GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P27361	P05976	1	phosphorylation	up-regulates	0.287	Activation of raf/mek/erk cascade can also result in the phosphorylation of the antiapoptotic mcl-1 protein and the pro-apoptotic bim protein.	SIGNOR-148002
Q14493	P0C5Y9	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-265411
P49840	Q14596	1	phosphorylation	down-regulates activity	0.322	The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation\|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.	SIGNOR-261794
P06400	Q13131	0	phosphorylation	down-regulates	0.2	Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site.	SIGNOR-184052
P23258	Q8TDC3	0	phosphorylation	up-regulates	0.248	Sadb kinases associate and phosphorylate gamma-tubulin on ser 131 s131d gamma-tubulin expression amplifies centrosome duplication	SIGNOR-187405
P35398	P48664	1	transcriptional regulation	up-regulates quantity by expression	0.251	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266850
Q96EB6	Q9UBK2	1	deacetylation	up-regulates activity	0.799	SIRT1 overexpression reduces muscle wasting by blocking the activation of FoxO1 and 3 SIRT1 activation has been reported to increase dramatically endurance exercise through the activation of PGC-1_ in muscle, which stimulates fatty acid oxidation	SIGNOR-217963
P22392	O15554	1	phosphorylation	up-regulates	0.419	We previously showed that nucleoside diphosphate kinase beta (ndpk-b), a mammalian histidine kinase, is required for kca3.1 channel activation in human cd4 t lymphocytes.	SIGNOR-181083
P18848	P49588	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269414
P17252	P26927	0	phosphorylation	up-regulates activity	0.2	Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.	SIGNOR-277179
Q00535	Q96QB1	1	phosphorylation	up-regulates activity	0.2	The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its Rho-GAP activity, and its ability to bind tensin and talin.	SIGNOR-276444
Q7LBC6	P84243	1	demethylation	down-regulates activity	0.2	We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.	SIGNOR-266636
P36894	O15169	0	ubiquitination	down-regulates	0.331	Other proteins, such as the serine/threonine kinase fused (fu), can function in concert with the e3 ligase smurf to regulate ubiquitination and proteolysis of the bmp receptor	SIGNOR-195552
P18858	P24941	0	phosphorylation	up-regulates activity	0.457	We show that three residues (ser51, ser76, and ser91), which are part of cyclin-dependent kinase sites, are phosphorylated in a cell cycle-dependent manner.	SIGNOR-103254
O14757	P43405	1	phosphorylation	down-regulates	0.311	We found that chk1 phosphorylated the tumor suppressor spleen tyrosine kinase (l) (syk[l]) and identified the phosphorylation site at ser295. Furthermore, chk1 phosphorylation of syk(l) promoted its subsequent proteasomal degradation.	SIGNOR-197528
P49354	P01112	1	null	up-regulates activity	0.413	Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.	SIGNOR-242568
Q15173	P42574	1	dephosphorylation	up-regulates	0.2	Dephosphorylation of caspase-3 at ser150 site by pp2a increased caspase-3 activity,which was essential to trigger apoptosis in neutrophils.	SIGNOR-131435
P35222	Q92729	0	dephosphorylation	down-regulates activity	0.4	Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating \u03b2-catenin and reducing the activation of \u03b2-catenin signaling.	SIGNOR-277095
O94856	Q01484	1	relocalization	up-regulates quantity	0.694	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266716
Q9GZM8	P06493	0	phosphorylation	up-regulates activity	0.66	In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites	SIGNOR-274074
P23467	Q02763	1	dephosphorylation	down-regulates activity	0.555	Simultaneous inhibition of Tie2 cleavage and VE-PTP synergistically enhances Tie2 activation by up to 10-fold (Fig. 7A).\|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects .\|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects.	SIGNOR-277059
Q13485	Q15797	0	phosphorylation	up-regulates	0.671	Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common(co-Smad; Smad4 in mammals) and shuttle into the nucleus.	SIGNOR-168734
Q13316	Q8IXL6	0	phosphorylation	up-regulates quantity	0.659	Fam20c knockdown decreased Dmp1 mRNA and increased Fgf23 mRNA in UMR-106 cells.\|Relative migration distances of OPN and DMP1, which were the ratio of the migration distances of OPN or DMP1 co-expressed with mutant FAM20C to that with WT FAM20C, showed that only WT FAM20C could fully phosphorylate OPN and DMP1.	SIGNOR-280011
P00533	P17706	0	dephosphorylation	down-regulates	0.635	Here, we report that the 45-kda variant of the protein tyrosine phosphatase tcptp (tc45) can recognize delta egfr as a cellular substrate	SIGNOR-132316
Q9HB75	Q13315	0	phosphorylation	up-regulates activity	0.636	ATM phosphorylates PIDD on Thr788 within the DD. This phosphorylation is necessary and sufficient for RAIDD binding and caspase-2 activation. Conversely, nonphosphorylatable PIDD fails to bind RAIDD or activate caspase-2, and engages prosurvival RIP1 instead. Thus, ATM phosphorylation of the PIDD DD enables a binary switch through which cells elect to survive or die upon DNA injury.	SIGNOR-262640
P04637	Q96EB6	0	deacetylation	down-regulates	0.803	Sirt1 has been shown to regulate cell fate in part by deacetylating the p53 protein at lysine 382 and inhibiting p53-mediated transcriptional activation and apoptosis.	SIGNOR-182515
P53350	P36956	1	phosphorylation	up-regulates activity	0.441	As illustrated in , the turnover of nuclear SREBP1a was attenuated in the presence of Plk1, confirming that Plk1 stabilizes nuclear SREBP1 by reducing its degradation.\|Figure 2.Plk1 phosphorylates threonine 424, serine 467 and serine 486 in nuclear SREBP1 during mitosis. (A) In vitro kinase assay with recombinant nuclear SREBP1a and Plk1.	SIGNOR-279382
O75688	Q02962	1	dephosphorylation	down-regulates activity	0.2	PPM1B can dephosphorylate the Pax2 activation domain and displace the adaptor protein PTIP, thus inhibiting H3K4 methylation and gene activation	SIGNOR-251712
P49841	P06401	1	phosphorylation	down-regulates quantity by destabilization	0.277	Here, we have found that glycogen synthase kinase (GSK)-3β phosphorylation of progesterone receptor-A (PR-A) facilitates its ubiquitination. GSK-3β-mediated phosphorylation of serine 390 in PR-A regulates its subsequent ubiquitination and protein stability.	SIGNOR-276498
P11137	Q9P0L2	0	phosphorylation	down-regulates activity	0.418	Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.	SIGNOR-250166
P48163	Q8N6T7	0	deacetylation	down-regulates activity	0.25	PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation.	SIGNOR-275572
O14503	P63279	0	polyubiquitination	down-regulates quantity by destabilization	0.326	Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9.	SIGNOR-272579
P35813	Q04206	1	dephosphorylation	down-regulates activity	0.353	23 Here we show that PPM1A directly dephosphorylated RelA at S536 and S276, with resultant inhibition of NF-kappaB transactivation and decreased expression of target genes, notably including MCP-1 and CCL2.\|Taken together, these data suggest that dephosphorylation of S276 by PPM1A may contribute to inhibit RelA transcriptional activity, but the majority of PPM1A activity to inhibit RelA transcription relies on dephos phorylation of S536 of RelA.\|We show that PPM1A directly dephosphorylated RelA at residues S536 and S276 and selectively inhibited Nuclear factor-\u03baB transcriptional activity, resulting in decreased expression of monocyte chemotactic protein-1/chemokine (C-C motif) ligand 2 and interleukin-6, cytokines implicated in cancer metastasis.	SIGNOR-276963
P00533	O15126	1	phosphorylation	up-regulates activity	0.335	In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation	SIGNOR-262857
Q96CV9	P53350	0	phosphorylation	up-regulates	0.539	Here we show that at mitotic entry, plk1 phosphorylates optineurin (optn) at serine 177 and that this dissociates optn from the golgi-localized gtpase rab8, inducing its translocation into the nucleus.	SIGNOR-196367
P46527	P07948	0	phosphorylation	down-regulates	0.553	We previously reported that y88 phosphorylation of p27(kip1) by oncogenic tyrosine kinases impairs p27(kip1)-mediated cdk inhibition, and initiates its ubiquitin-dependent proteasomal degradation.	SIGNOR-172904
P25098	P05129	0	phosphorylation	up-regulates	0.2	Phosphorylation of grk2 by protein kinase c abolishes its inhibition by calmodulinin vitro, grk2 was preferentially phosphorylated by pkc isoforms alpha, gamma, and delta	SIGNOR-83231
Q9NTG7	P48735	1	deacetylation	up-regulates	0.657	Site-specific, genetic incorporation of n(_)-acetyllysine into position 413 of idh2 revealed that acetylated idh2 displays a dramatic 44-fold loss in activity. Deacetylation by sirt3 fully restored maximum idh2 activity.	SIGNOR-196617
P49023	O14522	0	dephosphorylation	down-regulates activity	0.462	To this end, using a phospho-proteomics approach, we identified and validated paxillin and STAT3 as the substrates of PTPRT [15, 16]\|the PTPRT target site on paxillin is a previously uncharacterized tyrosine-88 residue (paxillin Y88)\|In this study, we also show how pY88 paxillin transduces a signal to activate Akt	SIGNOR-263978
Q8WYL5	Q15139	0	phosphorylation	down-regulates	0.479	Pkd-mediated phosphorylation of serines 937 and 978 regulates ssh1l subcellular localization by binding of 14-3-3 proteins 14-3-3 proteins associate with ssh1l when phosphorylated at serines 937 and 978, thereby sequestering ssh1l in the cytoplasm and preventing translocation of the phosphatase to f-actin_rich membrane protrusions	SIGNOR-186471
P55060	Q13490	0	polyubiquitination	down-regulates quantity by destabilization	0.333	We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase-8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation.	SIGNOR-272812
P15407	P17535	0	transcriptional regulation	up-regulates quantity by expression	0.817	Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription.	SIGNOR-261603
O15519	Q16539	0	phosphorylation	up-regulates	0.373	Here we demonstrate that m. tuberculosis?induced Tnf triggered reactive oxygen species?dependent Activation of ask1 and the tyrosine kinase c-abl (a000161) in mouse macrophages and that flips was phosphorylated on tyr211 and ser4 by c-abl and p38, respectively.	SIGNOR-187001
O95238	Q9UQ88	0	phosphorylation	down-regulates quantity by destabilization	0.356	In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues\|Western blot analysis demonstrated that only one of the mutant constructs, consisting of mutations of serine 238, 242 and 243, resulted in increased levels of SPDEF protein expression as compared to wild type SPDEF, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway.\|	SIGNOR-273022
P31751	Q05513	0	phosphorylation	up-regulates activity	0.498	The activation of PKBbeta and PKBgamma by PDK1 was accompanied by the phosphorylation of the residues equivalent to Thr308 in PKBalpha, namely Thr309 (PKBbeta) and Thr305 (PKBgamma). PKBgamma which had been activated by PDK1 possessed a substrate specificity identical with that of PKBalpha and PKBbeta towards a range of peptides. The activation of PKBgamma and its phosphorylation at Thr305 was triggered by insulin-like growth factor-1 in 293 cells.	SIGNOR-248997
P09874	P55210	0	cleavage	down-regulates	0.719	Caspase-7 cleaves parp;redundancy exists between the caspase-3 and -7 at the level of parp proteolysis.	SIGNOR-83703
Q16539	Q13202	0	dephosphorylation	down-regulates	0.591	M3/6 (dusp8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of jnk and, to a lesser extent, p38 mapk	SIGNOR-199695
P08559	Q15119	0	phosphorylation	down-regulates	0.679	Mammalian pyruvate dehydrogenase (?2_2) (e1) is regulated by phosphorylation-dephosphorylation, catalyzed by the e1-kinase and the phospho-e1-phosphatase.	SIGNOR-33141
Q9UQD0	Q9UQM7	0	phosphorylation	up-regulates activity	0.279	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275785
Q16236	P17252	0	phosphorylation	up-regulates	0.536	Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress	SIGNOR-91826
Q9BXW9	P38398	0	ubiquitination	up-regulates activity	0.845	The major genetic evidence supporting ubiquitin ligase function for BRCA1 in vivo comes from studies on the FANCD2 protein. Whereas in wild‐type cells the FANCD2 protein co‐localizes with BRCA1 in nuclear foci and becomes monoubiquitylated in response to DNA damage, HCC1937 cells, which encode a mutated form of BRCA1, are largely defective for both monoubiquitylation of FANCD2 and foci formation	SIGNOR-263236
Q9UHC6	Q12860	1	relocalization	up-regulates activity	0.477	These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.	SIGNOR-269074
P18848	P54577	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269431
Q16539	Q15910	1	phosphorylation	down-regulates quantity by destabilization	0.372	Here, we show that p38α kinase promotes EZH2 degradation in differentiating muscle cells through phosphorylation of threonine 372	SIGNOR-255663
Q96J02	Q13571	1	polyubiquitination	down-regulates quantity by destabilization	0.411	Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.	SIGNOR-272721
P28482	P08047	1	phosphorylation	up-regulates	0.644	Here we show that p42/p44 mapk directly phosphorylates sp1 on threonines 453 and 739 both in vitro and in vivo. Mutation of these sites to alanines decreases by half the mapk-dependent transcriptional activity of sp1. Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate sp1 on serine 59 and regulate cellular senescence via transcription of p21sdi1/cip1/waf1.	SIGNOR-116158
Q9H0X6	P11474	0	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner	SIGNOR-269052
P12931	P10275	1	phosphorylation	up-regulates activity	0.76	In addition to the ability of Src to promotes castration resistant progression and AR activation, Src is involved in regulating prostate cancer cell migration, invasion, and metastasis and affects bone remodeling.\|These data suggest that downstream of cell surface receptors, Ack1 mediates AR tyrosine phosphorylation at Tyr 267 and Src mediates AR tyrosine phosphorylation at Tyr 534.	SIGNOR-278168
P42336	O95819	0	phosphorylation	down-regulates activity	0.2	MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061	SIGNOR-277921
Q96GD4	Q8IX90	1	phosphorylation	up-regulates activity	0.455	Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments.	SIGNOR-262661
P08559	Q16654	0	phosphorylation	down-regulates	0.686	Mammalian pyruvate dehydrogenase (?2_2) (e1) is regulated by phosphorylation-dephosphorylation, catalyzed by the e1-kinase and the phospho-e1-phosphatase.	SIGNOR-33201
Q7L7X3	Q7KZI7	1	phosphorylation	up-regulates activity	0.414	MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.	SIGNOR-276164
Q9Y5P4	Q15139	0	phosphorylation	down-regulates	0.2	In this study, we identify cert as a novel in vivo pkd substrate. Phosphorylation on serine 132 by pkd decreases the affinity of cert toward its lipid target phosphatidylinositol 4-phosphate at golgi membranes and reduces ceramide transfer activity	SIGNOR-156500
P46527	O60674	0	phosphorylation	down-regulates activity	0.696	JAK2 phosphorylates tyrosine residue 88 (Y88) of p27(Kip1).	SIGNOR-278260
P00533	Q8TDY4	1	phosphorylation	up-regulates activity	0.2	How ACAP4 regulates membrane dynamics and curvature in response to EGF stimulation is unknown. Here, we show that phosphorylation of the N-terminal region of ACAP4, named the Bin, Amphiphysin, and RSV161/167 (BAR) domain, at Tyr34 is necessary for EGF-elicited membrane remodeling. \|EGF stimulation of cells causes phosphorylation of ACAP4 at Tyr34, which subsequently promotes ACAP4 homodimer curvature.	SIGNOR-272234
P35240	P17612	0	phosphorylation	up-regulates	0.405	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159840
Q9BVN2	Q9Y6K9	1	null	up-regulates quantity by stabilization	0.308	NESCA interacts with the IKK complex by the N-terminal region of NEMO. This experiment revealed that the overexpression of NESCA completely abolished the TRAF6-mediated polyubiquitination of NEMO, as it appears by using either anti-HA (Fig. 5A) or anti-NEMO (Fig. 5B) antibodies on immunoprecipitated extracts.	SIGNOR-272775
Q969H4	P12931	0	phosphorylation	up-regulates activity	0.506	We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression.	SIGNOR-275918
Q13188	O95835	1	phosphorylation	up-regulates	0.62	Since the N-terminal half of Lats1 (residues 1588) was dispensable for the activation of Lats1 by Mst2, mass spectrometry was used to identify phosphorylation sites within the C-terminal domain of Lats1.	SIGNOR-132927
O14490	Q00535	0	phosphorylation	down-regulates quantity by destabilization	0.408	Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.	SIGNOR-279153
Q15139	Q92481	1	phosphorylation	down-regulates activity	0.295	Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.\|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter.	SIGNOR-279267
P51692	P12931	0	phosphorylation	up-regulates	0.578	Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as src. these conformational differences may in part be due to differential effects of prl and src on stat5b tyrosine phosphorylation, since src induced several additional sites of tyrosine phosphorylation of stat5b at residues other than tyr-699, including tyr-724 and tyr-679.	SIGNOR-99002
O60885	O60674	0	phosphorylation	up-regulates quantity by stabilization	0.324	JAK2 induces tyrosine phosphorylation of BRD4 at Y97/Y98, resulting in BRD4 stabilization.	SIGNOR-277312
Q8N884	P51451	0	phosphorylation	down-regulates activity	0.2	DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS.	SIGNOR-275844
P49810	P68400	0	phosphorylation	up-regulates activity	0.307	In vitro the large hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC. Quantitative analysis of in vitro phosphorylation demonstrates the presence of two phosphorylation sites for CK-1 and a single site for CK-2. A deletion analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic sequence containing three potential phosphorylation sites for CKs (serines 327, 330, and 335). These data suggest that CK type protein kinases phosphorylate the CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites.	SIGNOR-250934
O95999	O76064	0	ubiquitination	up-regulates quantity by stabilization	0.328	Phosphorylated and ubiquitinated BCL10 is stabilized on the damage sites through binding to and presenting UBC13 to RNF168.\|We thus concluded that BCL10 is ubiquitinated mainly with K63-linked ubiquitination by RNF8.	SIGNOR-278778
Q9NX47	O95140	1	ubiquitination	up-regulates activity	0.2	Taken together, these results suggested that MITOL regulates endoplasmic reticulum tethering to mitochondria by activating Mfn2 via K192 ubiquitination.\|Therefore, MITOL specifically ubiquitinates mitochondrial Mfn2.	SIGNOR-278553
P07332	P11274	1	phosphorylation	down-regulates activity	0.368	In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.	SIGNOR-251137
O60674	P48029	1	relocalization	down-regulates activity	0.2	Janus-activated kinase-2 (JAK2) participates in the regulation of the Na⁺-coupled glucose transporter SGLT1 and the Na⁺-coupled amino acid transporter SLC6A19. JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane.	SIGNOR-265781
P12931	P17302	1	phosphorylation	down-regulates	0.588	The oncogenic tyrosine kinase, v-src, phosphorylates connexin43 (cx43) on y247 and y265 and inhibits cx43 gap junctional communication (gjc), the process of intercellular exchange of ions and metabolites.	SIGNOR-148913
Q9BY11	Q9NQU5	0	phosphorylation	up-regulates activity	0.2	We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.	SIGNOR-263021
Q9UHD2	Q13501	1	phosphorylation	up-regulates	0.709	Tbk-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on ser-403, a residue essential for its role in autophagic clearance.	SIGNOR-191944
P05129	P10636-2	1	phosphorylation	down-regulates activity	0.27	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275445
P0C1H6	Q14493	0	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-265395
O15297	Q9H2X6	0	phosphorylation	down-regulates quantity by destabilization	0.419	HIPK2 phosphorylates WIP1 at Ser54 and Ser85, and phosphorylated WIP1 is subject to proteasomal degradation so that WIP1 is maintained at low levels.	SIGNOR-278230
Q9HCK4	P23528	1	post transcriptional regulation	up-regulates quantity by expression	0.257	Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation.	SIGNOR-268378
Q86VE9	Q14004	0	phosphorylation	down-regulates quantity by destabilization	0.2	In addition, CDK13-KD disrupted Nef downregulation of SERINC5 from the cell surface, whereas CDK12-KD did not (Figures 2D and 2E).\|Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.\|Thus, we conclude that CycK/CDK13 phosphorylates the S360 residue of SERINC5.	SIGNOR-278918
O96013	P62826	1	phosphorylation	up-regulates	0.308	We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.	SIGNOR-167667
P48740	P0C0L5	1	cleavage	up-regulates activity	0.676	The classical complement activation pathway, like the MELinitiated pathway, involves the generation of a C3-converting complex, C4b2b, through enzymatic activation of C4 and C2. In the C1 complex (C1qr2s2), this specific protease activity is exhibited by C1s after activation of this enzyme by C1r. When C4 is activated, its reactive thiol ester is exposed and C4b binds covalently to nearby amino or hydroxyl groups. The C4-activating abilities of MASP-1 and MASP-2 were compared.\|Activation of C4 by Ct sand MASP-2 on western blots.	SIGNOR-263426
P17252	P08581	1	phosphorylation	down-regulates	0.256	These data show that phosphorylation of ser985 is a key mechanism for the negative regulation of hgf/sf receptor.	SIGNOR-37718
P12931	Q14721	1	phosphorylation	up-regulates	0.479	In the present study we show that an n-terminal tyrosine of kv2.1 (y124), which is a known target of src kinase, is critical for the apoptotic current surge..Kv2.1-mediated k+ currents are also enhanced during non-injurious conditions through direct phosphorylation of intracellular n-terminal residue tyrosine 124 (y124) by src kinase	SIGNOR-187201
P15172	P24941	0	phosphorylation	down-regulates	0.522	Cyclin e/cdk2 can phosphorylate myod at serine 200, which causes ubiquitination and degradation of this transcription factor during g1, preventing its accumulation and a commitment to differentiation.	SIGNOR-176509
P17252	P00533	1	phosphorylation	down-regulates activity	0.609	Biochemical and morphological analyses indicate that threonine-phosphorylated EGFR molecules undergo normal internalization, but instead of sorting to lysosomal degradation, they recycle back to the cell surfaceThe inhibitory effects of pkc are mediated by a single threonine residue (threonine 654) of egfr	SIGNOR-77421
O43524	P11309	0	phosphorylation	down-regulates activity	0.387	Pim1s expression induced the phosphorylation of foxo3a (fig. 5a and b) and inactivated its transcriptional activity (fig. 5c). A previous report showed that phosphorylation at t32, s253, and s315 residues in foxo3a induced 14-3-3 binding, nuclear export, and proteasomemediated degradation (42).	SIGNOR-179308
Q99062	P08631	0	phosphorylation	up-regulates activity	0.385	Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling. the ability of Hck to phosphorylate the G-CSF-R in vitro, both Y728 and Y763 fit the Src consensus phosphorylation site. we investigated the activation of Hck by the G-CSF-R in intact cells as well as in vitro. These studies revealed recruitment of Hck to activated G-CSF-R, mediated by direct binding via its SH2 domain to multiple phosphotyrosines of the receptor. In addition, we show that Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling.	SIGNOR-251264
Q8IYK4	P02462	1	glycosylation	up-regulates activity	0.452	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261159
P42681	P06241	0	phosphorylation	up-regulates activity	0.347	We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.	SIGNOR-249341
Q16620	Q6UB99	0	transcriptional regulation	up-regulates quantity by expression	0.2	Ankrd11 knockdown decreases the levels of bdnf and Trkb mRNAs. Next, we examine whether ANKRD11 accesses the Trkb promoter in cortical neurons. We performed the chromatin immunoprecipitation assay (ChIP) using an ANKRD11 antibody followed by PCR to amplify the Trkb promoter region. We found that ANKRD11 binds to the Trkb promoter (Fig. 6E). As expected, the level of ANKRD11 binding was decreased in the Ankrd11 knockdown condition.	SIGNOR-266731
P53350	Q06609	1	phosphorylation	up-regulates activity	0.508	Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin.\|Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase\u2013mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin.	SIGNOR-278187
Q03135	P06241	0	phosphorylation	down-regulates activity	0.721	Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn.Therefore,	SIGNOR-118003

P27361

P05976

1

phosphorylation

up-regulates

0.287

Activation of raf/mek/erk cascade can also result in the phosphorylation of the antiapoptotic mcl-1 protein and the pro-apoptotic bim protein.

SIGNOR-148002

Q14493

P0C5Y9

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-265411

P49840

Q14596

1

phosphorylation

down-regulates activity

0.322

The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.

SIGNOR-261794

P06400

Q13131

0

phosphorylation

down-regulates

0.2

Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site.

SIGNOR-184052

P23258

Q8TDC3

0

phosphorylation

up-regulates

0.248

Sadb kinases associate and phosphorylate gamma-tubulin on ser 131 s131d gamma-tubulin expression amplifies centrosome duplication

SIGNOR-187405

P35398

P48664

1

transcriptional regulation

up-regulates quantity by expression

0.251

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266850

Q96EB6

Q9UBK2

1

deacetylation

up-regulates activity

0.799

SIRT1 overexpression reduces muscle wasting by blocking the activation of FoxO1 and 3 SIRT1 activation has been reported to increase dramatically endurance exercise through the activation of PGC-1_ in muscle, which stimulates fatty acid oxidation

SIGNOR-217963

P22392

O15554

1

phosphorylation

up-regulates

0.419

We previously showed that nucleoside diphosphate kinase beta (ndpk-b), a mammalian histidine kinase, is required for kca3.1 channel activation in human cd4 t lymphocytes.

SIGNOR-181083

P18848

P49588

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269414

P17252

P26927

0

phosphorylation

up-regulates activity

0.2

Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.

SIGNOR-277179

Q00535

Q96QB1

1

phosphorylation

up-regulates activity

0.2

The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its Rho-GAP activity, and its ability to bind tensin and talin.

SIGNOR-276444

Q7LBC6

P84243

1

demethylation

down-regulates activity

0.2

We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.

SIGNOR-266636

P36894

O15169

0

ubiquitination

down-regulates

0.331

Other proteins, such as the serine/threonine kinase fused (fu), can function in concert with the e3 ligase smurf to regulate ubiquitination and proteolysis of the bmp receptor

SIGNOR-195552

P18858

P24941

0

phosphorylation

up-regulates activity

0.457

We show that three residues (ser51, ser76, and ser91), which are part of cyclin-dependent kinase sites, are phosphorylated in a cell cycle-dependent manner.

SIGNOR-103254

O14757

P43405

1

phosphorylation

down-regulates

0.311

We found that chk1 phosphorylated the tumor suppressor spleen tyrosine kinase (l) (syk[l]) and identified the phosphorylation site at ser295. Furthermore, chk1 phosphorylation of syk(l) promoted its subsequent proteasomal degradation.

SIGNOR-197528

P49354

P01112

1

null

up-regulates activity

0.413

Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.

SIGNOR-242568

Q15173

P42574

1

dephosphorylation

up-regulates

0.2

Dephosphorylation of caspase-3 at ser150 site by pp2a increased caspase-3 activity,which was essential to trigger apoptosis in neutrophils.

SIGNOR-131435

P35222

Q92729

0

dephosphorylation

down-regulates activity

0.4

Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating \u03b2-catenin and reducing the activation of \u03b2-catenin signaling.

SIGNOR-277095

O94856

Q01484

1

relocalization

up-regulates quantity

0.694

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266716

Q9GZM8

P06493

0

phosphorylation

up-regulates activity

0.66

In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites

SIGNOR-274074

P23467

Q02763

1

dephosphorylation

down-regulates activity

0.555

Simultaneous inhibition of Tie2 cleavage and VE-PTP synergistically enhances Tie2 activation by up to 10-fold (Fig. 7A).|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects .|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects.

SIGNOR-277059

Q13485

Q15797

0

phosphorylation

up-regulates

0.671

Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common(co-Smad; Smad4 in mammals) and shuttle into the nucleus.

SIGNOR-168734

Q13316

Q8IXL6

0

phosphorylation

up-regulates quantity

0.659

Fam20c knockdown decreased Dmp1 mRNA and increased Fgf23 mRNA in UMR-106 cells.|Relative migration distances of OPN and DMP1, which were the ratio of the migration distances of OPN or DMP1 co-expressed with mutant FAM20C to that with WT FAM20C, showed that only WT FAM20C could fully phosphorylate OPN and DMP1.

SIGNOR-280011

P00533

P17706

0

dephosphorylation

down-regulates

0.635

Here, we report that the 45-kda variant of the protein tyrosine phosphatase tcptp (tc45) can recognize delta egfr as a cellular substrate

SIGNOR-132316

Q9HB75

Q13315

0

phosphorylation

up-regulates activity

0.636

ATM phosphorylates PIDD on Thr788 within the DD. This phosphorylation is necessary and sufficient for RAIDD binding and caspase-2 activation. Conversely, nonphosphorylatable PIDD fails to bind RAIDD or activate caspase-2, and engages prosurvival RIP1 instead. Thus, ATM phosphorylation of the PIDD DD enables a binary switch through which cells elect to survive or die upon DNA injury.

SIGNOR-262640

P04637

Q96EB6

0

deacetylation

down-regulates

0.803

Sirt1 has been shown to regulate cell fate in part by deacetylating the p53 protein at lysine 382 and inhibiting p53-mediated transcriptional activation and apoptosis.

SIGNOR-182515

P53350

P36956

1

phosphorylation

up-regulates activity

0.441

As illustrated in , the turnover of nuclear SREBP1a was attenuated in the presence of Plk1, confirming that Plk1 stabilizes nuclear SREBP1 by reducing its degradation.|Figure 2.Plk1 phosphorylates threonine 424, serine 467 and serine 486 in nuclear SREBP1 during mitosis. (A) In vitro kinase assay with recombinant nuclear SREBP1a and Plk1.

SIGNOR-279382

O75688

Q02962

1

dephosphorylation

down-regulates activity

0.2

PPM1B can dephosphorylate the Pax2 activation domain and displace the adaptor protein PTIP, thus inhibiting H3K4 methylation and gene activation

SIGNOR-251712

P49841

P06401

1

phosphorylation

down-regulates quantity by destabilization

0.277

Here, we have found that glycogen synthase kinase (GSK)-3β phosphorylation of progesterone receptor-A (PR-A) facilitates its ubiquitination. GSK-3β-mediated phosphorylation of serine 390 in PR-A regulates its subsequent ubiquitination and protein stability.

SIGNOR-276498

P11137

Q9P0L2

0

phosphorylation

down-regulates activity

0.418

Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.

SIGNOR-250166

P48163

Q8N6T7

0

deacetylation

down-regulates activity

0.25

PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation.

SIGNOR-275572

O14503

P63279

0

polyubiquitination

down-regulates quantity by destabilization

0.326

Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9.

SIGNOR-272579

P35813

Q04206

1

dephosphorylation

down-regulates activity

0.353

23 Here we show that PPM1A directly dephosphorylated RelA at S536 and S276, with resultant inhibition of NF-kappaB transactivation and decreased expression of target genes, notably including MCP-1 and CCL2.|Taken together, these data suggest that dephosphorylation of S276 by PPM1A may contribute to inhibit RelA transcriptional activity, but the majority of PPM1A activity to inhibit RelA transcription relies on dephos phorylation of S536 of RelA.|We show that PPM1A directly dephosphorylated RelA at residues S536 and S276 and selectively inhibited Nuclear factor-\u03baB transcriptional activity, resulting in decreased expression of monocyte chemotactic protein-1/chemokine (C-C motif) ligand 2 and interleukin-6, cytokines implicated in cancer metastasis.

SIGNOR-276963

P00533

O15126

1

phosphorylation

up-regulates activity

0.335

In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation

SIGNOR-262857

Q96CV9

P53350

0

phosphorylation

up-regulates

0.539

Here we show that at mitotic entry, plk1 phosphorylates optineurin (optn) at serine 177 and that this dissociates optn from the golgi-localized gtpase rab8, inducing its translocation into the nucleus.

SIGNOR-196367

P46527

P07948

0

phosphorylation

down-regulates

0.553

We previously reported that y88 phosphorylation of p27(kip1) by oncogenic tyrosine kinases impairs p27(kip1)-mediated cdk inhibition, and initiates its ubiquitin-dependent proteasomal degradation.

SIGNOR-172904

P25098

P05129

0

phosphorylation

up-regulates

0.2

Phosphorylation of grk2 by protein kinase c abolishes its inhibition by calmodulinin vitro, grk2 was preferentially phosphorylated by pkc isoforms alpha, gamma, and delta

SIGNOR-83231

Q9NTG7

P48735

1

deacetylation

up-regulates

0.657

Site-specific, genetic incorporation of n(_)-acetyllysine into position 413 of idh2 revealed that acetylated idh2 displays a dramatic 44-fold loss in activity. Deacetylation by sirt3 fully restored maximum idh2 activity.

SIGNOR-196617

P49023

O14522

0

dephosphorylation

down-regulates activity

0.462

To this end, using a phospho-proteomics approach, we identified and validated paxillin and STAT3 as the substrates of PTPRT [15, 16]|the PTPRT target site on paxillin is a previously uncharacterized tyrosine-88 residue (paxillin Y88)|In this study, we also show how pY88 paxillin transduces a signal to activate Akt

SIGNOR-263978

Q8WYL5

Q15139

0

phosphorylation

down-regulates

0.479

Pkd-mediated phosphorylation of serines 937 and 978 regulates ssh1l subcellular localization by binding of 14-3-3 proteins 14-3-3 proteins associate with ssh1l when phosphorylated at serines 937 and 978, thereby sequestering ssh1l in the cytoplasm and preventing translocation of the phosphatase to f-actin_rich membrane protrusions

SIGNOR-186471

P55060

Q13490

0

polyubiquitination

down-regulates quantity by destabilization

0.333

We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase-8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation.

SIGNOR-272812

P15407

P17535

0

transcriptional regulation

up-regulates quantity by expression

0.817

Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription.

SIGNOR-261603

O15519

Q16539

0

phosphorylation

up-regulates

0.373

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

SIGNOR-187001

O95238

Q9UQ88

0

phosphorylation

down-regulates quantity by destabilization

0.356

In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues|Western blot analysis demonstrated that only one of the mutant constructs, consisting of mutations of serine 238, 242 and 243, resulted in increased levels of SPDEF protein expression as compared to wild type SPDEF, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway.|

SIGNOR-273022

P31751

Q05513

0

phosphorylation

up-regulates activity

0.498

The activation of PKBbeta and PKBgamma by PDK1 was accompanied by the phosphorylation of the residues equivalent to Thr308 in PKBalpha, namely Thr309 (PKBbeta) and Thr305 (PKBgamma). PKBgamma which had been activated by PDK1 possessed a substrate specificity identical with that of PKBalpha and PKBbeta towards a range of peptides. The activation of PKBgamma and its phosphorylation at Thr305 was triggered by insulin-like growth factor-1 in 293 cells.

SIGNOR-248997

P09874

P55210

0

cleavage

down-regulates

0.719

Caspase-7 cleaves parp;redundancy exists between the caspase-3 and -7 at the level of parp proteolysis.

SIGNOR-83703

Q16539

Q13202

0

dephosphorylation

down-regulates

0.591

M3/6 (dusp8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of jnk and, to a lesser extent, p38 mapk

SIGNOR-199695

P08559

Q15119

0

phosphorylation

down-regulates

0.679

Mammalian pyruvate dehydrogenase (?2_2) (e1) is regulated by phosphorylation-dephosphorylation, catalyzed by the e1-kinase and the phospho-e1-phosphatase.

SIGNOR-33141

Q9UQD0

Q9UQM7

0

phosphorylation

up-regulates activity

0.279

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275785

Q16236

P17252

0

phosphorylation

up-regulates

0.536

Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress

SIGNOR-91826

Q9BXW9

P38398

0

ubiquitination

up-regulates activity

0.845

The major genetic evidence supporting ubiquitin ligase function for BRCA1 in vivo comes from studies on the FANCD2 protein. Whereas in wild‐type cells the FANCD2 protein co‐localizes with BRCA1 in nuclear foci and becomes monoubiquitylated in response to DNA damage, HCC1937 cells, which encode a mutated form of BRCA1, are largely defective for both monoubiquitylation of FANCD2 and foci formation

SIGNOR-263236

Q9UHC6

Q12860

1

relocalization

up-regulates activity

0.477

These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.

SIGNOR-269074

P18848

P54577

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269431

Q16539

Q15910

1

phosphorylation

down-regulates quantity by destabilization

0.372

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

SIGNOR-255663

Q96J02

Q13571

1

polyubiquitination

down-regulates quantity by destabilization

0.411

Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.

SIGNOR-272721

P28482

P08047

1

phosphorylation

up-regulates

0.644

Here we show that p42/p44 mapk directly phosphorylates sp1 on threonines 453 and 739 both in vitro and in vivo. Mutation of these sites to alanines decreases by half the mapk-dependent transcriptional activity of sp1. Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate sp1 on serine 59 and regulate cellular senescence via transcription of p21sdi1/cip1/waf1.

SIGNOR-116158

Q9H0X6

P11474

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner

SIGNOR-269052

P12931

P10275

1

phosphorylation

up-regulates activity

0.76

In addition to the ability of Src to promotes castration resistant progression and AR activation, Src is involved in regulating prostate cancer cell migration, invasion, and metastasis and affects bone remodeling.|These data suggest that downstream of cell surface receptors, Ack1 mediates AR tyrosine phosphorylation at Tyr 267 and Src mediates AR tyrosine phosphorylation at Tyr 534.

SIGNOR-278168

P42336

O95819

0

phosphorylation

down-regulates activity

0.2

MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061

SIGNOR-277921

Q96GD4

Q8IX90

1

phosphorylation

up-regulates activity

0.455

Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments.

SIGNOR-262661

P08559

Q16654

0

phosphorylation

down-regulates

0.686

Mammalian pyruvate dehydrogenase (?2_2) (e1) is regulated by phosphorylation-dephosphorylation, catalyzed by the e1-kinase and the phospho-e1-phosphatase.

SIGNOR-33201

Q7L7X3

Q7KZI7

1

phosphorylation

up-regulates activity

0.414

MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.

SIGNOR-276164

Q9Y5P4

Q15139

0

phosphorylation

down-regulates

0.2

In this study, we identify cert as a novel in vivo pkd substrate. Phosphorylation on serine 132 by pkd decreases the affinity of cert toward its lipid target phosphatidylinositol 4-phosphate at golgi membranes and reduces ceramide transfer activity

SIGNOR-156500

P46527

O60674

0

phosphorylation

down-regulates activity

0.696

JAK2 phosphorylates tyrosine residue 88 (Y88) of p27(Kip1).

SIGNOR-278260

P00533

Q8TDY4

1

phosphorylation

up-regulates activity

0.2

How ACAP4 regulates membrane dynamics and curvature in response to EGF stimulation is unknown. Here, we show that phosphorylation of the N-terminal region of ACAP4, named the Bin, Amphiphysin, and RSV161/167 (BAR) domain, at Tyr34 is necessary for EGF-elicited membrane remodeling. |EGF stimulation of cells causes phosphorylation of ACAP4 at Tyr34, which subsequently promotes ACAP4 homodimer curvature.

SIGNOR-272234

P35240

P17612

0

phosphorylation

up-regulates

0.405

Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,

SIGNOR-159840

Q9BVN2

Q9Y6K9

1

null

up-regulates quantity by stabilization

0.308

NESCA interacts with the IKK complex by the N-terminal region of NEMO. This experiment revealed that the overexpression of NESCA completely abolished the TRAF6-mediated polyubiquitination of NEMO, as it appears by using either anti-HA (Fig. 5A) or anti-NEMO (Fig. 5B) antibodies on immunoprecipitated extracts.

SIGNOR-272775

Q969H4

P12931

0

phosphorylation

up-regulates activity

0.506

We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression.

SIGNOR-275918

Q13188

O95835

1

phosphorylation

up-regulates

0.62

Since the N-terminal half of Lats1 (residues 1588) was dispensable for the activation of Lats1 by Mst2, mass spectrometry was used to identify phosphorylation sites within the C-terminal domain of Lats1.

SIGNOR-132927

O14490

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.408

Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.

SIGNOR-279153

Q15139

Q92481

1

phosphorylation

down-regulates activity

0.295

Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter.

SIGNOR-279267

P51692

P12931

0

phosphorylation

up-regulates

0.578

Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as src. these conformational differences may in part be due to differential effects of prl and src on stat5b tyrosine phosphorylation, since src induced several additional sites of tyrosine phosphorylation of stat5b at residues other than tyr-699, including tyr-724 and tyr-679.

SIGNOR-99002

O60885

O60674

0

phosphorylation

up-regulates quantity by stabilization

0.324

JAK2 induces tyrosine phosphorylation of BRD4 at Y97/Y98, resulting in BRD4 stabilization.

SIGNOR-277312

Q8N884

P51451

0

phosphorylation

down-regulates activity

0.2

DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS.

SIGNOR-275844

P49810

P68400

0

phosphorylation

up-regulates activity

0.307

In vitro the large hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC. Quantitative analysis of in vitro phosphorylation demonstrates the presence of two phosphorylation sites for CK-1 and a single site for CK-2. A deletion analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic sequence containing three potential phosphorylation sites for CKs (serines 327, 330, and 335). These data suggest that CK type protein kinases phosphorylate the CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites.

SIGNOR-250934

O95999

O76064

0

ubiquitination

up-regulates quantity by stabilization

0.328

Phosphorylated and ubiquitinated BCL10 is stabilized on the damage sites through binding to and presenting UBC13 to RNF168.|We thus concluded that BCL10 is ubiquitinated mainly with K63-linked ubiquitination by RNF8.

SIGNOR-278778

Q9NX47

O95140

1

ubiquitination

up-regulates activity

0.2

Taken together, these results suggested that MITOL regulates endoplasmic reticulum tethering to mitochondria by activating Mfn2 via K192 ubiquitination.|Therefore, MITOL specifically ubiquitinates mitochondrial Mfn2.

SIGNOR-278553

P07332

P11274

1

phosphorylation

down-regulates activity

0.368

In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.

SIGNOR-251137

O60674

P48029

1

relocalization

down-regulates activity

0.2

Janus-activated kinase-2 (JAK2) participates in the regulation of the Na⁺-coupled glucose transporter SGLT1 and the Na⁺-coupled amino acid transporter SLC6A19. JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane.

SIGNOR-265781

P12931

P17302

1

phosphorylation

down-regulates

0.588

The oncogenic tyrosine kinase, v-src, phosphorylates connexin43 (cx43) on y247 and y265 and inhibits cx43 gap junctional communication (gjc), the process of intercellular exchange of ions and metabolites.

SIGNOR-148913

Q9BY11

Q9NQU5

0

phosphorylation

up-regulates activity

0.2

We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.

SIGNOR-263021

Q9UHD2

Q13501

1

phosphorylation

up-regulates

0.709

Tbk-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on ser-403, a residue essential for its role in autophagic clearance.

SIGNOR-191944

P05129

P10636-2

1

phosphorylation

down-regulates activity

0.27

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275445

P0C1H6

Q14493

0

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-265395

O15297

Q9H2X6

0

phosphorylation

down-regulates quantity by destabilization

0.419

HIPK2 phosphorylates WIP1 at Ser54 and Ser85, and phosphorylated WIP1 is subject to proteasomal degradation so that WIP1 is maintained at low levels.

SIGNOR-278230

Q9HCK4

P23528

1

post transcriptional regulation

up-regulates quantity by expression

0.257

Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation.

SIGNOR-268378

Q86VE9

Q14004

0

phosphorylation

down-regulates quantity by destabilization

0.2

In addition, CDK13-KD disrupted Nef downregulation of SERINC5 from the cell surface, whereas CDK12-KD did not (Figures 2D and 2E).|Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.|Thus, we conclude that CycK/CDK13 phosphorylates the S360 residue of SERINC5.

SIGNOR-278918

O96013

P62826

1

phosphorylation

up-regulates

0.308

We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.

SIGNOR-167667

P48740

P0C0L5

1

cleavage

up-regulates activity

0.676

The classical complement activation pathway, like the MELinitiated pathway, involves the generation of a C3-converting complex, C4b2b, through enzymatic activation of C4 and C2. In the C1 complex (C1qr2s2), this specific protease activity is exhibited by C1s after activation of this enzyme by C1r. When C4 is activated, its reactive thiol ester is exposed and C4b binds covalently to nearby amino or hydroxyl groups. The C4-activating abilities of MASP-1 and MASP-2 were compared.|Activation of C4 by Ct sand MASP-2 on western blots.

SIGNOR-263426

P17252

P08581

1

phosphorylation

down-regulates

0.256

These data show that phosphorylation of ser985 is a key mechanism for the negative regulation of hgf/sf receptor.

SIGNOR-37718

P12931

Q14721

1

phosphorylation

up-regulates

0.479

In the present study we show that an n-terminal tyrosine of kv2.1 (y124), which is a known target of src kinase, is critical for the apoptotic current surge..Kv2.1-mediated k+ currents are also enhanced during non-injurious conditions through direct phosphorylation of intracellular n-terminal residue tyrosine 124 (y124) by src kinase

SIGNOR-187201

P15172

P24941

0

phosphorylation

down-regulates

0.522

Cyclin e/cdk2 can phosphorylate myod at serine 200, which causes ubiquitination and degradation of this transcription factor during g1, preventing its accumulation and a commitment to differentiation.

SIGNOR-176509

P17252

P00533

1

phosphorylation

down-regulates activity

0.609

Biochemical and morphological analyses indicate that threonine-phosphorylated EGFR molecules undergo normal internalization, but instead of sorting to lysosomal degradation, they recycle back to the cell surfaceThe inhibitory effects of pkc are mediated by a single threonine residue (threonine 654) of egfr

SIGNOR-77421

O43524

P11309

0

phosphorylation

down-regulates activity

0.387

Pim1s expression induced the phosphorylation of foxo3a (fig. 5a and b) and inactivated its transcriptional activity (fig. 5c). A previous report showed that phosphorylation at t32, s253, and s315 residues in foxo3a induced 14-3-3 binding, nuclear export, and proteasomemediated degradation (42).

SIGNOR-179308

Q99062

P08631

0

phosphorylation

up-regulates activity

0.385

Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling. the ability of Hck to phosphorylate the G-CSF-R in vitro, both Y728 and Y763 fit the Src consensus phosphorylation site. we investigated the activation of Hck by the G-CSF-R in intact cells as well as in vitro. These studies revealed recruitment of Hck to activated G-CSF-R, mediated by direct binding via its SH2 domain to multiple phosphotyrosines of the receptor. In addition, we show that Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling.

SIGNOR-251264

Q8IYK4

P02462

1

glycosylation

up-regulates activity

0.452

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261159

P42681

P06241

0

phosphorylation

up-regulates activity

0.347

We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.

SIGNOR-249341

Q16620

Q6UB99

0

transcriptional regulation

up-regulates quantity by expression

0.2

Ankrd11 knockdown decreases the levels of bdnf and Trkb mRNAs. Next, we examine whether ANKRD11 accesses the Trkb promoter in cortical neurons. We performed the chromatin immunoprecipitation assay (ChIP) using an ANKRD11 antibody followed by PCR to amplify the Trkb promoter region. We found that ANKRD11 binds to the Trkb promoter (Fig. 6E). As expected, the level of ANKRD11 binding was decreased in the Ankrd11 knockdown condition.

SIGNOR-266731

P53350

Q06609

1

phosphorylation

up-regulates activity

0.508

Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin.|Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase\u2013mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin.

SIGNOR-278187

Q03135

P06241

0

phosphorylation

down-regulates activity

0.721

Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn.Therefore,

SIGNOR-118003