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
O14950	Q12852	0	phosphorylation	up-regulates	0.2	Zip kinase (hzipk) phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. In this study, we demonstrate that hzipk also induces the diphosphorylation of mrlc in nonmuscle cells.	SIGNOR-113664
Q16695	Q9C0A6	0	methylation	up-regulates activity	0.2	SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.	SIGNOR-264621
P27361	Q02447	1	phosphorylation	up-regulates	0.299	Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73.	SIGNOR-157276
P63000	Q96HP0	0	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
P08151	Q2M1P5	2	binding	up-regulates quantity by stabilization	0.622	Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling.	SIGNOR-209608
P12755	Q99717	2	binding	down-regulates	0.697	Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad6	SIGNOR-95468
P68431	Q92585	0	acetylation	down-regulates activity	0.2	The n-terminal domain of maml1 directly interacts with both p300 and histones, and the p300-maml1 complex specifically acetylates histone h3 and h4 tails in chromatin.	SIGNOR-153038
Q05513	Q96A00	1	phosphorylation	up-regulates activity	0.277	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-249261
P27361	Q12913	0	dephosphorylation	down-regulates activity	0.459	Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases\|Pulldown and in vitro dephosphorylation assays confirmed our prediction and demonstrated an overall specificity of DEP-1 in targeting the phosphorylated tyrosine 204 of ERK1/2.	SIGNOR-248707
P33316-2	P06493	0	phosphorylation	up-regulates quantity	0.386	DUTPase Is Phosphorylated at a Consensus Cyclin-dependent Protein Kinase Site: in Vitro Phosphorylation of Ser-11 by p34cdc2. It is conceivable that the exclusive phosphorylation of DUT-N may play a role in nuclear targeting of this protein. Taken a step further, Ser-11 may confer the ability of DUT-N to localize in specific regions of the nucleus where the dUTPase function is required. The Ser-11 Ala mutant should aid in the testing of these hypotheses.	SIGNOR-262693
Q99705	P09471	2	binding	up-regulates activity	0.273	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-257235
P37173	Q9HCE7	0	ubiquitination	down-regulates activity	0.615	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps.	SIGNOR-195672
P49336	Q16695	1	phosphorylation	down-regulates activity	0.2	However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.	SIGNOR-273175
O15530	Q15418	1	phosphorylation	up-regulates activity	0.63	Full-length RSK1, RSK2, and RSK3 Are Activated when Coexpressed with PDK1 in COS7 Cells. Ser221 phosphorylation is increased 2–3-fold during ERK-mediated activation of RSK1 in COS1 cells	SIGNOR-250270
P29474	P24723	0	phosphorylation	down-regulates activity	0.2	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251634
Q7Z6I6	P61586	1	gtpase-activating protein	down-regulates activity	0.449	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-260485
O00311	Q99459	1	phosphorylation	down-regulates activity	0.344	During SPOC, Dbf4 binds to Cdc5 and promotes Cdc7-mediated phosphorylation of Cdc5, which then presumably prevents Cdc5 from recognizing its substrates in the MEN pathway .	SIGNOR-280203
Q05655	Q16236	1	phosphorylation	up-regulates activity	0.371	Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription.	SIGNOR-249161
Q13309	P48735	1	ubiquitination	down-regulates quantity by destabilization	0.2	During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome	SIGNOR-267626
Q96M02	P04637	1	polyubiquitination	up-regulates quantity by stabilization	0.459	The E3 activity of FATS is required for promoting p53 stability and activation in response to DNA damage.FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage. Here, we show that FATS acts as a p53 activator by inhibiting Mdm2 binding to p53 and stimulating non-proteolytic polyubiquitination of p53.	SIGNOR-272142
Q13976	Q9NS28	1	phosphorylation	up-regulates activity	0.332	Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. S216 phosphorylation might activate PP1 leading to dephosphorylation of both 14-3-3 binding sites, S49 and S218, and detachment of 14-3-3. Removal of 14-3-3 activates RGS18 to turn off Gq signaling thus contributing to platelet inhibition.	SIGNOR-273785
O14503	P63279	0	polyubiquitination	down-regulates quantity by destabilization	0.326	Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9.	SIGNOR-272579
Q9Y570	P62714	1	demethylation	down-regulates activity	0.716	Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits \|Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans.	SIGNOR-265750
Q9ULV8	P07949	1	ubiquitination	down-regulates quantity by destabilization	0.368	Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.\|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.	SIGNOR-278674
Q13564	P05067	2	binding	up-regulates activity	0.732	Alzheimer's disease (AD) is the gradual loss of the cognitive function due to neuronal death. Currently no therapy is available to slow down, reverse or prevent the disease. Here we analyze the existing data in literature and hypothesize that the physiological function of the Amyloid Precursor Protein (APP) is activating the AppBp1 pathway and this function is gradually lost during the progression of AD pathogenesis.	SIGNOR-251577
O75398	P60763	1	transcriptional regulation	up-regulates quantity by expression	0.2	Affymetrix gene profiling studies revealed Rac3 as a potential target gene and quantitative RT-PCR analysis confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells.	SIGNOR-269059
P12757	Q15796	2	binding	down-regulates activity	0.801	The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway	SIGNOR-236099
P27361	P10242	1	phosphorylation	down-regulates	0.301	Functional analysis of phosphorylation at serine 532 of human c-myb by map kinase. expression of a polypeptide containing the c-myb c-terminal domain stimulated c-myb activity. This effect is reduced upon mapk-dependent phosphorylation of serine 532. Our data suggest that the mapk-dependent state of phosphorylation modifies the cellular function of c-myb by modulating its interaction with a putative inhibitory factor	SIGNOR-45348
P01112	Q96TA1	2	binding	up-regulates activity	0.2	EGFR phosphorylates FAM129B, resulting in binding of phosphorylated FAM129B to H-Ras and reduced the association of p120-RasGAP with H-Ras, thereby enhancing H-Ras activation for ERK1/2-dependent β-catenin transactivation for enhanced Warburg effect, tumor cell proliferation, and brain tumorigenesis.	SIGNOR-273659
Q16539	O15519	1	phosphorylation	up-regulates	0.373	Here we demonstrate that m. tuberculosis?induced Tnf triggered reactive oxygen species?dependent Activation of ask1 and the tyrosine kinase c-abl (a000161) in mouse macrophages and that flips was phosphorylated on tyr211 and ser4 by c-abl and p38, respectively.	SIGNOR-187001
Q92547	Q99638	2	binding	up-regulates	0.826	The 9-1-1 complex functions as a clamp, encircling the dna, and recruits the brct domain-containing protein topbp1 in a phospho-dependent manner	SIGNOR-179382
Q13315	P17096	1	phosphorylation	up-regulates activity	0.2	21 As shown in Fig. 2 b, ATM was able to phosphorylate in vitro the C-terminal peptide of HMGA1.	SIGNOR-279493
Q9UMX1	P17612	0	phosphorylation	up-regulates quantity by stabilization	0.467	We report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3? and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation	SIGNOR-172003
Q13530	P68400	0	phosphorylation	up-regulates activity	0.2	The two serines within the PSAC of Serinc3 are phosphorylated by casein kinase II and mediate interaction with the μ subunits in vitro.	SIGNOR-273631
P28482	Q02447	1	phosphorylation	up-regulates	0.305	Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. in the inducible cell lines, expression of wild-type form of sp3 increases vegf production whereas the s73a form has a reduced potential reflecting its lower transcriptional activity.	SIGNOR-157272
P0DP24	Q08209	2	binding	up-regulates	0.581	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-266327
O60674	O15524	0	ubiquitination	down-regulates quantity by destabilization	0.795	Shp-2 regulates socs-1-mediated janus kinase-2 ubiquitination/degradation downstream of the prolactin receptor	SIGNOR-118407
Q96MT8	P24941	1	relocalization	up-regulates activity	0.372	Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.	SIGNOR-271725
P55895	P42345	1	relocalization	up-regulates	0.267	Rag gtpases, together with a multi-protein complex called ragulator, mediate amino acid-mediated mtor recruitment to the lysosome surface where mtor becomes activated.	SIGNOR-198245
P00519	P56945	1	phosphorylation	up-regulates activity	0.462	Abl silencing inhibits CAS mediated process and constriction in resistance arteries.\|CAS phosphorylation was catalyzed by Abl in an in vitro study.	SIGNOR-279671
P05787	P18031	0	dephosphorylation	down-regulates activity	0.2	Keratin 8 phospho-Tyr-267 is dephosphorylated by PTP1B and promotes insolubility and filament organization, as does the paralogous GFAP tyrosine.	SIGNOR-265495
Q9NYZ3	P53350	0	phosphorylation	up-regulates	0.736	In this study, we show that g2 and s-phase-expressed 1 (gtse1) protein, a negative regulator of p53, is required for g2 checkpoint recovery and that plk1 phosphorylation of gtse1 at ser 435 promotes its nuclear localization, and thus shuttles p53 out of the nucleus to lead to its degradation during the recovery.	SIGNOR-166417
Q9P212	Q9UBI6	2	binding	up-regulates	0.2	In the non-canonical wntpathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor	SIGNOR-152612
P08173	P08754	2	binding	up-regulates activity	0.403	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-256829
P62714	Q00987	1	dephosphorylation	up-regulates activity	0.4	cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells	SIGNOR-248593
Q14457	Q9Y371	2	binding	up-regulates	0.543	Bif-1 forms a complex with beclin1 through uvrag and promotes the activation of the class iii pi3 kinase, vps34, in mammalian cells.	SIGNOR-171899
Q15628	O75509	2	binding	up-regulates	0.581	Dr6 interacts with tradd	SIGNOR-100184
Q9NPF7	Q5VWK5	2	binding	up-regulates	0.861	We identify a novel member of the hemopoietin receptor family as a subunit of the receptor for il-23, il-23r.	SIGNOR-87805
P10276	P78396	1	transcriptional regulation	down-regulates quantity by repression	0.244	RARα is involved in the regulation of cyclin A1. Further studies using ligands selective for various retinoic acid receptors suggested that cyclin A1 expression is negatively regulated by activated RARα.	SIGNOR-249636
Q8IXJ9	P37231	2	binding	down-regulates activity	0.2	Our genome-wide analysis confirmed the physiological roles of ASXL1 and ASXL2 in adipogenesis at the molecular level, supporting the hypothesis that ASXL1 is an authentic corepressor of PPARγ, whereas ASXL2 is a PPARγ coactivator, and that together ASXL1 and ASXL2 fine-tune adipogenesis via differential regulation of PPARγ.	SIGNOR-260064
O14745	P06493	0	phosphorylation	down-regulates activity	0.276	During the early stages of mitosis in HeLa cells, Cdc2 phosphorylates EBP50 on serine residues 280 and 302.\|Phosphorylation by Cdc2 inhibits EBP50's role in forming microvilli in interphase but not mitotic cells. (A) Results from scoring JEG-3 cells for the presence of microvilli; error bars indicate mean \u00b1 SD. (B) Representative images from the microvillar rescue assay.	SIGNOR-278305
O75581	O94921	0	phosphorylation	up-regulates	0.333	Low-density lipoprotein receptor related proteins 5 and 6 (lrp5/6) are transmembrane receptors that initiate wnt/beta-catenin signaling. Phosphorylation of pppsp motifs in the lrp6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide rnai screen, we show that pppsp phosphorylation requires the drosophila cyclin-dependent kinase (cdk) l63. L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.	SIGNOR-162924
P46527	Q12778	0	transcriptional regulation	up-regulates quantity by expression	0.627	To date , we have found that TNC regulates the transcriptional activity of FOXO1. And p27Kip1 is one of the transcriptional targets of FOXO1 (Fig. 5A). We speculated that TNC could regulate the binding of FOXO1 to the CDKN1B promoter.	SIGNOR-277739
P33076	P17612	0	phosphorylation	down-regulates activity	0.309	Downregulation of ciita function by protein kinase a (pka)-mediated phosphorylation phosphorylation at ciita serines 834 and 1050 accounts for the inhibitory effects of pka on ciita-driven class ii mhc transcription.	SIGNOR-108569
Q06413	P23409	1	transcriptional regulation	up-regulates quantity by expression	0.565	Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.	SIGNOR-238652
Q13131	P04637	1	phosphorylation	up-regulates	0.48	Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest	SIGNOR-135960
P07948	Q05655	1	phosphorylation	down-regulates activity	0.557	Src, Fyn, or Lyn are the essential kinases that tyrosine phosphorylate and inactivate PKC δ. Lyn phosphorylates tyrosine residue 565 in vitro	SIGNOR-251407
Q13315	Q8N0Z6	1	phosphorylation	up-regulates activity	0.538	Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex.	SIGNOR-262645
P00519	P06400	2	binding	down-regulates	0.57	A domain in the c-terminus of rb, outside of the a/b pocket, binds to the atp-binding lobe of the c-abl tyrosine kinase, resulting in kinase inhibition.	SIGNOR-37139
Q96IZ0	P31749	0	phosphorylation	down-regulates activity	0.39	Prostate apoptosis response protein-4 (Par-4) sensitizes cells to chemotherapy	SIGNOR-279668
Q9C0H5	P60953	1	gtpase-activating protein	down-regulates activity	0.577	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-260495
P11413	Q05655	0	phosphorylation	up-regulates	0.2	A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity.	SIGNOR-167053
P30679	O15552	2	binding	up-regulates activity	0.404	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-257276
O15530	Q96BR1	1	phosphorylation	up-regulates	0.461	Full-length sgk3 contains a complete phox homology (px) domain that targets the protein to endosomes. Both a functional px domain and pi3k activation are necessary for phosphorylation of sgk3 at two regulatory sites (thr-320 and ser-486) and subsequent induction of kinase activity. Pdk1 phosphorylates endosome-associated sgk3 at thr-320	SIGNOR-147213
Q92935	Q15465	2	binding	down-regulates	0.294	A study in mice suggests that ext1 proteins might negatively regulate shh signaling by synthesizing hspgs, which sequester the ligand	SIGNOR-132606
Q13315	Q9BXW9	1	phosphorylation	up-regulates	0.789	These results suggest that s222 and either s1401, s1404, or s1408 are sites of atm-dependent phosphorylation in vitro.Phosphorylation Of fancd2 is required for activation of an s phase checkpoint	SIGNOR-90117
Q9UJU2	P68400	0	phosphorylation	up-regulates	0.303	Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.	SIGNOR-23958
Q5FBB7	P0C0S8	0	relocalization	up-regulates activity	0.2	The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl.\|The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1.	SIGNOR-265262
P02533	P19438	2	binding	down-regulates activity	0.265	TRADD specifically bound K18 and K14, type I (acidic) keratins. it is possible that epidermal K14 may function as an inhibitor of TNF–TNFR1 signaling through an association with TRADD.	SIGNOR-251906
Q04759	Q15052	1	phosphorylation	up-regulates activity	0.2	Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation.\|More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation of the Rac 1/PYGM pathway.	SIGNOR-272168
Q99814	Q9Y2K7	1	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271581
Q00987	P41240	0	phosphorylation	up-regulates activity	0.2	Here we show that activated c-Src kinase phosphorylates Y281 and Y302 of Mdm2, resulting in an increase in Mdm2 stability and its association with Ubc12, the E2 enzyme of the neddylating complex.	SIGNOR-279163
P28482	Q15418	1	phosphorylation	up-regulates activity	0.759	Several lines of evidence indicate that the mapkap-k1 isoforms are also activated by mapks in vivo via the ras-dependent protein kinase cascade that is triggered by growth factors or tumor-promoting phorbol esters, such as phorbol 12-myristate 13-acetate (pma). here we identify six sites in mapkap-k1a that become phosphorylated in transfected cos-1 cells. The inactive form of mapkap-k1a in unstimulated cells is partially phosphorylated at ser222 and ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of thr360, ser364, thr574, and ser381 and increases the phosphorylation of ser222 and ser733.	SIGNOR-219308
O14746	Q96AP0	2	binding	up-regulates	0.557	We find that tpp1 and pot1 form a complex with telomeric dna that increases the activity and processivity of the human telomerase core enzyme.	SIGNOR-152321
Q9Y6A5	O14965	0	phosphorylation	up-regulates activity	0.937	We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.	SIGNOR-262655
Q96KB5	P45983	1	phosphorylation	up-regulates activity	0.303	Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.\|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.	SIGNOR-280061
P78337	P18146	2	binding	up-regulates activity	0.514	GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.	SIGNOR-254916
O43303	P24941	0	phosphorylation	down-regulates activity	0.515	GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)	SIGNOR-265956
P24941	P23771	1	phosphorylation	down-regulates quantity by destabilization	0.362	Phosphorylation of GATA3 Thr-156 was detected in mouse thymocytes, and cyclin-dependent kinase 2 (CDK2) was identified as a respondent for phosphorylation at Thr-156.	SIGNOR-276634
P63092	Q01718	2	binding	up-regulates activity	0.516	The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins	SIGNOR-268694
P12755	Q15796	2	binding	down-regulates activity	0.741	The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway	SIGNOR-236155
O15111	Q86VP1	1	phosphorylation	up-regulates activity	0.383	Here we demonstrate that tax1bp1 was inducibly phosphorylated on ser593 and ser624 in response to proinflammatory stimuli. The kinase ikkalpha, but not ikkbeta, was required for phosphorylation of tax1bp1 and directly phosphorylated tax1bp1 in response to stimulation with tumor necrosis factor (tnf) or interleukin 1 (il-1).	SIGNOR-175062
Q7KZI7	Q8TEW0	1	phosphorylation	up-regulates	0.493	Gab1 brings par1 and par3 into a transient complex, stimulating par3 phosphorylation by par1	SIGNOR-198742
P31785	P05112	2	binding	up-regulates	0.858	The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex	SIGNOR-108861
O96017	O15297	0	dephosphorylation	up-regulates activity	0.572	an in vitro phosphatase assay revealed that Wip1 (WT), but not Wip1 (D314A), dephosphorylates Thr68 on phosphorylated Chk2 in vitro, resulting in the inhibition of Chk2 kinase activity toward glutathione S-transferase-Cdc25C.	SIGNOR-248318
P68400	Q01534	1	phosphorylation	up-regulates activity	0.2	CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of TSPY protein	SIGNOR-250969
P56704	Q14332	2	binding	up-regulates	0.753	It was also shown that wnt5a inhibits the beta-catenin pathway by competing with wnt3a for binding to fz2, and that the impairment of clathrin-mediated internalization does not affect this wnt5a inhibitory action.	SIGNOR-189117
P18848	P07949	0	phosphorylation	down-regulates quantity by destabilization	0.2	We observed that RET physically interacted with and phosphorylated ATF4 at tyrosine and threonine residues. Indeed, RET kinase activity was required to inhibit the ATF4-dependent activation of the NOXA gene because the site-specific substitution mutations that block threonine phosphorylation increased ATF4 stability and activated its targets NOXA and PUMA.	SIGNOR-276448
Q05397	P43146	2	binding	up-regulates activity	0.72	Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin. Mutation of the tyrosine phosphorylation residue in DCC abolished its function of mediating netrin-induced axon attraction. On the basis of our observations, we suggest a model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling.	SIGNOR-268371
Q14195	Q00535	0	phosphorylation	up-regulates activity	0.603	Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro	SIGNOR-145963
P36896	P13385	2	binding	up-regulates activity	0.728	Nodal effects are dependent upon interactions with Cripto, a small cysteine-rich extracellular protein that is attached to the plasma membrane through a glycosyl phosphatidyl inositol linkage. Cripto interacts with Nodal and ALK4, independently, and promotes the formation of a stable high affinity complex with activin type II receptors.	SIGNOR-251938
P46108	P00519	0	phosphorylation	down-regulates activity	0.76	Negative regulation of crk by abl is essential for the antitumorigenic effects of ephrinb2,similar pathways may operate for crkl	SIGNOR-175135
Q9Y5F7	Q9Y5H9	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265693
Q8IWJ2	P11717	1	relocalization	up-regulates activity	0.529	Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector	SIGNOR-253085
Q16875	Q13131	0	phosphorylation	up-regulates	0.399	Ipfk-2 was phosphorylated on the homologous serine (ser-461) and activated by ampk in vitro.	SIGNOR-89760
P48454	P0DP25	2	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
P0DP23	P29474	2	binding	up-regulates activity	0.76	Electrons flow from the C-terminal reductase domain of one NOS monomer to the N-terminal oxygenase domain of the other NOS monomer (Siddhanta et al., 1998). The primary mode of enzyme activation is the binding of calcium-bound calmodulin to the N-terminal CaM-binding domain. This facilitates a structure change and the flow of electrons from NADPH through the flavins to the oxygenase domain of the other eNOS monomer	SIGNOR-251615
Q9UKV5	Q00535	0	phosphorylation	down-regulates quantity by destabilization	0.248	We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78.	SIGNOR-277356
P55085	P63096	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256895
Q13554	P35222	1	phosphorylation	down-regulates	0.289	Camkii represses transcriptionally active _-catenin to mediate acute ethanol neurodegeneration and can phosphorylate _-catenincamkii can directly phosphorylate _-catenin. Using targeted mutagenesis we identified camkii phosphorylation sites within human _-catenin at t332, t472, and s552.	SIGNOR-202833

O14950

Q12852

0

phosphorylation

up-regulates

0.2

Zip kinase (hzipk) phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. In this study, we demonstrate that hzipk also induces the diphosphorylation of mrlc in nonmuscle cells.

SIGNOR-113664

Q16695

Q9C0A6

0

methylation

up-regulates activity

0.2

SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.

SIGNOR-264621

P27361

Q02447

1

phosphorylation

up-regulates

0.299

Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73.

SIGNOR-157276

P63000

Q96HP0

0

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

P08151

Q2M1P5

2

binding

up-regulates quantity by stabilization

0.622

Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling.

SIGNOR-209608

P12755

Q99717

2

binding

down-regulates

0.697

Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad6

SIGNOR-95468

P68431

Q92585

0

acetylation

down-regulates activity

0.2

The n-terminal domain of maml1 directly interacts with both p300 and histones, and the p300-maml1 complex specifically acetylates histone h3 and h4 tails in chromatin.

SIGNOR-153038

Q05513

Q96A00

1

phosphorylation

up-regulates activity

0.277

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-249261

P27361

Q12913

0

dephosphorylation

down-regulates activity

0.459

Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases|Pulldown and in vitro dephosphorylation assays confirmed our prediction and demonstrated an overall specificity of DEP-1 in targeting the phosphorylated tyrosine 204 of ERK1/2.

SIGNOR-248707

P33316-2

P06493

0

phosphorylation

up-regulates quantity

0.386

DUTPase Is Phosphorylated at a Consensus Cyclin-dependent Protein Kinase Site: in Vitro Phosphorylation of Ser-11 by p34cdc2. It is conceivable that the exclusive phosphorylation of DUT-N may play a role in nuclear targeting of this protein. Taken a step further, Ser-11 may confer the ability of DUT-N to localize in specific regions of the nucleus where the dUTPase function is required. The Ser-11 Ala mutant should aid in the testing of these hypotheses.

SIGNOR-262693

Q99705

P09471

2

binding

up-regulates activity

0.273

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-257235

P37173

Q9HCE7

0

ubiquitination

down-regulates activity

0.615

Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps.

SIGNOR-195672

P49336

Q16695

1

phosphorylation

down-regulates activity

0.2

However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.

SIGNOR-273175

O15530

Q15418

1

phosphorylation

up-regulates activity

0.63

Full-length RSK1, RSK2, and RSK3 Are Activated when Coexpressed with PDK1 in COS7 Cells. Ser221 phosphorylation is increased 2–3-fold during ERK-mediated activation of RSK1 in COS1 cells

SIGNOR-250270

P29474

P24723

0

phosphorylation

down-regulates activity

0.2

The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites

SIGNOR-251634

Q7Z6I6

P61586

1

gtpase-activating protein

down-regulates activity

0.449

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-260485

O00311

Q99459

1

phosphorylation

down-regulates activity

0.344

During SPOC, Dbf4 binds to Cdc5 and promotes Cdc7-mediated phosphorylation of Cdc5, which then presumably prevents Cdc5 from recognizing its substrates in the MEN pathway .

SIGNOR-280203

Q05655

Q16236

1

phosphorylation

up-regulates activity

0.371

Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription.

SIGNOR-249161

Q13309

P48735

1

ubiquitination

down-regulates quantity by destabilization

0.2

During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome

SIGNOR-267626

Q96M02

P04637

1

polyubiquitination

up-regulates quantity by stabilization

0.459

The E3 activity of FATS is required for promoting p53 stability and activation in response to DNA damage.FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage. Here, we show that FATS acts as a p53 activator by inhibiting Mdm2 binding to p53 and stimulating non-proteolytic polyubiquitination of p53.

SIGNOR-272142

Q13976

Q9NS28

1

phosphorylation

up-regulates activity

0.332

Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. S216 phosphorylation might activate PP1 leading to dephosphorylation of both 14-3-3 binding sites, S49 and S218, and detachment of 14-3-3. Removal of 14-3-3 activates RGS18 to turn off Gq signaling thus contributing to platelet inhibition.

SIGNOR-273785

O14503

P63279

0

polyubiquitination

down-regulates quantity by destabilization

0.326

Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9.

SIGNOR-272579

Q9Y570

P62714

1

demethylation

down-regulates activity

0.716

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans.

SIGNOR-265750

Q9ULV8

P07949

1

ubiquitination

down-regulates quantity by destabilization

0.368

Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.

SIGNOR-278674

Q13564

P05067

2

binding

up-regulates activity

0.732

Alzheimer's disease (AD) is the gradual loss of the cognitive function due to neuronal death. Currently no therapy is available to slow down, reverse or prevent the disease. Here we analyze the existing data in literature and hypothesize that the physiological function of the Amyloid Precursor Protein (APP) is activating the AppBp1 pathway and this function is gradually lost during the progression of AD pathogenesis.

SIGNOR-251577

O75398

P60763

1

transcriptional regulation

up-regulates quantity by expression

0.2

Affymetrix gene profiling studies revealed Rac3 as a potential target gene and quantitative RT-PCR analysis confirmed that Rac3 was upregulated by Deaf-1 in immortalized mouse mammary epithelial cells.

SIGNOR-269059

P12757

Q15796

2

binding

down-regulates activity

0.801

The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway

SIGNOR-236099

P27361

P10242

1

phosphorylation

down-regulates

0.301

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

SIGNOR-45348

P01112

Q96TA1

2

binding

up-regulates activity

0.2

EGFR phosphorylates FAM129B, resulting in binding of phosphorylated FAM129B to H-Ras and reduced the association of p120-RasGAP with H-Ras, thereby enhancing H-Ras activation for ERK1/2-dependent β-catenin transactivation for enhanced Warburg effect, tumor cell proliferation, and brain tumorigenesis.

SIGNOR-273659

Q16539

O15519

1

phosphorylation

up-regulates

0.373

Here we demonstrate that m. tuberculosis?induced Tnf triggered reactive oxygen species?dependent Activation of ask1 and the tyrosine kinase c-abl (a000161) in mouse macrophages and that flips was phosphorylated on tyr211 and ser4 by c-abl and p38, respectively.

SIGNOR-187001

Q92547

Q99638

2

binding

up-regulates

0.826

The 9-1-1 complex functions as a clamp, encircling the dna, and recruits the brct domain-containing protein topbp1 in a phospho-dependent manner

SIGNOR-179382

Q13315

P17096

1

phosphorylation

up-regulates activity

0.2

21 As shown in Fig. 2 b, ATM was able to phosphorylate in vitro the C-terminal peptide of HMGA1.

SIGNOR-279493

Q9UMX1

P17612

0

phosphorylation

up-regulates quantity by stabilization

0.467

We report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3? and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation

SIGNOR-172003

Q13530

P68400

0

phosphorylation

up-regulates activity

0.2

The two serines within the PSAC of Serinc3 are phosphorylated by casein kinase II and mediate interaction with the μ subunits in vitro.

SIGNOR-273631

P28482

Q02447

1

phosphorylation

up-regulates

0.305

Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. in the inducible cell lines, expression of wild-type form of sp3 increases vegf production whereas the s73a form has a reduced potential reflecting its lower transcriptional activity.

SIGNOR-157272

P0DP24

Q08209

2

binding

up-regulates

0.581

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

SIGNOR-266327

O60674

O15524

0

ubiquitination

down-regulates quantity by destabilization

0.795

Shp-2 regulates socs-1-mediated janus kinase-2 ubiquitination/degradation downstream of the prolactin receptor

SIGNOR-118407

Q96MT8

P24941

1

relocalization

up-regulates activity

0.372

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.

SIGNOR-271725

P55895

P42345

1

relocalization

up-regulates

0.267

Rag gtpases, together with a multi-protein complex called ragulator, mediate amino acid-mediated mtor recruitment to the lysosome surface where mtor becomes activated.

SIGNOR-198245

P00519

P56945

1

phosphorylation

up-regulates activity

0.462

Abl silencing inhibits CAS mediated process and constriction in resistance arteries.|CAS phosphorylation was catalyzed by Abl in an in vitro study.

SIGNOR-279671

P05787

P18031

0

dephosphorylation

down-regulates activity

0.2

Keratin 8 phospho-Tyr-267 is dephosphorylated by PTP1B and promotes insolubility and filament organization, as does the paralogous GFAP tyrosine.

SIGNOR-265495

Q9NYZ3

P53350

0

phosphorylation

up-regulates

0.736

In this study, we show that g2 and s-phase-expressed 1 (gtse1) protein, a negative regulator of p53, is required for g2 checkpoint recovery and that plk1 phosphorylation of gtse1 at ser 435 promotes its nuclear localization, and thus shuttles p53 out of the nucleus to lead to its degradation during the recovery.

SIGNOR-166417

Q9P212

Q9UBI6

2

binding

up-regulates

0.2

In the non-canonical wntpathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor

SIGNOR-152612

P08173

P08754

2

binding

up-regulates activity

0.403

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-256829

P62714

Q00987

1

dephosphorylation

up-regulates activity

0.4

cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells

SIGNOR-248593

Q14457

Q9Y371

2

binding

up-regulates

0.543

Bif-1 forms a complex with beclin1 through uvrag and promotes the activation of the class iii pi3 kinase, vps34, in mammalian cells.

SIGNOR-171899

Q15628

O75509

2

binding

up-regulates

0.581

Dr6 interacts with tradd

SIGNOR-100184

Q9NPF7

Q5VWK5

2

binding

up-regulates

0.861

We identify a novel member of the hemopoietin receptor family as a subunit of the receptor for il-23, il-23r.

SIGNOR-87805

P10276

P78396

1

transcriptional regulation

down-regulates quantity by repression

0.244

RARα is involved in the regulation of cyclin A1. Further studies using ligands selective for various retinoic acid receptors suggested that cyclin A1 expression is negatively regulated by activated RARα.

SIGNOR-249636

Q8IXJ9

P37231

2

binding

down-regulates activity

0.2

Our genome-wide analysis confirmed the physiological roles of ASXL1 and ASXL2 in adipogenesis at the molecular level, supporting the hypothesis that ASXL1 is an authentic corepressor of PPARγ, whereas ASXL2 is a PPARγ coactivator, and that together ASXL1 and ASXL2 fine-tune adipogenesis via differential regulation of PPARγ.

SIGNOR-260064

O14745

P06493

0

phosphorylation

down-regulates activity

0.276

During the early stages of mitosis in HeLa cells, Cdc2 phosphorylates EBP50 on serine residues 280 and 302.|Phosphorylation by Cdc2 inhibits EBP50's role in forming microvilli in interphase but not mitotic cells. (A) Results from scoring JEG-3 cells for the presence of microvilli; error bars indicate mean \u00b1 SD. (B) Representative images from the microvillar rescue assay.

SIGNOR-278305

O75581

O94921

0

phosphorylation

up-regulates

0.333

Low-density lipoprotein receptor related proteins 5 and 6 (lrp5/6) are transmembrane receptors that initiate wnt/beta-catenin signaling. Phosphorylation of pppsp motifs in the lrp6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide rnai screen, we show that pppsp phosphorylation requires the drosophila cyclin-dependent kinase (cdk) l63. L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.

SIGNOR-162924

P46527

Q12778

0

transcriptional regulation

up-regulates quantity by expression

0.627

To date , we have found that TNC regulates the transcriptional activity of FOXO1. And p27Kip1 is one of the transcriptional targets of FOXO1 (Fig. 5A). We speculated that TNC could regulate the binding of FOXO1 to the CDKN1B promoter.

SIGNOR-277739

P33076

P17612

0

phosphorylation

down-regulates activity

0.309

Downregulation of ciita function by protein kinase a (pka)-mediated phosphorylation phosphorylation at ciita serines 834 and 1050 accounts for the inhibitory effects of pka on ciita-driven class ii mhc transcription.

SIGNOR-108569

Q06413

P23409

1

transcriptional regulation

up-regulates quantity by expression

0.565

Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.

SIGNOR-238652

Q13131

P04637

1

phosphorylation

up-regulates

0.48

Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest

SIGNOR-135960

P07948

Q05655

1

phosphorylation

down-regulates activity

0.557

Src, Fyn, or Lyn are the essential kinases that tyrosine phosphorylate and inactivate PKC δ. Lyn phosphorylates tyrosine residue 565 in vitro

SIGNOR-251407

Q13315

Q8N0Z6

1

phosphorylation

up-regulates activity

0.538

Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex.

SIGNOR-262645

P00519

P06400

2

binding

down-regulates

0.57

A domain in the c-terminus of rb, outside of the a/b pocket, binds to the atp-binding lobe of the c-abl tyrosine kinase, resulting in kinase inhibition.

SIGNOR-37139

Q96IZ0

P31749

0

phosphorylation

down-regulates activity

0.39

Prostate apoptosis response protein-4 (Par-4) sensitizes cells to chemotherapy

SIGNOR-279668

Q9C0H5

P60953

1

gtpase-activating protein

down-regulates activity

0.577

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-260495

P11413

Q05655

0

phosphorylation

up-regulates

0.2

A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity.

SIGNOR-167053

P30679

O15552

2

binding

up-regulates activity

0.404

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-257276

O15530

Q96BR1

1

phosphorylation

up-regulates

0.461

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

SIGNOR-147213

Q92935

Q15465

2

binding

down-regulates

0.294

A study in mice suggests that ext1 proteins might negatively regulate shh signaling by synthesizing hspgs, which sequester the ligand

SIGNOR-132606

Q13315

Q9BXW9

1

phosphorylation

up-regulates

0.789

These results suggest that s222 and either s1401, s1404, or s1408 are sites of atm-dependent phosphorylation in vitro.Phosphorylation Of fancd2 is required for activation of an s phase checkpoint

SIGNOR-90117

Q9UJU2

P68400

0

phosphorylation

up-regulates

0.303

Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.

SIGNOR-23958

Q5FBB7

P0C0S8

0

relocalization

up-regulates activity

0.2

The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl.|The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1.

SIGNOR-265262

P02533

P19438

2

binding

down-regulates activity

0.265

TRADD specifically bound K18 and K14, type I (acidic) keratins. it is possible that epidermal K14 may function as an inhibitor of TNF–TNFR1 signaling through an association with TRADD.

SIGNOR-251906

Q04759

Q15052

1

phosphorylation

up-regulates activity

0.2

Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation.|More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation of the Rac 1/PYGM pathway.

SIGNOR-272168

Q99814

Q9Y2K7

1

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-271581

Q00987

P41240

0

phosphorylation

up-regulates activity

0.2

Here we show that activated c-Src kinase phosphorylates Y281 and Y302 of Mdm2, resulting in an increase in Mdm2 stability and its association with Ubc12, the E2 enzyme of the neddylating complex.

SIGNOR-279163

P28482

Q15418

1

phosphorylation

up-regulates activity

0.759

Several lines of evidence indicate that the mapkap-k1 isoforms are also activated by mapks in vivo via the ras-dependent protein kinase cascade that is triggered by growth factors or tumor-promoting phorbol esters, such as phorbol 12-myristate 13-acetate (pma). here we identify six sites in mapkap-k1a that become phosphorylated in transfected cos-1 cells. The inactive form of mapkap-k1a in unstimulated cells is partially phosphorylated at ser222 and ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of thr360, ser364, thr574, and ser381 and increases the phosphorylation of ser222 and ser733.

SIGNOR-219308

O14746

Q96AP0

2

binding

up-regulates

0.557

We find that tpp1 and pot1 form a complex with telomeric dna that increases the activity and processivity of the human telomerase core enzyme.

SIGNOR-152321

Q9Y6A5

O14965

0

phosphorylation

up-regulates activity

0.937

We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.

SIGNOR-262655

Q96KB5

P45983

1

phosphorylation

up-regulates activity

0.303

Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.

SIGNOR-280061

P78337

P18146

2

binding

up-regulates activity

0.514

GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.

SIGNOR-254916

O43303

P24941

0

phosphorylation

down-regulates activity

0.515

GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)

SIGNOR-265956

P24941

P23771

1

phosphorylation

down-regulates quantity by destabilization

0.362

Phosphorylation of GATA3 Thr-156 was detected in mouse thymocytes, and cyclin-dependent kinase 2 (CDK2) was identified as a respondent for phosphorylation at Thr-156.

SIGNOR-276634

P63092

Q01718

2

binding

up-regulates activity

0.516

The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins

SIGNOR-268694

P12755

Q15796

2

binding

down-regulates activity

0.741

The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway

SIGNOR-236155

O15111

Q86VP1

1

phosphorylation

up-regulates activity

0.383

Here we demonstrate that tax1bp1 was inducibly phosphorylated on ser593 and ser624 in response to proinflammatory stimuli. The kinase ikkalpha, but not ikkbeta, was required for phosphorylation of tax1bp1 and directly phosphorylated tax1bp1 in response to stimulation with tumor necrosis factor (tnf) or interleukin 1 (il-1).

SIGNOR-175062

Q7KZI7

Q8TEW0

1

phosphorylation

up-regulates

0.493

Gab1 brings par1 and par3 into a transient complex, stimulating par3 phosphorylation by par1

SIGNOR-198742

P31785

P05112

2

binding

up-regulates

0.858

The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex

SIGNOR-108861

O96017

O15297

0

dephosphorylation

up-regulates activity

0.572

an in vitro phosphatase assay revealed that Wip1 (WT), but not Wip1 (D314A), dephosphorylates Thr68 on phosphorylated Chk2 in vitro, resulting in the inhibition of Chk2 kinase activity toward glutathione S-transferase-Cdc25C.

SIGNOR-248318

P68400

Q01534

1

phosphorylation

up-regulates activity

0.2

CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of TSPY protein

SIGNOR-250969

P56704

Q14332

2

binding

up-regulates

0.753

It was also shown that wnt5a inhibits the beta-catenin pathway by competing with wnt3a for binding to fz2, and that the impairment of clathrin-mediated internalization does not affect this wnt5a inhibitory action.

SIGNOR-189117

P18848

P07949

0

phosphorylation

down-regulates quantity by destabilization

0.2

We observed that RET physically interacted with and phosphorylated ATF4 at tyrosine and threonine residues. Indeed, RET kinase activity was required to inhibit the ATF4-dependent activation of the NOXA gene because the site-specific substitution mutations that block threonine phosphorylation increased ATF4 stability and activated its targets NOXA and PUMA.

SIGNOR-276448

Q05397

P43146

2

binding

up-regulates activity

0.72

Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin. Mutation of the tyrosine phosphorylation residue in DCC abolished its function of mediating netrin-induced axon attraction. On the basis of our observations, we suggest a model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling.

SIGNOR-268371

Q14195

Q00535

0

phosphorylation

up-regulates activity

0.603

Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro

SIGNOR-145963

P36896

P13385

2

binding

up-regulates activity

0.728

Nodal effects are dependent upon interactions with Cripto, a small cysteine-rich extracellular protein that is attached to the plasma membrane through a glycosyl phosphatidyl inositol linkage. Cripto interacts with Nodal and ALK4, independently, and promotes the formation of a stable high affinity complex with activin type II receptors.

SIGNOR-251938

P46108

P00519

0

phosphorylation

down-regulates activity

0.76

Negative regulation of crk by abl is essential for the antitumorigenic effects of ephrinb2,similar pathways may operate for crkl

SIGNOR-175135

Q9Y5F7

Q9Y5H9

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265693

Q8IWJ2

P11717

1

relocalization

up-regulates activity

0.529

Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector

SIGNOR-253085

Q16875

Q13131

0

phosphorylation

up-regulates

0.399

Ipfk-2 was phosphorylated on the homologous serine (ser-461) and activated by ampk in vitro.

SIGNOR-89760

P48454

P0DP25

2

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

P0DP23

P29474

2

binding

up-regulates activity

0.76

Electrons flow from the C-terminal reductase domain of one NOS monomer to the N-terminal oxygenase domain of the other NOS monomer (Siddhanta et al., 1998). The primary mode of enzyme activation is the binding of calcium-bound calmodulin to the N-terminal CaM-binding domain. This facilitates a structure change and the flow of electrons from NADPH through the flavins to the oxygenase domain of the other eNOS monomer

SIGNOR-251615

Q9UKV5

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.248

We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78.

SIGNOR-277356

P55085

P63096

2

binding

up-regulates activity

0.2

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

SIGNOR-256895

Q13554

P35222

1

phosphorylation

down-regulates

0.289

Camkii represses transcriptionally active _-catenin to mediate acute ethanol neurodegeneration and can phosphorylate _-catenincamkii can directly phosphorylate _-catenin. Using targeted mutagenesis we identified camkii phosphorylation sites within human _-catenin at t332, t472, and s552.

SIGNOR-202833