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
P19419	O75582	0	phosphorylation	up-regulates	0.2	Phosphorylation on ser383 and ser389 of elk-1 by mapk enhances this basal binding but, most importantly, elk-1 exhibits new interactions with p300.	SIGNOR-85514
O14777	Q96GD4	0	phosphorylation	down-regulates	0.848	To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant).	SIGNOR-165558
P42336	Q06187	1	phosphorylation	up-regulates activity	0.514	Activation of Btk occurs by transphosphorylation of tyrosine 551 in the catalytic domain, resulting in a dramatic increase in the catalytic activity of the kinase (11, 12, 13). This allows for autophosphorylation at tyrosine 223 in the SH3 domain (14). Both Lyn and Syk have been demonstrated to be involved in BCR-mediated Btk activation (11), but processes that drive colocalization of these kinases are ill-defined. Recently, it was suggested that phosphatidylinositol 3-kinase (PI3-K) is also involved in Btk activation	SIGNOR-249610
Q9UJU2	Q8WVD3	0	polyubiquitination	down-regulates quantity by destabilization	0.307	Here, we show that NARF induces the ubiquitylation of TCF/LEF in vitro and in vivo, and functions as an E3 ubiquitin-ligase that specifically cooperates with the E2 conjugating enzyme E2-25K. We found that NLK augmented NARF binding and ubiquitylation of TCF/LEF, and this required NLK kinase activity. The ubiquitylated TCF/LEF was subsequently degraded by the proteasome.	SIGNOR-271595
Q14116	Q13478	2	binding	up-regulates	0.835	Acpl was required for il-18 responsiveness in terms of nf?B Induction and jnk activation	SIGNOR-60991
O43524	Q08999	1	transcriptional regulation	up-regulates quantity	0.291	Here we show that the Forkheads AFX (FOXO4) and FKHR-L1 (FOXO3a) also directly control transcription of the retinoblastoma-like p130 protein and cause upregulation of p130 protein expression.	SIGNOR-238606
O14757	Q9Y294	1	phosphorylation	up-regulates activity	0.414	Chk1 activated by ataxia telangiectasia mutated (ATM) kinase on DNA breaks in G1 promotes NHEJ through direct phosphorylation of ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with the repair protein MDC1 and thus enhances MDC1's interaction with ATM and the stable localization of ATM at DNA breaks.	SIGNOR-277620
Q15831	P60484	1	phosphorylation	down-regulates activity	0.604	The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity	SIGNOR-161118
Q96P20	P07948	0	phosphorylation	down-regulates	0.29	Lyn phosphorylates NLRP3 at Tyr 918 and controls NLRP3 ubiquitination.\|Therefore, our data collectively indicate that Lyn inhibits the NLRP3 inflammasome in vivo.	SIGNOR-278485
P04843	Q8WXH4	0	polyubiquitination	down-regulates quantity by destabilization	0.357	We also demonstrated that ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. Moreover, expression of ASB11 can increase Ribophorin 1 protein turnover in vivo.	SIGNOR-272057
O43638	P98177	1	transcriptional regulation	down-regulates quantity by repression	0.2	Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.	SIGNOR-261611
Q14493	A0A2R8Y619	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265380
P27361	P19793	1	phosphorylation	down-regulates activity	0.523	In colon cancer cells, the Ras/mitogen‐activated protein kinase (MAPK) pathway phosphorylates RXRalpha, which impairs its function as a heterodimeric partner for PPARgamma\|A point‐mutated RXRalpha T82A/S260A, which mimics the unphosphorylated form of RXRalpha, can form a heterodimer with PPARgamma and thereby activate target gene expression by binding to the PPRE	SIGNOR-88662
P40424	Q96JM2	2	binding	down-regulates activity	0.308	We demonstrated that ZFPIP is expressed in embryonic female genital tract but also in other PBX1 expression domains such as the developing head and the limb buds. We further showed that ZFPIP is able to bind physically and in vivo to PBX1 and moreover, that it prevents the binding of HOXA9/PBX complexes to their consensus DNA site. We suggest that ZFPIP is a new type of PBX1 partner that could participate in PBX1 function during several developmental pathways.	SIGNOR-264477
Q13153	Q13586	1	phosphorylation	up-regulates activity	0.354	Taken together, our data demonstrate that PAK1 interacts with STIM1 and phosphorylates specific STIM1 cytosolic domains.	SIGNOR-279244
P01111	Q8TEU7	0	guanine nucleotide exchange factor	up-regulates	0.331	Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.	SIGNOR-183799
P31749	P12755	1	phosphorylation	down-regulates	0.337	The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7	SIGNOR-252527
P19838	P62877	0	ubiquitination	up-regulates	0.451	The scf-betatrcp complex is responsible for the ubiquitination of p100 and p105 following their phosphorylation by ikk.	SIGNOR-106781
Q00535	Q15078	2	phosphorylation	down-regulates	0.943	P35 phosphorylation by cdk5 interferes with the microtubule-binding and polymerizing activities of p35. Using a mutational approach, we found that only phosphorylation at thr-138, one of the two residues primarily phosphorylated in vivo, inhibits the polymerizing activity	SIGNOR-177967
O94921	P37802	1	phosphorylation	down-regulates activity	0.315	This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation\|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity.	SIGNOR-265103
Q13283	P0DTC9	2	binding	down-regulates activity	null	N targets stress granule protein G3BP1, an essential antiviral protein which is known to induce innate immune response through multiple mechanisms	SIGNOR-260749
P06733	O75385	0	phosphorylation	down-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274029
P14138	P24530	2	binding	up-regulates	0.798	These results demonstrate that lys-161 of the receptor is important for high affinity binding with et-3 which, in part, confers the non-selective binding characteristics of the etb receptor for et isopeptides.	SIGNOR-36017
P06748	O94992	2	binding	down-regulates activity	0.385	We identified NPM as a novel HEXIM1-binding protein. NPM functioned as a negative regulator of HEXIM1. cytoplasmic localization of endogenous HEXIM1 is detected in an acute myeloid leukemia (AML) cell line containing the NPMc+ mutation, suggesting the physiological importance of HEXIM1-NPMc+ interaction.	SIGNOR-260134
O15217	P0DMV8	0	relocalization	up-regulates activity	0.2	Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. \|Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation	SIGNOR-264799
Q969V5	O75385	1	ubiquitination	down-regulates quantity	0.347	MUL1 promotes ubiquitination of ULK1.\|Overexpression of MUL1 and treatment with selenite promotes ULK1 degradation through the proteasome pathway.	SIGNOR-278759
Q9NYY1	Q8N6P7	2	binding	up-regulates	0.606	An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.	SIGNOR-151877
Q13043	Q9NRM7	1	phosphorylation	up-regulates	0.636	Activation of mst1/2 leads to phosphorylation and activation of their direct substrates, lats1/2.	SIGNOR-175821
P84022	O15194	0	dephosphorylation	up-regulates activity	0.424	Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248306
P12931	Q86UR1	1	phosphorylation	up-regulates	0.408	Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.	SIGNOR-168545
P38398	Q13085	2	binding	down-regulates activity	0.548	ACCA binds BRCA1 when phosphorylated onSer1263, thus supporting a model in which controlof lipid synthesis would be mediated at least in part,viaphosphorylation of the Ser1263.	SIGNOR-267474
O14944	P21860	2	binding	up-regulates	0.591	For example, betacellulin binds to and activates both erbb1 and erbb4, whereas epiregulin binds to erbb1, erbb3 and erbb4	SIGNOR-191785
P32243	P48436	2	binding	up-regulates activity	0.349	BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.	SIGNOR-255184
Q15311	P17252	0	phosphorylation	up-regulates activity	0.389	In deletion mutant analyses of potential phosphorylation sites in RLIP76, we identified T297 and S509 as targets for phosphorylation by PKCalpha. Phosphorylation at T297 increased doxorubicin (DOX)-transport activity approximately 2-fold for RLIP76 purified from recombinant source	SIGNOR-263164
Q8IXJ6	P35558	1	deacetylation	up-regulates quantity by stabilization	0.426	Conversely, SIRT2 deacetylates and stabilizes PEPCK1.\|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1	SIGNOR-267599
Q4KMG0	O60271	2	binding	up-regulates activity	0.498	In this study, we report that the cdo intracellular region interacts with jlp, a scaffold protein for the p38alpha/beta mapk pathway.	SIGNOR-150282
Q9NYY3	Q16143	1	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
O14920	P53350	0	phosphorylation	down-regulates	0.343	Plk1 phosphorylates serines 733, 740, and 750 in the gammabd of ikkbeta in vitro. Phosphorylating gammabd with plk1 decreased its affinity for ikkgamma	SIGNOR-181802
Q05655	O14939	1	phosphorylation	up-regulates	0.463	Finally, we show that thr566 of pld2 is directly phosphorylated by pkc and that pld2 mutation in this region prevents pld2 activation, pld2 translocation to the edge of lamellipodia, rac translocation, and cell spreading after integrin activation	SIGNOR-167577
Q8N4C8	Q96P20	1	phosphorylation	up-regulates activity	0.2	MINK1-mediated NLRP3 phosphorylation at Ser725 is critical for inflammasome activation.\|These results suggest that MINK1 promotes NLRP3 inflammasome activation via direct interaction with NLRP3.\|To determine whether MINK1 phosphorylated NLRP3 directly, we used Phos-tag SDS\u2013PAGE to detect the phosphorylation of NLRP3.	SIGNOR-280042
P16104	Q13043	0	phosphorylation	up-regulates activity	0.2	Western blot and kinase assay results with a mutant S139A H2AX confirmed that MST1 phosphorylates H2AX at Ser-139.	SIGNOR-278457
Q03113	Q15077	2	binding	up-regulates activity	0.2	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-257343
Q00535	O43464	1	phosphorylation	up-regulates	0.456	Here we report that cyclin-dependent kinase-5 (cdk5), a kinase implicated in the pathogenesis of several neurodegenerative diseases, is responsible for phosphorylating htra2 at s400.We have shown previously that phosphomimetic mutants of htra2 at s400 result in increased proteolytic activity and contribute to enhanced resistance to mitochondrial stress	SIGNOR-174598
P17676	Q15418	0	phosphorylation	up-regulates activity	0.683	13 The data presented support previous findings that C/EBPbeta can be a molecular target of RSK1, 16 but provide the first indication that RSK1 can phosphorylate and activate C/EBPbeta to mediate the IL-6 signalling events in cholangiocarcinoma.\|As mentioned above, RSK1 has been shown to activate C/EBPbeta in hepatic stellate cells in an experimental model of liver fibrosis.	SIGNOR-280112
P22455	P05230	2	binding	up-regulates	0.827	Our results establish an fgf binding profile for fgfr-4 with afgf having the highest affinity, followed by k-fgf/hst-1 and bfgf. In addition, fgf-6 was found to bind to fgfr-4 in ligand competition experiments. Ligands binding to fgfr-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides.	SIGNOR-18454
O15111	Q92793	2	binding	up-regulates	0.518	Ikk-alpha interacts with creb-binding protein and in conjunction with rel a is recruited to nf-kappab-responsive promoters and mediates the cytokine-induced phosphorylation and subsequent acetylation of specific residues in histone h3.	SIGNOR-101539
Q9Y478	O75385	1	phosphorylation	up-regulates	0.537	Ampk and ulk1 interact and that the latter is phosphorylated by ampk. This phosphorylation leads to the direct activation of ulk1 by ampk bypassing mtor-inhibition	SIGNOR-173044
Q09472	O15105	1	acetylation	up-regulates	0.464	Here we present evidence that smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of smad7 on two lysine residues in its n terminus. Acetylation or mutation of these lysine residues stabilizes smad7 and protects it from tgfbeta-induced degradation. we have recently shown that smad7 is acetylated on lysine residues 64 and 70 by p300	SIGNOR-95169
P12931	O15524	1	phosphorylation	down-regulates activity	0.45	SOCS1 is phosphorylated on Y80 by SRC family kinase members SRC and YES1.	SIGNOR-276857
O95837	Q96P68	2	binding	up-regulates activity	0.2	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-257417
P25098	P62166	2	binding	down-regulates activity	0.2	Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization.	SIGNOR-263965
P05412	Q92630	0	phosphorylation	down-regulates	0.256	Degradation of c-jun/c-myc is a critical process for the g(1)/s transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 ? (gsk3?). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this gsk3? Modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase dyrk2 functions as a priming kinase of c-jun and c-myc.The finding that kinase-active dyrk2 phosphorylated gst_c-jun210_310-wt by detection with an anti_phospho_c-jun(ser243) antibody demonstrated that dyrk2 is a ser243 kinase in vitro	SIGNOR-195771
Q17RS7	Q8TEB1	2	binding	down-regulates quantity by destabilization	0.2	(WDR23) isoforms differentially ubiquitinate (GEN1). In the presence of the necessary components for a successful ubiquitination reaction (CUL4A-DDB1-WDR23 complex, UBE1, UBE2D1, ubiquitin, and ATP) GEN1 receives the addition of ubiquitin in a time dependent manner.	SIGNOR-272258
P16298	P0DP25	2	binding	up-regulates	0.576	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-266338
P07550	P06213	0	phosphorylation	down-regulates activity	0.377	Insulin (10 nM)-stimulated rIR-catalyzed phosphorylation of β2-adrenergic receptor peptides was found prominently in peptides L339 (Tyr350 and Tyr354), T362 (Tyr364), and to a lesser extent peptides Y132 (Tyr132 and Tyr141), and I135 (Tyr141). G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on β-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of β2-adrenergic receptors.	SIGNOR-251302
Q07912	Q9Y4C1	1	phosphorylation	down-regulates activity	0.37	We report that ACK1 phosphorylates the ER co-activator, KDM3A, a H3K9 demethylase, at an evolutionary conserved tyrosine 1114 site in a heregulin-dependent manner, even in the presence of tamoxifen.	SIGNOR-276842
P56159	Q99748	2	binding	up-regulates	0.738	A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling	SIGNOR-49119
Q13237	Q01970	1	phosphorylation	down-regulates activity	0.525	PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG.	SIGNOR-249078
Q02750	P27361	1	phosphorylation	up-regulates	0.752	Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis.	SIGNOR-210176
P34925	Q9H461	2	binding	up-regulates	0.711	Interaction between ryk and fz has been reported, suggesting that the two proteins may form a multi-receptor complex signalling through the canonical pathway	SIGNOR-150010
Q13164	Q05397	1	phosphorylation	up-regulates activity	0.291	Remarkably, the reduction in ERK5 expression correlated with decreased p-FAK(Tyr397) staining, consistent with the requirement of ERK5 for mediating FAK activation in vivo (Fig. 6C).\|We confirmed that JWG-045, a novel pharmacological inhibitor of ERK5 exhibiting significantly reduced affinity for BRD4 compared with XMD8-92 (25, 26), did not suppress FAK phosphorylation at Tyr397 in MDA-MB-231 cells (Supplementary Fig. S3B and C).	SIGNOR-279304
Q8TE73	Q96M91	2	binding	up-regulates activity	0.2	CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).	SIGNOR-265544
P11940	Q12986	2	binding	up-regulates activity	0.344	We identifiednew protein partners of NFX1-123, including several cytoplasmic poly(A) binding proteins (PABPCs) thatinteracted with NFX1-123 through its N-terminal PAM2 motif. Central to our findings were our observations that PABPCs copurify with NFX1-123, that a PAM2 motif is present in NFX1, and this motif and the PABPCs are important in the enhancement of hTERT activity by NFX1-123.	SIGNOR-261052
Q86T82	P24941	0	phosphorylation	up-regulates activity	0.447	There is positive reinforcement of this signaling mechanism because phosphorylation of Ser628 by CDK2/cyclin E and CDK2/cyclin A complexes produces maximal USP37 activity	SIGNOR-265045
Q16576	O14929	2	binding	up-regulates activity	0.898	AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314\| interaction between RBBP7 and HAT1 is required for acetyltransferase activity	SIGNOR-264786
Q06830	Q96KB5	0	phosphorylation	up-regulates	0.26	We report that prx1 is newly discovered direct target of topk. Our results demonstrate that topk phosphorylation of prx1 at ser-32 inhibits uvb-induced apoptosis in rpmi7951 melanoma cells by increasing prx1 peroxidase activity and decreasing the intracellular accumulation of h2o2.	SIGNOR-166901
P78352	Q9UIJ5	0	palmitoylation	up-regulates activity	0.379	Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation.	SIGNOR-261290
P06241	P54646	1	phosphorylation	down-regulates activity	0.257	Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex.	SIGNOR-277279
P16104	O15297	0	dephosphorylation	down-regulates	0.2	Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-h2ax and suppresses dna double strand break repair. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (wip1) also dephosphorylates gamma-h2ax at serine 139 in vitro and in vivo.	SIGNOR-163693
Q9HC97	Q03113	2	binding	up-regulates activity	0.2	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-257204
Q9UQF2	O14733	2	binding	up-regulates	0.722	Both jip1 and jip2 selectively bind the mapkk isoform mkk7.	SIGNOR-70848
P17612	P27708	1	phosphorylation	down-regulates	0.307	Protein kinase a phosphorylation at thr456 of the multifunctional protein cad antagonizes activation by the map kinase cascade.	SIGNOR-151816
Q05397	P49023	2	binding	up-regulates activity	0.914	Focal adhesion kinase (FAK) is activated by growth factors and integrins during migration, and functions as a receptor-proximal regulator of cell motility. At contacts between cells and the extracellular matrix, FAK functions as an adaptor protein to recruit other focal contact proteins or their regulators, which affects the assembly or disassembly of focal contacts. Whereas it was first hypothesized that FAK might bind directly to the cytoplasmic tails of integrins, accumulated evidence supports an indirect association of FAK with integrins through binding to integrin-associated proteins such as paxillin and talin.	SIGNOR-257732
P12931	Q9NPF5	1	phosphorylation	down-regulates activity	0.2	C-Src phosphorylates DMAP1 at Tyr246 and disrupts Bub3/DMAP1 complex formation.	SIGNOR-279431
Q8TDX7	Q15058	1	phosphorylation	up-regulates activity	0.371	Nek7 direct phosphorylation is required for the anaphase localization of Kif14. we generated an EGFP-Kif14-5A construct in which Ser56, Ser607, Ser1217, Ser1219, and Ser1220 were all mutated to Ala. When transfected into HeLa cells, EGFP-Kif14-5A was expressed to similar levels as WT Kif14 (Fig. S3 C), but its localization to the central spindle in anaphase cells was completely abolished (Fig. 6 C).	SIGNOR-266420
O14757	O75461	1	phosphorylation	down-regulates activity	0.574	the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters.	SIGNOR-266371
Q09472	Q06413	2	binding	up-regulates	0.742	Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription.	SIGNOR-232159
P28702	P37231	2	binding	up-regulates	0.668	Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology	SIGNOR-105454
P22681	Q96JA1	2	ubiquitination	down-regulates	0.589	We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation.	SIGNOR-127289
Q9UGI0	Q9P2Y5	1	deubiquitination	up-regulates activity	0.2	Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux.	SIGNOR-273651
Q9NYY3	Q9P253	0	ubiquitination	down-regulates quantity by destabilization	0.2	VPS18 Ubiquitylates SNK in Vitro and in Vivo. The ubiquitylation of proteins by hVPS18 was selectively mediated by UbcH4.	SIGNOR-271550
Q96EZ8	O14965	0	phosphorylation	up-regulates activity	0.316	We conclude that Aurora-A phosphorylates MCRS1 on Ser35/36 specifically during mitosis.	SIGNOR-278232
O14757	P84243	1	phosphorylation	down-regulates activity	0.2	We identify chk1 as the kinase responsible for h3-t11 phosphorylation. H3-t11 phosphorylation occurs throughout the cell cycle and is chk1 dependent in vivo.Phosphorylation at thr-12 (h3t11ph) by pkn1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of lys-10 (h3k9me) by kdm4c/jmjd2c.	SIGNOR-160557
P63000	O60890	0	gtpase-activating protein	up-regulates activity	0.591	OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro	SIGNOR-268399
P05305	Q14119	0	transcriptional regulation	up-regulates quantity by expression	0.276	Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone	SIGNOR-266884
Q99835	P25098	0	phosphorylation	up-regulates	0.2	We find that two molecules interact with mammalian smo in an activation-dependent manner: g protein-coupled receptor kinase 2 (grk2) leads to phosphorylation of smo, and beta-arrestin 2 fused to green fluorescent protein interacts with smo. Ck1a, grk2, and another still-unidentified protein kinase phosphorylate the c-tail of mammalian smo in the presence of hh proteins	SIGNOR-174539
Q9UL15	P0DMV9	2	binding	down-regulates activity	0.683	Here, we show that BAG5, a BAG domain-containing family member, interacts with both Hsp70 and parkin with deleterious functional consequences. Through these interactions, BAG5 inhibits Hsp70 chaperone activity and parkin E3 ubiquitin ligase activity; Thus, BAG5 interacts with Hsp70 in vitro and in vivo, and substitution of select residues within the BAG domains is sufficient to abolish this interaction.	SIGNOR-261197
O15530	P23443	2	phosphorylation	up-regulates	0.727	A regulatory link between p70s6k and pkb was demonstrated, as pdk1 was found to selectively phosphorylate p70s6k at thr229. More importantly, pdk1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive pdk1 blocked insulin-induced activation of p70s6k. One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. Phosphorylation and activation of p70s6k by pdk1.	SIGNOR-188907
P42574	P98170	0	ubiquitination	down-regulates quantity by destabilization	0.939	Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.	SIGNOR-109243
Q14938	Q9HD90	1	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-268905
P03952	P14210	1	cleavage	up-regulates activity	0.323	the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain.	SIGNOR-256513
P53667	Q9NQU5	0	phosphorylation	up-regulates activity	0.2	PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508.\|These data indicated that PAK6 directly phosphorylated LIMK1 at Thr-508.	SIGNOR-278970
Q96EP1	P53350	1	polyubiquitination	down-regulates quantity by destabilization	0.468	Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.	SIGNOR-271464
P12830	P49841	0	phosphorylation	up-regulates activity	0.558	Phosphorylation of the E-cadherin Cytoplasmic Domain by CKII and GSK-3β Increases the Binding to β-catenin. pre-phosphorylation by CKII at Ser-855 and/or Ser-853 of E-cadherin is required before GSK-3β can phosphorylate at Ser-849.	SIGNOR-251225
P19838	P50591	0	post transcriptional regulation	up-regulates quantity by expression	0.302	Treatment with TRAIL increased the NF-κB transcriptional activity by approximately twofold in MDA-MB-231 cells compared to the control.	SIGNOR-277936
O76064	Q9NS91	2	binding	up-regulates	0.415	Rnf8 depletion also significantly reduced the accumulation of rad18 to chromatin fraction after ir	SIGNOR-185593
P12643	Q13253	2	binding	down-regulates	0.81	Noggin acts by binding bmps, thus preventing them from binding to their receptors (180). Noggin binds with various degrees of affinity bmp-2, -4, -5, -6, and -7, gdf-5, gdf-6, and vg1, but not other members of the tgf- family of peptides	SIGNOR-100657
Q12933	Q92844	2	binding	down-regulates activity	0.734	IKK-i phosphorylates I-TRAF. In vitro kinase assays demonstrate that IKK‐i phosphorylates I‐TRAF in the middle portion that associates with TRAF2. Interestingly, TRAF2 is freed from the I‐TRAF/TRAF2 complex after I‐TRAF phosphorylation. TRAF2 isdistributed throughout the cytoplasm, in the formof inactive an I-TRAF/TRAF2 complex	SIGNOR-262714
P61586	Q14344	2	binding	up-regulates	0.574	Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism.	SIGNOR-192111
P24557	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.246	Ecotopic expression of NF-E2 related factors showed that Nrf2, but not Nrf1, Nrf3, or Bach1, activated TXAS promoter in a dose-dependent manner.	SIGNOR-253907

P19419

O75582

0

phosphorylation

up-regulates

0.2

Phosphorylation on ser383 and ser389 of elk-1 by mapk enhances this basal binding but, most importantly, elk-1 exhibits new interactions with p300.

SIGNOR-85514

O14777

Q96GD4

0

phosphorylation

down-regulates

0.848

To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant).

SIGNOR-165558

P42336

Q06187

1

phosphorylation

up-regulates activity

0.514

Activation of Btk occurs by transphosphorylation of tyrosine 551 in the catalytic domain, resulting in a dramatic increase in the catalytic activity of the kinase (11, 12, 13). This allows for autophosphorylation at tyrosine 223 in the SH3 domain (14). Both Lyn and Syk have been demonstrated to be involved in BCR-mediated Btk activation (11), but processes that drive colocalization of these kinases are ill-defined. Recently, it was suggested that phosphatidylinositol 3-kinase (PI3-K) is also involved in Btk activation

SIGNOR-249610

Q9UJU2

Q8WVD3

0

polyubiquitination

down-regulates quantity by destabilization

0.307

Here, we show that NARF induces the ubiquitylation of TCF/LEF in vitro and in vivo, and functions as an E3 ubiquitin-ligase that specifically cooperates with the E2 conjugating enzyme E2-25K. We found that NLK augmented NARF binding and ubiquitylation of TCF/LEF, and this required NLK kinase activity. The ubiquitylated TCF/LEF was subsequently degraded by the proteasome.

SIGNOR-271595

Q14116

Q13478

2

binding

up-regulates

0.835

Acpl was required for il-18 responsiveness in terms of nf?B Induction and jnk activation

SIGNOR-60991

O43524

Q08999

1

transcriptional regulation

up-regulates quantity

0.291

Here we show that the Forkheads AFX (FOXO4) and FKHR-L1 (FOXO3a) also directly control transcription of the retinoblastoma-like p130 protein and cause upregulation of p130 protein expression.

SIGNOR-238606

O14757

Q9Y294

1

phosphorylation

up-regulates activity

0.414

Chk1 activated by ataxia telangiectasia mutated (ATM) kinase on DNA breaks in G1 promotes NHEJ through direct phosphorylation of ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with the repair protein MDC1 and thus enhances MDC1's interaction with ATM and the stable localization of ATM at DNA breaks.

SIGNOR-277620

Q15831

P60484

1

phosphorylation

down-regulates activity

0.604

The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity

SIGNOR-161118

Q96P20

P07948

0

phosphorylation

down-regulates

0.29

Lyn phosphorylates NLRP3 at Tyr 918 and controls NLRP3 ubiquitination.|Therefore, our data collectively indicate that Lyn inhibits the NLRP3 inflammasome in vivo.

SIGNOR-278485

P04843

Q8WXH4

0

polyubiquitination

down-regulates quantity by destabilization

0.357

We also demonstrated that ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. Moreover, expression of ASB11 can increase Ribophorin 1 protein turnover in vivo.

SIGNOR-272057

O43638

P98177

1

transcriptional regulation

down-regulates quantity by repression

0.2

Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.

SIGNOR-261611

Q14493

A0A2R8Y619

1

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265380

P27361

P19793

1

phosphorylation

down-regulates activity

0.523

In colon cancer cells, the Ras/mitogen‐activated protein kinase (MAPK) pathway phosphorylates RXRalpha, which impairs its function as a heterodimeric partner for PPARgamma|A point‐mutated RXRalpha T82A/S260A, which mimics the unphosphorylated form of RXRalpha, can form a heterodimer with PPARgamma and thereby activate target gene expression by binding to the PPRE

SIGNOR-88662

P40424

Q96JM2

2

binding

down-regulates activity

0.308

We demonstrated that ZFPIP is expressed in embryonic female genital tract but also in other PBX1 expression domains such as the developing head and the limb buds. We further showed that ZFPIP is able to bind physically and in vivo to PBX1 and moreover, that it prevents the binding of HOXA9/PBX complexes to their consensus DNA site. We suggest that ZFPIP is a new type of PBX1 partner that could participate in PBX1 function during several developmental pathways.

SIGNOR-264477

Q13153

Q13586

1

phosphorylation

up-regulates activity

0.354

Taken together, our data demonstrate that PAK1 interacts with STIM1 and phosphorylates specific STIM1 cytosolic domains.

SIGNOR-279244

P01111

Q8TEU7

0

guanine nucleotide exchange factor

up-regulates

0.331

Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.

SIGNOR-183799

P31749

P12755

1

phosphorylation

down-regulates

0.337

The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7

SIGNOR-252527

P19838

P62877

0

ubiquitination

up-regulates

0.451

The scf-betatrcp complex is responsible for the ubiquitination of p100 and p105 following their phosphorylation by ikk.

SIGNOR-106781

Q00535

Q15078

2

phosphorylation

down-regulates

0.943

P35 phosphorylation by cdk5 interferes with the microtubule-binding and polymerizing activities of p35. Using a mutational approach, we found that only phosphorylation at thr-138, one of the two residues primarily phosphorylated in vivo, inhibits the polymerizing activity

SIGNOR-177967

O94921

P37802

1

phosphorylation

down-regulates activity

0.315

This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity.

SIGNOR-265103

Q13283

P0DTC9

2

binding

down-regulates activity

null

N targets stress granule protein G3BP1, an essential antiviral protein which is known to induce innate immune response through multiple mechanisms

SIGNOR-260749

P06733

O75385

0

phosphorylation

down-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274029

P14138

P24530

2

binding

up-regulates

0.798

These results demonstrate that lys-161 of the receptor is important for high affinity binding with et-3 which, in part, confers the non-selective binding characteristics of the etb receptor for et isopeptides.

SIGNOR-36017

P06748

O94992

2

binding

down-regulates activity

0.385

We identified NPM as a novel HEXIM1-binding protein. NPM functioned as a negative regulator of HEXIM1. cytoplasmic localization of endogenous HEXIM1 is detected in an acute myeloid leukemia (AML) cell line containing the NPMc+ mutation, suggesting the physiological importance of HEXIM1-NPMc+ interaction.

SIGNOR-260134

O15217

P0DMV8

0

relocalization

up-regulates activity

0.2

Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. |Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation

SIGNOR-264799

Q969V5

O75385

1

ubiquitination

down-regulates quantity

0.347

MUL1 promotes ubiquitination of ULK1.|Overexpression of MUL1 and treatment with selenite promotes ULK1 degradation through the proteasome pathway.

SIGNOR-278759

Q9NYY1

Q8N6P7

2

binding

up-regulates

0.606

An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.

SIGNOR-151877

Q13043

Q9NRM7

1

phosphorylation

up-regulates

0.636

Activation of mst1/2 leads to phosphorylation and activation of their direct substrates, lats1/2.

SIGNOR-175821

P84022

O15194

0

dephosphorylation

up-regulates activity

0.424

Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248306

P12931

Q86UR1

1

phosphorylation

up-regulates

0.408

Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.

SIGNOR-168545

P38398

Q13085

2

binding

down-regulates activity

0.548

ACCA binds BRCA1 when phosphorylated onSer1263, thus supporting a model in which controlof lipid synthesis would be mediated at least in part,viaphosphorylation of the Ser1263.

SIGNOR-267474

O14944

P21860

2

binding

up-regulates

0.591

For example, betacellulin binds to and activates both erbb1 and erbb4, whereas epiregulin binds to erbb1, erbb3 and erbb4

SIGNOR-191785

P32243

P48436

2

binding

up-regulates activity

0.349

BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.

SIGNOR-255184

Q15311

P17252

0

phosphorylation

up-regulates activity

0.389

In deletion mutant analyses of potential phosphorylation sites in RLIP76, we identified T297 and S509 as targets for phosphorylation by PKCalpha. Phosphorylation at T297 increased doxorubicin (DOX)-transport activity approximately 2-fold for RLIP76 purified from recombinant source

SIGNOR-263164

Q8IXJ6

P35558

1

deacetylation

up-regulates quantity by stabilization

0.426

Conversely, SIRT2 deacetylates and stabilizes PEPCK1.|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1

SIGNOR-267599

Q4KMG0

O60271

2

binding

up-regulates activity

0.498

In this study, we report that the cdo intracellular region interacts with jlp, a scaffold protein for the p38alpha/beta mapk pathway.

SIGNOR-150282

Q9NYY3

Q16143

1

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

O14920

P53350

0

phosphorylation

down-regulates

0.343

Plk1 phosphorylates serines 733, 740, and 750 in the gammabd of ikkbeta in vitro. Phosphorylating gammabd with plk1 decreased its affinity for ikkgamma

SIGNOR-181802

Q05655

O14939

1

phosphorylation

up-regulates

0.463

Finally, we show that thr566 of pld2 is directly phosphorylated by pkc and that pld2 mutation in this region prevents pld2 activation, pld2 translocation to the edge of lamellipodia, rac translocation, and cell spreading after integrin activation

SIGNOR-167577

Q8N4C8

Q96P20

1

phosphorylation

up-regulates activity

0.2

MINK1-mediated NLRP3 phosphorylation at Ser725 is critical for inflammasome activation.|These results suggest that MINK1 promotes NLRP3 inflammasome activation via direct interaction with NLRP3.|To determine whether MINK1 phosphorylated NLRP3 directly, we used Phos-tag SDS\u2013PAGE to detect the phosphorylation of NLRP3.

SIGNOR-280042

P16104

Q13043

0

phosphorylation

up-regulates activity

0.2

Western blot and kinase assay results with a mutant S139A H2AX confirmed that MST1 phosphorylates H2AX at Ser-139.

SIGNOR-278457

Q03113

Q15077

2

binding

up-regulates activity

0.2

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-257343

Q00535

O43464

1

phosphorylation

up-regulates

0.456

Here we report that cyclin-dependent kinase-5 (cdk5), a kinase implicated in the pathogenesis of several neurodegenerative diseases, is responsible for phosphorylating htra2 at s400.We have shown previously that phosphomimetic mutants of htra2 at s400 result in increased proteolytic activity and contribute to enhanced resistance to mitochondrial stress

SIGNOR-174598

P17676

Q15418

0

phosphorylation

up-regulates activity

0.683

13 The data presented support previous findings that C/EBPbeta can be a molecular target of RSK1, 16 but provide the first indication that RSK1 can phosphorylate and activate C/EBPbeta to mediate the IL-6 signalling events in cholangiocarcinoma.|As mentioned above, RSK1 has been shown to activate C/EBPbeta in hepatic stellate cells in an experimental model of liver fibrosis.

SIGNOR-280112

P22455

P05230

2

binding

up-regulates

0.827

Our results establish an fgf binding profile for fgfr-4 with afgf having the highest affinity, followed by k-fgf/hst-1 and bfgf. In addition, fgf-6 was found to bind to fgfr-4 in ligand competition experiments. Ligands binding to fgfr-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides.

SIGNOR-18454

O15111

Q92793

2

binding

up-regulates

0.518

Ikk-alpha interacts with creb-binding protein and in conjunction with rel a is recruited to nf-kappab-responsive promoters and mediates the cytokine-induced phosphorylation and subsequent acetylation of specific residues in histone h3.

SIGNOR-101539

Q9Y478

O75385

1

phosphorylation

up-regulates

0.537

Ampk and ulk1 interact and that the latter is phosphorylated by ampk. This phosphorylation leads to the direct activation of ulk1 by ampk bypassing mtor-inhibition

SIGNOR-173044

Q09472

O15105

1

acetylation

up-regulates

0.464

Here we present evidence that smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of smad7 on two lysine residues in its n terminus. Acetylation or mutation of these lysine residues stabilizes smad7 and protects it from tgfbeta-induced degradation. we have recently shown that smad7 is acetylated on lysine residues 64 and 70 by p300

SIGNOR-95169

P12931

O15524

1

phosphorylation

down-regulates activity

0.45

SOCS1 is phosphorylated on Y80 by SRC family kinase members SRC and YES1.

SIGNOR-276857

O95837

Q96P68

2

binding

up-regulates activity

0.2

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-257417

P25098

P62166

2

binding

down-regulates activity

0.2

Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization.

SIGNOR-263965

P05412

Q92630

0

phosphorylation

down-regulates

0.256

Degradation of c-jun/c-myc is a critical process for the g(1)/s transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 ? (gsk3?). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this gsk3? Modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase dyrk2 functions as a priming kinase of c-jun and c-myc.The finding that kinase-active dyrk2 phosphorylated gst_c-jun210_310-wt by detection with an anti_phospho_c-jun(ser243) antibody demonstrated that dyrk2 is a ser243 kinase in vitro

SIGNOR-195771

Q17RS7

Q8TEB1

2

binding

down-regulates quantity by destabilization

0.2

(WDR23) isoforms differentially ubiquitinate (GEN1). In the presence of the necessary components for a successful ubiquitination reaction (CUL4A-DDB1-WDR23 complex, UBE1, UBE2D1, ubiquitin, and ATP) GEN1 receives the addition of ubiquitin in a time dependent manner.

SIGNOR-272258

P16298

P0DP25

2

binding

up-regulates

0.576

Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.

SIGNOR-266338

P07550

P06213

0

phosphorylation

down-regulates activity

0.377

Insulin (10 nM)-stimulated rIR-catalyzed phosphorylation of β2-adrenergic receptor peptides was found prominently in peptides L339 (Tyr350 and Tyr354), T362 (Tyr364), and to a lesser extent peptides Y132 (Tyr132 and Tyr141), and I135 (Tyr141). G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on β-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of β2-adrenergic receptors.

SIGNOR-251302

Q07912

Q9Y4C1

1

phosphorylation

down-regulates activity

0.37

We report that ACK1 phosphorylates the ER co-activator, KDM3A, a H3K9 demethylase, at an evolutionary conserved tyrosine 1114 site in a heregulin-dependent manner, even in the presence of tamoxifen.

SIGNOR-276842

P56159

Q99748

2

binding

up-regulates

0.738

A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling

SIGNOR-49119

Q13237

Q01970

1

phosphorylation

down-regulates activity

0.525

PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG.

SIGNOR-249078

Q02750

P27361

1

phosphorylation

up-regulates

0.752

Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis.

SIGNOR-210176

P34925

Q9H461

2

binding

up-regulates

0.711

Interaction between ryk and fz has been reported, suggesting that the two proteins may form a multi-receptor complex signalling through the canonical pathway

SIGNOR-150010

Q13164

Q05397

1

phosphorylation

up-regulates activity

0.291

Remarkably, the reduction in ERK5 expression correlated with decreased p-FAK(Tyr397) staining, consistent with the requirement of ERK5 for mediating FAK activation in vivo (Fig. 6C).|We confirmed that JWG-045, a novel pharmacological inhibitor of ERK5 exhibiting significantly reduced affinity for BRD4 compared with XMD8-92 (25, 26), did not suppress FAK phosphorylation at Tyr397 in MDA-MB-231 cells (Supplementary Fig. S3B and C).

SIGNOR-279304

Q8TE73

Q96M91

2

binding

up-regulates activity

0.2

CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).

SIGNOR-265544

P11940

Q12986

2

binding

up-regulates activity

0.344

We identifiednew protein partners of NFX1-123, including several cytoplasmic poly(A) binding proteins (PABPCs) thatinteracted with NFX1-123 through its N-terminal PAM2 motif. Central to our findings were our observations that PABPCs copurify with NFX1-123, that a PAM2 motif is present in NFX1, and this motif and the PABPCs are important in the enhancement of hTERT activity by NFX1-123.

SIGNOR-261052

Q86T82

P24941

0

phosphorylation

up-regulates activity

0.447

There is positive reinforcement of this signaling mechanism because phosphorylation of Ser628 by CDK2/cyclin E and CDK2/cyclin A complexes produces maximal USP37 activity

SIGNOR-265045

Q16576

O14929

2

binding

up-regulates activity

0.898

AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314| interaction between RBBP7 and HAT1 is required for acetyltransferase activity

SIGNOR-264786

Q06830

Q96KB5

0

phosphorylation

up-regulates

0.26

We report that prx1 is newly discovered direct target of topk. Our results demonstrate that topk phosphorylation of prx1 at ser-32 inhibits uvb-induced apoptosis in rpmi7951 melanoma cells by increasing prx1 peroxidase activity and decreasing the intracellular accumulation of h2o2.

SIGNOR-166901

P78352

Q9UIJ5

0

palmitoylation

up-regulates activity

0.379

Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation.

SIGNOR-261290

P06241

P54646

1

phosphorylation

down-regulates activity

0.257

Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex.

SIGNOR-277279

P16104

O15297

0

dephosphorylation

down-regulates

0.2

Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-h2ax and suppresses dna double strand break repair. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (wip1) also dephosphorylates gamma-h2ax at serine 139 in vitro and in vivo.

SIGNOR-163693

Q9HC97

Q03113

2

binding

up-regulates activity

0.2

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-257204

Q9UQF2

O14733

2

binding

up-regulates

0.722

Both jip1 and jip2 selectively bind the mapkk isoform mkk7.

SIGNOR-70848

P17612

P27708

1

phosphorylation

down-regulates

0.307

Protein kinase a phosphorylation at thr456 of the multifunctional protein cad antagonizes activation by the map kinase cascade.

SIGNOR-151816

Q05397

P49023

2

binding

up-regulates activity

0.914

Focal adhesion kinase (FAK) is activated by growth factors and integrins during migration, and functions as a receptor-proximal regulator of cell motility. At contacts between cells and the extracellular matrix, FAK functions as an adaptor protein to recruit other focal contact proteins or their regulators, which affects the assembly or disassembly of focal contacts. Whereas it was first hypothesized that FAK might bind directly to the cytoplasmic tails of integrins, accumulated evidence supports an indirect association of FAK with integrins through binding to integrin-associated proteins such as paxillin and talin.

SIGNOR-257732

P12931

Q9NPF5

1

phosphorylation

down-regulates activity

0.2

C-Src phosphorylates DMAP1 at Tyr246 and disrupts Bub3/DMAP1 complex formation.

SIGNOR-279431

Q8TDX7

Q15058

1

phosphorylation

up-regulates activity

0.371

Nek7 direct phosphorylation is required for the anaphase localization of Kif14. we generated an EGFP-Kif14-5A construct in which Ser56, Ser607, Ser1217, Ser1219, and Ser1220 were all mutated to Ala. When transfected into HeLa cells, EGFP-Kif14-5A was expressed to similar levels as WT Kif14 (Fig. S3 C), but its localization to the central spindle in anaphase cells was completely abolished (Fig. 6 C).

SIGNOR-266420

O14757

O75461

1

phosphorylation

down-regulates activity

0.574

the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters.

SIGNOR-266371

Q09472

Q06413

2

binding

up-regulates

0.742

Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription.

SIGNOR-232159

P28702

P37231

2

binding

up-regulates

0.668

Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology

SIGNOR-105454

P22681

Q96JA1

2

ubiquitination

down-regulates

0.589

We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation.

SIGNOR-127289

Q9UGI0

Q9P2Y5

1

deubiquitination

up-regulates activity

0.2

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

SIGNOR-273651

Q9NYY3

Q9P253

0

ubiquitination

down-regulates quantity by destabilization

0.2

VPS18 Ubiquitylates SNK in Vitro and in Vivo. The ubiquitylation of proteins by hVPS18 was selectively mediated by UbcH4.

SIGNOR-271550

Q96EZ8

O14965

0

phosphorylation

up-regulates activity

0.316

We conclude that Aurora-A phosphorylates MCRS1 on Ser35/36 specifically during mitosis.

SIGNOR-278232

O14757

P84243

1

phosphorylation

down-regulates activity

0.2

We identify chk1 as the kinase responsible for h3-t11 phosphorylation. H3-t11 phosphorylation occurs throughout the cell cycle and is chk1 dependent in vivo.Phosphorylation at thr-12 (h3t11ph) by pkn1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of lys-10 (h3k9me) by kdm4c/jmjd2c.

SIGNOR-160557

P63000

O60890

0

gtpase-activating protein

up-regulates activity

0.591

OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro

SIGNOR-268399

P05305

Q14119

0

transcriptional regulation

up-regulates quantity by expression

0.276

Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone

SIGNOR-266884

Q99835

P25098

0

phosphorylation

up-regulates

0.2

We find that two molecules interact with mammalian smo in an activation-dependent manner: g protein-coupled receptor kinase 2 (grk2) leads to phosphorylation of smo, and beta-arrestin 2 fused to green fluorescent protein interacts with smo. Ck1a, grk2, and another still-unidentified protein kinase phosphorylate the c-tail of mammalian smo in the presence of hh proteins

SIGNOR-174539

Q9UL15

P0DMV9

2

binding

down-regulates activity

0.683

Here, we show that BAG5, a BAG domain-containing family member, interacts with both Hsp70 and parkin with deleterious functional consequences. Through these interactions, BAG5 inhibits Hsp70 chaperone activity and parkin E3 ubiquitin ligase activity; Thus, BAG5 interacts with Hsp70 in vitro and in vivo, and substitution of select residues within the BAG domains is sufficient to abolish this interaction.

SIGNOR-261197

O15530

P23443

2

phosphorylation

up-regulates

0.727

A regulatory link between p70s6k and pkb was demonstrated, as pdk1 was found to selectively phosphorylate p70s6k at thr229. More importantly, pdk1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive pdk1 blocked insulin-induced activation of p70s6k. One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. Phosphorylation and activation of p70s6k by pdk1.

SIGNOR-188907

P42574

P98170

0

ubiquitination

down-regulates quantity by destabilization

0.939

Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.

SIGNOR-109243

Q14938

Q9HD90

1

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-268905

P03952

P14210

1

cleavage

up-regulates activity

0.323

the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain.

SIGNOR-256513

P53667

Q9NQU5

0

phosphorylation

up-regulates activity

0.2

PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508.|These data indicated that PAK6 directly phosphorylated LIMK1 at Thr-508.

SIGNOR-278970

Q96EP1

P53350

1

polyubiquitination

down-regulates quantity by destabilization

0.468

Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.

SIGNOR-271464

P12830

P49841

0

phosphorylation

up-regulates activity

0.558

Phosphorylation of the E-cadherin Cytoplasmic Domain by CKII and GSK-3β Increases the Binding to β-catenin. pre-phosphorylation by CKII at Ser-855 and/or Ser-853 of E-cadherin is required before GSK-3β can phosphorylate at Ser-849.

SIGNOR-251225

P19838

P50591

0

post transcriptional regulation

up-regulates quantity by expression

0.302

Treatment with TRAIL increased the NF-κB transcriptional activity by approximately twofold in MDA-MB-231 cells compared to the control.

SIGNOR-277936

O76064

Q9NS91

2

binding

up-regulates

0.415

Rnf8 depletion also significantly reduced the accumulation of rad18 to chromatin fraction after ir

SIGNOR-185593

P12643

Q13253

2

binding

down-regulates

0.81

Noggin acts by binding bmps, thus preventing them from binding to their receptors (180). Noggin binds with various degrees of affinity bmp-2, -4, -5, -6, and -7, gdf-5, gdf-6, and vg1, but not other members of the tgf- family of peptides

SIGNOR-100657

Q12933

Q92844

2

binding

down-regulates activity

0.734

IKK-i phosphorylates I-TRAF. In vitro kinase assays demonstrate that IKK‐i phosphorylates I‐TRAF in the middle portion that associates with TRAF2. Interestingly, TRAF2 is freed from the I‐TRAF/TRAF2 complex after I‐TRAF phosphorylation. TRAF2 isdistributed throughout the cytoplasm, in the formof inactive an I-TRAF/TRAF2 complex

SIGNOR-262714

P61586

Q14344

2

binding

up-regulates

0.574

Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism.

SIGNOR-192111

P24557

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.246

Ecotopic expression of NF-E2 related factors showed that Nrf2, but not Nrf1, Nrf3, or Bach1, activated TXAS promoter in a dose-dependent manner.

SIGNOR-253907