GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P19438	Q12933	1	null	up-regulates	0.832	We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation	SIGNOR-256251
Q96PM5	Q9UQM7	0	phosphorylation	down-regulates	0.296	Phosphorylation of pirh2 by calmodulin-dependent kinase ii impairs its ability to ubiquitinate p53	SIGNOR-156064
Q96BR1	Q92597	1	phosphorylation	down-regulates activity	0.402	It has been shown that SGK3 phosphorylation of NDRG1 primes for subsequent phosphorylation by GSK-3beta.\|Since NDRG1 is a direct SGK substrate, this correlation suggests that SGK3 activation and signaling may modulate NDRG1 degradation.	SIGNOR-279282
P28482	P49841	1	phosphorylation	down-regulates activity	0.383	We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels	SIGNOR-262524
Q9NSE2	P42229	0	transcriptional regulation	up-regulates quantity by expression	0.669	The STAT5 target gene CIS, a member of the suppressor of cytokine signaling (SOCS) protein family, was highly induced by Flt3-ITD	SIGNOR-261544
P29322	O00712	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268903
O43561	Q9Y4K3	0	ubiquitination	up-regulates activity	0.345	Interestingly, this study has demonstrated that the membrane-proximal region of linker for activation of T cells preceding tyrosine-132 mediates its association with TRAF6, which promotes the ubiquitination of linker for activation of T cells and, in turn, the phosphorylation of tyrosine residues on linker for activation of T cells.\|Moreover, LAT was ubiquitinated at Lysine 88 by TRAF6 via K63 linked chain.	SIGNOR-278675
P12931	O15379	1	phosphorylation	up-regulates activity	0.385	C-Src also phosphorylated three tyrosine sites of HDAC3 at tyrosine 325, 328, and 331. Importantly, wild-type c-Src increases HDAC3 activity, but not mutant c-SrcK298M (kinase inactive form).	SIGNOR-277485
P51451	O15524	1	phosphorylation	down-regulates activity	0.2	These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors.	SIGNOR-277889
P48729	Q9NRF8	1	phosphorylation	down-regulates	0.2	Hctps2 ser(568) was phosphorylated by casein kinase 1 both in vitro and in vivo. Mutation of ser(568) (s568a) significantly increased hctps2 activity, demonstrating that ser(568) is a major inhibitory phosphorylation site.	SIGNOR-167623
Q9UL54	P19419	1	phosphorylation	up-regulates activity	0.31	Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.	SIGNOR-246638
P09237	P10451	1	cleavage	up-regulates activity	0.706	In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.	SIGNOR-253321
P06493	P52948	1	phosphorylation	down-regulates activity	0.397	We show that npc disassembly is a phosphorylation-driven process, dependent on cdk1 activity and supported by members of the nima-related kinase (nek) family. mitotic hyperphosphorylation of nup98 is accomplished by multiple kinases, including cdk1 and neks.	SIGNOR-172217
P00519	Q92918	1	phosphorylation	up-regulates activity	0.379	C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD	SIGNOR-251429
P0DP23	P06213	0	phosphorylation	down-regulates	0.403	The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-24782
P34897	Q9NXA8	0	post translational modification	down-regulates activity	0.235	Mitochondrial serine hydroxymethyl transferase (SHMT2) is a rate-limiting enzyme that catalyzes the catabolism of serine and drives the proliferation of osteosarcoma cells and colon cancer cells. SIRT5 directly mediates the desuccinylation of Lysine 280 on SHMT2. Therefore, SIRT5 is a candidate target to inhibit serine catabolism	SIGNOR-267644
P27361	P37231	1	relocalization	down-regulates activity	0.398	The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform	SIGNOR-179407
P43378	P40763	1	dephosphorylation	down-regulates activity	0.432	Results are presented as mean \u00b1 SD from three independent experiments. (B) PTPMeg2 inhibits STAT3-mediated transcriptional activity in a dose dependent manner.\|These results indicate that PTPMeg2 inhibits STAT3 activation with certain specificity.\|In this study, we demonstrated that PTPMeg2 dephosphorylates STAT3 at the Tyr705 residue by a direct interaction.	SIGNOR-276976
Q13976	Q9UH03	1	phosphorylation	up-regulates activity	0.2	Mutation of Ser-91 to Ala in recombinant Sept3 also abolished PKG phosphorylation, confirming that Ser-91 is the major site in vitro. Therefore Sept3 is phosphorylated on Ser-91 in nerve terminals and its phosphorylation may contribute to the regulation of its subcellular localization in neurons.	SIGNOR-263183
Q9NYY3	O15350	1	phosphorylation	down-regulates activity	0.275	PLK2 inhibits TAp73 translocation to the nucleus.\|PLK2 phosphorylated TAp73 at residue Ser48 within the TA domain; phosphorylation of TAp73 was abolished by mutating this residue.	SIGNOR-278218
P04155	O00170	0	transcriptional regulation	down-regulates quantity by repression	0.2	We show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells.	SIGNOR-259911
O75592	P62826	1	guanine nucleotide exchange factor	up-regulates activity	0.296	MYCBP2 Is a Nuclear GEF for Ran in DRG Neurons—Next, we studied whether or not MYCBP2 modulates the interaction between Ran/RanGAP1. MYCBP2 contains an N-terminal RCC1-like domain (Fig. 8C) (13), and RCC1 is a known GEF for Ran, indicating a potential functional interaction between MYCBP2 and Ran.	SIGNOR-261204
Q15398	Q9Y566	1	relocalization	up-regulates activity	0.448	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264598
Q9UKV3	P42574	0	cleavage	up-regulates	0.628	Induces apoptotic chromatin condensation after activation by casp3	SIGNOR-70800
Q9UHD2	Q9BRV8	1	phosphorylation	down-regulates quantity	0.718	Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).\|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity.	SIGNOR-280152
P55957	P19784	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-250978
Q9UJY1	P27361	0	phosphorylation	up-regulates activity	0.34	Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation	SIGNOR-107680
P48730	P30291	1	phosphorylation	down-regulates quantity by destabilization	0.308	Casein kinase 1-mediated N-terminal Weee1 phosphorylation is required for interaction with the F-box protein β-TrCP.MS/MS spectra of human Wee1 identifying serine 212 as phosphorylated after incubation with recombinant CK1δ.	SIGNOR-276631
Q8TDY4	P00533	0	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
P16870	P01178-PRO_0000020495	1	cleavage	up-regulates activity	0.2	First, OT preprohormone is produced, that will be cleaved and matured by successive enzymes. The OT gene encodes for the Pre-Pro-OT-Neurophysin I (pre-pro-hormone), which is cleaved by different enzymes to give rise to different OT intermediate forms and to the Neurophysin I, and finally to the mature amidated form that is released (Figure 2).	SIGNOR-270338
P34947	P30989	1	phosphorylation	up-regulates activity	0.594	Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively.	SIGNOR-278234
P07355	P07947	0	phosphorylation	up-regulates activity	0.2	Activated YES1 interacts with ANXA2 andphosphorylates ANXA2 at Tyr24 site that induces ANXA2 activation and increases ANXA2 nuclear distribution , leading to activation of the tumorpromoting transcription factors ( such as Myc , Stat3 , Stat6 ) that promotes GC invasion and metastasis .\|YES1 phosphorylates ANXA2 at Tyr24 site that leads to ANXA2 activation and increased ANXA2 nuclear distribution.	SIGNOR-279435
P07332	P40763	1	phosphorylation	up-regulates activity	0.402	Fes also induced Tyr 705 phosphorylation and DNA binding activity of STAT3, in agreement with the idea that Fes can regulate transcriptional activation through Fes dependent phosphorylation of transcription factors.On the basis of these findings, we propose that Fes activation of critical transcriptional regulators such as PU.1 is part of the mechanism by which this kinase induces macrophage differentiation of myeloid progenitors.\|We conclude that Fes may regulate granulocytic differentiation at least in part through activation of C/EBP-alpha and STAT3.In 32D cells, Fes activated STAT3 and C/EBP-alpha, two important regulators of granulocytic differentiation [14,15].	SIGNOR-278937
P09874	P42574	0	cleavage	down-regulates activity	0.775	Caspase-3 cleaves parp-1. During cd95-mediated apoptosis proteolytic inactivation of parp-1 by caspases prevents atp depletion and thereby ensures the execution of the apoptotic process	SIGNOR-116178
P05067	P07339	0	cleavage	down-regulates quantity by destabilization	0.489	The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. \| two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism.	SIGNOR-261767
P35659	P68400	0	phosphorylation	up-regulates	0.35	Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32	SIGNOR-125912
Q9Y314	P19235	1	ubiquitination	up-regulates activity	0.331	Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation. This receptor-associated ubiquitin ligase, RUL, co-precipitated with EpoR from mammalian cells and mediated ubiquitination of EpoR. RUL mediates EpoR ubiquitination in COS7 cells and is inducibly ubiquitinated after Epo treatment. This observation is consistent with the lack of effects on EpoR stability by RUL-mediated ubiquitination in COS7 cells (Fig. 4).	SIGNOR-271477
P09619	P34947	1	phosphorylation	up-regulates activity	0.2	Purified GRK5 was tyrosine-phosphorylated by the wild-type PDGFRbeta to a stoichiometry of 0.8 mol phosphate/mol GRK5, an extent approximately 5 times greater than observed with a Y857F PDGFRbeta mutant that fails to phosphorylate exogenous substrates but autophosphorylates and activates Src normally.\|We conclude that GRK5 tyrosyl phosphorylation is required for the activation of GRK5 by the PDGFRbeta, but not by the beta(2)-adrenergic receptor, and that by activating GRK5, the PDGFRbeta triggers its own desensitization.	SIGNOR-279642
O43566	P17612	0	phosphorylation	up-regulates activity	0.338	RGS14 is phosphorylated in vitro at Ser258 and Thr494 by PKA. cAMP-induced phosphorylation as an important modulator of RGS14 function since phosphorylation could enhance RGS14 binding to Galpha(i)-GDP	SIGNOR-250045
Q14721	O95292	1	relocalization	up-regulates quantity	0.2	Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.\|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.	SIGNOR-262121
Q8IXQ9	P38117	1	methylation	down-regulates activity	0.2	Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.	SIGNOR-269450
P55210	P49810	1	cleavage	up-regulates activity	0.318	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261751
P11387	P17252	0	phosphorylation	up-regulates activity	0.2	In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.	SIGNOR-276154
Q8WUI4	P62714	0	dephosphorylation	up-regulates activity	0.2	Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. \|Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs.	SIGNOR-248605
Q9Y6K9	Q13315	0	phosphorylation	down-regulates activity	0.739	Atm phosphorylates serine-85 of nemo to promote its ubiquitin-dependent nuclear export.	SIGNOR-144813
O94953	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.261	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271569
P14921	Q9UKX5	1	null	up-regulates quantity by expression	0.281	We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.	SIGNOR-253352
P67775	P27707	1	dephosphorylation	down-regulates activity	0.2	Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation\|Deoxycytidine kinase (dCK) is a critical enzyme for activation of anticancer nucleoside analogs. Its activity is controlled via Ser-74 phosphorylation. Here, we investigated which Ser/Thr phosphatase dephosphorylates Ser-74. In cells, the PP1/PP2A inhibitor okadaic acid increased both dCK activity and Ser-74 phosphorylation	SIGNOR-275803
Q13555	P42224	1	phosphorylation	up-regulates activity	0.507	For maximal gene activation, S727 in the transcription activation domain of Stat1 also is inducibly phosphorylated by IFN-gamma. We previously purified a group of nuclear proteins that interact specifically with the Stat1 transcription activation domain. In this report, we identified one of them as the multifunctional Ca(2+)/calmodulin-dependent kinase (CaMK) II. We demonstrate that IFN-gamma mobilizes a Ca(2+) flux in cells and activates CaMKII. CaMKII can interact directly with Stat1 and phosphorylate Stat1 on S727 in vitro. Inhibition of Ca(2+) flux or CaMKII results in a lack of S727 phosphorylation and Stat1-dependent gene activation, suggesting in vivo phosphorylation of Stat1 S727 by CaMKII.	SIGNOR-250706
P39880	P06493	0	phosphorylation	down-regulates	0.357	Phosphorylation of serines 1237 and 1270 caused inhibition of dna binding in vitro. In cotransfection studies, cyclin a-cdk1 inhibited cdp/cux stable dna binding and prevented repression of the p21(waf1) reporter.	SIGNOR-110912
P53350	Q99640	1	phosphorylation	down-regulates activity	0.721	Here, we have shown that Plk1 is responsible for part of the phosphorylation of Myt1 during M phase. The kinase activity of human Myt1 is reported to be decreased during M phase, and the decreased activity correlates with hyperphosphorylated forms of Myt1 (35, 37). We then tested the ability of these mutant forms of Myt1 (GST fusion proteins), to serve as a substrate for Plk1 in vitro. Quantification of the result (Fig. 5C) showed that Ser-426 is the major phosphorylation site by Plk1 in vitro and Thr-495 the second major site.	SIGNOR-263096
P36873	Q9BYX4	1	dephosphorylation	up-regulates activity	0.247	Exogenous PP1alpha or PP1gamma substantially decreased the S88 phosphorylation of Flag-MDA5\|we identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.	SIGNOR-264579
P27361	Q16690	0	dephosphorylation	down-regulates	0.76	Extracellular regulated kinases (erk) 1 and erk2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase vhr. A novel role in down-regulating the erk pathway	SIGNOR-67358
O14974	Q9H093	0	phosphorylation	down-regulates activity	0.466	NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).	SIGNOR-279081
Q15796	Q9H6Z4	0	relocalization	down-regulates activity	0.436	RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner.	SIGNOR-217634
P08908	Q00535	0	phosphorylation	down-regulates quantity by destabilization	0.27	Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT 1A receptor via phosphorylation\|5-HT1AR was phosphorylated by the Cdk5-p35 complex at Thr314 in the third cytoplasmic loop.	SIGNOR-264406
Q9Y4K3	Q9GZQ8	1	polyubiquitination	down-regulates quantity by destabilization	0.295	TRAF6 catalyzes K63-linked polyubiquitination of LC3B and promotes the formation of the LC3B-ATG7 and LC3B-CTNNB1 complexes.	SIGNOR-277439
P14598	Q05513	0	phosphorylation	up-regulates	0.394	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89280
Q9UBK2	Q6NUN9	0	transcriptional regulation	up-regulates quantity by expression	0.445	PARIS represses the expression of the transcriptional coactivator, PGC-1α and the PGC-1α target gene, NRF-1 by binding to insulin response sequences in the PGC-1α promoter.	SIGNOR-277627
P29597	P42224	1	phosphorylation	up-regulates activity	0.775	Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701Phosphorylation of purified Stat1 was necessary and sufficient for the acquisition of DNA binding activity.	SIGNOR-246943
P48729	Q8TB45	1	phosphorylation	down-regulates	0.2	Phosphorylation of all three serine residues in the deptor degron (ser286, ser287, and ser291) is necessary for - and directly mediates - the interaction with _trcp. ck1 phosphorylated the degron of deptor, as shown by western blotting with the phospho-specific antibody (fig. S3e-f). In contrast, mtor alone was unable to induce phosphorylation of deptor on ser286, ser287, and ser291.	SIGNOR-176871
P13569	P17612	0	phosphorylation	up-regulates	0.485	Cftr, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to camp agonists. Serines 660, 737, 795, and 813 were identified as in vivo targets for phosphorylation by protein kinase a.mutagenesis of all four sites abolished the response.	SIGNOR-21312
P29376	P22681	1	phosphorylation	up-regulates	0.369	Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.	SIGNOR-49528
Q9H9S0	P26358	1	transcriptional regulation	up-regulates quantity by expression	0.432	Oct4 and Nanog upregulate Dnmt1 through direct binding to its promoter, thereby leading to the repressed expression of p16 and p21 and genes associated with development and lineage differentiation	SIGNOR-253157
O60610	O14757	0	phosphorylation	down-regulates activity	0.2	Chk1 Phosphorylates Drf1 for beta-Trcp-Dependent Degradation.\|From this we conclude that Chk1 inhibits Drf1, but not the other three limiting factors at the MBT.	SIGNOR-279026
Q13237	P09619	1	phosphorylation	down-regulates activity	0.272	Secretory PKG II inhibited PDGF‐BB ‐induced PDGFRβ activation via phosphorylating its Ser254.	SIGNOR-277577
P51451	P16885	1	phosphorylation	up-regulates activity	0.557	Lyn, Syk, Btk, and Blk can also phosphorylate and enhance the activation of phospholipase C gamma 2 (PLCgamma2), which hydrolyzes PI (4,5) P2 to create inositol 3,4,5-trisphosphate (IP3) and diacylglycerol (DAG), stimulating Ca 2+ mobilization and protein kinase C (PKC), respectively.	SIGNOR-280195
P31749	Q99490	1	phosphorylation	up-regulates	0.497	In addition, we have found that activated akt can bind and phosphorylate ggap2 at serine 629, which enhances gtp binding by ggap2.	SIGNOR-183543
Q9UPX8	Q15398	0	relocalization	up-regulates activity	0.452	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264599
P40337	P12931	0	phosphorylation	down-regulates quantity by destabilization	0.29	We have found that elevated Src can trigger a drastic reduction in VHL stability even under normoxic conditions, through phosphorylation of VHL tyrosine residue 185, leading to ubiquitination and proteasome mediated degradation of VHL.	SIGNOR-279125
P41252	P18848	0	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-269427
Q8IYW5	P54132	1	ubiquitination	up-regulates activity	0.262	Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80.	SIGNOR-272114
P27361	P10242	1	phosphorylation	down-regulates	0.301	Functional analysis of phosphorylation at serine 532 of human c-myb by map kinase. expression of a polypeptide containing the c-myb c-terminal domain stimulated c-myb activity. This effect is reduced upon mapk-dependent phosphorylation of serine 532. Our data suggest that the mapk-dependent state of phosphorylation modifies the cellular function of c-myb by modulating its interaction with a putative inhibitory factor	SIGNOR-45348
Q96PG8	P04626	0	phosphorylation	down-regulates activity	0.281	These results show for the first time that PUMA can be phosphorylated at tyrosine residues directly by HER2.\|Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein.	SIGNOR-278224
Q16143	Q9NYY3	0	phosphorylation	down-regulates activity	0.248	Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.	SIGNOR-189049
P00451	P00734	0	cleavage	up-regulates activity	0.755	Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689.	SIGNOR-263640
O75943	Q13535	0	phosphorylation	up-regulates activity	0.858	Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival.	SIGNOR-111248
Q05086	P35998	1	ubiquitination	down-regulates quantity by destabilization	0.385	Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.	SIGNOR-265132
P19622	P55075	1	transcriptional regulation	down-regulates quantity by repression	0.416	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.	SIGNOR-265801
O15530	Q96BR1	1	phosphorylation	up-regulates	0.461	Full-length sgk3 contains a complete phox homology (px) domain that targets the protein to endosomes. Both a functional px domain and pi3k activation are necessary for phosphorylation of sgk3 at two regulatory sites (thr-320 and ser-486) and subsequent induction of kinase activity. Pdk1 phosphorylates endosome-associated sgk3 at thr-320	SIGNOR-147213
Q08050	Q14680	0	phosphorylation	up-regulates activity	0.501	MELK Activates FOXM1 Transcriptional Activity Leading to Upregulation of Mitotic Gene Expression.\|The autoradiogram clearly shows in vitro phosphorylation of FOXM1 by MELK and CDK2 and cyclinA.	SIGNOR-278412
P04637	Q86XK2	0	neddylation	down-regulates	0.671	Fbxo11 promotes the neddylation of p53 and inhibits its transcriptional activity / we found that fbxo11 also neddylates p53 on two lysines, lys-320 and lys-321	SIGNOR-150669
Q13115	P45983	1	dephosphorylation	down-regulates	0.714	Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2	SIGNOR-27756
Q96EQ8	O95786	1	polyubiquitination	down-regulates quantity by destabilization	0.671	Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.	SIGNOR-271647
P68036	O60260	1	ubiquitination	up-regulates activity	0.2	Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1).	SIGNOR-272734
P06493	Q02750	1	phosphorylation	down-regulates	0.496	P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well	SIGNOR-36116
Q7Z3C6	P12931	0	phosphorylation	up-regulates activity	0.342	Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.	SIGNOR-266367
P68400	O75925	1	phosphorylation	up-regulates	0.332	Ck2 phosphorylates serine residues adjacent to the sim of pias1 these findings show that the phosphosim module mediates binding to free sumo and sumo conjugates in a phosphorylation-dependent mode, with ck2 being the critical kinase involvedin this process.	SIGNOR-184047
O43264	Q13561	1	relocalization	up-regulates activity	0.685	ZW10 interacts with dynamitin, a subunit of the dynein-dynactin complex (Echeverri et al., 1996), thereby recruiting this motor to kinetochores	SIGNOR-265016
P09769	Q04760	1	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276188
Q14118	P12931	0	phosphorylation	down-regulates	0.55	Tyrosine 892 is now thought to be the principal site for recognition by the c-src tyrosine kinase;. We show that upon tyrosine phosphorylation, beta-dystroglycan undergoes a profound change in its sub-cellular localization (e.g., from the plasma membrane to an internal membrane compartment). One possibility is that the net negative charge at position 892 causes the redistribution of beta-dystroglycan to this intracellular vesicular location	SIGNOR-101655
O15111	Q5TCX8	0	phosphorylation	down-regulates activity	0.2	Immunoprecipitation and in vitro kinase analysis revealed that MLK4 physically interacts with both IKKalpha and beta, but preferentially phosphorylates IKKalpha over IKKbeta (XREF_FIG	SIGNOR-279067
P06493	P50548	1	phosphorylation	down-regulates	0.2	Consistent with the in vivo phosphorylation and inactivation by ras, erf is efficiently phosphorylated in vitro by erk2 and cdc2/cyclin b kinases, at sites similar to those detected in vivo. Furthermore, a single mutation at position 526 results in the loss of a specific phosphopeptide both in in vivo and in vitro (by erk2) labeling. Substitution of thr526 for glutamic acid also decreases the repression ability of erf	SIGNOR-29501
Q96GD4	P14136	1	phosphorylation	down-regulates activity	0.438	We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by aurora-b;thr-7/ser-13/ser-38 of gfap, and thr-16 of desmin are common with those related to rho-associated kinase (rho-kinase), which has been reported to phosphorylate gfap and desmin at cleavage furrow during cytokinesis. We identified ser-59 of desmin to be a specific site phosphorylated by aurora-b in vitro.	SIGNOR-100173
Q9C035	P19474	0	monoubiquitination	up-regulates quantity	0.344	Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm.	SIGNOR-271672
O43164	P13861	1	polyubiquitination	down-regulates quantity by destabilization	0.328	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271856
Q9Y4C1	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.415	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271568
Q13464	P15311	1	phosphorylation	up-regulates	0.732	Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. We performed an in vitro kinase assay with 80 selected kinases on an ezrin peptide containing the t567 phosphorylation site (figure 3a). In this screen, we identified the mst and rock kinases as the most potent kinases for the ezrin peptide	SIGNOR-185567
O43318	P46734	1	phosphorylation	up-regulates activity	0.505	Taken together, our data indicate that TAK1 and TAB1 play a pivotal role as upstream signal transducers activating the MKK3-p38 MAPK signaling cascade that leads to the induction of type I collagen expression by TGF-beta(1). In addition, our findings also suggest that TAK1 has a novel function in regulation of the steady-state protein levels of MKK3 and p38 MAPK.	SIGNOR-42402
Q5S007	P37840	1	phosphorylation	down-regulates activity	0.624	Here we show that full-length Lrrk2 or fragments containing its kinase domain have a significant capacity to phosphorylate recombinant alpha synuclein (Asyn) at serine 129. Such phosphorylated Asyn is the major component of pathological deposits in PD.	SIGNOR-249690

P19438

Q12933

1

null

up-regulates

0.832

We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation

SIGNOR-256251

Q96PM5

Q9UQM7

0

phosphorylation

down-regulates

0.296

Phosphorylation of pirh2 by calmodulin-dependent kinase ii impairs its ability to ubiquitinate p53

SIGNOR-156064

Q96BR1

Q92597

1

phosphorylation

down-regulates activity

0.402

It has been shown that SGK3 phosphorylation of NDRG1 primes for subsequent phosphorylation by GSK-3beta.|Since NDRG1 is a direct SGK substrate, this correlation suggests that SGK3 activation and signaling may modulate NDRG1 degradation.

SIGNOR-279282

P28482

P49841

1

phosphorylation

down-regulates activity

0.383

We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels

SIGNOR-262524

Q9NSE2

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.669

The STAT5 target gene CIS, a member of the suppressor of cytokine signaling (SOCS) protein family, was highly induced by Flt3-ITD

SIGNOR-261544

P29322

O00712

0

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268903

O43561

Q9Y4K3

0

ubiquitination

up-regulates activity

0.345

Interestingly, this study has demonstrated that the membrane-proximal region of linker for activation of T cells preceding tyrosine-132 mediates its association with TRAF6, which promotes the ubiquitination of linker for activation of T cells and, in turn, the phosphorylation of tyrosine residues on linker for activation of T cells.|Moreover, LAT was ubiquitinated at Lysine 88 by TRAF6 via K63 linked chain.

SIGNOR-278675

P12931

O15379

1

phosphorylation

up-regulates activity

0.385

C-Src also phosphorylated three tyrosine sites of HDAC3 at tyrosine 325, 328, and 331. Importantly, wild-type c-Src increases HDAC3 activity, but not mutant c-SrcK298M (kinase inactive form).

SIGNOR-277485

P51451

O15524

1

phosphorylation

down-regulates activity

0.2

These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors.

SIGNOR-277889

P48729

Q9NRF8

1

phosphorylation

down-regulates

0.2

Hctps2 ser(568) was phosphorylated by casein kinase 1 both in vitro and in vivo. Mutation of ser(568) (s568a) significantly increased hctps2 activity, demonstrating that ser(568) is a major inhibitory phosphorylation site.

SIGNOR-167623

Q9UL54

P19419

1

phosphorylation

up-regulates activity

0.31

Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.

SIGNOR-246638

P09237

P10451

1

cleavage

up-regulates activity

0.706

In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.

SIGNOR-253321

P06493

P52948

1

phosphorylation

down-regulates activity

0.397

We show that npc disassembly is a phosphorylation-driven process, dependent on cdk1 activity and supported by members of the nima-related kinase (nek) family. mitotic hyperphosphorylation of nup98 is accomplished by multiple kinases, including cdk1 and neks.

SIGNOR-172217

P00519

Q92918

1

phosphorylation

up-regulates activity

0.379

C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD

SIGNOR-251429

P0DP23

P06213

0

phosphorylation

down-regulates

0.403

The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-24782

P34897

Q9NXA8

0

post translational modification

down-regulates activity

0.235

Mitochondrial serine hydroxymethyl transferase (SHMT2) is a rate-limiting enzyme that catalyzes the catabolism of serine and drives the proliferation of osteosarcoma cells and colon cancer cells. SIRT5 directly mediates the desuccinylation of Lysine 280 on SHMT2. Therefore, SIRT5 is a candidate target to inhibit serine catabolism

SIGNOR-267644

P27361

P37231

1

relocalization

down-regulates activity

0.398

The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform

SIGNOR-179407

P43378

P40763

1

dephosphorylation

down-regulates activity

0.432

Results are presented as mean \u00b1 SD from three independent experiments. (B) PTPMeg2 inhibits STAT3-mediated transcriptional activity in a dose dependent manner.|These results indicate that PTPMeg2 inhibits STAT3 activation with certain specificity.|In this study, we demonstrated that PTPMeg2 dephosphorylates STAT3 at the Tyr705 residue by a direct interaction.

SIGNOR-276976

Q13976

Q9UH03

1

phosphorylation

up-regulates activity

0.2

Mutation of Ser-91 to Ala in recombinant Sept3 also abolished PKG phosphorylation, confirming that Ser-91 is the major site in vitro. Therefore Sept3 is phosphorylated on Ser-91 in nerve terminals and its phosphorylation may contribute to the regulation of its subcellular localization in neurons.

SIGNOR-263183

Q9NYY3

O15350

1

phosphorylation

down-regulates activity

0.275

PLK2 inhibits TAp73 translocation to the nucleus.|PLK2 phosphorylated TAp73 at residue Ser48 within the TA domain; phosphorylation of TAp73 was abolished by mutating this residue.

SIGNOR-278218

P04155

O00170

0

transcriptional regulation

down-regulates quantity by repression

0.2

We show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells.

SIGNOR-259911

O75592

P62826

1

guanine nucleotide exchange factor

up-regulates activity

0.296

MYCBP2 Is a Nuclear GEF for Ran in DRG Neurons—Next, we studied whether or not MYCBP2 modulates the interaction between Ran/RanGAP1. MYCBP2 contains an N-terminal RCC1-like domain (Fig. 8C) (13), and RCC1 is a known GEF for Ran, indicating a potential functional interaction between MYCBP2 and Ran.

SIGNOR-261204

Q15398

Q9Y566

1

relocalization

up-regulates activity

0.448

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264598

Q9UKV3

P42574

0

cleavage

up-regulates

0.628

Induces apoptotic chromatin condensation after activation by casp3

SIGNOR-70800

Q9UHD2

Q9BRV8

1

phosphorylation

down-regulates quantity

0.718

Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity.

SIGNOR-280152

P55957

P19784

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-250978

Q9UJY1

P27361

0

phosphorylation

up-regulates activity

0.34

Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation

SIGNOR-107680

P48730

P30291

1

phosphorylation

down-regulates quantity by destabilization

0.308

Casein kinase 1-mediated N-terminal Weee1 phosphorylation is required for interaction with the F-box protein β-TrCP.MS/MS spectra of human Wee1 identifying serine 212 as phosphorylated after incubation with recombinant CK1δ.

SIGNOR-276631

Q8TDY4

P00533

0

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

P16870

P01178-PRO_0000020495

1

cleavage

up-regulates activity

0.2

First, OT preprohormone is produced, that will be cleaved and matured by successive enzymes. The OT gene encodes for the Pre-Pro-OT-Neurophysin I (pre-pro-hormone), which is cleaved by different enzymes to give rise to different OT intermediate forms and to the Neurophysin I, and finally to the mature amidated form that is released (Figure 2).

SIGNOR-270338

P34947

P30989

1

phosphorylation

up-regulates activity

0.594

Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively.

SIGNOR-278234

P07355

P07947

0

phosphorylation

up-regulates activity

0.2

Activated YES1 interacts with ANXA2 andphosphorylates ANXA2 at Tyr24 site that induces ANXA2 activation and increases ANXA2 nuclear distribution , leading to activation of the tumorpromoting transcription factors ( such as Myc , Stat3 , Stat6 ) that promotes GC invasion and metastasis .|YES1 phosphorylates ANXA2 at Tyr24 site that leads to ANXA2 activation and increased ANXA2 nuclear distribution.

SIGNOR-279435

P07332

P40763

1

phosphorylation

up-regulates activity

0.402

Fes also induced Tyr 705 phosphorylation and DNA binding activity of STAT3, in agreement with the idea that Fes can regulate transcriptional activation through Fes dependent phosphorylation of transcription factors.On the basis of these findings, we propose that Fes activation of critical transcriptional regulators such as PU.1 is part of the mechanism by which this kinase induces macrophage differentiation of myeloid progenitors.|We conclude that Fes may regulate granulocytic differentiation at least in part through activation of C/EBP-alpha and STAT3.In 32D cells, Fes activated STAT3 and C/EBP-alpha, two important regulators of granulocytic differentiation [14,15].

SIGNOR-278937

P09874

P42574

0

cleavage

down-regulates activity

0.775

Caspase-3 cleaves parp-1. During cd95-mediated apoptosis proteolytic inactivation of parp-1 by caspases prevents atp depletion and thereby ensures the execution of the apoptotic process

SIGNOR-116178

P05067

P07339

0

cleavage

down-regulates quantity by destabilization

0.489

The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism.

SIGNOR-261767

P35659

P68400

0

phosphorylation

up-regulates

0.35

Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32

SIGNOR-125912

Q9Y314

P19235

1

ubiquitination

up-regulates activity

0.331

Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation. This receptor-associated ubiquitin ligase, RUL, co-precipitated with EpoR from mammalian cells and mediated ubiquitination of EpoR. RUL mediates EpoR ubiquitination in COS7 cells and is inducibly ubiquitinated after Epo treatment. This observation is consistent with the lack of effects on EpoR stability by RUL-mediated ubiquitination in COS7 cells (Fig. 4).

SIGNOR-271477

P09619

P34947

1

phosphorylation

up-regulates activity

0.2

Purified GRK5 was tyrosine-phosphorylated by the wild-type PDGFRbeta to a stoichiometry of 0.8 mol phosphate/mol GRK5, an extent approximately 5 times greater than observed with a Y857F PDGFRbeta mutant that fails to phosphorylate exogenous substrates but autophosphorylates and activates Src normally.|We conclude that GRK5 tyrosyl phosphorylation is required for the activation of GRK5 by the PDGFRbeta, but not by the beta(2)-adrenergic receptor, and that by activating GRK5, the PDGFRbeta triggers its own desensitization.

SIGNOR-279642

O43566

P17612

0

phosphorylation

up-regulates activity

0.338

RGS14 is phosphorylated in vitro at Ser258 and Thr494 by PKA. cAMP-induced phosphorylation as an important modulator of RGS14 function since phosphorylation could enhance RGS14 binding to Galpha(i)-GDP

SIGNOR-250045

Q14721

O95292

1

relocalization

up-regulates quantity

0.2

Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.

SIGNOR-262121

Q8IXQ9

P38117

1

methylation

down-regulates activity

0.2

Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.

SIGNOR-269450

P55210

P49810

1

cleavage

up-regulates activity

0.318

In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.

SIGNOR-261751

P11387

P17252

0

phosphorylation

up-regulates activity

0.2

In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.

SIGNOR-276154

Q8WUI4

P62714

0

dephosphorylation

up-regulates activity

0.2

Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. |Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs.

SIGNOR-248605

Q9Y6K9

Q13315

0

phosphorylation

down-regulates activity

0.739

Atm phosphorylates serine-85 of nemo to promote its ubiquitin-dependent nuclear export.

SIGNOR-144813

O94953

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.261

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

SIGNOR-271569

P14921

Q9UKX5

1

null

up-regulates quantity by expression

0.281

We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.

SIGNOR-253352

P67775

P27707

1

dephosphorylation

down-regulates activity

0.2

Protein phosphatase 2A regulates deoxycytidine kinase activity via Ser-74 dephosphorylation|Deoxycytidine kinase (dCK) is a critical enzyme for activation of anticancer nucleoside analogs. Its activity is controlled via Ser-74 phosphorylation. Here, we investigated which Ser/Thr phosphatase dephosphorylates Ser-74. In cells, the PP1/PP2A inhibitor okadaic acid increased both dCK activity and Ser-74 phosphorylation

SIGNOR-275803

Q13555

P42224

1

phosphorylation

up-regulates activity

0.507

For maximal gene activation, S727 in the transcription activation domain of Stat1 also is inducibly phosphorylated by IFN-gamma. We previously purified a group of nuclear proteins that interact specifically with the Stat1 transcription activation domain. In this report, we identified one of them as the multifunctional Ca(2+)/calmodulin-dependent kinase (CaMK) II. We demonstrate that IFN-gamma mobilizes a Ca(2+) flux in cells and activates CaMKII. CaMKII can interact directly with Stat1 and phosphorylate Stat1 on S727 in vitro. Inhibition of Ca(2+) flux or CaMKII results in a lack of S727 phosphorylation and Stat1-dependent gene activation, suggesting in vivo phosphorylation of Stat1 S727 by CaMKII.

SIGNOR-250706

P39880

P06493

0

phosphorylation

down-regulates

0.357

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

SIGNOR-110912

P53350

Q99640

1

phosphorylation

down-regulates activity

0.721

Here, we have shown that Plk1 is responsible for part of the phosphorylation of Myt1 during M phase. The kinase activity of human Myt1 is reported to be decreased during M phase, and the decreased activity correlates with hyperphosphorylated forms of Myt1 (35, 37). We then tested the ability of these mutant forms of Myt1 (GST fusion proteins), to serve as a substrate for Plk1 in vitro. Quantification of the result (Fig. 5C) showed that Ser-426 is the major phosphorylation site by Plk1 in vitro and Thr-495 the second major site.

SIGNOR-263096

P36873

Q9BYX4

1

dephosphorylation

up-regulates activity

0.247

Exogenous PP1alpha or PP1gamma substantially decreased the S88 phosphorylation of Flag-MDA5|we identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.

SIGNOR-264579

P27361

Q16690

0

dephosphorylation

down-regulates

0.76

Extracellular regulated kinases (erk) 1 and erk2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase vhr. A novel role in down-regulating the erk pathway

SIGNOR-67358

O14974

Q9H093

0

phosphorylation

down-regulates activity

0.466

NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).

SIGNOR-279081

Q15796

Q9H6Z4

0

relocalization

down-regulates activity

0.436

RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner.

SIGNOR-217634

P08908

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.27

Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT 1A receptor via phosphorylation|5-HT1AR was phosphorylated by the Cdk5-p35 complex at Thr314 in the third cytoplasmic loop.

SIGNOR-264406

Q9Y4K3

Q9GZQ8

1

polyubiquitination

down-regulates quantity by destabilization

0.295

TRAF6 catalyzes K63-linked polyubiquitination of LC3B and promotes the formation of the LC3B-ATG7 and LC3B-CTNNB1 complexes.

SIGNOR-277439

P14598

Q05513

0

phosphorylation

up-regulates

0.394

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89280

Q9UBK2

Q6NUN9

0

transcriptional regulation

up-regulates quantity by expression

0.445

PARIS represses the expression of the transcriptional coactivator, PGC-1α and the PGC-1α target gene, NRF-1 by binding to insulin response sequences in the PGC-1α promoter.

SIGNOR-277627

P29597

P42224

1

phosphorylation

up-regulates activity

0.775

Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701Phosphorylation of purified Stat1 was necessary and sufficient for the acquisition of DNA binding activity.

SIGNOR-246943

P48729

Q8TB45

1

phosphorylation

down-regulates

0.2

Phosphorylation of all three serine residues in the deptor degron (ser286, ser287, and ser291) is necessary for - and directly mediates - the interaction with _trcp. ck1 phosphorylated the degron of deptor, as shown by western blotting with the phospho-specific antibody (fig. S3e-f). In contrast, mtor alone was unable to induce phosphorylation of deptor on ser286, ser287, and ser291.

SIGNOR-176871

P13569

P17612

0

phosphorylation

up-regulates

0.485

Cftr, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to camp agonists. Serines 660, 737, 795, and 813 were identified as in vivo targets for phosphorylation by protein kinase a.mutagenesis of all four sites abolished the response.

SIGNOR-21312

P29376

P22681

1

phosphorylation

up-regulates

0.369

Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.

SIGNOR-49528

Q9H9S0

P26358

1

transcriptional regulation

up-regulates quantity by expression

0.432

Oct4 and Nanog upregulate Dnmt1 through direct binding to its promoter, thereby leading to the repressed expression of p16 and p21 and genes associated with development and lineage differentiation

SIGNOR-253157

O60610

O14757

0

phosphorylation

down-regulates activity

0.2

Chk1 Phosphorylates Drf1 for beta-Trcp-Dependent Degradation.|From this we conclude that Chk1 inhibits Drf1, but not the other three limiting factors at the MBT.

SIGNOR-279026

Q13237

P09619

1

phosphorylation

down-regulates activity

0.272

Secretory PKG II inhibited PDGF‐BB ‐induced PDGFRβ activation via phosphorylating its Ser254.

SIGNOR-277577

P51451

P16885

1

phosphorylation

up-regulates activity

0.557

Lyn, Syk, Btk, and Blk can also phosphorylate and enhance the activation of phospholipase C gamma 2 (PLCgamma2), which hydrolyzes PI (4,5) P2 to create inositol 3,4,5-trisphosphate (IP3) and diacylglycerol (DAG), stimulating Ca 2+ mobilization and protein kinase C (PKC), respectively.

SIGNOR-280195

P31749

Q99490

1

phosphorylation

up-regulates

0.497

In addition, we have found that activated akt can bind and phosphorylate ggap2 at serine 629, which enhances gtp binding by ggap2.

SIGNOR-183543

Q9UPX8

Q15398

0

relocalization

up-regulates activity

0.452

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264599

P40337

P12931

0

phosphorylation

down-regulates quantity by destabilization

0.29

We have found that elevated Src can trigger a drastic reduction in VHL stability even under normoxic conditions, through phosphorylation of VHL tyrosine residue 185, leading to ubiquitination and proteasome mediated degradation of VHL.

SIGNOR-279125

P41252

P18848

0

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-269427

Q8IYW5

P54132

1

ubiquitination

up-regulates activity

0.262

Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80.

SIGNOR-272114

P27361

P10242

1

phosphorylation

down-regulates

0.301

Functional analysis of phosphorylation at serine 532 of human c-myb by map kinase. expression of a polypeptide containing the c-myb c-terminal domain stimulated c-myb activity. This effect is reduced upon mapk-dependent phosphorylation of serine 532. Our data suggest that the mapk-dependent state of phosphorylation modifies the cellular function of c-myb by modulating its interaction with a putative inhibitory factor

SIGNOR-45348

Q96PG8

P04626

0

phosphorylation

down-regulates activity

0.281

These results show for the first time that PUMA can be phosphorylated at tyrosine residues directly by HER2.|Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein.

SIGNOR-278224

Q16143

Q9NYY3

0

phosphorylation

down-regulates activity

0.248

Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.

SIGNOR-189049

P00451

P00734

0

cleavage

up-regulates activity

0.755

Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689.

SIGNOR-263640

O75943

Q13535

0

phosphorylation

up-regulates activity

0.858

Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival.

SIGNOR-111248

Q05086

P35998

1

ubiquitination

down-regulates quantity by destabilization

0.385

Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.

SIGNOR-265132

P19622

P55075

1

transcriptional regulation

down-regulates quantity by repression

0.416

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.

SIGNOR-265801

O15530

Q96BR1

1

phosphorylation

up-regulates

0.461

Full-length sgk3 contains a complete phox homology (px) domain that targets the protein to endosomes. Both a functional px domain and pi3k activation are necessary for phosphorylation of sgk3 at two regulatory sites (thr-320 and ser-486) and subsequent induction of kinase activity. Pdk1 phosphorylates endosome-associated sgk3 at thr-320

SIGNOR-147213

Q08050

Q14680

0

phosphorylation

up-regulates activity

0.501

MELK Activates FOXM1 Transcriptional Activity Leading to Upregulation of Mitotic Gene Expression.|The autoradiogram clearly shows in vitro phosphorylation of FOXM1 by MELK and CDK2 and cyclinA.

SIGNOR-278412

P04637

Q86XK2

0

neddylation

down-regulates

0.671

Fbxo11 promotes the neddylation of p53 and inhibits its transcriptional activity / we found that fbxo11 also neddylates p53 on two lysines, lys-320 and lys-321

SIGNOR-150669

Q13115

P45983

1

dephosphorylation

down-regulates

0.714

Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2

SIGNOR-27756

Q96EQ8

O95786

1

polyubiquitination

down-regulates quantity by destabilization

0.671

Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.

SIGNOR-271647

P68036

O60260

1

ubiquitination

up-regulates activity

0.2

Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1).

SIGNOR-272734

P06493

Q02750

1

phosphorylation

down-regulates

0.496

P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well

SIGNOR-36116

Q7Z3C6

P12931

0

phosphorylation

up-regulates activity

0.342

Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.

SIGNOR-266367

P68400

O75925

1

phosphorylation

up-regulates

0.332

Ck2 phosphorylates serine residues adjacent to the sim of pias1 these findings show that the phosphosim module mediates binding to free sumo and sumo conjugates in a phosphorylation-dependent mode, with ck2 being the critical kinase involvedin this process.

SIGNOR-184047

O43264

Q13561

1

relocalization

up-regulates activity

0.685

ZW10 interacts with dynamitin, a subunit of the dynein-dynactin complex (Echeverri et al., 1996), thereby recruiting this motor to kinetochores

SIGNOR-265016

P09769

Q04760

1

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276188

Q14118

P12931

0

phosphorylation

down-regulates

0.55

Tyrosine 892 is now thought to be the principal site for recognition by the c-src tyrosine kinase;. We show that upon tyrosine phosphorylation, beta-dystroglycan undergoes a profound change in its sub-cellular localization (e.g., from the plasma membrane to an internal membrane compartment). One possibility is that the net negative charge at position 892 causes the redistribution of beta-dystroglycan to this intracellular vesicular location

SIGNOR-101655

O15111

Q5TCX8

0

phosphorylation

down-regulates activity

0.2

Immunoprecipitation and in vitro kinase analysis revealed that MLK4 physically interacts with both IKKalpha and beta, but preferentially phosphorylates IKKalpha over IKKbeta (XREF_FIG

SIGNOR-279067

P06493

P50548

1

phosphorylation

down-regulates

0.2

Consistent with the in vivo phosphorylation and inactivation by ras, erf is efficiently phosphorylated in vitro by erk2 and cdc2/cyclin b kinases, at sites similar to those detected in vivo. Furthermore, a single mutation at position 526 results in the loss of a specific phosphopeptide both in in vivo and in vitro (by erk2) labeling. Substitution of thr526 for glutamic acid also decreases the repression ability of erf

SIGNOR-29501

Q96GD4

P14136

1

phosphorylation

down-regulates activity

0.438

We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by aurora-b;thr-7/ser-13/ser-38 of gfap, and thr-16 of desmin are common with those related to rho-associated kinase (rho-kinase), which has been reported to phosphorylate gfap and desmin at cleavage furrow during cytokinesis. We identified ser-59 of desmin to be a specific site phosphorylated by aurora-b in vitro.

SIGNOR-100173

Q9C035

P19474

0

monoubiquitination

up-regulates quantity

0.344

Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm.

SIGNOR-271672

O43164

P13861

1

polyubiquitination

down-regulates quantity by destabilization

0.328

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271856

Q9Y4C1

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.415

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

SIGNOR-271568

Q13464

P15311

1

phosphorylation

up-regulates

0.732

Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. We performed an in vitro kinase assay with 80 selected kinases on an ezrin peptide containing the t567 phosphorylation site (figure 3a). In this screen, we identified the mst and rock kinases as the most potent kinases for the ezrin peptide

SIGNOR-185567

O43318

P46734

1

phosphorylation

up-regulates activity

0.505

Taken together, our data indicate that TAK1 and TAB1 play a pivotal role as upstream signal transducers activating the MKK3-p38 MAPK signaling cascade that leads to the induction of type I collagen expression by TGF-beta(1). In addition, our findings also suggest that TAK1 has a novel function in regulation of the steady-state protein levels of MKK3 and p38 MAPK.

SIGNOR-42402

Q5S007

P37840

1

phosphorylation

down-regulates activity

0.624

Here we show that full-length Lrrk2 or fragments containing its kinase domain have a significant capacity to phosphorylate recombinant alpha synuclein (Asyn) at serine 129. Such phosphorylated Asyn is the major component of pathological deposits in PD.

SIGNOR-249690