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
Q8IYT4	Q9UJT1	2	binding	down-regulates quantity by destabilization	0.257	Here we show that KATNAL2 is critical for numerous aspects of this developmental process, including the initiation of the axoneme from the basal body, suppression of the spermatid centriole duplication cycle, sperm nuclear sculpting via the manchette, the attachment of the acrosome to the nucleus and the tethering of elongated spermatids to Sertoli cells via the tubulobulbar complex and ultimately sperm release via spermiation. KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin	SIGNOR-267175
Q12959	P43403	1	phosphorylation	up-regulates activity	0.53	Immunoblot analysis showed that phosphorylation of the activating ZAP70 kinase domain residue Tyr 493 was decreased in the DLG1 KD cells. Similarly, the Tyr 319 residue of ZAP70 and Tyr 83 residue of TCR- ζ also showed reduced phosphorylation.	SIGNOR-274142
P04637	O14757	0	phosphorylation	up-regulates activity	0.78	Phosphorylation by chk1 of at least three of these sites, Ser366, Ser378, and Thr387, was induced by DNA damage.	SIGNOR-217861
P55317	P84022	2	binding	down-regulates activity	0.331	TGF-beta represses transcription of pulmonary surfactant protein-B gene in lung epithelial cells. Repression is mediated by SMAD3 through interactions with NKX2.1 and FOXA1, two key transcription factors that are positive regulators of SpB transcription. In this study, we found that SMAD3 interacts through its MAD domains, MH1 and MH2 with NKX2.1 and FOXA1 proteins. The sites of interaction on NKX2.1 are located within the NH2 and COOH domains, known to be involved in transactivation function.	SIGNOR-254168
Q13315	P04637	1	phosphorylation	up-regulates quantity by stabilization	0.843	In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.	SIGNOR-115348
P53350	Q49MG5	1	phosphorylation	up-regulates	0.275	We also demonstrate that asap is a novel substrate of plk1 phosphorylation and have identified serine 289 as the major phosphorylation site by plk1 in vivo. Asap phosphorylated on serine 289 is localized to centrosomes during mitosis, but this phosphorylation is not required for its plk1-dependent localization at the spindle poles. We show that phosphorylated asap on serine 289 contributes to spindle pole stability in a microtubule-dependent manner	SIGNOR-166564
Q13464	P35611	1	phosphorylation	up-regulates	0.376	Rho-associated kinase (rho- kinase), which is activated by the small guanosine triphosphatase rho, phosphorylates alpha-adducin and thereby enhances the f-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by rho-kinase as thr445 and thr480	SIGNOR-66996
O75525	Q8IUQ4	0	polyubiquitination	down-regulates quantity by destabilization	0.473	We found that SIAH1 bound to an octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation.	SIGNOR-272671
P21452	P20366	2	binding	up-regulates	0.874	The mammalian tachykinins include substance p, neurokinin a and neurokinin b, which exert their effects by binding to specific receptors. These tachykinin receptors are divided into three types, designated nk1, nk2 and nk3, respectively. The interaction of tachykinin with its receptor activates gq, which in turn activates phospholipase c to break down phosphatidyl inositol bisphosphate into inositol trisphosphate (ip3) and diacylglycerol (dag).	SIGNOR-44773
Q05586	Q14957	2	binding	up-regulates activity	0.612	Here, we demonstrate that PKB/Akt directly phosphorylates NR2C on serine 1096 (S1096). In addition, we identify 14-3-3epsilon as an NR2C interactor, whose binding is dependent on S1096 phosphorylation. These data are all consistent with a model in which NR1 and NR2C oligomerize, PKB phosphorylates S1096, and 14-3-3ε binds to phosphorylated NR2C thereby promoting NR2C-containing NMDA receptor surface expression in cerebellar granule cells.	SIGNOR-262621
Q8NES3	P78504	2	binding	down-regulates	0.486	Although jagged1-induced signaling was suppressed by lfng and mfng	SIGNOR-131560
Q5T0T0	P01903	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.	SIGNOR-271411
P63096	P32238	2	binding	up-regulates activity	0.252	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-257035
P11831	Q969V6	2	binding	up-regulates	0.2	Similarly, the myocd-related transcription factor (mrtf) family of proteins, mrtf-a and mrtf-b, are also involved in the transcriptional regulation of contractile gene markers as coactivators of srf.	SIGNOR-174264
P30307	P38398	0	ubiquitination	down-regulates quantity by destabilization	0.464	BRCA1 mediates cyclin B and Cdc25C ubiquitination.\|Thus, BRCA1 dependent proteasomal degradation of cyclin B and Cdc25C precede the subsequent BRCA1 dependent cell cycle arrest.	SIGNOR-278623
P0C0S5	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265408
P62136	P06493	0	phosphorylation	down-regulates activity	0.575	Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.	SIGNOR-151799
Q16543	P53041	0	dephosphorylation	down-regulates activity	0.672	Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13\|PP5/Ppt1 regulates phosphorylation of Ser13-Cdc37 in vivo, directly affecting activation of protein kinase clients by Hsp90-Cdc37.	SIGNOR-248539
P06241	Q03135	1	phosphorylation	down-regulates activity	0.721	Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn.Therefore,	SIGNOR-118003
P56817	P05067	1	cleavage	up-regulates activity	0.794	Beta-secretase 1 (BACE1) cleaves the type-I transmembrane protein APP to form the N-terminus of Aβ.	SIGNOR-255480
Q05513	Q5JVS0	1	phosphorylation	down-regulates activity	0.292	We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. \| This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. \| Ki-1/57 Exits the Nucleus upon PMA Activation	SIGNOR-249257
P05129	Q14155	1	phosphorylation	up-regulates	0.2	Pkc_ directly phosphorylates _pix at ser583 and indirectly at ser340 in cells. herefore, we propose that pkc_ positively modulates dopamine release through _2pix phosphorylation. The pkc_-_pix-cdc42/rac1 phosphorylation axis may provide a new therapeutic target for the treatment of parkinsonian syndrome	SIGNOR-205238
Q13535	P00519	0	phosphorylation	up-regulates	0.599	C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress.	SIGNOR-167632
Q9NR30	Q8IUC6	2	binding	up-regulates activity	0.266	We demonstrated here that DDX1-DDX21-DHX36 represents a dsRNA sensor that uses the adaptor molecule TRIF to activate the NF-ÎºB pathway and type I IFN responses in dendritic cells. Our study suggests that the DDX1-DDX21-DHX36 complex represents this missing poly I:C sensor, which uses DDX1 to bind poly I:C and uses DDX21 and DXH36 to bind TRIF. Poly I:C is a synthetic form of RNA that mimics double-stranded viral RNA.	SIGNOR-260192
Q13363	Q5H9F3	2	binding	up-regulates activity	0.437	BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay.	SIGNOR-259193
Q9UM73	P49841	1	phosphorylation	up-regulates activity	0.248	It has been reported that Alk phosphorylates and activates Gsk3beta in mouse neural crest explants and neuroblastoma cell lines.\|Therefore, we tested whether Alk indeed phosphorylates Y279-GSK3\u03b2 in stomach epithelial cells.	SIGNOR-280180
O95379	P04899	2	binding	up-regulates activity	0.2	TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation	SIGNOR-256492
O14647	P15172	2	binding	up-regulates activity	0.2	CHD2 also showed an interaction with MyoD, a master regulator of skeletal muscle differentiation, and together MyoD and CHD2 bind to myogenic gene promoters.	SIGNOR-264525
O95837	P21728	2	binding	up-regulates activity	0.265	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-257391
P05412	Q8WYK2	2	binding	down-regulates activity	0.607	JDP2 dimerizes with other AP-1 proteins such as activating transcription factor-2 (ATF2) and Jun to repress transcription from promoters that contain a cyclic AMP-responsive element (CRE).	SIGNOR-226398
Q03113	O95136	2	binding	up-regulates	0.47	Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.	SIGNOR-198556
P51878	P57764	1	cleavage	up-regulates activity	0.62	Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD\|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence \|	SIGNOR-256418
O60674	P22681	0	ubiquitination	down-regulates quantity by destabilization	0.587	K63 linked poly-ubiquitination on K970 of JAK2 kinase domain is promoted by Cbl.	SIGNOR-278538
Q00535	P07101	1	phosphorylation	up-regulates activity	0.408	In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.\|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.	SIGNOR-279022
Q9NZN5	Q14344	2	binding	up-regulates activity	0.772	P115 RhoGEF stimulates the intrinsic GTP hydrolysis activity of G alpha 12/13 subunits and acts as an effector for G13-coupled receptors by linking receptor activation to RhoA activation.	SIGNOR-256519
P17947	P05412	2	binding	up-regulates activity	0.555	These results indicate that AML1-ETO competes c-Jun away from binding to the β3β4 domain of PU.1. Thus, the c-Jun coactivation function of PU.1 is down-regulated and this in turn down-regulates transcriptional activity of PU.1.	SIGNOR-255660
Q16665	P27361	0	phosphorylation	up-regulates	0.695	We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_	SIGNOR-178731
Q4KMG0	Q12982	2	binding	up-regulates activity	0.506	Bnip-2 and jlp are brought together through mutual interaction with cdo. the cdo-bnip-2 interaction stimulates cdc42 activity, which in turn promotes p38alpha/beta activity and cell differentiation.	SIGNOR-179864
P0DP23	P48454	2	binding	up-regulates	0.661	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-114104
Q12879	Q00535	0	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
P06493	Q9GZM8	1	phosphorylation	up-regulates activity	0.66	In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites	SIGNOR-274074
P12931	P43403	1	phosphorylation	up-regulates activity	0.479	In the cluster, Zap70 will be rapidly phosphorylated by active Src and slowly phosphorylated by autoinhibited, inactive Src.\|We provide evidence that clusters harbor a positive feedback loop among Zap70, LAT, and Src-family kinases that binds phosphorylated LAT and further activates Zap70.	SIGNOR-279126
P42345	O95163	1	phosphorylation	up-regulates activity	0.2	Human ELP1 S1174 phosphorylation was triggered by insulin treatment, as shown by the specific phosphorylated (p)ELP1 (S1174) antibody, and addition of a phosphorylation-mutant variant of the ELP1 protein (ELP1(S1174A)) to ELP1-depleted BRAFV600E melanoma cells failed to rescue cell survival \|In line with these findings, mTORC2 activity, but not mTORC1, was required for the insulin-induced phosphorylation of Elp1 S1174	SIGNOR-275541
P56524	Q14814	2	binding	down-regulates	0.692	We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2.	SIGNOR-76237
P61812	P61812	2	binding	up-regulates	0.2	The active form of tgf-b is a dimer stabilized by hydrophobic interactions and usually further strengthened by an intersubunit disulfide bridge	SIGNOR-148608
P22307	Q2T9J0	0	cleavage	up-regulates activity	0.503	Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β-oxidation. In vitro cleavage of Acox1, Scp2 and prethiolase by recombinant Tysnd1.	SIGNOR-261055
Q13813	P42574	0	cleavage	down-regulates	0.675	Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis.	SIGNOR-57891
P17706	P52333	1	dephosphorylation	down-regulates activity	0.697	Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.	SIGNOR-133078
P42574	Q92934	1	cleavage	up-regulates activity	0.536	Casp3 cleaves bad at asp-61. In addition, caspases convert bad(l) into a pro-death fragment that resembles the short splice variant.	SIGNOR-126727
P84085	O43150	0	gtpase-activating protein	up-regulates activity	0.497	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. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro.	SIGNOR-269707
O00155	P63096	2	binding	up-regulates activity	0.25	GPR25 is expressed in human memory T-cells and NK-cells and identified as a primary causal gene associated with autoimmune \|Within the class A GPCR family, GPR25 shares a relatively high degree of amino acid sequence identity (29e34%) with vertebrate Apelin receptor (APLNR) diseases revealed by cis-eQTL mapping based on a genome-wide association study (GWAS).	SIGNOR-272501
Q5VWQ8	Q99683	2	binding	up-regulates activity	0.837	DAB2IP also mediates recruitment of PP2A to ASK1, binding both proteins through its C2 domain; this favors removal of the inhibitory S967 phosphorylation and further activation of ASK1	SIGNOR-254748
O43561	P62993	2	binding	up-regulates	0.804	Phosphorylated tyrosines 171, 191, and 226 [in LAT] bind to the SH2 domains of the Grb2 family of adaptor proteins and must be present for optimal signalling	SIGNOR-251520
Q9UKV3	P42574	0	cleavage	up-regulates	0.628	Induces apoptotic chromatin condensation after activation by casp3	SIGNOR-70800
P55291	P35222	2	binding	up-regulates activity	0.635	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265854
Q15831	P49841	1	phosphorylation	down-regulates activity	0.378	In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.\|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (XREF_FIG).	SIGNOR-280148
P15056	P62136	0	dephosphorylation	up-regulates activity	0.294	To address whether PP1\u03b1 activates B-Raf through these inhibitory sites, we made use of B-Raf protein mutants in which an individual inhibitory site, as well as all four sites (4A), were mutated to alanine.\|We confirmed that GST-B-Raf was phosphorylated by ERK2 in vitro xref , mainly on S151 and T753 (Fig.\u00a0 xref ), and found that PP1\u03b1 dephosphorylated B-Raf on both ERK phosphorylation sites (Fig.\u00a0 xref ).	SIGNOR-277160
P14923	P06241	0	phosphorylation	up-regulates activity	0.561	Phosphorylation of plakoglobin by Fer and Fyn kinases decreases plakoglobin-desmoplakin interaction and increases plakoglobin-α-catenin association. Fyn mainly phosphorylated Tyr549 and that it phosphorylated Tyr133 with a much lower activity	SIGNOR-251176
P54762	P45985	1	relocalization	up-regulates activity	0.2	The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.	SIGNOR-275922
Q96FI4	Q03468	2	binding	up-regulates activity	0.344	CSB stimulates NEIL1 incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co-localize in HeLa cells.	SIGNOR-251931
Q13501	P06493	0	phosphorylation	up-regulates	0.343	Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.	SIGNOR-169012
Q14938	P41221	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268889
P49716	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.384	Phosphorylation of C/EBPdelta by GSK-3beta is required for its degradation by FBXW7alpha.	SIGNOR-279180
O14595	Q15797	1	dephosphorylation	down-regulates	0.5	In human cells, rnai-mediated depletion of scp1 and scp2 increases the extent and duration of smad1 phosphorylation in response to bmp, the transcriptional action of smad1, and the strength of endogenous bmp gene responses. The present identification of the scp family as smad c-terminal phosphatases sheds light on the events that attenuate smad signaling and reveals unexpected links to the essential phosphatases that control rna polymerase ii in eukaryotes.	SIGNOR-148434
P41182	P28482	0	phosphorylation	down-regulates	0.489	Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.	SIGNOR-58481
P25054	O15169	2	binding	up-regulates activity	0.944	Axin, an inhibitor of the wnt pathway, interacts with beta-catenin, gsk-3beta and apc and reduces the beta-catenin level.	SIGNOR-60043
Q13535	Q9Y253	1	phosphorylation	up-regulates	0.415	Atr-mediated phosphorylation of dna polymerase _ is needed for efficient recovery from uv damage. We show that, after uv irradiation, pol_ becomes phosphorylated at ser601 by the ataxia-telangiectasia mutated and rad3-related (atr) kinase. Atr-dependent phosphorylation of pol_ is necessary to restore normal survival and postreplication repair	SIGNOR-171290
P04049	P01111	0	relocalization	up-regulates	0.87	The raf family of proteins (raf-1, a-raf, and b-raf) bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.	SIGNOR-175231
P62140	P35240	1	dephosphorylation	up-regulates	0.378	When serine 518 is dephosphorylated by the myosin phosphatase mypt-1-pp1?, The tumor suppressor function of merlin is activated, inhibiting the ras signaling pathway and leading to growth arrest	SIGNOR-159836
Q05655	P12830	1	phosphorylation	down-regulates activity	0.2	Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin.	SIGNOR-260893
P24941	P42771	2	binding	down-regulates	0.48	However, induction of p16(ink4a) also causes marked inhibition of cdk2 activity.	SIGNOR-64431
Q58F21	Q13541	2	binding	up-regulates quantity	0.2	It was revealed that eIF4EBP1 interacted with BRDT, a novel interacting protein. In addition, the present study further demonstrated that BRDT inhibitors PLX51107 and INCB054329 blocked the progression of RCC cells, along with suppressing eIF4EBP1 and c‑myc expression.	SIGNOR-262049
P22612	P46020	1	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267415
Q92843	Q16611	2	binding	down-regulates	0.467	Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax.	SIGNOR-152989
P23467	P33151	1	dephosphorylation	up-regulates activity	0.581	Because we had shown previously that VE-PTP supports VE-cadherin function when exogenously expressed in transfected cells, we expected it to be expressed at endothelial cell contacts.\|Indeed, tyrosine phosphorylation of VE-cadherin is reduced by VE-PTP in COS-7 and CHO cells.	SIGNOR-277131
Q16665	O76061	1	transcriptional regulation	up-regulates quantity by expression	0.297	With the ChIP assay, we demonstrated the direct binding of HIF-1alpha to STC2 promoter. These findings support the notion that HIF-1 is a potent stimulator of STC2 expression. Collectively, this is the first report to show that STC2 was aberrantly hypermethylated in human cancer cells. The findings demonstrated that STC2 epigenetic inactivation may interfere with HIF-1 mediated activation of STC2 expression.	SIGNOR-260389
P48729	P62745	1	phosphorylation	down-regulates	0.2	Mass spectrometry analysis demonstrates that rhob is monophosphorylated by ck1, in its c-terminal end, on serine 185. lastly we show that the inhibition of ck1 activates rhob and promotes rhob dependent actin fiber formation and egf-r level.	SIGNOR-179255
P36897	Q9Y5K5	2	binding	up-regulates quantity by stabilization	0.505	Smad7 can act as an adaptor able to recruit uch37 to the type i tgf-beta receptor. Consequently, uch37 dramatically up-regulates tgf-beta-dependent gene expression by de-ubiquitinating and stabilizing the type i tgf-beta receptor.	SIGNOR-150135
Q9Y3A5	Q7Z2Z2	2	binding	up-regulates	0.2	Sbds stimulates 60s-dependent gtp hydrolysis by efl1	SIGNOR-173533
P50148	P25116	2	binding	up-regulates activity	0.582	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-257219
Q9NQS7	O96017	0	phosphorylation	up-regulates activity	0.261	Also, inhibition of Chk2 by Chk2 inhibitor II in cytokinesis after release of cells from a nocodazole-induced prometaphase block diminished INCENP localization to the midbody center in late midbodies (Fig. 1, M and N).\|In turn, active Chk2 phosphorylates human INCENP at the newly identified site Ser91 to promote INCENP binding to Mklp2, resulting in recruitment of the INCENP\u2013Mklp2 complex to the midbody center through Mklp2\u2019s interaction with the midbody protein Cep55 to delay abscission.	SIGNOR-279695
Q92993	Q16539	0	phosphorylation	up-regulates activity	0.321	We found that phosphorylation of Tip60-T158 was increased by p38\u03b1 isolated from Dox- or \u03b3-radiation-treated cells over that from untreated cells (Figure xref ), indicating that DNA damage induces the protein kinase activity of p38\u03b1 towards Tip60-T158.	SIGNOR-278958
P19086	P33032	2	binding	up-regulates activity	0.25	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-257271
Q13315	P12956	1	phosphorylation	up-regulates activity	0.713	Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks.	SIGNOR-274020
O43293	Q00987	1	phosphorylation	up-regulates quantity by stabilization	0.342	Zip kinase was able to phosphorylate mdm2 at ser166, a site previously reported to be modified by akt kinase, thus demonstrating that zip kinase is a bona fide mdm2-binding protein.	SIGNOR-123159
P10415	Q16539	0	phosphorylation	down-regulates activity	0.334	Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein.	SIGNOR-146786
P35398	Q8N2Q7	1	transcriptional regulation	up-regulates quantity by expression	0.2	Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).	SIGNOR-265136
O75581	Q03135	2	binding	up-regulates	0.676	Overall, our data suggest that wnt-3a triggers the interaction of lrp6 with caveolin and promotes recruitment of axin to lrp6 phosphorylated by glycogen synthase kinase-3beta and that caveolin thereby inhibits the binding of beta-catenin to axin.	SIGNOR-148665
Q12986	P01903	1	transcriptional regulation	down-regulates quantity by repression	0.396	A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor	SIGNOR-266224
P68400	Q6ZMG9	1	phosphorylation	up-regulates activity	0.2	Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.	SIGNOR-273992
Q9UQM7	P35367	1	phosphorylation	down-regulates	0.282	As we have shown previously, human h1r can be phosphorylated in vitro by several kinases includingpka, pkc, pkg, and camk ii in summary, these data suggest that thr140, thr142, ser396, ser398, and thr478 can be phosphorylated by the kinases described above (table 2).	SIGNOR-124348
Q13882	P18031	0	dephosphorylation	down-regulates activity	0.575	Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342.	SIGNOR-277082
Q16820	P05771	0	phosphorylation	down-regulates quantity	0.2	These findings suggest that activation of a protein kinase, presumably PKC, mediates PMA-induced hmeprinβ shedding. By labeling COS-1 cells transfected with mutant constructs lacking the potential phosphorylation sites, we identified Ser687 as the main 32P-acceptor. These data provide evidence that the cytoplasmic domain of hmeprinβ can function as a PKC substrate.	SIGNOR-263173
P0DP25	P00533	0	phosphorylation	down-regulates	0.382	Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-266335
P04637	P50613	0	phosphorylation	up-regulates	0.458	The cdk7-cych-p36 complex of transcription factor iih phosphorylates p53, enhancing its sequence-specific dna binding activity in vitro. serines 371, 376, 378, and 392 may be the potential sites for this kinase.	SIGNOR-51292
P12931	Q03135	1	phosphorylation	down-regulates activity	0.764	Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn	SIGNOR-118007
P54652	Q99683	2	binding	down-regulates	0.2	Coimmunoprecipitation analysis revealed a physical interaction between endogenous hsp72 and ask1 in nih 3t3 cells exposed to mild heat shock. Hsp72 blocked both the homo-oligomerization of ask1 and ask1-dependent apoptosis.	SIGNOR-94565
P50502	P34947	0	phosphorylation	up-regulates activity	0.268	An in vitro screen for novel GRK substrates revealed Hsp70 interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and stoichiometrically phosphorylated Hip in vitro. The primary binding domain of GRK5 was mapped to residues 303-319 on Hip, while the major site of phosphorylation was identified to be Ser-346. GRK5 also bound to and phosphorylated Hip on Ser-346 in cells.we found that the phosphorylation of Ser-346 was required for proper agonist-induced internalization of the chemokine receptor CXCR4.	SIGNOR-262877
P68400	Q9BXW9	1	phosphorylation	down-regulates activity	0.2	Here, we report a cluster of phosphosites on FANCD2 whose phosphorylation by CK2 inhibits both FANCD2 recruitment to ICLs and its monoubiquitination in vitro and in vivo. We have found that phosphorylated FANCD2 possesses reduced DNA binding activity, explaining the previous observations.	SIGNOR-276730
P07288	P12272	1	cleavage	down-regulates activity	0.422	Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. \| Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.	SIGNOR-270547

Q8IYT4

Q9UJT1

2

binding

down-regulates quantity by destabilization

0.257

Here we show that KATNAL2 is critical for numerous aspects of this developmental process, including the initiation of the axoneme from the basal body, suppression of the spermatid centriole duplication cycle, sperm nuclear sculpting via the manchette, the attachment of the acrosome to the nucleus and the tethering of elongated spermatids to Sertoli cells via the tubulobulbar complex and ultimately sperm release via spermiation. KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin

SIGNOR-267175

Q12959

P43403

1

phosphorylation

up-regulates activity

0.53

Immunoblot analysis showed that phosphorylation of the activating ZAP70 kinase domain residue Tyr 493 was decreased in the DLG1 KD cells. Similarly, the Tyr 319 residue of ZAP70 and Tyr 83 residue of TCR- ζ also showed reduced phosphorylation.

SIGNOR-274142

P04637

O14757

0

phosphorylation

up-regulates activity

0.78

Phosphorylation by chk1 of at least three of these sites, Ser366, Ser378, and Thr387, was induced by DNA damage.

SIGNOR-217861

P55317

P84022

2

binding

down-regulates activity

0.331

TGF-beta represses transcription of pulmonary surfactant protein-B gene in lung epithelial cells. Repression is mediated by SMAD3 through interactions with NKX2.1 and FOXA1, two key transcription factors that are positive regulators of SpB transcription. In this study, we found that SMAD3 interacts through its MAD domains, MH1 and MH2 with NKX2.1 and FOXA1 proteins. The sites of interaction on NKX2.1 are located within the NH2 and COOH domains, known to be involved in transactivation function.

SIGNOR-254168

Q13315

P04637

1

phosphorylation

up-regulates quantity by stabilization

0.843

In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.

SIGNOR-115348

P53350

Q49MG5

1

phosphorylation

up-regulates

0.275

We also demonstrate that asap is a novel substrate of plk1 phosphorylation and have identified serine 289 as the major phosphorylation site by plk1 in vivo. Asap phosphorylated on serine 289 is localized to centrosomes during mitosis, but this phosphorylation is not required for its plk1-dependent localization at the spindle poles. We show that phosphorylated asap on serine 289 contributes to spindle pole stability in a microtubule-dependent manner

SIGNOR-166564

Q13464

P35611

1

phosphorylation

up-regulates

0.376

Rho-associated kinase (rho- kinase), which is activated by the small guanosine triphosphatase rho, phosphorylates alpha-adducin and thereby enhances the f-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by rho-kinase as thr445 and thr480

SIGNOR-66996

O75525

Q8IUQ4

0

polyubiquitination

down-regulates quantity by destabilization

0.473

We found that SIAH1 bound to an octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation.

SIGNOR-272671

P21452

P20366

2

binding

up-regulates

0.874

The mammalian tachykinins include substance p, neurokinin a and neurokinin b, which exert their effects by binding to specific receptors. These tachykinin receptors are divided into three types, designated nk1, nk2 and nk3, respectively. The interaction of tachykinin with its receptor activates gq, which in turn activates phospholipase c to break down phosphatidyl inositol bisphosphate into inositol trisphosphate (ip3) and diacylglycerol (dag).

SIGNOR-44773

Q05586

Q14957

2

binding

up-regulates activity

0.612

Here, we demonstrate that PKB/Akt directly phosphorylates NR2C on serine 1096 (S1096). In addition, we identify 14-3-3epsilon as an NR2C interactor, whose binding is dependent on S1096 phosphorylation. These data are all consistent with a model in which NR1 and NR2C oligomerize, PKB phosphorylates S1096, and 14-3-3ε binds to phosphorylated NR2C thereby promoting NR2C-containing NMDA receptor surface expression in cerebellar granule cells.

SIGNOR-262621

Q8NES3

P78504

2

binding

down-regulates

0.486

Although jagged1-induced signaling was suppressed by lfng and mfng

SIGNOR-131560

Q5T0T0

P01903

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.

SIGNOR-271411

P63096

P32238

2

binding

up-regulates activity

0.252

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-257035

P11831

Q969V6

2

binding

up-regulates

0.2

Similarly, the myocd-related transcription factor (mrtf) family of proteins, mrtf-a and mrtf-b, are also involved in the transcriptional regulation of contractile gene markers as coactivators of srf.

SIGNOR-174264

P30307

P38398

0

ubiquitination

down-regulates quantity by destabilization

0.464

BRCA1 mediates cyclin B and Cdc25C ubiquitination.|Thus, BRCA1 dependent proteasomal degradation of cyclin B and Cdc25C precede the subsequent BRCA1 dependent cell cycle arrest.

SIGNOR-278623

P0C0S5

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265408

P62136

P06493

0

phosphorylation

down-regulates activity

0.575

Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.

SIGNOR-151799

Q16543

P53041

0

dephosphorylation

down-regulates activity

0.672

Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13|PP5/Ppt1 regulates phosphorylation of Ser13-Cdc37 in vivo, directly affecting activation of protein kinase clients by Hsp90-Cdc37.

SIGNOR-248539

P06241

Q03135

1

phosphorylation

down-regulates activity

0.721

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

SIGNOR-118003

P56817

P05067

1

cleavage

up-regulates activity

0.794

Beta-secretase 1 (BACE1) cleaves the type-I transmembrane protein APP to form the N-terminus of Aβ.

SIGNOR-255480

Q05513

Q5JVS0

1

phosphorylation

down-regulates activity

0.292

We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation

SIGNOR-249257

P05129

Q14155

1

phosphorylation

up-regulates

0.2

Pkc_ directly phosphorylates _pix at ser583 and indirectly at ser340 in cells. herefore, we propose that pkc_ positively modulates dopamine release through _2pix phosphorylation. The pkc_-_pix-cdc42/rac1 phosphorylation axis may provide a new therapeutic target for the treatment of parkinsonian syndrome

SIGNOR-205238

Q13535

P00519

0

phosphorylation

up-regulates

0.599

C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress.

SIGNOR-167632

Q9NR30

Q8IUC6

2

binding

up-regulates activity

0.266

We demonstrated here that DDX1-DDX21-DHX36 represents a dsRNA sensor that uses the adaptor molecule TRIF to activate the NF-ÎºB pathway and type I IFN responses in dendritic cells. Our study suggests that the DDX1-DDX21-DHX36 complex represents this missing poly I:C sensor, which uses DDX1 to bind poly I:C and uses DDX21 and DXH36 to bind TRIF. Poly I:C is a synthetic form of RNA that mimics double-stranded viral RNA.

SIGNOR-260192

Q13363

Q5H9F3

2

binding

up-regulates activity

0.437

BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay.

SIGNOR-259193

Q9UM73

P49841

1

phosphorylation

up-regulates activity

0.248

It has been reported that Alk phosphorylates and activates Gsk3beta in mouse neural crest explants and neuroblastoma cell lines.|Therefore, we tested whether Alk indeed phosphorylates Y279-GSK3\u03b2 in stomach epithelial cells.

SIGNOR-280180

O95379

P04899

2

binding

up-regulates activity

0.2

TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation

SIGNOR-256492

O14647

P15172

2

binding

up-regulates activity

0.2

CHD2 also showed an interaction with MyoD, a master regulator of skeletal muscle differentiation, and together MyoD and CHD2 bind to myogenic gene promoters.

SIGNOR-264525

O95837

P21728

2

binding

up-regulates activity

0.265

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-257391

P05412

Q8WYK2

2

binding

down-regulates activity

0.607

JDP2 dimerizes with other AP-1 proteins such as activating transcription factor-2 (ATF2) and Jun to repress transcription from promoters that contain a cyclic AMP-responsive element (CRE).

SIGNOR-226398

Q03113

O95136

2

binding

up-regulates

0.47

Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.

SIGNOR-198556

P51878

P57764

1

cleavage

up-regulates activity

0.62

Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence |

SIGNOR-256418

O60674

P22681

0

ubiquitination

down-regulates quantity by destabilization

0.587

K63 linked poly-ubiquitination on K970 of JAK2 kinase domain is promoted by Cbl.

SIGNOR-278538

Q00535

P07101

1

phosphorylation

up-regulates activity

0.408

In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.

SIGNOR-279022

Q9NZN5

Q14344

2

binding

up-regulates activity

0.772

P115 RhoGEF stimulates the intrinsic GTP hydrolysis activity of G alpha 12/13 subunits and acts as an effector for G13-coupled receptors by linking receptor activation to RhoA activation.

SIGNOR-256519

P17947

P05412

2

binding

up-regulates activity

0.555

These results indicate that AML1-ETO competes c-Jun away from binding to the β3β4 domain of PU.1. Thus, the c-Jun coactivation function of PU.1 is down-regulated and this in turn down-regulates transcriptional activity of PU.1.

SIGNOR-255660

Q16665

P27361

0

phosphorylation

up-regulates

0.695

We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_

SIGNOR-178731

Q4KMG0

Q12982

2

binding

up-regulates activity

0.506

Bnip-2 and jlp are brought together through mutual interaction with cdo. the cdo-bnip-2 interaction stimulates cdc42 activity, which in turn promotes p38alpha/beta activity and cell differentiation.

SIGNOR-179864

P0DP23

P48454

2

binding

up-regulates

0.661

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

SIGNOR-114104

Q12879

Q00535

0

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

P06493

Q9GZM8

1

phosphorylation

up-regulates activity

0.66

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

SIGNOR-274074

P12931

P43403

1

phosphorylation

up-regulates activity

0.479

In the cluster, Zap70 will be rapidly phosphorylated by active Src and slowly phosphorylated by autoinhibited, inactive Src.|We provide evidence that clusters harbor a positive feedback loop among Zap70, LAT, and Src-family kinases that binds phosphorylated LAT and further activates Zap70.

SIGNOR-279126

P42345

O95163

1

phosphorylation

up-regulates activity

0.2

Human ELP1 S1174 phosphorylation was triggered by insulin treatment, as shown by the specific phosphorylated (p)ELP1 (S1174) antibody, and addition of a phosphorylation-mutant variant of the ELP1 protein (ELP1(S1174A)) to ELP1-depleted BRAFV600E melanoma cells failed to rescue cell survival |In line with these findings, mTORC2 activity, but not mTORC1, was required for the insulin-induced phosphorylation of Elp1 S1174

SIGNOR-275541

P56524

Q14814

2

binding

down-regulates

0.692

We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2.

SIGNOR-76237

P61812

2

binding

up-regulates

0.2

The active form of tgf-b is a dimer stabilized by hydrophobic interactions and usually further strengthened by an intersubunit disulfide bridge

SIGNOR-148608

P22307

Q2T9J0

0

cleavage

up-regulates activity

0.503

Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β-oxidation. In vitro cleavage of Acox1, Scp2 and prethiolase by recombinant Tysnd1.

SIGNOR-261055

Q13813

P42574

0

cleavage

down-regulates

0.675

Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis.

SIGNOR-57891

P17706

P52333

1

dephosphorylation

down-regulates activity

0.697

Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.

SIGNOR-133078

P42574

Q92934

1

cleavage

up-regulates activity

0.536

Casp3 cleaves bad at asp-61. In addition, caspases convert bad(l) into a pro-death fragment that resembles the short splice variant.

SIGNOR-126727

P84085

O43150

0

gtpase-activating protein

up-regulates activity

0.497

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. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro.

SIGNOR-269707

O00155

P63096

2

binding

up-regulates activity

0.25

GPR25 is expressed in human memory T-cells and NK-cells and identified as a primary causal gene associated with autoimmune |Within the class A GPCR family, GPR25 shares a relatively high degree of amino acid sequence identity (29e34%) with vertebrate Apelin receptor (APLNR) diseases revealed by cis-eQTL mapping based on a genome-wide association study (GWAS).

SIGNOR-272501

Q5VWQ8

Q99683

2

binding

up-regulates activity

0.837

DAB2IP also mediates recruitment of PP2A to ASK1, binding both proteins through its C2 domain; this favors removal of the inhibitory S967 phosphorylation and further activation of ASK1

SIGNOR-254748

O43561

P62993

2

binding

up-regulates

0.804

Phosphorylated tyrosines 171, 191, and 226 [in LAT] bind to the SH2 domains of the Grb2 family of adaptor proteins and must be present for optimal signalling

SIGNOR-251520

Q9UKV3

P42574

0

cleavage

up-regulates

0.628

Induces apoptotic chromatin condensation after activation by casp3

SIGNOR-70800

P55291

P35222

2

binding

up-regulates activity

0.635

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

SIGNOR-265854

Q15831

P49841

1

phosphorylation

down-regulates activity

0.378

In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (XREF_FIG).

SIGNOR-280148

P15056

P62136

0

dephosphorylation

up-regulates activity

0.294

To address whether PP1\u03b1 activates B-Raf through these inhibitory sites, we made use of B-Raf protein mutants in which an individual inhibitory site, as well as all four sites (4A), were mutated to alanine.|We confirmed that GST-B-Raf was phosphorylated by ERK2 in vitro xref , mainly on S151 and T753 (Fig.\u00a0 xref ), and found that PP1\u03b1 dephosphorylated B-Raf on both ERK phosphorylation sites (Fig.\u00a0 xref ).

SIGNOR-277160

P14923

P06241

0

phosphorylation

up-regulates activity

0.561

Phosphorylation of plakoglobin by Fer and Fyn kinases decreases plakoglobin-desmoplakin interaction and increases plakoglobin-α-catenin association. Fyn mainly phosphorylated Tyr549 and that it phosphorylated Tyr133 with a much lower activity

SIGNOR-251176

P54762

P45985

1

relocalization

up-regulates activity

0.2

The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.

SIGNOR-275922

Q96FI4

Q03468

2

binding

up-regulates activity

0.344

CSB stimulates NEIL1 incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co-localize in HeLa cells.

SIGNOR-251931

Q13501

P06493

0

phosphorylation

up-regulates

0.343

Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.

SIGNOR-169012

Q14938

P41221

1

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268889

P49716

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.384

Phosphorylation of C/EBPdelta by GSK-3beta is required for its degradation by FBXW7alpha.

SIGNOR-279180

O14595

Q15797

1

dephosphorylation

down-regulates

0.5

In human cells, rnai-mediated depletion of scp1 and scp2 increases the extent and duration of smad1 phosphorylation in response to bmp, the transcriptional action of smad1, and the strength of endogenous bmp gene responses. The present identification of the scp family as smad c-terminal phosphatases sheds light on the events that attenuate smad signaling and reveals unexpected links to the essential phosphatases that control rna polymerase ii in eukaryotes.

SIGNOR-148434

P41182

P28482

0

phosphorylation

down-regulates

0.489

Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.

SIGNOR-58481

P25054

O15169

2

binding

up-regulates activity

0.944

Axin, an inhibitor of the wnt pathway, interacts with beta-catenin, gsk-3beta and apc and reduces the beta-catenin level.

SIGNOR-60043

Q13535

Q9Y253

1

phosphorylation

up-regulates

0.415

Atr-mediated phosphorylation of dna polymerase _ is needed for efficient recovery from uv damage. We show that, after uv irradiation, pol_ becomes phosphorylated at ser601 by the ataxia-telangiectasia mutated and rad3-related (atr) kinase. Atr-dependent phosphorylation of pol_ is necessary to restore normal survival and postreplication repair

SIGNOR-171290

P04049

P01111

0

relocalization

up-regulates

0.87

The raf family of proteins (raf-1, a-raf, and b-raf) bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.

SIGNOR-175231

P62140

P35240

1

dephosphorylation

up-regulates

0.378

When serine 518 is dephosphorylated by the myosin phosphatase mypt-1-pp1?, The tumor suppressor function of merlin is activated, inhibiting the ras signaling pathway and leading to growth arrest

SIGNOR-159836

Q05655

P12830

1

phosphorylation

down-regulates activity

0.2

Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin.

SIGNOR-260893

P24941

P42771

2

binding

down-regulates

0.48

However, induction of p16(ink4a) also causes marked inhibition of cdk2 activity.

SIGNOR-64431

Q58F21

Q13541

2

binding

up-regulates quantity

0.2

It was revealed that eIF4EBP1 interacted with BRDT, a novel interacting protein. In addition, the present study further demonstrated that BRDT inhibitors PLX51107 and INCB054329 blocked the progression of RCC cells, along with suppressing eIF4EBP1 and c‑myc expression.

SIGNOR-262049

P22612

P46020

1

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267415

Q92843

Q16611

2

binding

down-regulates

0.467

Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax.

SIGNOR-152989

P23467

P33151

1

dephosphorylation

up-regulates activity

0.581

Because we had shown previously that VE-PTP supports VE-cadherin function when exogenously expressed in transfected cells, we expected it to be expressed at endothelial cell contacts.|Indeed, tyrosine phosphorylation of VE-cadherin is reduced by VE-PTP in COS-7 and CHO cells.

SIGNOR-277131

Q16665

O76061

1

transcriptional regulation

up-regulates quantity by expression

0.297

With the ChIP assay, we demonstrated the direct binding of HIF-1alpha to STC2 promoter. These findings support the notion that HIF-1 is a potent stimulator of STC2 expression. Collectively, this is the first report to show that STC2 was aberrantly hypermethylated in human cancer cells. The findings demonstrated that STC2 epigenetic inactivation may interfere with HIF-1 mediated activation of STC2 expression.

SIGNOR-260389

P48729

P62745

1

phosphorylation

down-regulates

0.2

Mass spectrometry analysis demonstrates that rhob is monophosphorylated by ck1, in its c-terminal end, on serine 185. lastly we show that the inhibition of ck1 activates rhob and promotes rhob dependent actin fiber formation and egf-r level.

SIGNOR-179255

P36897

Q9Y5K5

2

binding

up-regulates quantity by stabilization

0.505

Smad7 can act as an adaptor able to recruit uch37 to the type i tgf-beta receptor. Consequently, uch37 dramatically up-regulates tgf-beta-dependent gene expression by de-ubiquitinating and stabilizing the type i tgf-beta receptor.

SIGNOR-150135

Q9Y3A5

Q7Z2Z2

2

binding

up-regulates

0.2

Sbds stimulates 60s-dependent gtp hydrolysis by efl1

SIGNOR-173533

P50148

P25116

2

binding

up-regulates activity

0.582

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-257219

Q9NQS7

O96017

0

phosphorylation

up-regulates activity

0.261

Also, inhibition of Chk2 by Chk2 inhibitor II in cytokinesis after release of cells from a nocodazole-induced prometaphase block diminished INCENP localization to the midbody center in late midbodies (Fig. 1, M and N).|In turn, active Chk2 phosphorylates human INCENP at the newly identified site Ser91 to promote INCENP binding to Mklp2, resulting in recruitment of the INCENP\u2013Mklp2 complex to the midbody center through Mklp2\u2019s interaction with the midbody protein Cep55 to delay abscission.

SIGNOR-279695

Q92993

Q16539

0

phosphorylation

up-regulates activity

0.321

We found that phosphorylation of Tip60-T158 was increased by p38\u03b1 isolated from Dox- or \u03b3-radiation-treated cells over that from untreated cells (Figure xref ), indicating that DNA damage induces the protein kinase activity of p38\u03b1 towards Tip60-T158.

SIGNOR-278958

P19086

P33032

2

binding

up-regulates activity

0.25

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-257271

Q13315

P12956

1

phosphorylation

up-regulates activity

0.713

Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks.

SIGNOR-274020

O43293

Q00987

1

phosphorylation

up-regulates quantity by stabilization

0.342

Zip kinase was able to phosphorylate mdm2 at ser166, a site previously reported to be modified by akt kinase, thus demonstrating that zip kinase is a bona fide mdm2-binding protein.

SIGNOR-123159

P10415

Q16539

0

phosphorylation

down-regulates activity

0.334

Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein.

SIGNOR-146786

P35398

Q8N2Q7

1

transcriptional regulation

up-regulates quantity by expression

0.2

Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).

SIGNOR-265136

O75581

Q03135

2

binding

up-regulates

0.676

Overall, our data suggest that wnt-3a triggers the interaction of lrp6 with caveolin and promotes recruitment of axin to lrp6 phosphorylated by glycogen synthase kinase-3beta and that caveolin thereby inhibits the binding of beta-catenin to axin.

SIGNOR-148665

Q12986

P01903

1

transcriptional regulation

down-regulates quantity by repression

0.396

A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor

SIGNOR-266224

P68400

Q6ZMG9

1

phosphorylation

up-regulates activity

0.2

Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.

SIGNOR-273992

Q9UQM7

P35367

1

phosphorylation

down-regulates

0.282

As we have shown previously, human h1r can be phosphorylated in vitro by several kinases includingpka, pkc, pkg, and camk ii in summary, these data suggest that thr140, thr142, ser396, ser398, and thr478 can be phosphorylated by the kinases described above (table 2).

SIGNOR-124348

Q13882

P18031

0

dephosphorylation

down-regulates activity

0.575

Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342.

SIGNOR-277082

Q16820

P05771

0

phosphorylation

down-regulates quantity

0.2

These findings suggest that activation of a protein kinase, presumably PKC, mediates PMA-induced hmeprinβ shedding. By labeling COS-1 cells transfected with mutant constructs lacking the potential phosphorylation sites, we identified Ser687 as the main 32P-acceptor. These data provide evidence that the cytoplasmic domain of hmeprinβ can function as a PKC substrate.

SIGNOR-263173

P0DP25

P00533

0

phosphorylation

down-regulates

0.382

Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-266335

P04637

P50613

0

phosphorylation

up-regulates

0.458

The cdk7-cych-p36 complex of transcription factor iih phosphorylates p53, enhancing its sequence-specific dna binding activity in vitro. serines 371, 376, 378, and 392 may be the potential sites for this kinase.

SIGNOR-51292

P12931

Q03135

1

phosphorylation

down-regulates activity

0.764

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

SIGNOR-118007

P54652

Q99683

2

binding

down-regulates

0.2

Coimmunoprecipitation analysis revealed a physical interaction between endogenous hsp72 and ask1 in nih 3t3 cells exposed to mild heat shock. Hsp72 blocked both the homo-oligomerization of ask1 and ask1-dependent apoptosis.

SIGNOR-94565

P50502

P34947

0

phosphorylation

up-regulates activity

0.268

An in vitro screen for novel GRK substrates revealed Hsp70 interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and stoichiometrically phosphorylated Hip in vitro. The primary binding domain of GRK5 was mapped to residues 303-319 on Hip, while the major site of phosphorylation was identified to be Ser-346. GRK5 also bound to and phosphorylated Hip on Ser-346 in cells.we found that the phosphorylation of Ser-346 was required for proper agonist-induced internalization of the chemokine receptor CXCR4.

SIGNOR-262877

P68400

Q9BXW9

1

phosphorylation

down-regulates activity

0.2

Here, we report a cluster of phosphosites on FANCD2 whose phosphorylation by CK2 inhibits both FANCD2 recruitment to ICLs and its monoubiquitination in vitro and in vivo. We have found that phosphorylated FANCD2 possesses reduced DNA binding activity, explaining the previous observations.

SIGNOR-276730

P07288

P12272

1

cleavage

down-regulates activity

0.422

Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. | Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.

SIGNOR-270547