GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P17612	Q8N752	1	phosphorylation	up-regulates	0.39	Mutation of either the three pka sites or pka-primed cki sites prevents phosphorylation of ci by cki in vitro and blocks ci cleavage in embryos	SIGNOR-144557
Q07866	O14656	1	binding	up-regulates activity	0.39	We identified the light chain subunit (KLC1) of kinesin-I as an interacting partner for torsinA, with binding occurring between the tetratricopeptide repeat domain of KLC1 and the carboxyl-terminal region of torsinA. Coimmunoprecipitation analysis demonstrated that wildtype torsinA and kinesin-I form a complex in vivo. These studies suggest that wild-type torsinA undergoes anterograde transport along microtubules mediated by kinesin and may act as a molecular chaperone regulating kinesin activity and/or cargo binding.	SIGNOR-261172
Q14586	P09238	1	transcriptional regulation	down-regulates quantity by repression	0.39	Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10	SIGNOR-266211
Q00535	Q9Y4G8	1	phosphorylation	up-regulates activity	0.39	Our results demonstrate that the Cdk5-dependent activation of RapGEF2, spatial activation of Rap1 signalling and Rap1-facilitated surface localization of N-cadherin in the upper intermediate zone control neuronal migration and ultimately the architecture of the mammalian cerebral cortex.\|This demonstrates that Cdk5 phosphorylates RapGEF2 at Ser1124 in vitro .	SIGNOR-278258
P35555	Q9UBX5	1	binding	down-regulates activity	0.39	Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. We have determined how they interact with tropoelastin, lysyl oxidase, and fibrillin-1, thereby revealing how they differentially regulate assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin.	SIGNOR-252138
P30542	P09471	1	binding	up-regulates activity	0.39	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-256976
P27361	Q15831	1	phosphorylation	down-regulates activity	0.39	Directly and/or through the activation of p90RSK, ERK phosphorylates LKB-1 at Ser325 and Ser428. The phosphorylation of LKB-1 causes the dissociation of LKB-1 from AMPK, resulting in the impaired activation of AMPK.	SIGNOR-209880
Q8WVD3	O75771	1	ubiquitination	down-regulates quantity by destabilization	0.39	RNF138 dependent ubiquitination of RAD51D and proteasome mediated degradation.	SIGNOR-278775
P12931	Q9UHR4	1	phosphorylation	up-regulates activity	0.389	Here, we report that overexpression of IRTKS increases the speed of wound closure of HT1080 cells in a Src-dependent manner. Active Src phosphorylates IRTKS in vivo and in vitro. Deletion mapping and mutation analysis revealed that six tyrosine residues (Y37, Y156, Y163, Y274, Y293 and Y439) were Src-stimulated phosphorylation sites on IRTKS. Disruption of Src-stimulated IRTKS phosphorylation abolished the effect of IRTKS on wound closure. Collectively, these data suggest Src-stimulated IRTKS phosphorylation is essential for its function in cell motility.	SIGNOR-263041
P16949	Q8NG68	1	binding	down-regulates	0.389	Stathmin depresses ttl tubulin tyrosination activityin vitro.	SIGNOR-193465
P49841	P46527	1	phosphorylation	up-regulates quantity by stabilization	0.389	GSK-3\u03b2 phosphorylates p27 Kip1 at S160 and S161, resulting in increased p27 Kip1 stability [ xref ].	SIGNOR-278938
Q8WVI7	P62136	1	binding	down-regulates activity	0.389	IPP5, a novel inhibitor of protein phosphatase 1, suppresses tumor growth and progression of cervical carcinoma cells by inducing G2/M arrest	SIGNOR-275726
Q00987	P37231	1	ubiquitination	down-regulates quantity by destabilization	0.389	Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase.	SIGNOR-277191
P12931	P04083	1	phosphorylation	up-regulates	0.389	The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].Finally in 2013 caron et al. showed the relevance of y21 phosphorylation for the anxa1 stability. In fact the authors demonstrated that the tyrosine 21 phosphorylation is crucial for anxa1 sumoylation induced by egf	SIGNOR-202796
Q99527	P00533	1	binding	up-regulates	0.389	Gpcr-mediated transactivation of egfrs by estrogen provides a previously unappreciated mechanism of cross-talk between estrogen and serum growth factors, and explains prior data reporting the egf-like effects of estrogen	SIGNOR-115988
P06493	O95835	1	phosphorylation	up-regulates	0.389	Warts is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that cdc2/cyclin b forms a complex with a fraction of warts in the centrosome and phosphorylates the ser613 site of warts during mitosisit can be speculated that phosphorylation of warts by cdc2/cyclin b promotes a protein complex formation on the mitotic apparatus at early mitosis, which may be required for subsequent activation of warts kinase at the metaphase-anaphase transition.	SIGNOR-94160
P06241	P35354	1	phosphorylation	up-regulates activity	0.389	We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro.	SIGNOR-276644
P56178	P28360	2	binding	down-regulates activity	0.389	We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.	SIGNOR-240921
Q9UKA9	P31943	1	binding	up-regulates activity	0.389	Splicing of the c-src N1 exon in neuronal cells depends in part on an intronic cluster of RNA regulatory elements called the downstream control sequence (DCS). \|nPTB binds more stably to the DCS RNA than PTB does but is a weaker repressor of splicing in vitro. nPTB also greatly enhances the binding of two other proteins, hnRNP H and KSRP, to the DCS RNA.	SIGNOR-261269
O60285	O95835	1	phosphorylation	down-regulates	0.389	Moreover, we show that nuak1 phosphorylates lats1 at s464 and this has a role in controlling its stabilitycells that constitutively express nuak1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator lats1	SIGNOR-161792
P17252	Q15311	1	phosphorylation	up-regulates activity	0.389	In deletion mutant analyses of potential phosphorylation sites in RLIP76, we identified T297 and S509 as targets for phosphorylation by PKCalpha. Phosphorylation at T297 increased doxorubicin (DOX)-transport activity approximately 2-fold for RLIP76 purified from recombinant source	SIGNOR-263164
Q9H6Z4	P84022	1	relocalization	down-regulates	0.389	Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner	SIGNOR-184608
Q9H2X6	P16220	1	phosphorylation	up-regulates	0.389	Ere we found that homeodomain-interacting protein kinase 2 (hipk2), a dna-damage responsive nuclear kinase, is a new creb kinase for phosphorylation at ser-271 but not ser-133, and activates creb transactivation function	SIGNOR-166338
Q9Y297	P84022	1	ubiquitination	down-regulates	0.389	An e3 ubiquitin ligase complex roc1-scffbw1a consisting of roc1, skp1, cullin1, and fbw1a (also termed trcp1) induces ubiquitination of smad3.	SIGNOR-108237
P31751	Q7Z6J0	1	phosphorylation	down-regulates	0.389	Overexpression of posh induces apoptosis in a variety of cell types, but apoptosis can be prevented by co-expressing the pro-survival protein kinase akt. We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac	SIGNOR-155233
Q5U5R9	O75925	1	polyubiquitination	down-regulates quantity by destabilization	0.389	We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model.	SIGNOR-272421
Q14012	Q92974	1	phosphorylation	up-regulates activity	0.389	In this study, we found that CaMKI phosphorylated GEF-H1 at Thr103, which is located close to the C1 domain.	SIGNOR-279359
P28360	P56178	2	binding	down-regulates activity	0.389	We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.	SIGNOR-240987
P05771	P17302	1	phosphorylation	down-regulates activity	0.388	Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.\|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.	SIGNOR-249049
Q6ZNA4	Q9H6T0	1	ubiquitination	up-regulates activity	0.388	These findings suggest that Arkadia ubiquitinates ESRP2 and potentiates the splicing function of ESRP2 ( ).	SIGNOR-278613
P08581	P09874	1	phosphorylation	up-regulates activity	0.388	Here we show that the receptor tyrosine kinase c-Met associates with and phosphorylates PARP1 at Tyr907 (PARP1 pTyr907 or pY907).\|To address whether c-Met activates PARP1, we exposed MDA-MB-231 cells expressing control shRNA or c-Met shRNA to H 2 O 2 and subjected them to a comet assay to evaluate the extent of DNA damage.	SIGNOR-279470
P11309	Q00987	1	phosphorylation	up-regulates	0.388	Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt.	SIGNOR-178619
Q9Y297	Q13485	1	ubiquitination	down-regulates	0.388	Here we show that beta-trcp1, a f-box protein in the scf e3 ligase complex, interacts with smad4 and induces the degradation of smad4	SIGNOR-123057
P06241	Q9C0B5	1	phosphorylation	up-regulates quantity by stabilization	0.388	Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).	SIGNOR-279738
P08238	O14727	1	binding	down-regulates	0.388	The present studies demonstrate that heat shock protein 90 (hsp90) forms a cytosolic complex with apaf-1 and thereby inhibits the formation of the active complex.	SIGNOR-81043
Q9HBW0	P63092	1	binding	up-regulates activity	0.388	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256784
P06493	Q15149	1	phosphorylation	down-regulates	0.388	Identification of plectin as a substrate of p34cdc2 kinase and mapping of a single phosphorylation site. threonine 4542 was identified as the major target for the kinase. Phosphorylation of plectin by cyclin-dependent kinase 1/cyclin b (cdk1/cycb) kinase has been reported to abolish its cross-linking function during mitosis. Here, we induced phosphorylation of plectin in prepared fractions of hela cells by adding activated cdk1/cycb kinase. Consequently, there was significant dissociation of the centrosome from the nuclear membrane.	SIGNOR-41319
P49841	O00429	1	phosphorylation	up-regulates activity	0.388	We identified glycogen synthase kinase (GSK)3β-dependent Drp1 phosphorylation at Ser(40) and Ser(44), which increases Drp1 GTPase activity and its mitochondrial distribution and could induce mitochondrial fragmentation.	SIGNOR-276849
P07477	P55085	1	cleavage	up-regulates activity	0.388	Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3.	SIGNOR-263602
O95747	P55017	1	phosphorylation	up-regulates	0.388	We demonstrate that the spak and osr1 kinases that are activated by wnk1 phosphorylate human ncc at three conserved residues (thr46, thr55 and thr60) / our results also indicate that phosphorylation of thr60 plays the most crucial role in triggering the activation of ncc in hek293 cells and its mutation also inhibits phosphorylation of the adjacent thr46 and thr55 sites.	SIGNOR-160833
P51812	Q13315	1	phosphorylation	up-regulates activity	0.388	Furthermore, using RSK2 knockout mouse fibroblasts and RSK2 deficient cells from CLS patients, we demonstrate that ablation of RSK2 impairs the phosphorylation of Atm at Ser1981 and the phosphorylation of p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.\|We postulate that the phosphorylation of RSK2 is required to fully activate Atm at Ser1981 and p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.	SIGNOR-280118
O14965	P16949	1	phosphorylation	down-regulates activity	0.388	Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.\|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref .	SIGNOR-278913
P22413	P06213	1	binding	down-regulates activity	0.388	Plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor (IR) tyrosine kinase activity and subsequent cellular signaling. PC-1 may inhibit the IR by interacting directly with a specific region in the IR alpha-subunit.	SIGNOR-252190
Q969H0	P23769	1	ubiquitination	down-regulates quantity by destabilization	0.388	Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation.	SIGNOR-256005
Q13627	P55211	1	phosphorylation	down-regulates activity	0.388	Depletion of DYRK1A from human cells by short interfering RNA inhibits the basal phosphorylation of caspase 9 at an inhibitory site, Thr125. DYRK1A-dependent phosphorylation of Thr125 is also blocked by harmine, confirming the use of this beta-carboline alkaloid as a potent inhibitor of DYRK1A in cells.\|When co-expressed in cells, DYRK1A interacts with caspase 9, strongly induces Thr125 phosphorylation and inhibits caspase 9 auto-processing.	SIGNOR-279326
Q13164	O00141	1	phosphorylation	up-regulates	0.388	Bmk1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinasebmk1 activates sgk by phosphorylation at serine 78.	SIGNOR-105728
P35030	P55085	1	cleavage	up-regulates activity	0.388	Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3.	SIGNOR-263604
Q15139	P35222	1	phosphorylation	up-regulates	0.388	This study provides evidence that pkd1 interacts with and phosphorylates beta-catenin at thr(112) and thr(120) we postulate that pkd1 phosphorylation is required to maintain _-catenin transcription activity.	SIGNOR-183384
P27635	P07947	1	binding	down-regulates	0.388	Several c-yes kinase activity assays indicated that the qm protein reduced c-yes kinase activity by 70%	SIGNOR-90805
O15516	Q15466	1	transcriptional regulation	up-regulates quantity by expression	0.388	CLOCK knockdown activated MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK upregulated SHP by binding to its E box.	SIGNOR-253698
P49841	P19838	1	phosphorylation	up-regulates quantity by stabilization	0.388	GSK-3 beta forms an in vivo complex with and specifically phosphorylates NF-kappa B1/p105 at Ser-903 and Ser-907 in vitro. GSK-3 beta has a dual effect on p105: it stabilizes p105 under resting conditions and primes p105 for degradation upon tumor necrosis factor (TNF)-alpha treatment. Indeed, constitutive processing of p105 to p50 occurs at a higher rate in cells lacking GSK-3 beta with respect to wild-type cells and can be reduced upon reintroduction of GSK-3 beta by transfection. S903A and S907A point mutations impair p105 proteolysis in response to TNF-α.	SIGNOR-251251
P21554	O43613	1	binding	up-regulates activity	0.388	Another example is the heteromer between CB1 and orexin 1 receptor (OX1R). The CB1 activation potentiated the OX1R signaling (218), suggesting the interaction of these two receptors. Interaction of their surface distribution was also reported.	SIGNOR-264269
P51668	P50542	1	ubiquitination	up-regulates activity	0.388	Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.	SIGNOR-253022
Q9NWF9	O00206	1	ubiquitination	down-regulates quantity by destabilization	0.388	Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.	SIGNOR-271504
Q00987	P10914	1	ubiquitination	down-regulates quantity	0.388	HIV-1 Tat Recruits HDM2 E3 Ligase To Target IRF-1 for Ubiquitination and Proteasomal Degradation.\|IRF-1 ubiquitination by HDM2 is specifically increased during HIV-1 infection in the presence of increasing amounts of Tat and is mediated by the formation of a trimeric complex between Tat, IRF-1, and HDM2, as demonstrated by coimmunoprecipitation analysis (XREF_FIG).	SIGNOR-278590
Q14012	Q9NP62	1	phosphorylation	up-regulates activity	0.388	We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.	SIGNOR-262680
Q02446	O43186	1	binding	up-regulates activity	0.388	Sp4 directly binds Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.	SIGNOR-225333
P00533	Q8NFJ5	1	phosphorylation	down-regulates activity	0.387	EGFR phosphorylates and inhibits lung tumor suppressor GPRC5A in lung cancer.\|Together, these results indicate that endogenous EGFR can phosphorylate GPRC5A at four identified tyrosine residues (Y317, Y320, Y347 and Y350) in response to EGF stimulation in the lung cancer H1792 cells.	SIGNOR-278336
Q15643	P10827	1	binding	up-regulates	0.387	Trip230 binds to rb independently of thyroid hormone while it forms a complex with tr in a thyroid hormone-dependent manner. Ectopic expression of the protein trip230 in cells, but not a mutant form that does not bind to tr, enhances specifically tr-dependent transcriptional activity.	SIGNOR-50348
P68400	Q13371	1	phosphorylation	up-regulates	0.387	Phosducin-like protein (phlp) is a widely expressed binding partner of the g protein betagamma subunit complex (gbetagamma) that has been recently shown to catalyze the formation of the gbetagamma dimer from its nascent polypeptides. Phosphorylation of phlp at one or more of three consecutive serines (ser-18, ser-19, and ser-20) is necessary for gbetagamma dimer formation and is believed to be mediated by the protein kinase ck2.	SIGNOR-146833
Q9NWF9	P58753	1	ubiquitination	down-regulates quantity by destabilization	0.387	Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.	SIGNOR-271607
Q9Y2R2	P22681	1	dephosphorylation	down-regulates	0.387	The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state.	SIGNOR-65405
Q12913	P40198	1	dephosphorylation	down-regulates activity	0.387	We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.\|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.	SIGNOR-277091
P00519	Q06830	1	phosphorylation	down-regulates activity	0.387	Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.	SIGNOR-276278
P11309	O43524	1	phosphorylation	down-regulates activity	0.387	Pim1s expression induced the phosphorylation of foxo3a (fig. 5a and b) and inactivated its transcriptional activity (fig. 5c). A previous report showed that phosphorylation at t32, s253, and s315 residues in foxo3a induced 14-3-3 binding, nuclear export, and proteasomemediated degradation (42).	SIGNOR-179308
P02671	P20702	1	binding	up-regulates	0.387	To map the binding sites for four distinct ligands for mac-l: ic3b, fibrinogen, icam-1. __the i domain on the ot chain of mac-1 is an important recognition site for all four ligands.	SIGNOR-31320
Q6ZRV2	P48729	1	binding	up-regulates quantity	0.387	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273747
P28482	Q8WZ42	1	phosphorylation	up-regulates quantity	0.387	ERK2 phosphorylates three serines in titin\u2019s N2B-Us: S3918, S3960, and S4010 (the latter of which is well conserved) ().	SIGNOR-279636
O95835	Q16635	1	phosphorylation	down-regulates activity	0.387	When the inhibitory Hippo kinase module is ' on ', LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.\|When the inhibitory Hippo kinase module is \u2018on\u2019, LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.	SIGNOR-279200
Q9Y608	Q92997	1	binding	up-regulates	0.387	In particular, a previously unrecognized activator, lrrfip2 (leucine-rich repeat in flightless interaction protein 2), was found that interacts with dvl to increase the cellular levels of _-catenin and activate _-catenin/lef/tcf-dependent transcriptional activity	SIGNOR-133429
O14757	Q96AV8	1	phosphorylation	down-regulates activity	0.387	Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.\|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage.	SIGNOR-279692
P27635	P05412	1	binding	down-regulates	0.387	The qm gene encodes a 24.5 kda ribosomal protein l10 known to be highly homologous to a jun-binding protein (jif-1), which inhibits the formation of jun-jun dimers.	SIGNOR-90750
O95136	P08754	1	binding	up-regulates activity	0.387	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-256871
Q86X55	Q02078	1	methylation	up-regulates	0.387	The first evidence alluding to a role of PRMTs in mediating skeletal muscle plasticity, specifically myogenesis, arose from the identification of CARM1 as a glucocorticoid receptor-interacting protein 1 (GRIP1) binding protein. (Chen et al., 2000). Here, GRIP1 and MEF2 were co-expressed in the nucleus during skeletal muscle differentiation. These initial findings led to an investigation that revealed that this methyltransferase was responsible for coactivating the transcription of myocyte enhancer factor-2C (MEF2C) via GRIP1	SIGNOR-255964
Q9UNE7	Q06787	1	ubiquitination	down-regulates quantity by destabilization	0.387	The results showed that FMR1 was ubiquitinated by CHIP WT or CHIP K30A. Also, ubiquitinated FMR1 accumulated in the presence of MG132, indicating that CHIP ubiquitinates FMR1 for proteasomal degradation ( Fig. 3 B).	SIGNOR-278599
P49840	Q6R327	1	phosphorylation	down-regulates quantity by destabilization	0.387	We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.	SIGNOR-276899
Q9UBR4	P01215	1	transcriptional regulation	up-regulates quantity by expression	0.387	Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing hormone (TRH). P-Lim binds to CBP in TRH-dependent manner on this site and that these proteins synergistically activate the human α-GSU promoter during TRH stimulation.	SIGNOR-267207
P17612	P52565	1	phosphorylation	down-regulates	0.387	The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.	SIGNOR-180576
Q8IZL9	P24941	1	phosphorylation	up-regulates	0.387	P42 is essential for the phosphorylation of thr-160 and activation of cdk2.	SIGNOR-118986
O00308	P24928	1	ubiquitination	down-regulates quantity	0.387	WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks\|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.	SIGNOR-268851
P11142	Q99942	1	binding	up-regulates activity	0.387	JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex	SIGNOR-271493
P30411	O95837	1	binding	up-regulates activity	0.387	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-257199
Q8IXL6	P07237	1	phosphorylation	up-regulates activity	0.387	The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.	SIGNOR-275574
Q92731	P06850	1	transcriptional regulation	up-regulates quantity by expression	0.386	Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.\|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro.	SIGNOR-268722
P68400	Q13144	1	phosphorylation	up-regulates activity	0.386	Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.	SIGNOR-250859
Q15418	P25963	1	phosphorylation	up-regulates activity	0.386	Mitogen activated ribosomal S6 kinase (p90 rsk1) phosphorylates IkappaBalpha at S32, binds IkappaBalpha in vivo, and overexpression of dominant negative p90 rsk1 inhibits degradation of IkappaBalpha in response to TPA.	SIGNOR-279311
P62140	P31749	1	dephosphorylation	down-regulates activity	0.386	Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells\|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells	SIGNOR-252604
P78527	P03372	1	phosphorylation	up-regulates quantity by stabilization	0.386	DNA-PK phosphorylates ERalpha at Ser-118.\|Phosphorylation resulted in stabilization of ERalpha protein as inhibition of DNA-PK resulted in its proteasomal degradation.	SIGNOR-279561
P17252	P35568	1	phosphorylation	down-regulates activity	0.386	We show that pkcalpha is likely to be directly involved in ser24 phosphorylation...These observations are entirely consistent with a recent independent study demonstrating that the IRS1-S24D mutant shows impaired insulin-stimulated IR-IRS-1 interactions, tyrosine phosphorylation of IRS-1, recruitment/activation of PI 3-Kinase, and insulin-stimulated Glut4 translocation	SIGNOR-145398
Q13304	P08754	1	binding	up-regulates activity	0.386	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-256835
O75116	P05067	1	phosphorylation	up-regulates quantity	0.386	Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.\|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms.	SIGNOR-280109
Q38SD2	P51149	1	phosphorylation	up-regulates activity	0.386	Overall, these data suggest that LRRK1 is able to phosphorylate endogenous Rab7A at Ser72.	SIGNOR-278212
O43609	Q07889	1	binding	down-regulates	0.386	Taken together, these results establish mammalian sprouty proteins as important negative regulators of growth factor signaling and suggest that sprouty proteins act downstream of the grb2.Sos Complex to selectively uncouple growth factor signals from ras activation and the map kinase pathway.	SIGNOR-110948
P12931	P10721	1	phosphorylation	up-regulates activity	0.386	C-src phosphorylates tyr900 in the second part of the kinase domain of c-kit.	SIGNOR-103999
P46934	P37231	1	ubiquitination	up-regulates activity	0.386	First, NEDD4 interacts with and ubiquitinates PPARgamma.\|NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation.	SIGNOR-278540
P31749	P51617	1	phosphorylation	down-regulates activity	0.386	CaMKKc and Akt overexpression increases IRAK1 phosphorylation at Thr100, and point mutation of this site abrogates the inhibitory effect of Akt on IRAK1-mediated NF-kappaB activation.	SIGNOR-252551
P05129	P61764	1	phosphorylation	down-regulates activity	0.386	Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.	SIGNOR-249187
Q00536	P04637	1	phosphorylation	down-regulates activity	0.386	In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.\|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.	SIGNOR-278354
Q86UX7	P05556	1	binding	up-regulates activity	0.386	Mechanistically, Kindlin-3 can directly bind to regions of beta-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis\|Kindlin-3 was also able to interact with the wild-type beta1 and beta3 integrin tails (Fig. 3c), in the presence and absence of Talin1 (Supplementary Fig. 3 online), and the F3 subdomain of Kindlin-3 was sufficient for this interaction and this interaction occurred in a direct manner	SIGNOR-266065
Q53ET0	P35558	1	transcriptional regulation	up-regulates quantity	0.386	These results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.	SIGNOR-256106

P17612

Q8N752

1

phosphorylation

up-regulates

0.39

Mutation of either the three pka sites or pka-primed cki sites prevents phosphorylation of ci by cki in vitro and blocks ci cleavage in embryos

SIGNOR-144557

Q07866

O14656

1

binding

up-regulates activity

0.39

We identified the light chain subunit (KLC1) of kinesin-I as an interacting partner for torsinA, with binding occurring between the tetratricopeptide repeat domain of KLC1 and the carboxyl-terminal region of torsinA. Coimmunoprecipitation analysis demonstrated that wildtype torsinA and kinesin-I form a complex in vivo. These studies suggest that wild-type torsinA undergoes anterograde transport along microtubules mediated by kinesin and may act as a molecular chaperone regulating kinesin activity and/or cargo binding.

SIGNOR-261172

Q14586

P09238

1

transcriptional regulation

down-regulates quantity by repression

0.39

Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10

SIGNOR-266211

Q00535

Q9Y4G8

1

phosphorylation

up-regulates activity

0.39

Our results demonstrate that the Cdk5-dependent activation of RapGEF2, spatial activation of Rap1 signalling and Rap1-facilitated surface localization of N-cadherin in the upper intermediate zone control neuronal migration and ultimately the architecture of the mammalian cerebral cortex.|This demonstrates that Cdk5 phosphorylates RapGEF2 at Ser1124 in vitro .

SIGNOR-278258

P35555

Q9UBX5

1

binding

down-regulates activity

0.39

Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. We have determined how they interact with tropoelastin, lysyl oxidase, and fibrillin-1, thereby revealing how they differentially regulate assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin.

SIGNOR-252138

P30542

P09471

1

binding

up-regulates activity

0.39

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-256976

P27361

Q15831

1

phosphorylation

down-regulates activity

0.39

Directly and/or through the activation of p90RSK, ERK phosphorylates LKB-1 at Ser325 and Ser428. The phosphorylation of LKB-1 causes the dissociation of LKB-1 from AMPK, resulting in the impaired activation of AMPK.

SIGNOR-209880

Q8WVD3

O75771

1

ubiquitination

down-regulates quantity by destabilization

0.39

RNF138 dependent ubiquitination of RAD51D and proteasome mediated degradation.

SIGNOR-278775

P12931

Q9UHR4

1

phosphorylation

up-regulates activity

0.389

Here, we report that overexpression of IRTKS increases the speed of wound closure of HT1080 cells in a Src-dependent manner. Active Src phosphorylates IRTKS in vivo and in vitro. Deletion mapping and mutation analysis revealed that six tyrosine residues (Y37, Y156, Y163, Y274, Y293 and Y439) were Src-stimulated phosphorylation sites on IRTKS. Disruption of Src-stimulated IRTKS phosphorylation abolished the effect of IRTKS on wound closure. Collectively, these data suggest Src-stimulated IRTKS phosphorylation is essential for its function in cell motility.

SIGNOR-263041

P16949

Q8NG68

1

binding

down-regulates

0.389

Stathmin depresses ttl tubulin tyrosination activityin vitro.

SIGNOR-193465

P49841

P46527

1

phosphorylation

up-regulates quantity by stabilization

0.389

GSK-3\u03b2 phosphorylates p27 Kip1 at S160 and S161, resulting in increased p27 Kip1 stability [ xref ].

SIGNOR-278938

Q8WVI7

P62136

1

binding

down-regulates activity

0.389

IPP5, a novel inhibitor of protein phosphatase 1, suppresses tumor growth and progression of cervical carcinoma cells by inducing G2/M arrest

SIGNOR-275726

Q00987

P37231

1

ubiquitination

down-regulates quantity by destabilization

0.389

Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase.

SIGNOR-277191

P12931

P04083

1

phosphorylation

up-regulates

0.389

The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].Finally in 2013 caron et al. showed the relevance of y21 phosphorylation for the anxa1 stability. In fact the authors demonstrated that the tyrosine 21 phosphorylation is crucial for anxa1 sumoylation induced by egf

SIGNOR-202796

Q99527

P00533

1

binding

up-regulates

0.389

Gpcr-mediated transactivation of egfrs by estrogen provides a previously unappreciated mechanism of cross-talk between estrogen and serum growth factors, and explains prior data reporting the egf-like effects of estrogen

SIGNOR-115988

P06493

O95835

1

phosphorylation

up-regulates

0.389

Warts is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that cdc2/cyclin b forms a complex with a fraction of warts in the centrosome and phosphorylates the ser613 site of warts during mitosisit can be speculated that phosphorylation of warts by cdc2/cyclin b promotes a protein complex formation on the mitotic apparatus at early mitosis, which may be required for subsequent activation of warts kinase at the metaphase-anaphase transition.

SIGNOR-94160

P06241

P35354

1

phosphorylation

up-regulates activity

0.389

We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro.

SIGNOR-276644

P56178

P28360

2

binding

down-regulates activity

0.389

We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.

SIGNOR-240921

Q9UKA9

P31943

1

binding

up-regulates activity

0.389

Splicing of the c-src N1 exon in neuronal cells depends in part on an intronic cluster of RNA regulatory elements called the downstream control sequence (DCS). |nPTB binds more stably to the DCS RNA than PTB does but is a weaker repressor of splicing in vitro. nPTB also greatly enhances the binding of two other proteins, hnRNP H and KSRP, to the DCS RNA.

SIGNOR-261269

O60285

O95835

1

phosphorylation

down-regulates

0.389

Moreover, we show that nuak1 phosphorylates lats1 at s464 and this has a role in controlling its stabilitycells that constitutively express nuak1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator lats1

SIGNOR-161792

P17252

Q15311

1

phosphorylation

up-regulates activity

0.389

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

SIGNOR-263164

Q9H6Z4

P84022

1

relocalization

down-regulates

0.389

Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner

SIGNOR-184608

Q9H2X6

P16220

1

phosphorylation

up-regulates

0.389

Ere we found that homeodomain-interacting protein kinase 2 (hipk2), a dna-damage responsive nuclear kinase, is a new creb kinase for phosphorylation at ser-271 but not ser-133, and activates creb transactivation function

SIGNOR-166338

Q9Y297

P84022

1

ubiquitination

down-regulates

0.389

An e3 ubiquitin ligase complex roc1-scffbw1a consisting of roc1, skp1, cullin1, and fbw1a (also termed trcp1) induces ubiquitination of smad3.

SIGNOR-108237

P31751

Q7Z6J0

1

phosphorylation

down-regulates

0.389

Overexpression of posh induces apoptosis in a variety of cell types, but apoptosis can be prevented by co-expressing the pro-survival protein kinase akt. We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac

SIGNOR-155233

Q5U5R9

O75925

1

polyubiquitination

down-regulates quantity by destabilization

0.389

We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model.

SIGNOR-272421

Q14012

Q92974

1

phosphorylation

up-regulates activity

0.389

In this study, we found that CaMKI phosphorylated GEF-H1 at Thr103, which is located close to the C1 domain.

SIGNOR-279359

P28360

P56178

2

binding

down-regulates activity

0.389

We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.

SIGNOR-240987

P05771

P17302

1

phosphorylation

down-regulates activity

0.388

Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.

SIGNOR-249049

Q6ZNA4

Q9H6T0

1

ubiquitination

up-regulates activity

0.388

These findings suggest that Arkadia ubiquitinates ESRP2 and potentiates the splicing function of ESRP2 ( ).

SIGNOR-278613

P08581

P09874

1

phosphorylation

up-regulates activity

0.388

Here we show that the receptor tyrosine kinase c-Met associates with and phosphorylates PARP1 at Tyr907 (PARP1 pTyr907 or pY907).|To address whether c-Met activates PARP1, we exposed MDA-MB-231 cells expressing control shRNA or c-Met shRNA to H 2 O 2 and subjected them to a comet assay to evaluate the extent of DNA damage.

SIGNOR-279470

P11309

Q00987

1

phosphorylation

up-regulates

0.388

Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt.

SIGNOR-178619

Q9Y297

Q13485

1

ubiquitination

down-regulates

0.388

Here we show that beta-trcp1, a f-box protein in the scf e3 ligase complex, interacts with smad4 and induces the degradation of smad4

SIGNOR-123057

P06241

Q9C0B5

1

phosphorylation

up-regulates quantity by stabilization

0.388

Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).

SIGNOR-279738

P08238

O14727

1

binding

down-regulates

0.388

The present studies demonstrate that heat shock protein 90 (hsp90) forms a cytosolic complex with apaf-1 and thereby inhibits the formation of the active complex.

SIGNOR-81043

Q9HBW0

P63092

1

binding

up-regulates activity

0.388

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

SIGNOR-256784

P06493

Q15149

1

phosphorylation

down-regulates

0.388

Identification of plectin as a substrate of p34cdc2 kinase and mapping of a single phosphorylation site. threonine 4542 was identified as the major target for the kinase. Phosphorylation of plectin by cyclin-dependent kinase 1/cyclin b (cdk1/cycb) kinase has been reported to abolish its cross-linking function during mitosis. Here, we induced phosphorylation of plectin in prepared fractions of hela cells by adding activated cdk1/cycb kinase. Consequently, there was significant dissociation of the centrosome from the nuclear membrane.

SIGNOR-41319

P49841

O00429

1

phosphorylation

up-regulates activity

0.388

We identified glycogen synthase kinase (GSK)3β-dependent Drp1 phosphorylation at Ser(40) and Ser(44), which increases Drp1 GTPase activity and its mitochondrial distribution and could induce mitochondrial fragmentation.

SIGNOR-276849

P07477

P55085

1

cleavage

up-regulates activity

0.388

Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3.

SIGNOR-263602

O95747

P55017

1

phosphorylation

up-regulates

0.388

We demonstrate that the spak and osr1 kinases that are activated by wnk1 phosphorylate human ncc at three conserved residues (thr46, thr55 and thr60) / our results also indicate that phosphorylation of thr60 plays the most crucial role in triggering the activation of ncc in hek293 cells and its mutation also inhibits phosphorylation of the adjacent thr46 and thr55 sites.

SIGNOR-160833

P51812

Q13315

1

phosphorylation

up-regulates activity

0.388

Furthermore, using RSK2 knockout mouse fibroblasts and RSK2 deficient cells from CLS patients, we demonstrate that ablation of RSK2 impairs the phosphorylation of Atm at Ser1981 and the phosphorylation of p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.|We postulate that the phosphorylation of RSK2 is required to fully activate Atm at Ser1981 and p53 at Ser18 (mouse) or Ser15 (human) in response to genotoxic stress.

SIGNOR-280118

O14965

P16949

1

phosphorylation

down-regulates activity

0.388

Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref .

SIGNOR-278913

P22413

P06213

1

binding

down-regulates activity

0.388

Plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor (IR) tyrosine kinase activity and subsequent cellular signaling. PC-1 may inhibit the IR by interacting directly with a specific region in the IR alpha-subunit.

SIGNOR-252190

Q969H0

P23769

1

ubiquitination

down-regulates quantity by destabilization

0.388

Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation.

SIGNOR-256005

Q13627

P55211

1

phosphorylation

down-regulates activity

0.388

Depletion of DYRK1A from human cells by short interfering RNA inhibits the basal phosphorylation of caspase 9 at an inhibitory site, Thr125. DYRK1A-dependent phosphorylation of Thr125 is also blocked by harmine, confirming the use of this beta-carboline alkaloid as a potent inhibitor of DYRK1A in cells.|When co-expressed in cells, DYRK1A interacts with caspase 9, strongly induces Thr125 phosphorylation and inhibits caspase 9 auto-processing.

SIGNOR-279326

Q13164

O00141

1

phosphorylation

up-regulates

0.388

Bmk1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinasebmk1 activates sgk by phosphorylation at serine 78.

SIGNOR-105728

P35030

P55085

1

cleavage

up-regulates activity

0.388

Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3.

SIGNOR-263604

Q15139

P35222

1

phosphorylation

up-regulates

0.388

This study provides evidence that pkd1 interacts with and phosphorylates beta-catenin at thr(112) and thr(120) we postulate that pkd1 phosphorylation is required to maintain _-catenin transcription activity.

SIGNOR-183384

P27635

P07947

1

binding

down-regulates

0.388

Several c-yes kinase activity assays indicated that the qm protein reduced c-yes kinase activity by 70%

SIGNOR-90805

O15516

Q15466

1

transcriptional regulation

up-regulates quantity by expression

0.388

CLOCK knockdown activated MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK upregulated SHP by binding to its E box.

SIGNOR-253698

P49841

P19838

1

phosphorylation

up-regulates quantity by stabilization

0.388

GSK-3 beta forms an in vivo complex with and specifically phosphorylates NF-kappa B1/p105 at Ser-903 and Ser-907 in vitro. GSK-3 beta has a dual effect on p105: it stabilizes p105 under resting conditions and primes p105 for degradation upon tumor necrosis factor (TNF)-alpha treatment. Indeed, constitutive processing of p105 to p50 occurs at a higher rate in cells lacking GSK-3 beta with respect to wild-type cells and can be reduced upon reintroduction of GSK-3 beta by transfection. S903A and S907A point mutations impair p105 proteolysis in response to TNF-α.

SIGNOR-251251

P21554

O43613

1

binding

up-regulates activity

0.388

Another example is the heteromer between CB1 and orexin 1 receptor (OX1R). The CB1 activation potentiated the OX1R signaling (218), suggesting the interaction of these two receptors. Interaction of their surface distribution was also reported.

SIGNOR-264269

P51668

P50542

1

ubiquitination

up-regulates activity

0.388

Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.

SIGNOR-253022

Q9NWF9

O00206

1

ubiquitination

down-regulates quantity by destabilization

0.388

Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.

SIGNOR-271504

Q00987

P10914

1

ubiquitination

down-regulates quantity

0.388

HIV-1 Tat Recruits HDM2 E3 Ligase To Target IRF-1 for Ubiquitination and Proteasomal Degradation.|IRF-1 ubiquitination by HDM2 is specifically increased during HIV-1 infection in the presence of increasing amounts of Tat and is mediated by the formation of a trimeric complex between Tat, IRF-1, and HDM2, as demonstrated by coimmunoprecipitation analysis (XREF_FIG).

SIGNOR-278590

Q14012

Q9NP62

1

phosphorylation

up-regulates activity

0.388

We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.

SIGNOR-262680

Q02446

O43186

1

binding

up-regulates activity

0.388

Sp4 directly binds Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.

SIGNOR-225333

P00533

Q8NFJ5

1

phosphorylation

down-regulates activity

0.387

EGFR phosphorylates and inhibits lung tumor suppressor GPRC5A in lung cancer.|Together, these results indicate that endogenous EGFR can phosphorylate GPRC5A at four identified tyrosine residues (Y317, Y320, Y347 and Y350) in response to EGF stimulation in the lung cancer H1792 cells.

SIGNOR-278336

Q15643

P10827

1

binding

up-regulates

0.387

Trip230 binds to rb independently of thyroid hormone while it forms a complex with tr in a thyroid hormone-dependent manner. Ectopic expression of the protein trip230 in cells, but not a mutant form that does not bind to tr, enhances specifically tr-dependent transcriptional activity.

SIGNOR-50348

P68400

Q13371

1

phosphorylation

up-regulates

0.387

Phosducin-like protein (phlp) is a widely expressed binding partner of the g protein betagamma subunit complex (gbetagamma) that has been recently shown to catalyze the formation of the gbetagamma dimer from its nascent polypeptides. Phosphorylation of phlp at one or more of three consecutive serines (ser-18, ser-19, and ser-20) is necessary for gbetagamma dimer formation and is believed to be mediated by the protein kinase ck2.

SIGNOR-146833

Q9NWF9

P58753

1

ubiquitination

down-regulates quantity by destabilization

0.387

Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.

SIGNOR-271607

Q9Y2R2

P22681

1

dephosphorylation

down-regulates

0.387

The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state.

SIGNOR-65405

Q12913

P40198

1

dephosphorylation

down-regulates activity

0.387

We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.

SIGNOR-277091

P00519

Q06830

1

phosphorylation

down-regulates activity

0.387

Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.

SIGNOR-276278

P11309

O43524

1

phosphorylation

down-regulates activity

0.387

Pim1s expression induced the phosphorylation of foxo3a (fig. 5a and b) and inactivated its transcriptional activity (fig. 5c). A previous report showed that phosphorylation at t32, s253, and s315 residues in foxo3a induced 14-3-3 binding, nuclear export, and proteasomemediated degradation (42).

SIGNOR-179308

P02671

P20702

1

binding

up-regulates

0.387

To map the binding sites for four distinct ligands for mac-l: ic3b, fibrinogen, icam-1. __the i domain on the ot chain of mac-1 is an important recognition site for all four ligands.

SIGNOR-31320

Q6ZRV2

P48729

1

binding

up-regulates quantity

0.387

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273747

P28482

Q8WZ42

1

phosphorylation

up-regulates quantity

0.387

ERK2 phosphorylates three serines in titin\u2019s N2B-Us: S3918, S3960, and S4010 (the latter of which is well conserved) ().

SIGNOR-279636

O95835

Q16635

1

phosphorylation

down-regulates activity

0.387

When the inhibitory Hippo kinase module is ' on ', LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.|When the inhibitory Hippo kinase module is \u2018on\u2019, LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.

SIGNOR-279200

Q9Y608

Q92997

1

binding

up-regulates

0.387

In particular, a previously unrecognized activator, lrrfip2 (leucine-rich repeat in flightless interaction protein 2), was found that interacts with dvl to increase the cellular levels of _-catenin and activate _-catenin/lef/tcf-dependent transcriptional activity

SIGNOR-133429

O14757

Q96AV8

1

phosphorylation

down-regulates activity

0.387

Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage.

SIGNOR-279692

P27635

P05412

1

binding

down-regulates

0.387

The qm gene encodes a 24.5 kda ribosomal protein l10 known to be highly homologous to a jun-binding protein (jif-1), which inhibits the formation of jun-jun dimers.

SIGNOR-90750

O95136

P08754

1

binding

up-regulates activity

0.387

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-256871

Q86X55

Q02078

1

methylation

up-regulates

0.387

The first evidence alluding to a role of PRMTs in mediating skeletal muscle plasticity, specifically myogenesis, arose from the identification of CARM1 as a glucocorticoid receptor-interacting protein 1 (GRIP1) binding protein. (Chen et al., 2000). Here, GRIP1 and MEF2 were co-expressed in the nucleus during skeletal muscle differentiation. These initial findings led to an investigation that revealed that this methyltransferase was responsible for coactivating the transcription of myocyte enhancer factor-2C (MEF2C) via GRIP1

SIGNOR-255964

Q9UNE7

Q06787

1

ubiquitination

down-regulates quantity by destabilization

0.387

The results showed that FMR1 was ubiquitinated by CHIP WT or CHIP K30A. Also, ubiquitinated FMR1 accumulated in the presence of MG132, indicating that CHIP ubiquitinates FMR1 for proteasomal degradation ( Fig. 3 B).

SIGNOR-278599

P49840

Q6R327

1

phosphorylation

down-regulates quantity by destabilization

0.387

We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.

SIGNOR-276899

Q9UBR4

P01215

1

transcriptional regulation

up-regulates quantity by expression

0.387

Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing hormone (TRH). P-Lim binds to CBP in TRH-dependent manner on this site and that these proteins synergistically activate the human α-GSU promoter during TRH stimulation.

SIGNOR-267207

P17612

P52565

1

phosphorylation

down-regulates

0.387

The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.

SIGNOR-180576

Q8IZL9

P24941

1

phosphorylation

up-regulates

0.387

P42 is essential for the phosphorylation of thr-160 and activation of cdk2.

SIGNOR-118986

O00308

P24928

1

ubiquitination

down-regulates quantity

0.387

WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.

SIGNOR-268851

P11142

Q99942

1

binding

up-regulates activity

0.387

JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex

SIGNOR-271493

P30411

O95837

1

binding

up-regulates activity

0.387

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-257199

Q8IXL6

P07237

1

phosphorylation

up-regulates activity

0.387

The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.

SIGNOR-275574

Q92731

P06850

1

transcriptional regulation

up-regulates quantity by expression

0.386

Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro.

SIGNOR-268722

P68400

Q13144

1

phosphorylation

up-regulates activity

0.386

Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.

SIGNOR-250859

Q15418

P25963

1

phosphorylation

up-regulates activity

0.386

Mitogen activated ribosomal S6 kinase (p90 rsk1) phosphorylates IkappaBalpha at S32, binds IkappaBalpha in vivo, and overexpression of dominant negative p90 rsk1 inhibits degradation of IkappaBalpha in response to TPA.

SIGNOR-279311

P62140

P31749

1

dephosphorylation

down-regulates activity

0.386

Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells

SIGNOR-252604

P78527

P03372

1

phosphorylation

up-regulates quantity by stabilization

0.386

DNA-PK phosphorylates ERalpha at Ser-118.|Phosphorylation resulted in stabilization of ERalpha protein as inhibition of DNA-PK resulted in its proteasomal degradation.

SIGNOR-279561

P17252

P35568

1

phosphorylation

down-regulates activity

0.386

We show that pkcalpha is likely to be directly involved in ser24 phosphorylation...These observations are entirely consistent with a recent independent study demonstrating that the IRS1-S24D mutant shows impaired insulin-stimulated IR-IRS-1 interactions, tyrosine phosphorylation of IRS-1, recruitment/activation of PI 3-Kinase, and insulin-stimulated Glut4 translocation

SIGNOR-145398

Q13304

P08754

1

binding

up-regulates activity

0.386

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-256835

O75116

P05067

1

phosphorylation

up-regulates quantity

0.386

Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms.

SIGNOR-280109

Q38SD2

P51149

1

phosphorylation

up-regulates activity

0.386

Overall, these data suggest that LRRK1 is able to phosphorylate endogenous Rab7A at Ser72.

SIGNOR-278212

O43609

Q07889

1

binding

down-regulates

0.386

Taken together, these results establish mammalian sprouty proteins as important negative regulators of growth factor signaling and suggest that sprouty proteins act downstream of the grb2.Sos Complex to selectively uncouple growth factor signals from ras activation and the map kinase pathway.

SIGNOR-110948

P12931

P10721

1

phosphorylation

up-regulates activity

0.386

C-src phosphorylates tyr900 in the second part of the kinase domain of c-kit.

SIGNOR-103999

P46934

P37231

1

ubiquitination

up-regulates activity

0.386

First, NEDD4 interacts with and ubiquitinates PPARgamma.|NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation.

SIGNOR-278540

P31749

P51617

1

phosphorylation

down-regulates activity

0.386

CaMKKc and Akt overexpression increases IRAK1 phosphorylation at Thr100, and point mutation of this site abrogates the inhibitory effect of Akt on IRAK1-mediated NF-kappaB activation.

SIGNOR-252551

P05129

P61764

1

phosphorylation

down-regulates activity

0.386

Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.

SIGNOR-249187

Q00536

P04637

1

phosphorylation

down-regulates activity

0.386

In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.

SIGNOR-278354

Q86UX7

P05556

1

binding

up-regulates activity

0.386

Mechanistically, Kindlin-3 can directly bind to regions of beta-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis|Kindlin-3 was also able to interact with the wild-type beta1 and beta3 integrin tails (Fig. 3c), in the presence and absence of Talin1 (Supplementary Fig. 3 online), and the F3 subdomain of Kindlin-3 was sufficient for this interaction and this interaction occurred in a direct manner

SIGNOR-266065

Q53ET0

P35558

1

transcriptional regulation

up-regulates quantity

0.386

These results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

SIGNOR-256106