GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 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
P29320	P12931	1	binding	up-regulates	0.528	We propose src kinase as a downstream effector that mediates the neuron's response to eph receptor activation.	SIGNOR-58139
Q9UER7	P37173	1	binding	up-regulates	0.528	Tgf-beta-induced apoptosis is mediated by the adapter protein daxx that facilitates jnk activation	SIGNOR-109542
P06493	Q96EB6	1	phosphorylation	up-regulates	0.528	We identified cyclinb/cdk1 as a cell cycle-dependent kinase that forms a complex with and phosphorylates sirt1. Mutation of two residues phosphorylated by cyclin b/cdk1 (threonine 530 and serine 540) disturbs normal cell cycle progression and fails to rescue proliferation defects in sirt1-deficient cells	SIGNOR-182863
P06213	P22681	2	phosphorylation	up-regulates activity	0.528	Insulin receptor phosphorylates Cbl on tyrosines 371, 700, and 774 in the presence of APS. This phosphorylation event is required for the recruitment of Crk to the CAP/Cbl complex and for the subsequent activation of GLUT4 translocation.	SIGNOR-251304
Q15131	P15036	1	phosphorylation	down-regulates quantity by destabilization	0.528	Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines.	SIGNOR-260914
P31751	P55211	1	phosphorylation	down-regulates	0.528	Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity	SIGNOR-61561
P49715	P17947	1	transcriptional regulation	up-regulates quantity by expression	0.528	Activation of C/EBPα induces PU.1 expression, cell cycle arrest, and differentiation in 32D cells expressing FLT3/ITD	SIGNOR-261531
Q15569	P23528	1	phosphorylation	down-regulates activity	0.528	Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin	SIGNOR-246723
Q96HP0	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.528	Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton.	SIGNOR-275670
Q5S007	P10636	1	phosphorylation	down-regulates	0.528	Lrrk2 directly phosphorylates tubulin-associated tau, but not free tau;(iii) lrrk2 phosphorylates tau at thr181 as one of the target sites;. furthermore, we revealed that lrrk2-mediated phosphorylation of tau reduces its tubulin-binding ability.	SIGNOR-195756
P51608	P26358	1	binding	up-regulates activity	0.528	Thus, these results indicate that MeCP2-interacting Dnmt1 has significant maintenance DNA methyltransferase activity and that MeCP2 does not vanish Dnmt1 enzymatic activity.	SIGNOR-264541
Q05655	P31431	1	phosphorylation	up-regulates activity	0.528	The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant.	SIGNOR-116265
Q96J02	O43353	1	binding	up-regulates activity	0.528	ITCH preferentially binds to RIPK2, promoting its K63-linked ubiquitination while simultaneously protecting YAP protein levels and maintaining its nuclear localization in CRC cells.	SIGNOR-280458
P15172	P51532	1	binding	up-regulates	0.528	Myod targets brg1 to the myogenin promoter during the initiation of myogenesis in tissue culture models for skeletal muscle differentiation /initiation of myogenin transcription is dependent upon myod, the pbx homeodomain factor, and swi/snf chromatin-remodeling enzymes	SIGNOR-151685
P22681	P06213	2	ubiquitination	down-regulates	0.528	Aps couples c-cbl to theinsulinreceptor, resulting in ubiquitination of theinsulinreceptor	SIGNOR-109688
P23458	P29597	1	phosphorylation	up-regulates	0.527	These results indicate that tyk2 is activated by phosphorylation on tyr-1054 and/or tyr-1055 and that this phosphorylation requires another kinase, most likely jak1.	SIGNOR-43080
P12931	P29350	2	phosphorylation	up-regulates	0.527	Recombinant shp-1 had elevated activity subsequent to phosphorylation by src in vitro, and shp-1 variants with mutated phosphorylation sites in the c terminus, shp-1 y538f, and shp-1 y538f,y566f were less active toward src-generated phosphoproteins in intact cells.	SIGNOR-120492
P00519	P09619	2	phosphorylation	down-regulates activity	0.527	C-Abl phosphorylates three tyrosine residues on PDGFR-β (Y686, Y934, Y970) \| These data are exciting as they indicate that abl kinases not only are activated by pdgfr and promote pdgfr-mediated proliferation and migration,but also act in an intricate negative feedback loop to turn-off pdgfr-mediated chemotaxis.	SIGNOR-260931
P27105	P11166	1	binding	down-regulates activity	0.527	Similar to the results obtained in the RBC, Glut1 and stomatin immunoprecipitated with each other in lysates of Clone 9 cells. The above results suggest that stomatin is closely associated with Glut1 in the plasma membrane and that overexpression of stomatin results in a depression in the basal rate of glucose transport.	SIGNOR-261278
P09619	P00519	2	phosphorylation	up-regulates activity	0.527	Here, we show that PDGFR-beta-phosphorylation of Abl kinases has functional consequences as PDGFR-beta phosphorylates Abl kinases on Y245 and Y412, sites known to be required for activation of Abl kinases.	SIGNOR-278319
P49841	P46821	1	phosphorylation	down-regulates activity	0.527	GSK-3beta phosphorylates MAP1B and the adenomatous polyposis coil gene product (APC; Grimes and Jope 2001; Frame and Cohen 2001). The phosphorylation of MAP1B by GSK-3beta suppresses detyrosination of microtubules and decreases the numbers of stable microtubules	SIGNOR-264843
P54829	P06241	1	dephosphorylation	down-regulates	0.527	Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.	SIGNOR-86791
Q6UWE0	Q99816	1	monoubiquitination	down-regulates quantity	0.527	Tal increases ubiquitylation of Tsg101 and affects its solubility in a RING- and PTAP-dependent manner. Tal-mediated ubiquitylation of Tsg101 inactivates this sorting function and concomitantly translocates Tsg101 from relatively insoluble membrane subdomains. Presumably, the coordinated action of Tal and a deubiquitylation enzyme (DUB) enables recycling of Tsg101 and reloading of cargo.	SIGNOR-271509
Q16649	P08700	1	transcriptional regulation	up-regulates quantity by expression	0.527	NF-IL3A transactivates the IL-3 promoter through the A region sequences.	SIGNOR-266222
P28482	Q07820	1	phosphorylation	up-regulates	0.527	We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.	SIGNOR-92593
O75365	P05556	1	dephosphorylation	down-regulates activity	0.527	In this study, we demonstrate that PRL-3 directly binds to integrin \u03b21 and dephosphorylates integrin \u03b21-Y783, a key residue for integrin \u03b21 function [ ].\|These results indicate that PRL-3 dephosphorylates integrin \u03b21 in vitro and in vivo.	SIGNOR-277050
P08588	P63092	1	binding	up-regulates activity	0.527	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-256758
P31749	P26358	1	phosphorylation	up-regulates	0.527	Akt1 kinase colocalizes and directly interacts with dnmt1 and phosphorylates ser143. Phosphorylated dnmt1 peaks during dna synthesis, before dnmt1 methylation. Depletion of akt1 or overexpression of dominant-negative akt1 increases methylated dnmt1, resulting in a decrease in dnmt1 abundance. In mammalian cells, phosphorylated dnmt1 is more stable than methylated dnmt1.	SIGNOR-170530
P29350	P12931	2	dephosphorylation	up-regulates activity	0.527	Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B	SIGNOR-248472
P03372	Q92731	1	binding	up-regulates	0.527	It was recently shown that er? And er? Could form a heterodimer complex both in vitro and in vivo	SIGNOR-64427
P45983	P37231	1	phosphorylation	down-regulates activity	0.527	The a/b domain of human ppargamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (s84a) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by erk2 and jnk, and this was markedly reduced in the s84a mutant. Thus, phosphorylation of a mitogen-activated protein kinase site in the a/b region of ppargamma inhibits both ligand-independent and ligand-dependent transactivation functions.	SIGNOR-46518
P61764	Q9ULB1	1	binding	up-regulates activity	0.527	We propose that all these neurexin complexes can interact with Munc18. Both Mint1 and Mint2 could function as direct adaptors of Munc18 to neurexins, whereas Mint1 in addition could recruit Munc18 to CASK-neurexin (Fig. 5 B).	SIGNOR-264040
P55283	P35222	1	binding	up-regulates activity	0.527	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265866
P12931	P52735	1	phosphorylation	up-regulates activity	0.527	Since we find that Vav2 is necessary for cell spreading and Src activity is necessary for Vav2 activation of Rac and lamellipodia formation, our data suggest a model of Rac activation by integrins that depends on Src phosphorylation of Vav2.\|We did not detect increased Rac activation when Vav2 was cotransfected with activated Src, although Vav2 tyrosine phosphorylation was increased (data not shown), indicating that endogenous Src activity is sufficient to fully activate Vav2.	SIGNOR-280138
Q2Q1W2	Q6ZN17	1	polyubiquitination	down-regulates quantity by destabilization	0.527	In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination.	SIGNOR-272054
Q14289	P06396	1	phosphorylation	down-regulates activity	0.527	Our results demonstrate that PYK2 inhibits this EGTA stable gelsolin-actin monomer association.\|PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids.	SIGNOR-278325
Q16539	Q9Y6Q9	1	phosphorylation	up-regulates activity	0.526	P38 MAPK and JNK can phosphorylate multiple sites on SRC-3, including S505, S543, S860, and S867. Our results suggest that several kinases are important for phosphorylating SRC-3 and enhancing its interaction with DNA-dependent transcription factors and other coactivators.	SIGNOR-250103
P00519	P05412	1	phosphorylation	up-regulates activity	0.526	Active nuclear Abl efficiently phosphorylate c-Jun. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl.	SIGNOR-251428
P08311	P55085	1	cleavage	down-regulates activity	0.526	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263585
P45983	Q07820	1	phosphorylation	up-regulates	0.526	We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.	SIGNOR-92597
P24941	P55273	1	phosphorylation	up-regulates	0.526	Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation.	SIGNOR-197270
Q16539	P19419	1	phosphorylation	up-regulates	0.526	We demonstrate here that elk-1 is barely activated by a third subclass of map kinases (p38), most likely because the critical residues ser383 and ser389 are poorly phosphorylated by p38 map kinase.	SIGNOR-47630
P16591	P14923	1	phosphorylation	up-regulates activity	0.526	The tyrosine kinase Fer, which modifies beta-catenin Tyr142, lessening its association with alpha-catenin, phosphorylates plakoglobin Tyr549 and exerts the contrary effect: it raises the binding of plakoglobin to alpha-catenin. Fer stimulation, through modification of Tyr549, causes diminished binding of plakoglobin to components of desmosomes (desmoplakin) and increased interaction with adherens junction proteins (α-catenin)	SIGNOR-251134
Q13191	P16333	1	binding	up-regulates activity	0.526	Activated Cbl and Cbl-b interacted with Crk-L, Zap-70, Nck, PLC-gamma	SIGNOR-236054
Q92830	P84022	1	binding	up-regulates	0.526	Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo.	SIGNOR-123318
P06239	Q05655	1	phosphorylation	up-regulates activity	0.526	The tyrosine phosphorylation sites of PKC delta in the H(2)O(2)-treated cells were identified as Tyr-311, Tyr-332, and Tyr-512 by mass spectrometric analysis with the use of the precursor-scan method and by immunoblot analysis with the use of phosphorylation site-specific antibodies. Tyr-311 was the predominant modification site among them. In an in vitro study, phosphorylation at this site by Lck, a non-receptor-type tyrosine kinase, enhanced the basal enzymatic activity and elevated its maximal velocity in the presence of diacylglycerol. phosphorylation at Tyr-311 between the regulatory and catalytic domains is a critical step for generation of the active PKC delta in response to H(2)O(2).	SIGNOR-251386
P12931	O15455	1	phosphorylation	up-regulates activity	0.526	Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.\|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .	SIGNOR-279657
P06493	P62820	1	phosphorylation	down-regulates activity	0.526	We now present biochemical evidence for a mitosis-specific p34cdc2 phosphorylation of RablAp and Rab4p.We also show that the distribution of RablAp and Rab4p between cytosolic and membrane-bound forms is different in interphase and mitotic cells.	SIGNOR-261284
P04899	O95622	1	binding	down-regulates activity	0.526	Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3	SIGNOR-278075
Q9BRX9	Q02750	1	binding	up-regulates	0.526	Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.	SIGNOR-124470
O96017	P51530	1	phosphorylation	up-regulates activity	0.526	We later observed that Dna2 phosphorylation by Cds1 is necessary for Dna2 association with chromatin in HU treated cells.	SIGNOR-279729
O96017	P54132	1	phosphorylation	down-regulates quantity by destabilization	0.526	We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates.Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges.	SIGNOR-276908
P12931	P17655	1	phosphorylation	up-regulates activity	0.525	CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation.	SIGNOR-277598
Q00535	Q12879	1	phosphorylation	up-regulates activity	0.525	Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.	SIGNOR-250666
Q14289	O43150	1	phosphorylation	up-regulates activity	0.525	Tyrosine phosphorylation of Pap by Pyk2 or Src kinases. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells.	SIGNOR-269704
P53778	P10636	1	phosphorylation	down-regulates activity	0.525	Phosphorylation of tau by SAPK3 and SAPK4 markedly reduced the ability of tau to promote microtubule assembly. SAPK3 (also called ERK6 and p38) and SAPK4 phosphorylate recombinant tau protein at multiple Ser/Thr-Pro sites that are hyperphosphorylated in PHF-tau, with SAPK4 and SAPK3 being the most effective.	SIGNOR-250087
Q9BRX9	P04049	1	binding	up-regulates	0.525	Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.	SIGNOR-124476
P36888	Q06124	1	binding	up-regulates activity	0.525	Y599 was additionally found to interact with the protein tyrosine phosphatase SHP2 in a phosphorylation-dependent manner. As Y599F-Flt3-32D was unable to associate with and to phosphorylate SHP2 and since silencing of SHP2 in WT-Flt3-expressing cells mimicked the Y599F-Flt3 phenotype, we hypothesize that recruitment of SHP2 to pY599 contributes to FL-mediated Erk activation and proliferation.	SIGNOR-245057
Q9UKV5	O15503	1	ubiquitination	down-regulates quantity by destabilization	0.525	The ubiquitination of Insig-1 is mediated by gp78 and regulated by sterols.\|gp78 mediates the degradation of Insig-1 and Insig-2.	SIGNOR-278567
Q96GX9	O14727	1	binding	down-regulates	0.525	Taken together, these results suggest that apip functions to inhibit muscle ischemic damage by binding to apaf-1 in the apaf-1/caspase-9 apoptosis pathway.	SIGNOR-126797
O15013	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.525	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260535
P0DP25	P48454	1	binding	up-regulates	0.525	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-266340
P38435	Q14393	1	carboxylation	up-regulates activity	0.525	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-265923
Q99578	Q01851	1	binding	up-regulates activity	0.525	we describe the evidence for a functional interaction between Brn-3a and Rin and demonstrate the role of Rin in modulating the activation of the Brn-3a regulated egr-1 promoter by the N-terminal domain of Brn-3a.	SIGNOR-224546
Q9BYP7	P55011	1	phosphorylation	up-regulates activity	0.525	We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities\|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs	SIGNOR-264625
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
P31751	Q92934	1	phosphorylation	down-regulates	0.525	Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155.	SIGNOR-81114
Q9H6Y7	Q96BI1	1	polyubiquitination	down-regulates quantity by destabilization	0.525	Here, we present evidences indicating that RING105, a novel conserved RING-finger protein with a PA (protease-associated) domain and a PEST sequence, is a ubiquitin ligase for TSSC5 that can function in concert with the ubiquitin-conjugating enzyme UbcH6. The polyubiquitin target site on TSSC5 was mapped to a region in the 6th hydrophilic loop.	SIGNOR-271551
P14316	P33076	1	transcriptional regulation	up-regulates quantity by expression	0.525	In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays.	SIGNOR-271681
P78527	P09874	1	phosphorylation	down-regulates activity	0.525	Therefore, through its interaction with Ku70/80 in the presence of dsDNA , DNA-PK phosphorylated PARP-1 at its catalytic CTD.	SIGNOR-280093
P31749	P23769	1	phosphorylation	down-regulates	0.524	We show that insulin induces gata2 phosphorylation on serine 401 in a pi-3k/akt-dependent manner. Insulin-dependent phosphorylation of serine 401 impairs gata2 translocation to the nucleus and its dna binding activity	SIGNOR-135614
P12931	P04637	1	phosphorylation	down-regulates quantity by destabilization	0.524	We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.	SIGNOR-276668
Q14974	P84022	1	relocalization	up-regulates	0.524	Here we show that the isolated smad 3 mh1 domain displays significant specific binding to importin beta. we propose that activation of all of the pathway-specific smad proteins (smads 1, 2, 3, 5, 8, and 9) exposes the conserved nls motif, which then binds directly to importin beta and triggers nuclear translocation.	SIGNOR-78191
Q03113	Q12802	1	binding	up-regulates activity	0.524	These data suggest that G12 is an upstream activator of AKAP-Lbc in the Rho signaling pathway.	SIGNOR-278882
Q96CW1	P00533	1	relocalization	down-regulates	0.524	The removal of the epidermal growth factor receptor (egfr) from the cell surface by endocytosis is triggered by receptor activation, but many facets of egfr trafficking remain unresolvedthe ap-2 complex is involved in the internalization of activated egfr.	SIGNOR-185124
Q99836	Q9H2U1	1	binding	up-regulates activity	0.524	We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing.	SIGNOR-260956
O95747	P55011	1	phosphorylation	up-regulates	0.524	The secretory na-k-cl cotransporter nkcc1 is activated by secretagogues through a phosphorylation-dependent mechanism. three phosphoacceptor sites were identified in the n-terminal domain of the protein (at thr184, thr189, and thr202) none of these residues occurs in the context of strong consensus sites for known ser/thr kinases.	SIGNOR-90927
Q9Y2N7	Q16665	1	transcriptional regulation	down-regulates quantity by repression	0.524	None of the long HIF-3α variants was capable of efficient induction of an HRE reporter in overexpression experiments, but instead inhibited the transcriptional activation of the reporter by HIF-1 and HIF-2.	SIGNOR-261615
P29275	P38405	1	binding	up-regulates activity	0.524	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-256910
P27348	P46527	1	binding	down-regulates	0.524	14-3-3_, 14-3-3_, and 14-3-3_ (but not 14-3-3_ and 14-3-3_) could form a complex with p27kip1 / we discovered that akt-mediated p27kip1phosphorylation directly induces p27kip1binding to 14-3-3 and cytoplasmic localization through phosphorylating the newly identified thr198residue.	SIGNOR-88300
P26927	Q13043	1	phosphorylation	up-regulates	0.524	We directly show that okadaic acid induces phosphorylation in the activation loop of mst, and, once phosphorylated, mst is rapidly translocated to the nucleus. when thr183 in mst1 was mutated to ala, no band could be detected by oa treatment,2 indicating that thr183 was the site of phosphorylation.	SIGNOR-114289
P53350	Q9H1A4	1	phosphorylation	up-regulates	0.524	Our analysis revealed an unexpected and unprecedented complexity of mitotic phosphorylation sites and suggests that other kinases than cdk1 and plk1 also contribute to apc phosphorylation.	SIGNOR-119881
P30872	P63096	1	binding	up-regulates activity	0.524	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-256679
P56524	Q13950	1	deacetylation	down-regulates activity	0.524	HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation	SIGNOR-227547
Q03112	Q01196	1	binding	down-regulates activity	0.524	The results that we present here support this model and show that EVI1 interacts with and inhibits RUNX1. As for GATA1, EVI1 seems to repress RUNX1 function by interacting specifically with its DNA-binding domain Runt, leading to destabilization and dissolution of the DNA-RUNX1 complex.	SIGNOR-255716
Q14289	Q05397	1	phosphorylation	up-regulates	0.524	Activated rock phosphorylates fak on ser732, which is essential for phosphorylation of tyr407 and for cell migration. We further show that pyk2 is activated by vegf-induced clustering of integrin v 3 and is responsible for the phosphorylation of tyr407.	SIGNOR-147070
Q9UK22	P56817	1	binding	down-regulates quantity by destabilization	0.523	SCFFbx2-E3-ligase-mediated degradation of BACE1 attenuates Alzheimer’s disease amyloidosis and improves synaptic function. We report that the SCF(Fbx2) -E3 ligase is involved in the binding and ubiquitination of BACE1 via its Trp 280 residue of F-box-associated domain. we found that overexpression of Fbx2 in the primary cortical and hippocampal neurons derived from Tg2576 transgenic mice significantly promoted BACE1 degradation and reduced β-amyloid production.	SIGNOR-271904
P23443	P08151	1	phosphorylation	up-regulates	0.523	In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.	SIGNOR-196756
P21333	P45985	1	binding	up-regulates activity	0.523	We used Filamin-A-deficient cells to show that Filamin A enhances MKK7 activation and is important for synergistic stress-induced JNK activation in vivo. Thus Filamin A is a novel member of the group of scaffold proteins whose function is to link two MAPKKs together and promote JNK activation. The present study provides evidence that Filamin A is one of the ‘binder’ molecules presumed to directly and closely connect MKK4 and MKK7 so that they can mediate this tyrosine/threonine phosphorylation. We showed that Filamin A (as well as Filamin B and C) associate with MKK7 and MKK4, but not with JNK1 itself	SIGNOR-260629
P84022	Q9BZS1	1	null	up-regulates	0.523	The TCR, IL-2R, and TbetaR must all be stimulated to induce Foxp3 + Tregs. Failure to engage any one of these receptors prevents the generation of Foxp3 + Tregs	SIGNOR-254363
P53350	Q14203	1	phosphorylation	up-regulates	0.523	Plk1-mediated phosphorylation of p150(glued) at ser-179 positively regulates its accumulation at the nuclear envelope during prophase.	SIGNOR-167281
P63096	P60953	1	binding	up-regulates activity	0.523	These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin	SIGNOR-256531
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
P17252	Q96A00	1	phosphorylation	up-regulates activity	0.523	A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.	SIGNOR-249259
P30550	P50148	1	binding	up-regulates activity	0.523	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-257372
Q16539	Q15717	1	phosphorylation	up-regulates	0.523	P38 mapk phosphorylates the mrna binding protein hur on thr118, which results in cytoplasmic accumulation of hur and its enhanced binding to the p21cip1 mrna.	SIGNOR-186135
O95835	Q4VCS5	1	phosphorylation	up-regulates quantity by stabilization	0.523	Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130	SIGNOR-275843
Q8N6P7	P23458	1	binding	up-regulates	0.523	Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain.	SIGNOR-124489
Q9HD26	Q14457	1	binding	up-regulates	0.523	Npist binds beclin 1 by a ccd	SIGNOR-171896
P54727	P15927	1	binding	up-regulates activity	0.523	GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).\|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo	SIGNOR-275699

P29320

P12931

1

binding

up-regulates

0.528

We propose src kinase as a downstream effector that mediates the neuron's response to eph receptor activation.

SIGNOR-58139

Q9UER7

P37173

1

binding

up-regulates

0.528

Tgf-beta-induced apoptosis is mediated by the adapter protein daxx that facilitates jnk activation

SIGNOR-109542

P06493

Q96EB6

1

phosphorylation

up-regulates

0.528

We identified cyclinb/cdk1 as a cell cycle-dependent kinase that forms a complex with and phosphorylates sirt1. Mutation of two residues phosphorylated by cyclin b/cdk1 (threonine 530 and serine 540) disturbs normal cell cycle progression and fails to rescue proliferation defects in sirt1-deficient cells

SIGNOR-182863

P06213

P22681

2

phosphorylation

up-regulates activity

0.528

Insulin receptor phosphorylates Cbl on tyrosines 371, 700, and 774 in the presence of APS. This phosphorylation event is required for the recruitment of Crk to the CAP/Cbl complex and for the subsequent activation of GLUT4 translocation.

SIGNOR-251304

Q15131

P15036

1

phosphorylation

down-regulates quantity by destabilization

0.528

Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines.

SIGNOR-260914

P31751

P55211

1

phosphorylation

down-regulates

0.528

Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity

SIGNOR-61561

P49715

P17947

1

transcriptional regulation

up-regulates quantity by expression

0.528

Activation of C/EBPα induces PU.1 expression, cell cycle arrest, and differentiation in 32D cells expressing FLT3/ITD

SIGNOR-261531

Q15569

P23528

1

phosphorylation

down-regulates activity

0.528

Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin

SIGNOR-246723

Q96HP0

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.528

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

SIGNOR-275670

Q5S007

P10636

1

phosphorylation

down-regulates

0.528

Lrrk2 directly phosphorylates tubulin-associated tau, but not free tau;(iii) lrrk2 phosphorylates tau at thr181 as one of the target sites;. furthermore, we revealed that lrrk2-mediated phosphorylation of tau reduces its tubulin-binding ability.

SIGNOR-195756

P51608

P26358

1

binding

up-regulates activity

0.528

Thus, these results indicate that MeCP2-interacting Dnmt1 has significant maintenance DNA methyltransferase activity and that MeCP2 does not vanish Dnmt1 enzymatic activity.

SIGNOR-264541

Q05655

P31431

1

phosphorylation

up-regulates activity

0.528

The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant.

SIGNOR-116265

Q96J02

O43353

1

binding

up-regulates activity

0.528

ITCH preferentially binds to RIPK2, promoting its K63-linked ubiquitination while simultaneously protecting YAP protein levels and maintaining its nuclear localization in CRC cells.

SIGNOR-280458

P15172

P51532

1

binding

up-regulates

0.528

Myod targets brg1 to the myogenin promoter during the initiation of myogenesis in tissue culture models for skeletal muscle differentiation /initiation of myogenin transcription is dependent upon myod, the pbx homeodomain factor, and swi/snf chromatin-remodeling enzymes

SIGNOR-151685

P22681

P06213

2

ubiquitination

down-regulates

0.528

Aps couples c-cbl to theinsulinreceptor, resulting in ubiquitination of theinsulinreceptor

SIGNOR-109688

P23458

P29597

1

phosphorylation

up-regulates

0.527

These results indicate that tyk2 is activated by phosphorylation on tyr-1054 and/or tyr-1055 and that this phosphorylation requires another kinase, most likely jak1.

SIGNOR-43080

P12931

P29350

2

phosphorylation

up-regulates

0.527

Recombinant shp-1 had elevated activity subsequent to phosphorylation by src in vitro, and shp-1 variants with mutated phosphorylation sites in the c terminus, shp-1 y538f, and shp-1 y538f,y566f were less active toward src-generated phosphoproteins in intact cells.

SIGNOR-120492

P00519

P09619

2

phosphorylation

down-regulates activity

0.527

C-Abl phosphorylates three tyrosine residues on PDGFR-β (Y686, Y934, Y970) | These data are exciting as they indicate that abl kinases not only are activated by pdgfr and promote pdgfr-mediated proliferation and migration,but also act in an intricate negative feedback loop to turn-off pdgfr-mediated chemotaxis.

SIGNOR-260931

P27105

P11166

1

binding

down-regulates activity

0.527

Similar to the results obtained in the RBC, Glut1 and stomatin immunoprecipitated with each other in lysates of Clone 9 cells. The above results suggest that stomatin is closely associated with Glut1 in the plasma membrane and that overexpression of stomatin results in a depression in the basal rate of glucose transport.

SIGNOR-261278

P09619

P00519

2

phosphorylation

up-regulates activity

0.527

Here, we show that PDGFR-beta-phosphorylation of Abl kinases has functional consequences as PDGFR-beta phosphorylates Abl kinases on Y245 and Y412, sites known to be required for activation of Abl kinases.

SIGNOR-278319

P49841

P46821

1

phosphorylation

down-regulates activity

0.527

GSK-3beta phosphorylates MAP1B and the adenomatous polyposis coil gene product (APC; Grimes and Jope 2001; Frame and Cohen 2001). The phosphorylation of MAP1B by GSK-3beta suppresses detyrosination of microtubules and decreases the numbers of stable microtubules

SIGNOR-264843

P54829

P06241

1

dephosphorylation

down-regulates

0.527

Wild-type step(61) dephosphorylates fyn at tyr(420) but not at tyr(531). These results suggest that step regulates the activity of fyn by specifically dephosphorylating the regulatory tyr(420) and may be one mechanism by which fyn activity is decreased within psds.

SIGNOR-86791

Q6UWE0

Q99816

1

monoubiquitination

down-regulates quantity

0.527

Tal increases ubiquitylation of Tsg101 and affects its solubility in a RING- and PTAP-dependent manner. Tal-mediated ubiquitylation of Tsg101 inactivates this sorting function and concomitantly translocates Tsg101 from relatively insoluble membrane subdomains. Presumably, the coordinated action of Tal and a deubiquitylation enzyme (DUB) enables recycling of Tsg101 and reloading of cargo.

SIGNOR-271509

Q16649

P08700

1

transcriptional regulation

up-regulates quantity by expression

0.527

NF-IL3A transactivates the IL-3 promoter through the A region sequences.

SIGNOR-266222

P28482

Q07820

1

phosphorylation

up-regulates

0.527

We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.

SIGNOR-92593

O75365

P05556

1

dephosphorylation

down-regulates activity

0.527

In this study, we demonstrate that PRL-3 directly binds to integrin \u03b21 and dephosphorylates integrin \u03b21-Y783, a key residue for integrin \u03b21 function [ ].|These results indicate that PRL-3 dephosphorylates integrin \u03b21 in vitro and in vivo.

SIGNOR-277050

P08588

P63092

1

binding

up-regulates activity

0.527

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-256758

P31749

P26358

1

phosphorylation

up-regulates

0.527

Akt1 kinase colocalizes and directly interacts with dnmt1 and phosphorylates ser143. Phosphorylated dnmt1 peaks during dna synthesis, before dnmt1 methylation. Depletion of akt1 or overexpression of dominant-negative akt1 increases methylated dnmt1, resulting in a decrease in dnmt1 abundance. In mammalian cells, phosphorylated dnmt1 is more stable than methylated dnmt1.

SIGNOR-170530

P29350

P12931

2

dephosphorylation

up-regulates activity

0.527

Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B

SIGNOR-248472

P03372

Q92731

1

binding

up-regulates

0.527

It was recently shown that er? And er? Could form a heterodimer complex both in vitro and in vivo

SIGNOR-64427

P45983

P37231

1

phosphorylation

down-regulates activity

0.527

The a/b domain of human ppargamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (s84a) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by erk2 and jnk, and this was markedly reduced in the s84a mutant. Thus, phosphorylation of a mitogen-activated protein kinase site in the a/b region of ppargamma inhibits both ligand-independent and ligand-dependent transactivation functions.

SIGNOR-46518

P61764

Q9ULB1

1

binding

up-regulates activity

0.527

We propose that all these neurexin complexes can interact with Munc18. Both Mint1 and Mint2 could function as direct adaptors of Munc18 to neurexins, whereas Mint1 in addition could recruit Munc18 to CASK-neurexin (Fig. 5 B).

SIGNOR-264040

P55283

P35222

1

binding

up-regulates activity

0.527

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

SIGNOR-265866

P12931

P52735

1

phosphorylation

up-regulates activity

0.527

Since we find that Vav2 is necessary for cell spreading and Src activity is necessary for Vav2 activation of Rac and lamellipodia formation, our data suggest a model of Rac activation by integrins that depends on Src phosphorylation of Vav2.|We did not detect increased Rac activation when Vav2 was cotransfected with activated Src, although Vav2 tyrosine phosphorylation was increased (data not shown), indicating that endogenous Src activity is sufficient to fully activate Vav2.

SIGNOR-280138

Q2Q1W2

Q6ZN17

1

polyubiquitination

down-regulates quantity by destabilization

0.527

In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination.

SIGNOR-272054

Q14289

P06396

1

phosphorylation

down-regulates activity

0.527

Our results demonstrate that PYK2 inhibits this EGTA stable gelsolin-actin monomer association.|PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids.

SIGNOR-278325

Q16539

Q9Y6Q9

1

phosphorylation

up-regulates activity

0.526

P38 MAPK and JNK can phosphorylate multiple sites on SRC-3, including S505, S543, S860, and S867. Our results suggest that several kinases are important for phosphorylating SRC-3 and enhancing its interaction with DNA-dependent transcription factors and other coactivators.

SIGNOR-250103

P00519

P05412

1

phosphorylation

up-regulates activity

0.526

Active nuclear Abl efficiently phosphorylate c-Jun. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl.

SIGNOR-251428

P08311

P55085

1

cleavage

down-regulates activity

0.526

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3

SIGNOR-263585

P45983

Q07820

1

phosphorylation

up-regulates

0.526

We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.

SIGNOR-92597

P24941

P55273

1

phosphorylation

up-regulates

0.526

Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation.

SIGNOR-197270

Q16539

P19419

1

phosphorylation

up-regulates

0.526

We demonstrate here that elk-1 is barely activated by a third subclass of map kinases (p38), most likely because the critical residues ser383 and ser389 are poorly phosphorylated by p38 map kinase.

SIGNOR-47630

P16591

P14923

1

phosphorylation

up-regulates activity

0.526

The tyrosine kinase Fer, which modifies beta-catenin Tyr142, lessening its association with alpha-catenin, phosphorylates plakoglobin Tyr549 and exerts the contrary effect: it raises the binding of plakoglobin to alpha-catenin. Fer stimulation, through modification of Tyr549, causes diminished binding of plakoglobin to components of desmosomes (desmoplakin) and increased interaction with adherens junction proteins (α-catenin)

SIGNOR-251134

Q13191

P16333

1

binding

up-regulates activity

0.526

Activated Cbl and Cbl-b interacted with Crk-L, Zap-70, Nck, PLC-gamma

SIGNOR-236054

Q92830

P84022

1

binding

up-regulates

0.526

Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo.

SIGNOR-123318

P06239

Q05655

1

phosphorylation

up-regulates activity

0.526

The tyrosine phosphorylation sites of PKC delta in the H(2)O(2)-treated cells were identified as Tyr-311, Tyr-332, and Tyr-512 by mass spectrometric analysis with the use of the precursor-scan method and by immunoblot analysis with the use of phosphorylation site-specific antibodies. Tyr-311 was the predominant modification site among them. In an in vitro study, phosphorylation at this site by Lck, a non-receptor-type tyrosine kinase, enhanced the basal enzymatic activity and elevated its maximal velocity in the presence of diacylglycerol. phosphorylation at Tyr-311 between the regulatory and catalytic domains is a critical step for generation of the active PKC delta in response to H(2)O(2).

SIGNOR-251386

P12931

O15455

1

phosphorylation

up-regulates activity

0.526

Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .

SIGNOR-279657

P06493

P62820

1

phosphorylation

down-regulates activity

0.526

We now present biochemical evidence for a mitosis-specific p34cdc2 phosphorylation of RablAp and Rab4p.We also show that the distribution of RablAp and Rab4p between cytosolic and membrane-bound forms is different in interphase and mitotic cells.

SIGNOR-261284

P04899

O95622

1

binding

down-regulates activity

0.526

Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3

SIGNOR-278075

Q9BRX9

Q02750

1

binding

up-regulates

0.526

Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.

SIGNOR-124470

O96017

P51530

1

phosphorylation

up-regulates activity

0.526

We later observed that Dna2 phosphorylation by Cds1 is necessary for Dna2 association with chromatin in HU treated cells.

SIGNOR-279729

O96017

P54132

1

phosphorylation

down-regulates quantity by destabilization

0.526

We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates.Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges.

SIGNOR-276908

P12931

P17655

1

phosphorylation

up-regulates activity

0.525

CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation.

SIGNOR-277598

Q00535

Q12879

1

phosphorylation

up-regulates activity

0.525

Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.

SIGNOR-250666

Q14289

O43150

1

phosphorylation

up-regulates activity

0.525

Tyrosine phosphorylation of Pap by Pyk2 or Src kinases. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells.

SIGNOR-269704

P53778

P10636

1

phosphorylation

down-regulates activity

0.525

Phosphorylation of tau by SAPK3 and SAPK4 markedly reduced the ability of tau to promote microtubule assembly. SAPK3 (also called ERK6 and p38) and SAPK4 phosphorylate recombinant tau protein at multiple Ser/Thr-Pro sites that are hyperphosphorylated in PHF-tau, with SAPK4 and SAPK3 being the most effective.

SIGNOR-250087

Q9BRX9

P04049

1

binding

up-regulates

0.525

Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.

SIGNOR-124476

P36888

Q06124

1

binding

up-regulates activity

0.525

Y599 was additionally found to interact with the protein tyrosine phosphatase SHP2 in a phosphorylation-dependent manner. As Y599F-Flt3-32D was unable to associate with and to phosphorylate SHP2 and since silencing of SHP2 in WT-Flt3-expressing cells mimicked the Y599F-Flt3 phenotype, we hypothesize that recruitment of SHP2 to pY599 contributes to FL-mediated Erk activation and proliferation.

SIGNOR-245057

Q9UKV5

O15503

1

ubiquitination

down-regulates quantity by destabilization

0.525

The ubiquitination of Insig-1 is mediated by gp78 and regulated by sterols.|gp78 mediates the degradation of Insig-1 and Insig-2.

SIGNOR-278567

Q96GX9

O14727

1

binding

down-regulates

0.525

Taken together, these results suggest that apip functions to inhibit muscle ischemic damage by binding to apaf-1 in the apaf-1/caspase-9 apoptosis pathway.

SIGNOR-126797

O15013

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.525

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260535

P0DP25

P48454

1

binding

up-regulates

0.525

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

SIGNOR-266340

P38435

Q14393

1

carboxylation

up-regulates activity

0.525

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-265923

Q99578

Q01851

1

binding

up-regulates activity

0.525

we describe the evidence for a functional interaction between Brn-3a and Rin and demonstrate the role of Rin in modulating the activation of the Brn-3a regulated egr-1 promoter by the N-terminal domain of Brn-3a.

SIGNOR-224546

Q9BYP7

P55011

1

phosphorylation

up-regulates activity

0.525

We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs

SIGNOR-264625

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

P31751

Q92934

1

phosphorylation

down-regulates

0.525

Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155.

SIGNOR-81114

Q9H6Y7

Q96BI1

1

polyubiquitination

down-regulates quantity by destabilization

0.525

Here, we present evidences indicating that RING105, a novel conserved RING-finger protein with a PA (protease-associated) domain and a PEST sequence, is a ubiquitin ligase for TSSC5 that can function in concert with the ubiquitin-conjugating enzyme UbcH6. The polyubiquitin target site on TSSC5 was mapped to a region in the 6th hydrophilic loop.

SIGNOR-271551

P14316

P33076

1

transcriptional regulation

up-regulates quantity by expression

0.525

In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays.

SIGNOR-271681

P78527

P09874

1

phosphorylation

down-regulates activity

0.525

Therefore, through its interaction with Ku70/80 in the presence of dsDNA , DNA-PK phosphorylated PARP-1 at its catalytic CTD.

SIGNOR-280093

P31749

P23769

1

phosphorylation

down-regulates

0.524

We show that insulin induces gata2 phosphorylation on serine 401 in a pi-3k/akt-dependent manner. Insulin-dependent phosphorylation of serine 401 impairs gata2 translocation to the nucleus and its dna binding activity

SIGNOR-135614

P12931

P04637

1

phosphorylation

down-regulates quantity by destabilization

0.524

We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.

SIGNOR-276668

Q14974

P84022

1

relocalization

up-regulates

0.524

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

SIGNOR-78191

Q03113

Q12802

1

binding

up-regulates activity

0.524

These data suggest that G12 is an upstream activator of AKAP-Lbc in the Rho signaling pathway.

SIGNOR-278882

Q96CW1

P00533

1

relocalization

down-regulates

0.524

The removal of the epidermal growth factor receptor (egfr) from the cell surface by endocytosis is triggered by receptor activation, but many facets of egfr trafficking remain unresolvedthe ap-2 complex is involved in the internalization of activated egfr.

SIGNOR-185124

Q99836

Q9H2U1

1

binding

up-regulates activity

0.524

We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing.

SIGNOR-260956

O95747

P55011

1

phosphorylation

up-regulates

0.524

The secretory na-k-cl cotransporter nkcc1 is activated by secretagogues through a phosphorylation-dependent mechanism. three phosphoacceptor sites were identified in the n-terminal domain of the protein (at thr184, thr189, and thr202) none of these residues occurs in the context of strong consensus sites for known ser/thr kinases.

SIGNOR-90927

Q9Y2N7

Q16665

1

transcriptional regulation

down-regulates quantity by repression

0.524

None of the long HIF-3α variants was capable of efficient induction of an HRE reporter in overexpression experiments, but instead inhibited the transcriptional activation of the reporter by HIF-1 and HIF-2.

SIGNOR-261615

P29275

P38405

1

binding

up-regulates activity

0.524

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-256910

P27348

P46527

1

binding

down-regulates

0.524

14-3-3_, 14-3-3_, and 14-3-3_ (but not 14-3-3_ and 14-3-3_) could form a complex with p27kip1 / we discovered that akt-mediated p27kip1phosphorylation directly induces p27kip1binding to 14-3-3 and cytoplasmic localization through phosphorylating the newly identified thr198residue.

SIGNOR-88300

P26927

Q13043

1

phosphorylation

up-regulates

0.524

We directly show that okadaic acid induces phosphorylation in the activation loop of mst, and, once phosphorylated, mst is rapidly translocated to the nucleus. when thr183 in mst1 was mutated to ala, no band could be detected by oa treatment,2 indicating that thr183 was the site of phosphorylation.

SIGNOR-114289

P53350

Q9H1A4

1

phosphorylation

up-regulates

0.524

Our analysis revealed an unexpected and unprecedented complexity of mitotic phosphorylation sites and suggests that other kinases than cdk1 and plk1 also contribute to apc phosphorylation.

SIGNOR-119881

P30872

P63096

1

binding

up-regulates activity

0.524

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-256679

P56524

Q13950

1

deacetylation

down-regulates activity

0.524

HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation

SIGNOR-227547

Q03112

Q01196

1

binding

down-regulates activity

0.524

The results that we present here support this model and show that EVI1 interacts with and inhibits RUNX1. As for GATA1, EVI1 seems to repress RUNX1 function by interacting specifically with its DNA-binding domain Runt, leading to destabilization and dissolution of the DNA-RUNX1 complex.

SIGNOR-255716

Q14289

Q05397

1

phosphorylation

up-regulates

0.524

Activated rock phosphorylates fak on ser732, which is essential for phosphorylation of tyr407 and for cell migration. We further show that pyk2 is activated by vegf-induced clustering of integrin v 3 and is responsible for the phosphorylation of tyr407.

SIGNOR-147070

Q9UK22

P56817

1

binding

down-regulates quantity by destabilization

0.523

SCFFbx2-E3-ligase-mediated degradation of BACE1 attenuates Alzheimer’s disease amyloidosis and improves synaptic function. We report that the SCF(Fbx2) -E3 ligase is involved in the binding and ubiquitination of BACE1 via its Trp 280 residue of F-box-associated domain. we found that overexpression of Fbx2 in the primary cortical and hippocampal neurons derived from Tg2576 transgenic mice significantly promoted BACE1 degradation and reduced β-amyloid production.

SIGNOR-271904

P23443

P08151

1

phosphorylation

up-regulates

0.523

In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.

SIGNOR-196756

P21333

P45985

1

binding

up-regulates activity

0.523

We used Filamin-A-deficient cells to show that Filamin A enhances MKK7 activation and is important for synergistic stress-induced JNK activation in vivo. Thus Filamin A is a novel member of the group of scaffold proteins whose function is to link two MAPKKs together and promote JNK activation. The present study provides evidence that Filamin A is one of the ‘binder’ molecules presumed to directly and closely connect MKK4 and MKK7 so that they can mediate this tyrosine/threonine phosphorylation. We showed that Filamin A (as well as Filamin B and C) associate with MKK7 and MKK4, but not with JNK1 itself

SIGNOR-260629

P84022

Q9BZS1

1

null

up-regulates

0.523

The TCR, IL-2R, and TbetaR must all be stimulated to induce Foxp3 + Tregs. Failure to engage any one of these receptors prevents the generation of Foxp3 + Tregs

SIGNOR-254363

P53350

Q14203

1

phosphorylation

up-regulates

0.523

Plk1-mediated phosphorylation of p150(glued) at ser-179 positively regulates its accumulation at the nuclear envelope during prophase.

SIGNOR-167281

P63096

P60953

1

binding

up-regulates activity

0.523

These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin

SIGNOR-256531

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

P17252

Q96A00

1

phosphorylation

up-regulates activity

0.523

A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.

SIGNOR-249259

P30550

P50148

1

binding

up-regulates activity

0.523

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-257372

Q16539

Q15717

1

phosphorylation

up-regulates

0.523

P38 mapk phosphorylates the mrna binding protein hur on thr118, which results in cytoplasmic accumulation of hur and its enhanced binding to the p21cip1 mrna.

SIGNOR-186135

O95835

Q4VCS5

1

phosphorylation

up-regulates quantity by stabilization

0.523

Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130

SIGNOR-275843

Q8N6P7

P23458

1

binding

up-regulates

0.523

Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain.

SIGNOR-124489

Q9HD26

Q14457

1

binding

up-regulates

0.523

Npist binds beclin 1 by a ccd

SIGNOR-171896

P54727

P15927

1

binding

up-regulates activity

0.523

GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo

SIGNOR-275699