaminase 2 (GLS2) can be directly transactivated by p53 and can therefore mediate p53-dependent regulation of cellular energy metabolism. G	SIGNOR-268041
P10645	P16220	0	transcriptional regulation	up-regulates quantity by expression	0.265	Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation.	SIGNOR-254276
P17612	Q05086	1	phosphorylation	down-regulates activity	0.328	These data suggest that PKA phosphorylation at T485 inhibits UBE3A ubiquitin ligase activity in cells.	SIGNOR-236899
Q13464	P45983	1	phosphorylation	up-regulates activity	0.296	Instead, we found that rock activates jnk, which then phosphorylates c-jun and atf2 when bound to the c-jun promoter.	SIGNOR-123717
P15927	P06493	0	phosphorylation	up-regulates activity	0.508	Cdc2 family kinases phosphorylate a human cell dna replication factor, rpa, and activate dna replication. therefore, the serines on rpa p34 that were necessary for phosphorylation by cdc2 kinase were also necessary for phosphorylation in the cell	SIGNOR-16975
O43602	Q9HCK8	0	transcriptional regulation	down-regulates quantity	0.2	Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells	SIGNOR-268915
Q9UKI8	Q8IW41	1	phosphorylation	up-regulates activity	0.2	We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.	SIGNOR-276747
P27361	P78536	1	phosphorylation	up-regulates	0.361	Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated sheddingwe show that extracellular signal-regulated kinase (erk) acts as an intermediate in protein kinase c-regulated trka cleavage. We report that the cytosolic tail of the tumor necrosis factor alpha-converting enzyme (tace) is phosphorylated by erk at threonine 735. In addition, we show that erk and tace associate. This association is favored by erk activation and by the presence of threonine 735. In contrast to the erk route, the p38 mapk was able to stimulate trka cleavage in cells devoid of tace activity, indicating that other proteases are also involved in trka shedding.	SIGNOR-89625

P0C6X7-PRO_0000037311

Q14653

1

deubiquitination

down-regulates activity

0.2

Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response.

SIGNOR-260249

P45985

Q16539

1

phosphorylation

up-regulates activity

0.591

Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase.

SIGNOR-34121

P53355

P37840

1

phosphorylation

up-regulates quantity

0.27

We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates.

SIGNOR-278440

P55957

P48729

0

phosphorylation

up-regulates activity

0.286

Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid.

SIGNOR-250785

Q969H0

P17252

0

phosphorylation

down-regulates activity

0.345

Here, we report that Fbw7α, the only Fbw7 isoform detected in eggs, is phosphorylated by PKC (protein kinase C) at a key residue (S18) in a manner coincident with Fbw7α inactivation.

SIGNOR-277249

P46527

O00141

0

phosphorylation

down-regulates

0.469

Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.

SIGNOR-179117

Q9NYJ7

Q86YT6

0

ubiquitination

up-regulates activity

0.35

Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.

SIGNOR-209672

P17252

O60674

1

phosphorylation

up-regulates activity

0.26

These results suggest that PKC activates JAK2 and thereby STAT3 by directly phosphorylating T174 and S518.

SIGNOR-277262

Q96RG2

P61964

1

phosphorylation

up-regulates activity

0.307

Pask directly interacts with and phosphorylates Wdr5 at Ser49.|We therefore believe that differentiation cues act, at least in part, to drive the myogenic transcriptional program via Pask activation and phosphorylation of Wdr5.

SIGNOR-278266

P02810

P48730

0

phosphorylation

up-regulates

0.2

Ser22 may be phosphorylated by a g-ck that recognizes an atypical substrate sequence or by a novel kinase. While prp1 secreted from salivary glands is fully phosphorylated at ser8 and 22

SIGNOR-75272

Q9P2Y5

Q9UGI0

0

deubiquitination

up-regulates activity

0.2

Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux.

SIGNOR-273651

Q08050

P12931

0

phosphorylation

up-regulates activity

0.324

Hence, c-Src-dependent phosphorylation of MPP2 could be part of a negative feedback loop within the circuitry that modulates c-Src activity by MPP2.

SIGNOR-279117

Q9BYU1

P55075

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265806

P17987

P52747

0

transcriptional regulation

up-regulates quantity by expression

0.279

The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.

SIGNOR-266220

Q9Y463

P46734

0

phosphorylation

up-regulates

0.348

Mkk3 enhanced mirk kinase activity. Mkk3 possibly activates mirk by phosphorylating it.

SIGNOR-86731

Q05397

Q14680

0

phosphorylation

up-regulates activity

0.2

As the aforementioned results showed that MELK promotes FAK phosphorylation, and it is well known that FAK is an important regulator of cell migration and invasion, we speculated that MELK could regulate cell migration and invasion via the FAK/Paxillin pathway.|Finally, knockdown of MELK decreased the phosphorylation of the FAK and paxillin, and prevented gastrin stimulated FAK and paxillin phosphorylation.

SIGNOR-279230

Q9ULT8

P07900

1

ubiquitination

down-regulates quantity

0.2

We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Identification of Hsp90 in both proteomic screens suggested that members of the Hsp90 superfamily may be substrates of Hectd1. Myc-Hectd1ANK and HA-Hsp90bd (the fragment identified in the yeast two-hybrid screen) bind in an in vitro binding assay (Fig. 3 D) and when coexpressed in HEK293T cells. Hectd1 is required for K63-linked Ubn of Hsp90. Together, these results demonstrate that Hectd1-dependent Ubn of Hsp90 targets it away from the membrane and the secretory pathway.

SIGNOR-261199

Q99986

P04637

1

phosphorylation

up-regulates

0.523

Vrk1 phosphorylates murine p53 in threonine 18. This threonine is within the p53 hydrophobic loop (residues 13-23) required for the interaction of p53 with the cleft of its inhibitor mdm-2.

SIGNOR-81222

Q14493

Q8N257

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-265388

P00742

P00734

1

cleavage

up-regulates activity

0.459

The present data point to key roles of FVIII and FIX in FX activation at the site of a platelet thrombus by supporting: (i) thrombin generation, (ii) thrombus growth and platelet phosphatidylserine exposure, and (iii) fibrin formation at the platelet surface. The likely mechanism is that tenase activity via FVIIIa and FIXa, which is confined to the sites of platelet thrombi, generates FXa that directly catalyzes the conversion of prothrombin into thrombin.

SIGNOR-263539

Q12802

P17612

0

phosphorylation

up-regulates

0.332

Using a combination of biochemical, enzymatic, and immunofluorescence techniques, we show that the anchoring protein contributes to pkd activation in two ways: it recruits an upstream kinase pkceta and coordinates pka phosphorylation events that release activated protein kinase d. Thus, akap-lbc synchronizes pka and pkc activities in a manner that leads to the activation of a third kinase.

SIGNOR-129345

P50549

P17612

0

phosphorylation

up-regulates activity

0.292

The camp-dependent protein kinase a (pka) phosphorylates er81 on ser(191)/ser(216)ser(191) and ser(216), were identified, whose mutation to alanine reduces er81 activity upon erk-mapk stimulation.

SIGNOR-92447

P35568

Q15418

0

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

P49841

Q13950

1

phosphorylation

down-regulates activity

0.301

Collectively, these data demonstrate that the kinase activity of GSK-3beta suppresses the Runx2 transcriptional activity.|In vitro kinase assay confirmed that the Runx2 phosphorylation by GSK-3\u03b2 was reduced by the S369-S373-S377 mutation ( xref ).

SIGNOR-279051

P27361

P06401

1

phosphorylation

down-regulates

0.561

Specifically, down-regulation of mature prs occurs by a mechanism in which ligand binding activates pr phosphorylation by mapks at a unique serine residue, which then targets the receptors for degradation.

SIGNOR-74716

Q15788

P28482

0

phosphorylation

up-regulates

0.364

Furthermore, erk-2 phosphorylated threonine 1179 and serine 1185 (and to a lesser extent, serine 395) in vitro, suggesting the importance of this pathway for src-1 regulation. Treatment of cells expressing src-1 with epidermal growth factor enhanced the ligand-dependent, progesterone receptor-mediated activation of a target reporter gene.

SIGNOR-74880

P49841

P04150

1

phosphorylation

down-regulates activity

0.54

We found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta [ ]Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB

SIGNOR-181541

Q13882

P49023

1

phosphorylation

up-regulates activity

0.63

It was also observed that the attenuation of BRK phosphorylation in turn inhibits BRK mediated activation of its direct targets, STAT3, SAM68, and Paxillin.|The EGF pathway also stimulates BRK 's phosphorylation of paxillin to promote migratory and invasive characteristics in breast cancer cells.

SIGNOR-280102

P61586

Q6P4F7

0

gtpase-activating protein

down-regulates activity

0.549

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-260466

P45983

Q14451

1

phosphorylation

down-regulates quantity by destabilization

0.262

Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N-terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. I

SIGNOR-277280

P67775

P56524

1

dephosphorylation

up-regulates

0.35

Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a

SIGNOR-159492

Q9UNE7

O14654

1

polyubiquitination

down-regulates quantity by destabilization

0.2

IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).

SIGNOR-277616

P36776

P49675

1

cleavage

down-regulates quantity by destabilization

0.268

Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: the unexpected effect of proteasome inhibitors

SIGNOR-265726

P16112

O75173

0

cleavage

down-regulates quantity by destabilization

0.767

Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE373

SIGNOR-266984

P84022

Q14974

0

relocalization

up-regulates

0.524

Here we show that the isolated smad 3 mh1 domain displays significant specific binding to importin beta. we propose that activation of all of the pathway-specific smad proteins (smads 1, 2, 3, 5, 8, and 9) exposes the conserved nls motif, which then binds directly to importin beta and triggers nuclear translocation.

SIGNOR-78191

P12931

P23467

0

dephosphorylation

down-regulates activity

0.445

Collectively, these results suggest that PTPRB inhibits Src activation and down -- regulation of PTPRB activates Src signalling pathway required for cell invasion in A549 cells.|Knockdown of PTPRB increased Src phosphorylation and cell invasion, which was reversed by Src inhibitor PP2.

SIGNOR-277132

P36888

Q13191

0

ubiquitination

down-regulates activity

0.326

Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.

SIGNOR-260106

Q8N4N8

P53350

0

phosphorylation

up-regulates activity

0.66

We show that Plk1 directly phosphorylates Kif2b at threonine 125 (T125) and serine 204 (S204), and that these two sites differentially regulate Kif2b function. Phosphorylation of S204 is required for the kinetochore localization and activity of Kif2b in prometaphase, and phosphorylation of T125 is required for Kif2b activity in the correction of k-MT attachment errors.

SIGNOR-252049

P41970

P45983

0

phosphorylation

down-regulates activity

0.323

JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export.

SIGNOR-250139

P19838

P17612

0

phosphorylation

up-regulates

0.509

In this study, we demonstrate that the phosphorylation of p50 and p65 by the catalytic subunit of protein kinase a (pkac) is essential for nf-kappab dna binding and transactivation activity. treatment with h89 and knockdown of pkac in cells led to the inhibition of phosphorylation at p50 ser(337) and p65 ser(276) and loss of dna binding by nf-kappab.

SIGNOR-158595

Q7Z5G4

P01112

1

palmitoylation

up-regulates activity

0.349

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261351

Q13546

Q13233

1

phosphorylation

up-regulates activity

0.455

These findings strongly suggest that rip phosphorylates mekk1 at ser-957 and ser-994.

SIGNOR-108257

Q9UM11

O00429

1

ubiquitination

down-regulates quantity

0.349

Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1 catalyzed by the APC/Ccdh1 (anaphase-promoting complex/cyclosome and its coactivator (Cdh1) E3 ubiquiting ligase complex

SIGNOR-274127

P24941

Q01167

1

phosphorylation

up-regulates

0.369

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

SIGNOR-167834

Q96G01

P49841

0

phosphorylation

up-regulates activity

0.331

Therefore, at least Ser585 and Thr597 in BICD1 are important phosphorylation sites for BICD1 to exert its functions, and GSK-3β-dependent phosphorylation is required for the interaction of BICD1 with dynein.

SIGNOR-262744

P12931

P05107

1

phosphorylation

down-regulates activity

0.449

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254740

P54762

P40763

1

phosphorylation

up-regulates activity

0.353

By integrating mouse in vivo and in vitro models with human iPSC derived astrocytes, we provide direct evidence that EphB1 can induce early astrocytic STAT3 activation via ephrin-B1 signalling.|We confirmed that EphB1 activates astrocytes by inducing ephrin-B1 dependent STAT3 phosphorylation.

SIGNOR-279709

P49761

Q92995

1

phosphorylation

up-regulates activity

0.2

CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes.

SIGNOR-274122

Q9P2N2

P61586

1

gtpase-activating protein

down-regulates activity

0.504

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-260483

Q3KR16

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.583

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-260567

P13674

Q01581

1

transcriptional regulation

up-regulates quantity by expression

0.2

In this study, we found that the prolyl 4-hydroxylase (P4H) subunit P4HA1 protects NPC cells from erastin-induced ferroptosis by activating HMGCS1, a key enzyme in the mevalonate pathway. Our results show that HMGCS1 and HMGCR are regulated by P4HA subunits at the transcriptional level (Fig. S4).

SIGNOR-279853

Q9NR28

Q16611

0

relocalization

up-regulates

0.522

Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi

SIGNOR-118905

P19174

P09619

0

phosphorylation

up-regulates

0.859

Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.

SIGNOR-28179

P15056

Q02750

1

phosphorylation

up-regulates activity

0.789

Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.

SIGNOR-235475

Q12923

O00506

1

dephosphorylation

down-regulates activity

0.421

To investigate dephosphorylation of CCM3 by FAP-1, phosphorylated GST-CCM3 was incubated with cdFAP-1, and reactions were analyzed by autoradiography. Again, GST-STK25 phosphorylated GST-CCM3 and possessed autophosphorylation activity. cdFAP-1 of 0.005 U were sufficient to dephosphorylate GST-CCM3 as well as the kinase GST-STK25.|More recently, the Golgi matrix protein GM130 was shown to function as a scaffold protein for STK25 and to activate STK25 through stimulation of autophosphorylation.

SIGNOR-248711

P43405

P17252

1

phosphorylation

up-regulates activity

0.391

We present evidence that Tyr-662 and Tyr-658 of PKCbetaI and PKCalpha, respectively, are phosphorylated by Syk in the membrane compartment of FcepsilonRI-stimulated mast cells. These phosphorylations require prior PKC autophosphorylation of the adjacent serine residues (Ser-661 and Ser-657, respectively) and generate a binding site for the SH2 domain of the adaptor protein Grb-2.

SIGNOR-246581

P01100

Q13536

0

transcriptional regulation

up-regulates quantity by expression

0.2

CROC-4: a novel brain specific transcriptional activator of c-fos expressed from proliferation through to maturation of multiple neuronal cell types.

SIGNOR-261569

O15360

Q13535

0

phosphorylation

up-regulates

0.598

The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site

SIGNOR-182953

Q9BY44

Q9P2K8

0

phosphorylation

down-regulates activity

0.484

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

SIGNOR-280005

Q6PJ69

Q8NDV7

1

polyubiquitination

down-regulates quantity by destabilization

0.445

Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6.

SIGNOR-272174

O15198

Q9HAU4

0

ubiquitination

down-regulates

0.644

Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps

SIGNOR-193390

P67775

Q13043

1

dephosphorylation

down-regulates

0.367

Rassf1a apparently protects mst1/2 against inactivation by pp2a , the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.

SIGNOR-201270

Q8TBB1

Q96BR9

1

polyubiquitination

down-regulates quantity by destabilization

0.2

LNX (ligand of Numb protein-X) is a RING finger and four PDZ domain-containing E3 ubiquitin ligase. Lnx-l induced K48-linked polyubiquitylation of Boz, leading to its proteasomal degradation in human 293T cells and in zebrafish embryos.

SIGNOR-272777

P12931

O00206

1

phosphorylation

up-regulates activity

0.588

Src dependent phosphorylation of TLR4 is significantly increased in Cftr-KO cholangiocytes.|TLR4 can be activated through the phosphorylation of its TIR domains by Src, a non receptor tyrosine kinase 28.

SIGNOR-279658

P68400

O15379

1

phosphorylation

up-regulates activity

0.531

A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity.

SIGNOR-250889

Q92574

P53350

0

phosphorylation

down-regulates quantity by destabilization

0.467

The Hsp90 client Plk1 phosphorylates Sgt1, which had a positive impact on Sgt1 function, whereas phosphorylation of Tsc1 by Plk1 led to its ubiquitination and degradation.

SIGNOR-280072

P55795

Q15554

1

post transcriptional regulation

down-regulates quantity

0.332

During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.

SIGNOR-266806

P35712

P49715

1

transcriptional regulation

up-regulates quantity by expression

0.292

We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST

SIGNOR-255824

Q9H6E5

Q05655

0

phosphorylation

up-regulates activity

0.2

PKCdelta associates with and directly phosphorylates Star-PAP.

SIGNOR-279385

P08183

P11309

0

dephosphorylation

up-regulates activity

0.438

Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function|P-gp is known to be phosphorylated at Ser667, Ser671, and Ser683 by PKA; at Ser661, Ser667, and Ser671 by PKC; and at Ser683 by Pim-1|simultaneous expression of PP5 and PPP2R3C reduced the phosphorylation detected by the antibodies that specifically recognize serine/threonine phosphorylated by PKA or serine phosphorylated by PKC. These results suggest that the PP5/PPP2R3C complex dephosphorylates PKA- and PKC-phosphorylated serine residues on P-gp

SIGNOR-272511

Q9HAU4

P20333

1

ubiquitination

up-regulates activity

0.326

However, co-transfection of Smurf2, but not Smurf2-C/A, drastically increased the potential of TNF-R2 to induce JNK phosphorylation.|In conclusion, these results indicate that Smurf2 is able to ubiquitinate TNF-R2, which is further enhanced by the TRAF2-mediated targeting of Smurf2 to TNF-R2.

SIGNOR-278716

Q06609

P24941

0

phosphorylation

down-regulates quantity by destabilization

0.595

Phosphorylation of the BRCA2 C-terminal RAD51 binding site by CDK2 promotes RAD51 filament disassembly, leading to nucleolitic cleavage of newly synthesized DNA and compromised fork integrity.

SIGNOR-280213

P35568

Q05655

0

phosphorylation

down-regulates activity

0.646

Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).

SIGNOR-249267

P15882

P63000

1

gtpase-activating protein

down-regulates activity

0.666

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-260499

Q9Y266

P53350

0

phosphorylation

up-regulates activity

0.73

Here, we characterize the interaction between plk1 and nudc, show that plk1 phosphorylates nudc at conserved s274 and s326 residues in vitro, and present evidence that nudc is also a substrate for plk1 in vivo. Downregulation of nudc by rna interference results in multiple mitotic defects, including multinucleation and cells arrested at the midbody stage, which are rescued by ectopic expression of wild-type nudc, but not by nudc with mutations in the plk1 phosphorylation sites.

SIGNOR-103403

Q05655

Q15717

1

phosphorylation

up-regulates

0.637

Tandem phosphorylation of serines 221 and 318 by protein kinase cdelta coordinates mrna binding and nucleocytoplasmic shuttling of hurstabilization of mrna by the ubiquitous rna binding protein human antigen r (hur), a member of the embryonic lethal abnormal vision (elav) protein family, requires canonical binding to au-rich element (are)-bearing target mrna and export of nuclear hur-mrna complexes to the cytoplasm. In human mesangial cells (hmc) both processes are induced by angiotensin ii (angii) via protein kinase cdelta (pkcdelta)-triggered serine phosphorylation of hur.

SIGNOR-163524

P40763

P18031

0

dephosphorylation

down-regulates activity

0.552

PTP1B was able to dephosphorylate activated JAK2 and STAT3 in vitro, whereas either no or a minimal effect was observed with cluster of differentiation 45 (CD45), PTPalpha and leukocyte antigen-related (LAR). By utilisation of a selective PTP1B inhibitor, the leptin-induced STAT3 activation was enhanced in cells. In conclusion, these results suggested that the negative regulatory role of PTP1B on leptin signalling is mediated through a direct and selective dephosphorylation of the two signalling molecules, JAK2 and STAT3.

SIGNOR-248427

P43405

Q8WV28

1

phosphorylation

up-regulates

0.806

The phosphorylation of multiple tyrosine residues not only amplifies plcgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex.

SIGNOR-96044

P49841

O15273

1

phosphorylation

down-regulates quantity by destabilization

0.2

GSK-3beta phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation.|These results show direct GSK-3beta phosphorylation of TCAP S157 and FBXL21 T33 sites.

SIGNOR-264852

Q13144

P49840

0

phosphorylation

down-regulates activity

0.368

We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B

SIGNOR-251215

P18754

Q13188

0

phosphorylation

up-regulates

0.2

MST2 Phosphorylates RCC1 In Vitro and In Vivo. Using an antibody generated against phospho-S2/11 in RCC1 [18], we found that these two residues were also efficiently phosphorylated by MST1 and MST2 (Figure 2D), further supporting that S2 and/or S11 are genuine MST2 phosphorylation targets.

SIGNOR-263146

P49840

P13051

1

phosphorylation

down-regulates quantity by destabilization

0.2

Here we show that glycogen synthase kinase 3 (GSK-3) interacts with and phosphorylates UNG2 at Thr60 and that Thr60 phosphorylation requires a Ser64 priming phosphorylation event.|phosphorylation of Thr60 and Ser64 creates a cyclin E/c-Myc-like phosphodegron that promotes polyubiquitylation and proteasome-mediated degradation

SIGNOR-264886

Q16236

P36969

1

transcriptional regulation

up-regulates quantity by expression

0.383

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis.

SIGNOR-279874

Q16512

P10275

1

phosphorylation

up-regulates

0.587

Rho can sensitize the ar to low levels of circulating androgens by promoting the nuclear translocation of a transcriptional co-activator, fhl2 (four and a half lim domains 2), which binds ar, and by stimulating protein kinase n (pkn), which phosphorylates ar directly.

SIGNOR-152762

O15033

Q9NR28

1

ubiquitination

down-regulates quantity by destabilization

0.377

AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 |E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination.

SIGNOR-267672

P05129

P04049

1

phosphorylation

up-regulates

0.403

Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation.

SIGNOR-37545

Q99933

Q8NI51

0

transcriptional regulation

up-regulates quantity by expression

0.28

DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation

SIGNOR-254107

P51608

P41145

1

post transcriptional regulation

up-regulates quantity by expression

0.272

MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.

SIGNOR-264677

P18031

P35568

1

dephosphorylation

down-regulates

0.779

Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein.

SIGNOR-74852

P06493

Q9Y5B0

0

dephosphorylation

down-regulates activity

0.333

Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression.|We can not exclude that, in addition to S90 and S453, other Cdk1 phosphorylation sites in Gwl are dephosphorylated by Fcp1; nevertheless, assaying S67-Ensa kinase activity of V5-GwlS90A and V5-GwlS453A mutant proteins, isolated from transfected and prometaphase arrested HeLa cells, revealed that both mutants had significantly reduced S67-Ensa kinase activity compared to V5-GwlWT (XREF_FIG).|We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells.

SIGNOR-277141

P28482

O43353

0

phosphorylation

up-regulates activity

0.295

RIP2 directly phosphorylates and activates ERK2 in vivo and in vitro.

SIGNOR-279106

O60566

P53350

0

phosphorylation

up-regulates

0.84

We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions.

SIGNOR-157646

P04637

Q9UI32

1

transcriptional regulation

up-regulates quantity by expression

0.631

Glutaminase 2 (GLS2) can be directly transactivated by p53 and can therefore mediate p53-dependent regulation of cellular energy metabolism. G

SIGNOR-268041

P10645

P16220

0

transcriptional regulation

up-regulates quantity by expression

0.265

Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation.

SIGNOR-254276

P17612

Q05086

1

phosphorylation

down-regulates activity

0.328

These data suggest that PKA phosphorylation at T485 inhibits UBE3A ubiquitin ligase activity in cells.

SIGNOR-236899

Q13464

P45983

1

phosphorylation

up-regulates activity

0.296

Instead, we found that rock activates jnk, which then phosphorylates c-jun and atf2 when bound to the c-jun promoter.

SIGNOR-123717

P15927

P06493

0

phosphorylation

up-regulates activity

0.508

Cdc2 family kinases phosphorylate a human cell dna replication factor, rpa, and activate dna replication. therefore, the serines on rpa p34 that were necessary for phosphorylation by cdc2 kinase were also necessary for phosphorylation in the cell

SIGNOR-16975

O43602

Q9HCK8

0

transcriptional regulation

down-regulates quantity

0.2

Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells

SIGNOR-268915

Q9UKI8

Q8IW41

1

phosphorylation

up-regulates activity

0.2

We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells.

SIGNOR-276747

P27361

P78536

1

phosphorylation

up-regulates

0.361

Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated sheddingwe show that extracellular signal-regulated kinase (erk) acts as an intermediate in protein kinase c-regulated trka cleavage. We report that the cytosolic tail of the tumor necrosis factor alpha-converting enzyme (tace) is phosphorylated by erk at threonine 735. In addition, we show that erk and tace associate. This association is favored by erk activation and by the presence of threonine 735. In contrast to the erk route, the p38 mapk was able to stimulate trka cleavage in cells devoid of tace activity, indicating that other proteases are also involved in trka shedding.

SIGNOR-89625