GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q04760	P09769	0	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
P31327	Q9NXA8	0	post translational modification	up-regulates activity	0.508	Glutarylation suppresses CPS1 activity, which is targeted by SIRT5 for removal\|SIRT5 can catalyze the enzymatic removal of lysine glutarylation	SIGNOR-267643
P30556	P29992	2	binding	up-regulates activity	0.512	The angiotensin II type 1 receptor (AT1 R) is a G q/11-coupled G protein-coupled receptor that is widely expressed in multiple tissues, including vascular smooth muscle cells, brain, and kidney.	SIGNOR-278125
P00519	P04629	2	binding	up-regulates	0.536	Autophosphorylated trka binds directly to plc?, Abl, and shc.	SIGNOR-75402
P35637	O00571	1	relocalization	down-regulates activity	0.256	We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.\|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. \| We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons	SIGNOR-262811
P62979	Q93008	0	cleavage	up-regulates quantity	0.504	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270826
Q6ZUJ8	P27986	2	binding	up-regulates	0.626	Bcap is constitutively phosphorylated and associated with the p85 subunit of pi3k in macrophages. Tlr signaling causes the phosphorylation of the small amount of bcap that is associated with membranes in the resting state or the translocation of phosphorylated bcap from the cytoplasm to the membrane. This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Bcap is an essential activator of the pi3k pathway downstream of tlr signaling	SIGNOR-191673
Q86TM6	P04035	1	polyubiquitination	down-regulates quantity by destabilization	0.562	In the presence of the ubiquitin-conjugating enzyme UBC7, the RING-H2 finger has in vitro ubiquitination activity for Lys(48)-specific polyubiquitin linkage, suggesting that human HRD1 is an E3 ubiquitin ligase involved in protein degradation.Human HRD1 appears to be involved in the basal degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase but not in the degradation that is regulated by sterols.	SIGNOR-272594
Q12968	P45983	0	phosphorylation	down-regulates	0.837	Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin	SIGNOR-118220
P62987	P15374	0	cleavage	up-regulates quantity	0.801	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270827
Q9BZL6	Q9BZL6	2	phosphorylation	up-regulates	0.2	The addition of phorbol 12,13-dibutyrate in the presence of dioleoylphosphatidylserine stimulated the autophosphorylation of pkd2 in a synergistic fashion.In addition, we could identify the c-terminal ser(876) residue as an in vivo phosphorylation site within pkd2. Phosphorylation of ser(876) of pkd2 correlated with the activation status of the kinase.	SIGNOR-83834
P17661	P23409	0	transcriptional regulation	up-regulates quantity by expression	0.242	Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression	SIGNOR-241497
P18031	O75886	1	dephosphorylation	up-regulates quantity by stabilization	0.472	Together, the results presented here demonstrate that PTP1B can influence RTK signaling in a previously unrecognized manner. We show that PTP1B directly targets STAM2, part of the ESCRT-0 endosomal sorting complex, and we provide the first evidence that tyrosine phosphorylation affects STAM localization and function. This regulatory mechanism could impact signaling downstream of numerous cell surface receptors that are ubiquitinated and recognized by this conserved sorting machinery.	SIGNOR-248406
Q9NWZ3	P14598	1	phosphorylation	up-regulates	0.38	Phosphorylation of the cytosolic factor p47phox is essential for activation of the nadph oxidase.We found that thr133, ser288 and thr356, targets for irak-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after lps stimulation. We conclude that irak-4 phosphorylates p47phox and regulates nadph oxidase activation after lps stimulation.	SIGNOR-152027
P42229	Q9P1W9	1	transcriptional regulation	up-regulates quantity by expression	0.41	The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.	SIGNOR-249622
P35222	Q9H251	2	binding	up-regulates activity	0.288	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265861
Q13131	P22460	1	phosphorylation	down-regulates activity	0.2	Thus, AMPK directly phosphorylates the  subunit of KV1.5 at Ser592 and, to a lesser extent, at Ser560	SIGNOR-277814
A6ND36	Q15139	0	phosphorylation	up-regulates activity	0.2	Taken together, these data demonstrate that FAM83G S356 phosphorylation modulates HSP27 phosphorylation and apoptosis regulation and that HSP27 is a counterpart of FAM83G.\|an active form of PKD1/PKCm could phosphorylate the FAM83G peptide, including the S356 portion.\|We also demonstrated that the phosphorylation of the FAM83G S356 residue was required for the reduction of the live cell number, as the CHO cells were unaffected upon the overexpression of a FAM83G S356A mutant resistant to S356 phosphorylation.	SIGNOR-264764
Q9Y6K1	Q03112	2	binding	up-regulates activity	0.293	The oncoprotein EVI1 and the DNA methyltransferase Dnmt3 co-operate in binding and de novo methylation of target DNA\|Here we show that EVI1 physically interacts with DNA methyltransferases 3a and 3b (Dnmt3a/b), which are the only de novo DNA methyltransferases identified to date in mouse and man, and that it forms an enzymatically active protein complex that induces de novo DNA methylation in vitro.	SIGNOR-273432
P02818	P38435	0	carboxylation	up-regulates activity	0.687	Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation.	SIGNOR-265922
Q13064	P11940	1	ubiquitination	down-regulates activity	0.2	MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA\|Altogether, it is thus clear that the ubiquitination of PABPC1 or PABPC4 by MKRN3 negatively regulates the formation of translation initiation complex (TIC), attenuates their binding to poly (A)-tail contained mRNAs, and leads to the shortened poly (A) tail-length of GNRH1 mRNA.	SIGNOR-278764
P45985	Q99683	0	phosphorylation	up-regulates activity	0.631	A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)	SIGNOR-45373
Q02156	Q92993	1	phosphorylation	up-regulates activity	0.365	At least two TIP60 residues, Thr298 and Ser300, can be targeted in vitro by PKCepsilon.\|In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain.	SIGNOR-279309
P15498	P62993	2	binding	up-regulates	0.686	Recently, we have shown that the proto-oncogene vav product (vav) is also tyrosine-phosphorylated by treatment with gm-csf and epo and is constitutively associated with the sh3 domain of grb2/ash in ut-7.	SIGNOR-49362
Q13153	Q92974	1	phosphorylation	down-regulates	0.353	We identify gef-h1 as a binding target and substrate for p21-activated kinase 1 (pak1), we show that phosphorylation of gef-h1 at ser(885) by pak1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules.	SIGNOR-187573
O95551	Q9Y4K3	2	binding	up-regulates activity	0.378	TTRAP associates with TRAF6.The TAK1-TTRAP-TRAF6 complex is stabilized by ubiquitylation and recruited to TβRI.	SIGNOR-277189
Q8TAB3	Q16445	2	binding	up-regulates quantity by stabilization	0.2	Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.	SIGNOR-267221
P32243	Q9Y261	2	binding	down-regulates activity	0.548	Here we show that OTX2 directly associates with LIM1 and HNF-3beta. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression.	SIGNOR-221164
O43318	Q9BXM7	0	phosphorylation	up-regulates activity	0.33	PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1.	SIGNOR-279644
Q9Y566	Q06787	0	post transcriptional regulation	up-regulates quantity	0.4	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.	SIGNOR-262109
P04004	P05129	0	phosphorylation	up-regulates quantity by stabilization	0.285	Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.	SIGNOR-248964
O15519	Q96J02	0	ubiquitination	down-regulates quantity	0.614	Depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, which specifically ubiquitinates c-FLIP and induces its proteasomal degradation.	SIGNOR-245307
Q9Y4D1	P54792	2	binding	up-regulates	0.2	Importantly, daam1 binds to disheveled (dvl) and thus functions downstream of the frizzled receptors. Little is known of how daam1 is localized and functions in mammalian cells.	SIGNOR-199451
Q86YT6	Q9NYJ7	1	ubiquitination	up-regulates activity	0.35	Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.	SIGNOR-209672
Q8IWA4	Q9NX47	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH5, a mitochondrial E3 ubiquitin ligase, has been identified as a molecule that binds mitochondrial fission 1 protein (hFis1), dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2), key proteins in the control of mitochondrial fission and fusion.\|Notably, a significant increase in Mfn1 level, but not Mfn2, Drp1 or hFis1 levels, was observed in MARCH5-depleted cells, indicating that Mfn1 is a major ubiquitylation substrate.	SIGNOR-274133
P45983	P63104	1	phosphorylation	down-regulates	0.371	Jnk phosphorylated 14-3-3 at ser-184 and 14-3-3 at ser-186 both in vitro and in vivo, and such phosphorylation reduced the affinity of 14-3-3 proteins for bax	SIGNOR-124020
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
P53355	Q14457	1	phosphorylation	up-regulates	0.727	The activated form of DAPK triggers autophagy in a beclin-1-dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl-XL and the induction of autophagy.	SIGNOR-183548
P36382	P17612	0	phosphorylation	up-regulates activity	0.307	Gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation. Macroscopic conductance and permeability of Cx40 gap junctions is strongly increased by cAMP. two serine residues that can be phosphorylated by PKA, S120 and S345	SIGNOR-249982
P42336	P35568	2	binding	up-regulates activity	0.722	Irs proteins are capable of both regulating and activating pi3k, depending on the cell of origin.	SIGNOR-168985
Q9UNE7	Q9UPR3	1	polyubiquitination	down-regulates quantity by destabilization	0.398	Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B.	SIGNOR-272649
Q86XK2	Q9NZJ0	2	binding	down-regulates	0.544	We determined that the f-box protein fbxo11 interacts with cdt2,a dcaf protein that controls cell-cycle progression, and recruits cdt2 to the scf(fbxo11)complex to promote its proteasomal degradation.	SIGNOR-192325
P35222	P31751	0	phosphorylation	up-regulates	0.57	Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activitywe have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.	SIGNOR-152958
Q8N6I1	P84022	2	binding	down-regulates	0.397	In this study, we examined the effect of eid-2 on smad-mediated tgf- signaling. Here, we show that eid-2 inhibits tgf- /smad transcriptional responses. Eid-2 interacts constitutively with smad proteins, and most strongly with smad3.	SIGNOR-119171
O95631	O95185	2	binding	up-regulates	0.832	We provide evidence that netrin-1 triggers the formation of a receptor complex of dcc and unc5 proteins and simultaneously derepresses the interaction between their cytoplasmic domains, thereby converting dcc-mediated attraction to unc5/dcc-mediated repulsion.	SIGNOR-69047
Q13177	P01236	1	phosphorylation	up-regulates	0.337	Phosphorylated form of prolactin has a higher affinity for heparin.	SIGNOR-186211
O00418	O00418	2	phosphorylation	down-regulates	0.2	The combination of eef2k autophosphorylation (targeting ser445) and a yet to be identified kinase (targeting ser441) would be needed to generate the eef2k phosphodegron specifically in response to dna damage.	SIGNOR-197725
P31749	P99999	1	phosphorylation	down-regulates activity	0.465	Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.	SIGNOR-277237
Q00535	P26358	1	phosphorylation	up-regulates	0.358	We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5	SIGNOR-173685
Q08050	P24941	0	phosphorylation	up-regulates activity	0.75	We demonstrated that FoxM1B transcriptional activity requires binding of either S-phase or M-phase Cdk-cyclin complexes to mediate efficient Cdk phosphorylation of the FoxM1B Thr 596 residue, which is essential for recruitment of p300/CBP coactivator proteins.	SIGNOR-250731
P12931	P04629	1	phosphorylation	up-regulates activity	0.292	Direct phosphorylation of TrkA by Src family kinases has been demonstrated in vitro, and our studies suggest that Src may lead to selective activation of TrkA.	SIGNOR-279291
P84243	Q9H3R0	0	demethylation	down-regulates activity	0.2	As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation	SIGNOR-263869
Q12967	Q13671	2	binding	up-regulates activity	0.497	Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.	SIGNOR-220923
P62993	Q07889	1	relocalization	up-regulates activity	0.912	Interaction domains of sos1/grb2 are finely tuned for cooperative control of embryonic stem cell fate.	SIGNOR-235773
P12931	Q99961	1	phosphorylation	down-regulates	0.639	Further, we identified an interaction between fak's second pro-rich motif and endophilin a2's sh3 domain. This interaction served as an autophosphorylation-dependent scaffold to allow src phosphorylation of endophilin a2 at tyr315. Tyr315 phosphorylation inhibited endophilin/dynamin interactions, and blockade of tyr315 phosphorylation promoted endocytosis of mt1-mmp. Together, these results suggest a regulatory mechanism of cell invasion whereby fak promotes cell-surface presentation of mt1-mmp by inhibiting endophilin a2-dependent endocytosis.	SIGNOR-139150
Q14192	P61586	0	relocalization	up-regulates	0.348	Here, we show that stimulation of the rho pathway induces translocation of the transcriptional lim-only coactivator fhl2 to the nucleus and subsequent activation of fhl2- and androgen receptor-dependent genes.	SIGNOR-114071
Q9UK99	Q9UKC9	2	binding	down-regulates quantity by destabilization	0.549	F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.	SIGNOR-272445
A8MYZ6	P48729	0	phosphorylation	down-regulates	0.2	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.	SIGNOR-183667
Q9P2Y5	Q8NEB9	2	binding	up-regulates activity	0.809	Although both human atg14 and uvrag interact with beclin 1 and vps34.	SIGNOR-181554
P17948	P63096	1	phosphorylation	up-regulates activity	0.257	RTKs directly phosphorylate Gαi on Y154, 155, and Y320.	SIGNOR-277230
P12931	Q13761	1	phosphorylation	down-regulates activity	0.58	In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.\|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases.	SIGNOR-278199
P62993	P08581	2	binding	up-regulates activity	0.695	For activation of the mitogen-activated protein kinase (MAPK) cascades, c-MET activation stimulates the activity of the rat sarcoma viral oncogene homolog (RAS) guanine nucleotide exchanger son of sevenless (SOS) via binding with SHC and GRB2 leading to the activation of RAS.	SIGNOR-256261
Q13131	Q9NR19	1	phosphorylation	up-regulates activity	0.275	This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding. In the nucleus, ACSS2 forms a complex with TFEB (transcription factor EB) and utilizes the acetate generated from histone deacetylation to locally produce acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes.	SIGNOR-271822
Q02763	P27986	2	binding	up-regulates activity	0.538	Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival	SIGNOR-242634
P63279	Q92985	1	sumoylation	down-regulates activity	0.287	One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. we identified that IRF7 is sumoylated at lysine 452.	SIGNOR-266837
O14807	Q9UQ13	2	binding	up-regulates	0.69	Sur-8 interacts with ras and raf and is able to form a ternary complex with the two proteins. Thus, sur-8 may function as a scaffold that enhances ras-map kinase signal transduction by facilitating the interaction between ras and raf.	SIGNOR-77082
Q15052	Q8TDY4	2	binding	up-regulates activity	0.294	ArfGAP With Coiled-Coil, Ankyrin Repeat And PH Domains 4 (ACAP4) is an ADP-ribosylation factor 6 (ARF6) GTPase-activating protein essential for EGF-elicited cell migration. \|The crystal structure of the catalytic core of ACAP4 in a complex with ARF6 reveals the structural determinants underlying ACAP4 selectivity and specificity as an ARF6 GTPase-activating protein	SIGNOR-272235
Q96FW1	P61088	2	binding	down-regulates	0.704	The deubiquitinating enzyme otub1 suppresses rnf168 dependent ubiquitination by direct the e2 ligase ubc13	SIGNOR-175050
P54764	P52797	2	binding	up-regulates	0.826	Eph receptors are activated by their ligands, which are membrane-anchored molecules	SIGNOR-52315
P08047	P68400	0	phosphorylation	down-regulates activity	0.34	Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. \| Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding.	SIGNOR-250954
Q12888	Q13315	0	phosphorylation	up-regulates	0.873	Here we report phosphorylation of 53bp1 at several novel residues, using mass spectrometry and phospho-specific antibodies, and show that ionising radiation-stimulated phosphorylation of these residues requires atm.	SIGNOR-197615
Q96GD4	Q9UJP4	2	binding	up-regulates activity	0.507	KLHL21 directly binds to Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate Aurora B during mitosis, possibly by ubiquitinating different pools of Aurora B at distinct subcellular localizations.	SIGNOR-271848
P42574	P49810	1	cleavage	up-regulates activity	0.405	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261743
P17612	P24588	0	relocalization	up-regulates activity	0.561	In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150	SIGNOR-261292
C9JLW8	P27361	0	phosphorylation	down-regulates activity	0.2	When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.\| While substitution of S4 or S18 with Ala did not affect the phosphorylation of MCRIP1 by ERK, substitution of either S21 or T30 significantly reduced MCRIP1 phosphorylation	SIGNOR-264772
O14733	O43283	0	phosphorylation	up-regulates	0.584	Lzk directly phosphorylated and activated mkk7.	SIGNOR-112349
Q96EB6	Q04206	1	deacetylation	down-regulates activity	0.722	SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310.	SIGNOR-238817
P68400	Q9UGP8	1	phosphorylation	up-regulates activity	0.291	Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.	SIGNOR-265267
Q7Z6Z7	O43474	1	ubiquitination	down-regulates quantity by destabilization	0.34	K48 linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.\|Instead, we identified the transcription factor KLF4 as a novel Mule substrate that is ubiquitinated by this E3 ligase and thus undergoes proteasomal degradation in T cells.\|Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase.	SIGNOR-278749
P27348	P30307	1	relocalization	down-regulates	0.575	Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins.	SIGNOR-163237
Q01860	P28482	0	phosphorylation	down-regulates	0.38	We demonstrate that oct4a interacts with erk1/2 by using both in vitro gst pulldown and in vivo co-immunoprecipitation assays. Ms analysis identified phosphorylation of oct4a at ser-111. / serine 111 phosphorylation regulates oct4a protein subcellular distribution and degradation.	SIGNOR-192097
P63096	P43115	2	binding	up-regulates activity	0.451	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256716
P07948	P33993	1	phosphorylation	up-regulates activity	0.453	Lyn phosphorylates MCM7 at Y600.\|These evidences suggest that Lyn mediated Y600 phosphorylation may regulate MCM7 function in DNA replication licensing.	SIGNOR-278407
Q03113	Q9HBW0	2	binding	up-regulates	0.491	Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies.	SIGNOR-135834
P07196	P31946	2	binding	down-regulates activity	0.254	These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments.	SIGNOR-252396
P14373	A8K0Z3	1	ubiquitination	up-regulates activity	0.2	Our mechanistic studies uncovered that K63-linked ubiquitination of WASH K220 by MAGE-L2-TRIM27 is required for endosomal F-actin nucleation and retrograde transport. These results suggest that K63-linked ubiquitination of WASH K220 by TRIM27 is required for WASH function in retrograde transport.	SIGNOR-253514
Q9UNE7	Q01860	1	ubiquitination	down-regulates quantity by destabilization	0.303	CHIP overexpression decreased OCT4 stability through proteasomal degradation.\|CHIP E3 ligase ubiquitinates OCT4 at lysine 284.\|These data suggest that CHIP induces OCT4 ubiquitination and degradation.	SIGNOR-278562
O00750	P00533	0	phosphorylation	up-regulates	0.44	The n-terminal region of pi3k-c2beta was found to selectively interact with the egf receptor in vitro, suggesting that it mediates the association of this pi3k with the receptor.	SIGNOR-77195
P50616	P27361	0	phosphorylation	down-regulates	0.352	Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro. Erk catalyzes the phosphorylation more efficiently than jnk	SIGNOR-88728
P63092	P32238	2	binding	up-regulates activity	0.264	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256763
O43521	P28482	0	phosphorylation	down-regulates quantity by destabilization	0.716	In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel	SIGNOR-129874
P60953	Q13153	2	binding	up-regulates activity	0.942	A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.	SIGNOR-248243
P53778	O15297	0	dephosphorylation	down-regulates	0.297	Ppm1d selectively inhibits p38 activation by dephosphorylating thr 180.	SIGNOR-135976
P06493	Q9NTG7	1	phosphorylation	up-regulates activity	0.315	Both SIRT3 T150 and S159 phosphorylated by CDK1 indicates that CDK1-SIRT3 pathway may play a role in the overall mitochondrial protein acetylation involved in mitochondrial homeostasis and apoptosis.	SIGNOR-279395
Q96HP0	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.677	Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton.	SIGNOR-275671
Q96AQ6	P40425	2	binding	down-regulates activity	0.267	This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences.	SIGNOR-273667
P67775	Q13315	1	dephosphorylation	down-regulates activity	0.333	Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro.	SIGNOR-248644
Q00535	P21860	1	phosphorylation	up-regulates activity	0.341	We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival.	SIGNOR-250663
P42684	P42684	2	phosphorylation	up-regulates quantity by stabilization	0.2	The results show that Arg is stabilized in response to 0.1 mM H2O2 by autophosphorylation of Y-261, consistent with involvement of the Arg kinase function in regulating Arg levels. The results further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly confers Arg stabilization.. These findings indicate that abrogation of the Arg kinase function by the Y261F mutation is dependent on phosphorylation of the Y-439 site.	SIGNOR-276033
Q13698	P67870	0	phosphorylation	up-regulates activity	0.2	To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.	SIGNOR-263115

Q04760

P09769

0

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

P31327

Q9NXA8

0

post translational modification

up-regulates activity

0.508

Glutarylation suppresses CPS1 activity, which is targeted by SIRT5 for removal|SIRT5 can catalyze the enzymatic removal of lysine glutarylation

SIGNOR-267643

P30556

P29992

2

binding

up-regulates activity

0.512

The angiotensin II type 1 receptor (AT1 R) is a G q/11-coupled G protein-coupled receptor that is widely expressed in multiple tissues, including vascular smooth muscle cells, brain, and kidney.

SIGNOR-278125

P00519

P04629

2

binding

up-regulates

0.536

Autophosphorylated trka binds directly to plc?, Abl, and shc.

SIGNOR-75402

P35637

O00571

1

relocalization

down-regulates activity

0.256

We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons

SIGNOR-262811

P62979

Q93008

0

cleavage

up-regulates quantity

0.504

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270826

Q6ZUJ8

P27986

2

binding

up-regulates

0.626

Bcap is constitutively phosphorylated and associated with the p85 subunit of pi3k in macrophages. Tlr signaling causes the phosphorylation of the small amount of bcap that is associated with membranes in the resting state or the translocation of phosphorylated bcap from the cytoplasm to the membrane. This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Bcap is an essential activator of the pi3k pathway downstream of tlr signaling

SIGNOR-191673

Q86TM6

P04035

1

polyubiquitination

down-regulates quantity by destabilization

0.562

In the presence of the ubiquitin-conjugating enzyme UBC7, the RING-H2 finger has in vitro ubiquitination activity for Lys(48)-specific polyubiquitin linkage, suggesting that human HRD1 is an E3 ubiquitin ligase involved in protein degradation.Human HRD1 appears to be involved in the basal degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase but not in the degradation that is regulated by sterols.

SIGNOR-272594

Q12968

P45983

0

phosphorylation

down-regulates

0.837

Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin

SIGNOR-118220

P62987

P15374

0

cleavage

up-regulates quantity

0.801

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270827

Q9BZL6

2

phosphorylation

up-regulates

0.2

The addition of phorbol 12,13-dibutyrate in the presence of dioleoylphosphatidylserine stimulated the autophosphorylation of pkd2 in a synergistic fashion.In addition, we could identify the c-terminal ser(876) residue as an in vivo phosphorylation site within pkd2. Phosphorylation of ser(876) of pkd2 correlated with the activation status of the kinase.

SIGNOR-83834

P17661

P23409

0

transcriptional regulation

up-regulates quantity by expression

0.242

Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression

SIGNOR-241497

P18031

O75886

1

dephosphorylation

up-regulates quantity by stabilization

0.472

Together, the results presented here demonstrate that PTP1B can influence RTK signaling in a previously unrecognized manner. We show that PTP1B directly targets STAM2, part of the ESCRT-0 endosomal sorting complex, and we provide the first evidence that tyrosine phosphorylation affects STAM localization and function. This regulatory mechanism could impact signaling downstream of numerous cell surface receptors that are ubiquitinated and recognized by this conserved sorting machinery.

SIGNOR-248406

Q9NWZ3

P14598

1

phosphorylation

up-regulates

0.38

Phosphorylation of the cytosolic factor p47phox is essential for activation of the nadph oxidase.We found that thr133, ser288 and thr356, targets for irak-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after lps stimulation. We conclude that irak-4 phosphorylates p47phox and regulates nadph oxidase activation after lps stimulation.

SIGNOR-152027

P42229

Q9P1W9

1

transcriptional regulation

up-regulates quantity by expression

0.41

The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.

SIGNOR-249622

P35222

Q9H251

2

binding

up-regulates activity

0.288

At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin

SIGNOR-265861

Q13131

P22460

1

phosphorylation

down-regulates activity

0.2

Thus, AMPK directly phosphorylates the  subunit of KV1.5 at Ser592 and, to a lesser extent, at Ser560

SIGNOR-277814

A6ND36

Q15139

0

phosphorylation

up-regulates activity

0.2

Taken together, these data demonstrate that FAM83G S356 phosphorylation modulates HSP27 phosphorylation and apoptosis regulation and that HSP27 is a counterpart of FAM83G.|an active form of PKD1/PKCm could phosphorylate the FAM83G peptide, including the S356 portion.|We also demonstrated that the phosphorylation of the FAM83G S356 residue was required for the reduction of the live cell number, as the CHO cells were unaffected upon the overexpression of a FAM83G S356A mutant resistant to S356 phosphorylation.

SIGNOR-264764

Q9Y6K1

Q03112

2

binding

up-regulates activity

0.293

The oncoprotein EVI1 and the DNA methyltransferase Dnmt3 co-operate in binding and de novo methylation of target DNA|Here we show that EVI1 physically interacts with DNA methyltransferases 3a and 3b (Dnmt3a/b), which are the only de novo DNA methyltransferases identified to date in mouse and man, and that it forms an enzymatically active protein complex that induces de novo DNA methylation in vitro.

SIGNOR-273432

P02818

P38435

0

carboxylation

up-regulates activity

0.687

Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation.

SIGNOR-265922

Q13064

P11940

1

ubiquitination

down-regulates activity

0.2

MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA|Altogether, it is thus clear that the ubiquitination of PABPC1 or PABPC4 by MKRN3 negatively regulates the formation of translation initiation complex (TIC), attenuates their binding to poly (A)-tail contained mRNAs, and leads to the shortened poly (A) tail-length of GNRH1 mRNA.

SIGNOR-278764

P45985

Q99683

0

phosphorylation

up-regulates activity

0.631

A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)

SIGNOR-45373

Q02156

Q92993

1

phosphorylation

up-regulates activity

0.365

At least two TIP60 residues, Thr298 and Ser300, can be targeted in vitro by PKCepsilon.|In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain.

SIGNOR-279309

P15498

P62993

2

binding

up-regulates

0.686

Recently, we have shown that the proto-oncogene vav product (vav) is also tyrosine-phosphorylated by treatment with gm-csf and epo and is constitutively associated with the sh3 domain of grb2/ash in ut-7.

SIGNOR-49362

Q13153

Q92974

1

phosphorylation

down-regulates

0.353

We identify gef-h1 as a binding target and substrate for p21-activated kinase 1 (pak1), we show that phosphorylation of gef-h1 at ser(885) by pak1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules.

SIGNOR-187573

O95551

Q9Y4K3

2

binding

up-regulates activity

0.378

TTRAP associates with TRAF6.The TAK1-TTRAP-TRAF6 complex is stabilized by ubiquitylation and recruited to TβRI.

SIGNOR-277189

Q8TAB3

Q16445

2

binding

up-regulates quantity by stabilization

0.2

Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.

SIGNOR-267221

P32243

Q9Y261

2

binding

down-regulates activity

0.548

Here we show that OTX2 directly associates with LIM1 and HNF-3beta. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression.

SIGNOR-221164

O43318

Q9BXM7

0

phosphorylation

up-regulates activity

0.33

PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1.

SIGNOR-279644

Q9Y566

Q06787

0

post transcriptional regulation

up-regulates quantity

0.4

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.

SIGNOR-262109

P04004

P05129

0

phosphorylation

up-regulates quantity by stabilization

0.285

Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.

SIGNOR-248964

O15519

Q96J02

0

ubiquitination

down-regulates quantity

0.614

Depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, which specifically ubiquitinates c-FLIP and induces its proteasomal degradation.

SIGNOR-245307

Q9Y4D1

P54792

2

binding

up-regulates

0.2

Importantly, daam1 binds to disheveled (dvl) and thus functions downstream of the frizzled receptors. Little is known of how daam1 is localized and functions in mammalian cells.

SIGNOR-199451

Q86YT6

Q9NYJ7

1

ubiquitination

up-regulates activity

0.35

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

SIGNOR-209672

Q8IWA4

Q9NX47

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH5, a mitochondrial E3 ubiquitin ligase, has been identified as a molecule that binds mitochondrial fission 1 protein (hFis1), dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2), key proteins in the control of mitochondrial fission and fusion.|Notably, a significant increase in Mfn1 level, but not Mfn2, Drp1 or hFis1 levels, was observed in MARCH5-depleted cells, indicating that Mfn1 is a major ubiquitylation substrate.

SIGNOR-274133

P45983

P63104

1

phosphorylation

down-regulates

0.371

Jnk phosphorylated 14-3-3 at ser-184 and 14-3-3 at ser-186 both in vitro and in vivo, and such phosphorylation reduced the affinity of 14-3-3 proteins for bax

SIGNOR-124020

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

P53355

Q14457

1

phosphorylation

up-regulates

0.727

The activated form of DAPK triggers autophagy in a beclin-1-dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl-XL and the induction of autophagy.

SIGNOR-183548

P36382

P17612

0

phosphorylation

up-regulates activity

0.307

Gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation. Macroscopic conductance and permeability of Cx40 gap junctions is strongly increased by cAMP. two serine residues that can be phosphorylated by PKA, S120 and S345

SIGNOR-249982

P42336

P35568

2

binding

up-regulates activity

0.722

Irs proteins are capable of both regulating and activating pi3k, depending on the cell of origin.

SIGNOR-168985

Q9UNE7

Q9UPR3

1

polyubiquitination

down-regulates quantity by destabilization

0.398

Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B.

SIGNOR-272649

Q86XK2

Q9NZJ0

2

binding

down-regulates

0.544

We determined that the f-box protein fbxo11 interacts with cdt2,a dcaf protein that controls cell-cycle progression, and recruits cdt2 to the scf(fbxo11)complex to promote its proteasomal degradation.

SIGNOR-192325

P35222

P31751

0

phosphorylation

up-regulates

0.57

Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activitywe have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.

SIGNOR-152958

Q8N6I1

P84022

2

binding

down-regulates

0.397

In this study, we examined the effect of eid-2 on smad-mediated tgf- signaling. Here, we show that eid-2 inhibits tgf- /smad transcriptional responses. Eid-2 interacts constitutively with smad proteins, and most strongly with smad3.

SIGNOR-119171

O95631

O95185

2

binding

up-regulates

0.832

We provide evidence that netrin-1 triggers the formation of a receptor complex of dcc and unc5 proteins and simultaneously derepresses the interaction between their cytoplasmic domains, thereby converting dcc-mediated attraction to unc5/dcc-mediated repulsion.

SIGNOR-69047

Q13177

P01236

1

phosphorylation

up-regulates

0.337

Phosphorylated form of prolactin has a higher affinity for heparin.

SIGNOR-186211

O00418

2

phosphorylation

down-regulates

0.2

The combination of eef2k autophosphorylation (targeting ser445) and a yet to be identified kinase (targeting ser441) would be needed to generate the eef2k phosphodegron specifically in response to dna damage.

SIGNOR-197725

P31749

P99999

1

phosphorylation

down-regulates activity

0.465

Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.

SIGNOR-277237

Q00535

P26358

1

phosphorylation

up-regulates

0.358

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

SIGNOR-173685

Q08050

P24941

0

phosphorylation

up-regulates activity

0.75

We demonstrated that FoxM1B transcriptional activity requires binding of either S-phase or M-phase Cdk-cyclin complexes to mediate efficient Cdk phosphorylation of the FoxM1B Thr 596 residue, which is essential for recruitment of p300/CBP coactivator proteins.

SIGNOR-250731

P12931

P04629

1

phosphorylation

up-regulates activity

0.292

Direct phosphorylation of TrkA by Src family kinases has been demonstrated in vitro, and our studies suggest that Src may lead to selective activation of TrkA.

SIGNOR-279291

P84243

Q9H3R0

0

demethylation

down-regulates activity

0.2

As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation

SIGNOR-263869

Q12967

Q13671

2

binding

up-regulates activity

0.497

Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.

SIGNOR-220923

P62993

Q07889

1

relocalization

up-regulates activity

0.912

Interaction domains of sos1/grb2 are finely tuned for cooperative control of embryonic stem cell fate.

SIGNOR-235773

P12931

Q99961

1

phosphorylation

down-regulates

0.639

Further, we identified an interaction between fak's second pro-rich motif and endophilin a2's sh3 domain. This interaction served as an autophosphorylation-dependent scaffold to allow src phosphorylation of endophilin a2 at tyr315. Tyr315 phosphorylation inhibited endophilin/dynamin interactions, and blockade of tyr315 phosphorylation promoted endocytosis of mt1-mmp. Together, these results suggest a regulatory mechanism of cell invasion whereby fak promotes cell-surface presentation of mt1-mmp by inhibiting endophilin a2-dependent endocytosis.

SIGNOR-139150

Q14192

P61586

0

relocalization

up-regulates

0.348

Here, we show that stimulation of the rho pathway induces translocation of the transcriptional lim-only coactivator fhl2 to the nucleus and subsequent activation of fhl2- and androgen receptor-dependent genes.

SIGNOR-114071

Q9UK99

Q9UKC9

2

binding

down-regulates quantity by destabilization

0.549

F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.

SIGNOR-272445

A8MYZ6

P48729

0

phosphorylation

down-regulates

0.2

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.

SIGNOR-183667

Q9P2Y5

Q8NEB9

2

binding

up-regulates activity

0.809

Although both human atg14 and uvrag interact with beclin 1 and vps34.

SIGNOR-181554

P17948

P63096

1

phosphorylation

up-regulates activity

0.257

RTKs directly phosphorylate Gαi on Y154, 155, and Y320.

SIGNOR-277230

P12931

Q13761

1

phosphorylation

down-regulates activity

0.58

In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases.

SIGNOR-278199

P62993

P08581

2

binding

up-regulates activity

0.695

For activation of the mitogen-activated protein kinase (MAPK) cascades, c-MET activation stimulates the activity of the rat sarcoma viral oncogene homolog (RAS) guanine nucleotide exchanger son of sevenless (SOS) via binding with SHC and GRB2 leading to the activation of RAS.

SIGNOR-256261

Q13131

Q9NR19

1

phosphorylation

up-regulates activity

0.275

This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding. In the nucleus, ACSS2 forms a complex with TFEB (transcription factor EB) and utilizes the acetate generated from histone deacetylation to locally produce acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes.

SIGNOR-271822

Q02763

P27986

2

binding

up-regulates activity

0.538

Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival

SIGNOR-242634

P63279

Q92985

1

sumoylation

down-regulates activity

0.287

One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. we identified that IRF7 is sumoylated at lysine 452.

SIGNOR-266837

O14807

Q9UQ13

2

binding

up-regulates

0.69

Sur-8 interacts with ras and raf and is able to form a ternary complex with the two proteins. Thus, sur-8 may function as a scaffold that enhances ras-map kinase signal transduction by facilitating the interaction between ras and raf.

SIGNOR-77082

Q15052

Q8TDY4

2

binding

up-regulates activity

0.294

ArfGAP With Coiled-Coil, Ankyrin Repeat And PH Domains 4 (ACAP4) is an ADP-ribosylation factor 6 (ARF6) GTPase-activating protein essential for EGF-elicited cell migration. |The crystal structure of the catalytic core of ACAP4 in a complex with ARF6 reveals the structural determinants underlying ACAP4 selectivity and specificity as an ARF6 GTPase-activating protein

SIGNOR-272235

Q96FW1

P61088

2

binding

down-regulates

0.704

The deubiquitinating enzyme otub1 suppresses rnf168 dependent ubiquitination by direct the e2 ligase ubc13

SIGNOR-175050

P54764

P52797

2

binding

up-regulates

0.826

Eph receptors are activated by their ligands, which are membrane-anchored molecules

SIGNOR-52315

P08047

P68400

0

phosphorylation

down-regulates activity

0.34

Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. | Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding.

SIGNOR-250954

Q12888

Q13315

0

phosphorylation

up-regulates

0.873

Here we report phosphorylation of 53bp1 at several novel residues, using mass spectrometry and phospho-specific antibodies, and show that ionising radiation-stimulated phosphorylation of these residues requires atm.

SIGNOR-197615

Q96GD4

Q9UJP4

2

binding

up-regulates activity

0.507

KLHL21 directly binds to Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate Aurora B during mitosis, possibly by ubiquitinating different pools of Aurora B at distinct subcellular localizations.

SIGNOR-271848

P42574

P49810

1

cleavage

up-regulates activity

0.405

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

SIGNOR-261743

P17612

P24588

0

relocalization

up-regulates activity

0.561

In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150

SIGNOR-261292

C9JLW8

P27361

0

phosphorylation

down-regulates activity

0.2

When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.| While substitution of S4 or S18 with Ala did not affect the phosphorylation of MCRIP1 by ERK, substitution of either S21 or T30 significantly reduced MCRIP1 phosphorylation

SIGNOR-264772

O14733

O43283

0

phosphorylation

up-regulates

0.584

Lzk directly phosphorylated and activated mkk7.

SIGNOR-112349

Q96EB6

Q04206

1

deacetylation

down-regulates activity

0.722

SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310.

SIGNOR-238817

P68400

Q9UGP8

1

phosphorylation

up-regulates activity

0.291

Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.

SIGNOR-265267

Q7Z6Z7

O43474

1

ubiquitination

down-regulates quantity by destabilization

0.34

K48 linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.|Instead, we identified the transcription factor KLF4 as a novel Mule substrate that is ubiquitinated by this E3 ligase and thus undergoes proteasomal degradation in T cells.|Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase.

SIGNOR-278749

P27348

P30307

1

relocalization

down-regulates

0.575

Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins.

SIGNOR-163237

Q01860

P28482

0

phosphorylation

down-regulates

0.38

We demonstrate that oct4a interacts with erk1/2 by using both in vitro gst pulldown and in vivo co-immunoprecipitation assays. Ms analysis identified phosphorylation of oct4a at ser-111. / serine 111 phosphorylation regulates oct4a protein subcellular distribution and degradation.

SIGNOR-192097

P63096

P43115

2

binding

up-regulates activity

0.451

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256716

P07948

P33993

1

phosphorylation

up-regulates activity

0.453

Lyn phosphorylates MCM7 at Y600.|These evidences suggest that Lyn mediated Y600 phosphorylation may regulate MCM7 function in DNA replication licensing.

SIGNOR-278407

Q03113

Q9HBW0

2

binding

up-regulates

0.491

Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies.

SIGNOR-135834

P07196

P31946

2

binding

down-regulates activity

0.254

These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments.

SIGNOR-252396

P14373

A8K0Z3

1

ubiquitination

up-regulates activity

0.2

Our mechanistic studies uncovered that K63-linked ubiquitination of WASH K220 by MAGE-L2-TRIM27 is required for endosomal F-actin nucleation and retrograde transport. These results suggest that K63-linked ubiquitination of WASH K220 by TRIM27 is required for WASH function in retrograde transport.

SIGNOR-253514

Q9UNE7

Q01860

1

ubiquitination

down-regulates quantity by destabilization

0.303

CHIP overexpression decreased OCT4 stability through proteasomal degradation.|CHIP E3 ligase ubiquitinates OCT4 at lysine 284.|These data suggest that CHIP induces OCT4 ubiquitination and degradation.

SIGNOR-278562

O00750

P00533

0

phosphorylation

up-regulates

0.44

The n-terminal region of pi3k-c2beta was found to selectively interact with the egf receptor in vitro, suggesting that it mediates the association of this pi3k with the receptor.

SIGNOR-77195

P50616

P27361

0

phosphorylation

down-regulates

0.352

Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro. Erk catalyzes the phosphorylation more efficiently than jnk

SIGNOR-88728

P63092

P32238

2

binding

up-regulates activity

0.264

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256763

O43521

P28482

0

phosphorylation

down-regulates quantity by destabilization

0.716

In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel

SIGNOR-129874

P60953

Q13153

2

binding

up-regulates activity

0.942

A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.

SIGNOR-248243

P53778

O15297

0

dephosphorylation

down-regulates

0.297

Ppm1d selectively inhibits p38 activation by dephosphorylating thr 180.

SIGNOR-135976

P06493

Q9NTG7

1

phosphorylation

up-regulates activity

0.315

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

SIGNOR-279395

Q96HP0

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.677

Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton.

SIGNOR-275671

Q96AQ6

P40425

2

binding

down-regulates activity

0.267

This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences.

SIGNOR-273667

P67775

Q13315

1

dephosphorylation

down-regulates activity

0.333

Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro.

SIGNOR-248644

Q00535

P21860

1

phosphorylation

up-regulates activity

0.341

We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival.

SIGNOR-250663

P42684

2

phosphorylation

up-regulates quantity by stabilization

0.2

The results show that Arg is stabilized in response to 0.1 mM H2O2 by autophosphorylation of Y-261, consistent with involvement of the Arg kinase function in regulating Arg levels. The results further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly confers Arg stabilization.. These findings indicate that abrogation of the Arg kinase function by the Y261F mutation is dependent on phosphorylation of the Y-439 site.

SIGNOR-276033

Q13698

P67870

0

phosphorylation

up-regulates activity

0.2

To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.

SIGNOR-263115