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
O96014	O75084	2	binding	up-regulates activity	0.712	Consistent with this, xfz7 biochemically and functionally interacts with xwnt11	SIGNOR-78406
P29474	P62136	0	dephosphorylation	up-regulates activity	0.2	The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation	SIGNOR-248558
P21728	P38405	2	binding	up-regulates activity	0.571	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-256939
Q9Y2A9	Q9NZQ7	1	glycosylation	up-regulates activity	0.2	These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation	SIGNOR-275389
P20702	P02671	2	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
Q16512	Q9NYL2	1	phosphorylation	up-regulates	0.2	Phosphorylation of mltkalpha by pknalpha enhances its kinase activity	SIGNOR-152768
Q9UPR3	Q9UNE7	0	polyubiquitination	down-regulates quantity by destabilization	0.398	Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B.	SIGNOR-272649
Q14676	Q13315	0	phosphorylation	up-regulates	0.846	We show that, in response to ionizing radiation, mdc1 is hyperphosphorylated in an atm-dependent manner, and rapidly relocalizes to nuclear foci that also contain the mre11 complex, phosphorylated histone h2ax and 53bp1.	SIGNOR-98798
O60260	O00429	1	ubiquitination	down-regulates quantity	0.2	Parkin interacts with and subsequently ubiquitinates Drp1, thus promoting its proteasome dependent degradation .\|We have demonstrated that parkin promotes Drp1 degradation after OGDR insult.	SIGNOR-278589
P52565	Q05209	0	dephosphorylation	up-regulates activity	0.2	Integrin-bound PTP-PEST dephosphorylates RhoGDI1.\|Translocation of Src phosphorylated RhoGDI1 to the cell 's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1 and Cdc42 in the cytoplasm.\|Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm.	SIGNOR-277175
P12931	Q8TEW6	2	binding	up-regulates	0.419	Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells.	SIGNOR-101002
Q9UGL1	P48431	1	transcriptional regulation	down-regulates quantity by repression	0.309	Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.	SIGNOR-273450
P11831	Q09013	0	phosphorylation	up-regulates	0.289	Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. \| Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha.	SIGNOR-236982
P05121	P00748	2	binding	down-regulates activity	0.305	C1INH is a serine protease inhibitor (serpin) that acts on both the complement pathway and the contact system and is the main inhibitor of the contact system by targeting both FXIIa and PK 9. Additionally, FXIIa can be inhibited by α1‐antitrypsin and plasminogen activator inhibitor‐1 (PAI‐1).	SIGNOR-263516
Q00534	P19484	1	phosphorylation	up-regulates activity	0.2	CDK4 and CDK6 phosphorylate TFEB and TFE3.	SIGNOR-279454
P49407	P28482	0	phosphorylation	down-regulates	0.727	Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation	SIGNOR-67630
Q13464	P42574	0	cleavage	up-regulates	0.734	Rock i is cleaved by casp3 at a conserved detd1113/g sequence and its carboxy-terminal inhibitory domain is removed, resulting in deregulated and constitutive kinase activity.	SIGNOR-106546
Q8TD43	P17252	0	phosphorylation	up-regulates	0.2	Phorbol ester-induced activation of protein kinase c (pkc) increased the ca(2+) sensitivity of wild-type trpm4 but not of two mutants mutated at putative pkc phosphorylation sites.	SIGNOR-132243
Q15468	Q13526	2	binding	up-regulates	0.361	Cell cycle-dependent phosphorylation of sil is required for its interaction with pin1, a regulator of mitosis. Point mutation of the seven (s/t)p sites between amino acids 567 and 760 reduces mitotic phosphorylation of sil, pin1 binding, and spindle checkpoint duration.	SIGNOR-138677
P26038	Q5S007	0	phosphorylation	up-regulates activity	0.551	This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process.	SIGNOR-154498
P37231	Q9HAZ2	2	binding	up-regulates	0.469	Prdm16 stimulates brown adipogenesis by binding to ppar-gamma (peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function	SIGNOR-180298
O00592	P19544	0	transcriptional regulation	up-regulates quantity by expression	0.409	Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.	SIGNOR-252300
Q08050	P53350	0	phosphorylation	up-regulates	0.705	It has been reported that plk1 could directly phosphorylate foxm1 at ser-715 and ser-724 for full activation and proper mitotic progression	SIGNOR-187892
P61586	Q70Z35	0	guanine nucleotide exchange factor	up-regulates activity	0.406	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-260570
P51795	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.292	The presence of albumin triggers the formation of an endocytic complex that includes ClC-5. (iii) Nedd4-2 is recruited to this complex and ubiquitinates ClC-5. This ubiquitination by Nedd4-2 shunts ClC-5 into the albumin uptake/degradative pathway.	SIGNOR-272665
Q9UQK1	P13807	2	binding	up-regulates	0.851	In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)	SIGNOR-271733
P51587	Q06609	2	binding	up-regulates activity	0.947	We suggest that interactions of the BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51 multimers on DNA and thereby stimulate recombination-mediated repair.	SIGNOR-259905
Q00613	P19784	0	phosphorylation	up-regulates	0.348	Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio	SIGNOR-99606
Q14258	Q969H0	1	ubiquitination	down-regulates activity	0.264	This newly stabilized TRIM25 then directly ubiquitinates Lys412 of FBXW7α, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex involved in Myc ubiquitination, thereby stabilizing Myc.	SIGNOR-277457
Q13541	P19784	0	phosphorylation	down-regulates activity	0.333	The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex.	SIGNOR-249334
Q13642	P12931	0	phosphorylation	up-regulates activity	0.26	However, overexpression of Src promoted most of the Flag-FHL1-WT to translocate to the nucleus, whereas the Flag-FHL1-Y149-272F mutant (phosphorylation deficient mutant) remained in the cytoplasm (XREF_FIG).\|We found that Src phosphorylates FHL1 at Y149 and Y272, demonstrating that FHL1 is a bona fide novel substrate of Src.	SIGNOR-278213
O75592	P10275	1	ubiquitination	down-regulates quantity by destabilization	0.2	We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.	SIGNOR-267149
P04049	Q02750	2	phosphorylation	up-regulates activity	0.749	Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2 active raf phosphorylates mek phospholpeptide analysis demostrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.	SIGNOR-235987
P00533	P51452	0	dephosphorylation	down-regulates activity	0.357	We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR.	SIGNOR-248532
Q7Z434	Q9BQ95	2	binding	up-regulates activity	0.428	ECSIT interacts with IPS-1\|ECSIT enhances IPS-1-mediated IFN-Beta promoter activation	SIGNOR-260371
Q05655	P07948	0	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
Q8IU57	Q8IU54	2	binding	up-regulates	0.873	Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha.	SIGNOR-96174
Q8IVT5	Q7Z569	0	ubiquitination	down-regulates quantity by destabilization	0.661	Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.	SIGNOR-272028
Q16695	Q96T68	0	methylation	up-regulates activity	0.2	Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.	SIGNOR-263895
P63096	P32745	2	binding	up-regulates activity	0.58	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-256677
P48454	P24588	0	relocalization	up-regulates activity	0.262	Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin	SIGNOR-261291
Q14247	Q05397	0	phosphorylation	down-regulates activity	0.745	FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility.\|GFP-FAK re-expression in FAK-/- MEFs enhances FA turnover (XREF_FIG) and cortactin knockdown slows FA turnover (XREF_FIG).	SIGNOR-278283
Q9Y294	Q86UE8	0	phosphorylation	up-regulates quantity by stabilization	0.668	We found that only S192A in hASF1a and S198A in hASF1b significantly affected phosphorylation by hTLK2 \| Consistent	SIGNOR-260787
P12830	P24941	0	phosphorylation	down-regulates quantity by destabilization	0.429	Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP	SIGNOR-274049
Q7L590	P09884	1	relocalization	up-regulates quantity by stabilization	0.862	Mcm10 is an essential eukaryotic protein required for the initiation and elongation phases of chromosomal replication. Specifically, Mcm10 is required for the association of several replication proteins, including DNA polymerase alpha (pol alpha), with chromatin.	SIGNOR-261271
P00519	Q00987	1	phosphorylation	down-regulates activity	0.716	C-abl binds and phosphorylates mdm2 in vivo and in vitro;phosphorylation of mdm2 by c-abl impairs the inhibition of p53 by mdm2.	SIGNOR-90512
P12931	P29474	1	phosphorylation	up-regulates activity	0.42	Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS.	SIGNOR-277520
P63151	P30291	1	dephosphorylation	up-regulates quantity by stabilization	0.385	Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.	SIGNOR-266381
Q96GD4	Q3KR16	1	phosphorylation	up-regulates	0.254	In this study we report that aurora b-mediated phosphorylation of myogef at thr-544 creates a docking site for plk1, leading to the localization and activation of myogef at the central spindle.	SIGNOR-204534
Q05655	Q9Y2R2	1	phosphorylation	down-regulates	0.314	We show that lyp is phosphorylated exclusively at ser-35 by pkc both in vitro and in vivo. our data establish a mechanism by which pkc could attenuate the cellular function of lyp, thereby augmenting t cell activation.	SIGNOR-159591
Q9NR96	Q8IUC6	2	binding	up-regulates activity	0.439	To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group	SIGNOR-266749
P60891	Q9UHD2	0	phosphorylation	up-regulates activity	0.2	Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.	SIGNOR-277316
Q16566	P14866	1	phosphorylation	up-regulates	0.379	Here we show that the regulation of the stress axis-regulated exon of the slo1 potassium channel transcripts by membrane depolarization requires a highly conserved camkiv target serine (ser-513) of the heterogeneous ribonucleoprotein l. Ser-513 phosphorylation within the rna recognition motif 4 enhanced heterogeneous ribonucleoprotein l interaction with the camkiv-responsive rna element 1 of stress axis-regulated exon and inhibited binding of the large subunit of the u2 auxiliary factor u2af65.	SIGNOR-197367
Q9BPV8	Q03113	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257231
P32119	P00519	0	phosphorylation	down-regulates activity	0.284	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-276280
P38936	P24941	2	binding	down-regulates	0.954	Considering that akt1 phosphorylates p21, this dissociation likely results from phosphorylation of p21 and release of cdk2.	SIGNOR-149711
Q16611	Q9NR28	1	relocalization	up-regulates	0.522	Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi	SIGNOR-118905
Q13224	Q00535	0	phosphorylation	down-regulates quantity	0.443	Cdk5 phosphorylates NR2B at Ser1116 and controls surface level expression.\|Reduction in Cdk5 activity, as well as disruption of Cdk5-NR2B interactions consistently increased NR2B surface levels and facilitated NMDA mediated synaptic function.	SIGNOR-278265
Q9UHD2	P31749	1	phosphorylation	up-regulates	0.407	Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling.	SIGNOR-252608
P50542	P51668	0	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
Q13131	P49815	1	phosphorylation	up-regulates activity	0.682	However, AMP-activated protein kinase (AMPK), an essential cellular energy sensor, phosphorylates and activates TSC2 [ xref ].	SIGNOR-278981
Q9HA82	P68400	0	phosphorylation	up-regulates activity	0.2	Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.	SIGNOR-273984
Q13568	O14920	0	phosphorylation	up-regulates activity	0.37	Here we present evidence that the kinase IKKbeta phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll like receptors and retinoic acid inducible gene I like receptors.\|Recombinant IKK\u03b2 phosphorylated IRF5 at Ser-445 in vitro, and a point mutation of this serine abolished IRF5 activation and cytokine production.	SIGNOR-279466
O14920	Q9H765	2	phosphorylation	up-regulates activity	0.2	We found that ASB8 was phosphorylated at the N-terminal Ser-31 by host IkappaB kinase beta (IKKbeta). In turn, ASB8 facilitated K48-linked ubiquitination and degradation of IKKbeta via the ubiquitin-proteasome pathway, resulting in remarkable inhibition of I-kappa-B-alpha (IkappaBalpha) and of p65 phosphorylation, consequently suppressing NF-kappaB activity.	SIGNOR-272242
O14965	Q9UM11	2	binding	down-regulates quantity by destabilization	0.561	We previously showed that human Aurora-A is turned over through the anaphase promoting complex/cyclosome (APC/C)–ubiquitin–proteasome pathway. The association of two distinct WD40 repeat proteins known as Cdc20 and Cdh1, respectively, sequentially activates the APC/C. The present study shows that Aurora-A degradation is dependent on hCdh1 in vivo, not on hCdc20, and that Aurora-A is targeted for proteolysis through distinct structural features of the destruction box, the KEN box motifs and its kinase activity.	SIGNOR-272610
P12757	Q15797	2	binding	down-regulates	0.482	Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7	SIGNOR-195636
P16885	Q96QT4	0	phosphorylation	up-regulates activity	0.263	We present data indicating that TRPM7 phosphorylates phospholipase C\u03b32 at position Ser1164 in the C2-domain, and at position Thr1045 in the linker between the catalytic region and the C2 domain.	SIGNOR-278460
Q13882	P22681	1	phosphorylation	down-regulates activity	0.488	Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl.	SIGNOR-279348
Q13185	O14965	0	phosphorylation	up-regulates activity	0.363	We report for the first time that during mitotic cell division, heterochromatin protein 1\u03b3 colocalizes and is phosphorylated at serine 83 in G2/M phase by Aurora A.	SIGNOR-280185
P60953	Q12982	2	binding	up-regulates activity	0.709	Cdo-bnip-2-cdc42 complex stimulates cdc42 activation which in turn promotes p38 alpha/beta activity and cell differentiation.	SIGNOR-179861
P17252	P21731-2	1	phosphorylation	down-regulates activity	0.521	These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.	SIGNOR-274092
P04637	P14921	2	binding	down-regulates activity	0.53	We demonstrate that p53 and ets-1 coregulate TXSA in an antagonistic and inter-related manner, with ets-1 being a potent transcriptional activator and p53 inhibiting ets-1-dependent transcription. We show that ets-1 and p53 associate physically in vitro and in vivo and that their interaction, rather than a direct binding of p53 to the TXSA promoter, is required for transcriptional repression of TXSA by wild-type p53.	SIGNOR-254087
P31749	Q12906	1	phosphorylation	up-regulates activity	0.367	Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.\|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.	SIGNOR-252512
O96017	P78527	0	phosphorylation	up-regulates	0.59	We have found that dna-pk is the major constituent of an activity present in extracts of mammalian cells that phosphorylates chk2. Our results suggest that hypophosphorylated chk2 can be phosphorylated at thr68 by dna-pk in vitro.	SIGNOR-133384
Q9NSA3	P35222	2	binding	down-regulates	0.816	We identify a novel beta-catenin-interacting protein, icat, that was found to inhibit the interaction of beta-catenin with tcf-4 and represses beta-catenin-tcf-4-mediated transactivation.	SIGNOR-79399
Q16644	Q14457	1	phosphorylation	up-regulates activity	0.425	Taken together, these data indicate that MK2 and MK3 directly phosphorylate Beclin 1 S90 in vitro, and that MK2 like kinase activity also mediates starvation induced Beclin 1 S90 phosphorylation in cultured cells.	SIGNOR-279342
O95837	P28335	2	binding	up-regulates activity	0.435	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-257295
O00230	Q92847	2	binding	up-regulates	0.471	In human tissues cst-14 as well as cst-17 but not ss-14 bind the gh secretagogue receptor (ghs-r).	SIGNOR-91134
O15511	P17252	0	phosphorylation	up-regulates activity	0.2	PKC\u03b1 phosphorylates and activates ARPC5, which organizes the actin net dorsolateral of nucleus.	SIGNOR-280078
P02461	Q8IYK4	0	glycosylation	up-regulates activity	0.404	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261158
Q92574	O43524	0	transcriptional regulation	up-regulates quantity	0.448	FoxO3a binds to and transactivates the TSC1 promoter, indicating a key role for FoxO3a in regulating TSC1 expression. Together, these data demonstrate that FoxO3a regulates glycolysis downstream of Akt through transcriptional control of Tsc1	SIGNOR-259382
Q14653	P01574	1	transcriptional regulation	up-regulates quantity by expression	0.665	Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants	SIGNOR-252257
P02462	Q8NBJ5	0	glycosylation	up-regulates activity	0.402	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261155
P63104	P53779	0	phosphorylation	down-regulates	0.2	Jnk phosphorylates 14-3-3zetaat ser-184 and 14-3-3sigmaat ser-190	SIGNOR-124009
Q9UN36	P53355	0	phosphorylation	up-regulates activity	0.273	DAPK1 phosphorylates and activates N-myc downstream-regulated gene 2 (NDRG2), resulting in increased tau phosphorylation via a reduction in Pin1 expression ( xref ; xref ).	SIGNOR-279983
P35372	P01213	0	chemical activation	up-regulates activity	0.674	Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.	SIGNOR-258414
P25103	P19086	2	binding	up-regulates activity	0.289	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-257316
Q9BZM5	P26718	2	binding	up-regulates	0.586	Here we describe a family of gpi-anchored cell surface proteins that function as ligands for the mouse activating nkg2d receptor. These molecules are encoded by the retinoic acid early inducible (rae-1) and h60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with mhc class i.	SIGNOR-79233
O14757	P30305	1	phosphorylation	down-regulates activity	0.785	Here, we show that cdc25b is phosphorylated by chk1 in vitro on multiple residues, including s230 and s563.We show that the s230-phosphorylated form of cdc25b is located at the centrosome from early s phase until mitosis. Furthermore, mutation of s230 to alanine increases the mitotic-inducing activity of cdc25b	SIGNOR-149898
Q15139	Q8NEB9	1	phosphorylation	up-regulates activity	0.371	PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate formation, and autophagosome formation.\|Therefore, PKD phosphorylates Vps34 on multiple sites, including Thr677 within the catalytic domain.	SIGNOR-278495
P15498	P06241	0	phosphorylation	up-regulates	0.636	Study of t cells from a fyn-deficient tcr transgenic mouse also showed that fyn was required for tyrosine phosphorylation and activation of vav induced by both antagonist and agonist peptides.	SIGNOR-82287
Q15768	P54764	2	binding	up-regulates	0.838	Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor	SIGNOR-52621
Q9H300	Q9BXM7	1	cleavage	down-regulates quantity by destabilization	0.613	Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy.	SIGNOR-261364
Q8NFZ4	Q9NQX3	2	binding	up-regulates activity	0.473	Gephyrin is believed to act as a scaffold at inhibitory synapses, in a manner analogous to that of the prototypic excitatory synaptic scaffold, PSD-95. The best-known function of gephyrin is to bring the inhibitory synaptic receptors and to stabilize them at the inhibitory synapses. gephyrin interacts with NL-2 and collybistin, suggesting that it may be critical for the maturation or maintenance of inhibitory synapses.	SIGNOR-264974
P06400	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.667	In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB	SIGNOR-278530
O14746	P49711	0	transcriptional regulation	down-regulates quantity by repression	0.328	CTCF binds the proximal exonic region of hTERT and inhibits its transcription	SIGNOR-253832
Q9Y4I1	P31751	0	phosphorylation	up-regulates activity	0.458	Here we identify an Akt consensus phosphorylation motif in the actin-based motor protein myosin 5a and show that insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact with the actin cytoskeleton.Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface.	SIGNOR-262632
Q13422	P43405	0	phosphorylation	up-regulates	0.404	Syk phoshorylatesikarosat unique c-terminal serine phosphorylation sites s358 and s361, thereby augmenting its nuclear localization and sequence-specific dna binding activity. Mechanistically, we establish that syk-inducedikarosactivation is essential for its nuclear localization and optimal transcription factor function.	SIGNOR-199100
P78352	P00519	0	phosphorylation	up-regulates activity	0.441	Moreover, c-Abl phosphorylates PSD-95 at tyrosine 533.\|c-Abl modulates the synaptic contact number and PSD-95 clustering.	SIGNOR-278391
P12931	P84022	1	phosphorylation	up-regulates activity	0.377	Although the role of ERK in mediating phosphorylation of Smad2/3 remains to be investigated, our data indicate that early Smad3 phosphorylation is independent of transient EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas Src mediated chronic EGFR transactivation and ERK1/2 activation involve late Smad3 activation induced by TGF-beta1.\|Inhibition of Src not only decreases Smad3 phosphorylation but also decreases phosphorylation dependent nuclear translocation of Smad2/3, suggesting that Src kinase could modulate Smad3 activity.	SIGNOR-279292

O96014

O75084

2

binding

up-regulates activity

0.712

Consistent with this, xfz7 biochemically and functionally interacts with xwnt11

SIGNOR-78406

P29474

P62136

0

dephosphorylation

up-regulates activity

0.2

The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation

SIGNOR-248558

P21728

P38405

2

binding

up-regulates activity

0.571

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-256939

Q9Y2A9

Q9NZQ7

1

glycosylation

up-regulates activity

0.2

These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation

SIGNOR-275389

P20702

P02671

2

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

Q16512

Q9NYL2

1

phosphorylation

up-regulates

0.2

Phosphorylation of mltkalpha by pknalpha enhances its kinase activity

SIGNOR-152768

Q9UPR3

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.398

Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B.

SIGNOR-272649

Q14676

Q13315

0

phosphorylation

up-regulates

0.846

We show that, in response to ionizing radiation, mdc1 is hyperphosphorylated in an atm-dependent manner, and rapidly relocalizes to nuclear foci that also contain the mre11 complex, phosphorylated histone h2ax and 53bp1.

SIGNOR-98798

O60260

O00429

1

ubiquitination

down-regulates quantity

0.2

Parkin interacts with and subsequently ubiquitinates Drp1, thus promoting its proteasome dependent degradation .|We have demonstrated that parkin promotes Drp1 degradation after OGDR insult.

SIGNOR-278589

P52565

Q05209

0

dephosphorylation

up-regulates activity

0.2

Integrin-bound PTP-PEST dephosphorylates RhoGDI1.|Translocation of Src phosphorylated RhoGDI1 to the cell 's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1 and Cdc42 in the cytoplasm.|Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm.

SIGNOR-277175

P12931

Q8TEW6

2

binding

up-regulates

0.419

Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells.

SIGNOR-101002

Q9UGL1

P48431

1

transcriptional regulation

down-regulates quantity by repression

0.309

Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.

SIGNOR-273450

P11831

Q09013

0

phosphorylation

up-regulates

0.289

Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha.

SIGNOR-236982

P05121

P00748

2

binding

down-regulates activity

0.305

C1INH is a serine protease inhibitor (serpin) that acts on both the complement pathway and the contact system and is the main inhibitor of the contact system by targeting both FXIIa and PK 9. Additionally, FXIIa can be inhibited by α1‐antitrypsin and plasminogen activator inhibitor‐1 (PAI‐1).

SIGNOR-263516

Q00534

P19484

1

phosphorylation

up-regulates activity

0.2

CDK4 and CDK6 phosphorylate TFEB and TFE3.

SIGNOR-279454

P49407

P28482

0

phosphorylation

down-regulates

0.727

Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation

SIGNOR-67630

Q13464

P42574

0

cleavage

up-regulates

0.734

Rock i is cleaved by casp3 at a conserved detd1113/g sequence and its carboxy-terminal inhibitory domain is removed, resulting in deregulated and constitutive kinase activity.

SIGNOR-106546

Q8TD43

P17252

0

phosphorylation

up-regulates

0.2

Phorbol ester-induced activation of protein kinase c (pkc) increased the ca(2+) sensitivity of wild-type trpm4 but not of two mutants mutated at putative pkc phosphorylation sites.

SIGNOR-132243

Q15468

Q13526

2

binding

up-regulates

0.361

Cell cycle-dependent phosphorylation of sil is required for its interaction with pin1, a regulator of mitosis. Point mutation of the seven (s/t)p sites between amino acids 567 and 760 reduces mitotic phosphorylation of sil, pin1 binding, and spindle checkpoint duration.

SIGNOR-138677

P26038

Q5S007

0

phosphorylation

up-regulates activity

0.551

This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process.

SIGNOR-154498

P37231

Q9HAZ2

2

binding

up-regulates

0.469

Prdm16 stimulates brown adipogenesis by binding to ppar-gamma (peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function

SIGNOR-180298

O00592

P19544

0

transcriptional regulation

up-regulates quantity by expression

0.409

Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.

SIGNOR-252300

Q08050

P53350

0

phosphorylation

up-regulates

0.705

It has been reported that plk1 could directly phosphorylate foxm1 at ser-715 and ser-724 for full activation and proper mitotic progression

SIGNOR-187892

P61586

Q70Z35

0

guanine nucleotide exchange factor

up-regulates activity

0.406

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-260570

P51795

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.292

The presence of albumin triggers the formation of an endocytic complex that includes ClC-5. (iii) Nedd4-2 is recruited to this complex and ubiquitinates ClC-5. This ubiquitination by Nedd4-2 shunts ClC-5 into the albumin uptake/degradative pathway.

SIGNOR-272665

Q9UQK1

P13807

2

binding

up-regulates

0.851

In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)

SIGNOR-271733

P51587

Q06609

2

binding

up-regulates activity

0.947

We suggest that interactions of the BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51 multimers on DNA and thereby stimulate recombination-mediated repair.

SIGNOR-259905

Q00613

P19784

0

phosphorylation

up-regulates

0.348

Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio

SIGNOR-99606

Q14258

Q969H0

1

ubiquitination

down-regulates activity

0.264

This newly stabilized TRIM25 then directly ubiquitinates Lys412 of FBXW7α, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex involved in Myc ubiquitination, thereby stabilizing Myc.

SIGNOR-277457

Q13541

P19784

0

phosphorylation

down-regulates activity

0.333

The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex.

SIGNOR-249334

Q13642

P12931

0

phosphorylation

up-regulates activity

0.26

However, overexpression of Src promoted most of the Flag-FHL1-WT to translocate to the nucleus, whereas the Flag-FHL1-Y149-272F mutant (phosphorylation deficient mutant) remained in the cytoplasm (XREF_FIG).|We found that Src phosphorylates FHL1 at Y149 and Y272, demonstrating that FHL1 is a bona fide novel substrate of Src.

SIGNOR-278213

O75592

P10275

1

ubiquitination

down-regulates quantity by destabilization

0.2

We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.

SIGNOR-267149

P04049

Q02750

2

phosphorylation

up-regulates activity

0.749

Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2 active raf phosphorylates mek phospholpeptide analysis demostrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.

SIGNOR-235987

P00533

P51452

0

dephosphorylation

down-regulates activity

0.357

We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR.

SIGNOR-248532

Q7Z434

Q9BQ95

2

binding

up-regulates activity

0.428

ECSIT interacts with IPS-1|ECSIT enhances IPS-1-mediated IFN-Beta promoter activation

SIGNOR-260371

Q05655

P07948

0

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

Q8IU57

Q8IU54

2

binding

up-regulates

0.873

Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha.

SIGNOR-96174

Q8IVT5

Q7Z569

0

ubiquitination

down-regulates quantity by destabilization

0.661

Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.

SIGNOR-272028

Q16695

Q96T68

0

methylation

up-regulates activity

0.2

Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.

SIGNOR-263895

P63096

P32745

2

binding

up-regulates activity

0.58

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-256677

P48454

P24588

0

relocalization

up-regulates activity

0.262

Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin

SIGNOR-261291

Q14247

Q05397

0

phosphorylation

down-regulates activity

0.745

FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility.|GFP-FAK re-expression in FAK-/- MEFs enhances FA turnover (XREF_FIG) and cortactin knockdown slows FA turnover (XREF_FIG).

SIGNOR-278283

Q9Y294

Q86UE8

0

phosphorylation

up-regulates quantity by stabilization

0.668

We found that only S192A in hASF1a and S198A in hASF1b significantly affected phosphorylation by hTLK2 | Consistent

SIGNOR-260787

P12830

P24941

0

phosphorylation

down-regulates quantity by destabilization

0.429

Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP

SIGNOR-274049

Q7L590

P09884

1

relocalization

up-regulates quantity by stabilization

0.862

Mcm10 is an essential eukaryotic protein required for the initiation and elongation phases of chromosomal replication. Specifically, Mcm10 is required for the association of several replication proteins, including DNA polymerase alpha (pol alpha), with chromatin.

SIGNOR-261271

P00519

Q00987

1

phosphorylation

down-regulates activity

0.716

C-abl binds and phosphorylates mdm2 in vivo and in vitro;phosphorylation of mdm2 by c-abl impairs the inhibition of p53 by mdm2.

SIGNOR-90512

P12931

P29474

1

phosphorylation

up-regulates activity

0.42

Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS.

SIGNOR-277520

P63151

P30291

1

dephosphorylation

up-regulates quantity by stabilization

0.385

Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.

SIGNOR-266381

Q96GD4

Q3KR16

1

phosphorylation

up-regulates

0.254

In this study we report that aurora b-mediated phosphorylation of myogef at thr-544 creates a docking site for plk1, leading to the localization and activation of myogef at the central spindle.

SIGNOR-204534

Q05655

Q9Y2R2

1

phosphorylation

down-regulates

0.314

We show that lyp is phosphorylated exclusively at ser-35 by pkc both in vitro and in vivo. our data establish a mechanism by which pkc could attenuate the cellular function of lyp, thereby augmenting t cell activation.

SIGNOR-159591

Q9NR96

Q8IUC6

2

binding

up-regulates activity

0.439

To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group

SIGNOR-266749

P60891

Q9UHD2

0

phosphorylation

up-regulates activity

0.2

Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.

SIGNOR-277316

Q16566

P14866

1

phosphorylation

up-regulates

0.379

Here we show that the regulation of the stress axis-regulated exon of the slo1 potassium channel transcripts by membrane depolarization requires a highly conserved camkiv target serine (ser-513) of the heterogeneous ribonucleoprotein l. Ser-513 phosphorylation within the rna recognition motif 4 enhanced heterogeneous ribonucleoprotein l interaction with the camkiv-responsive rna element 1 of stress axis-regulated exon and inhibited binding of the large subunit of the u2 auxiliary factor u2af65.

SIGNOR-197367

Q9BPV8

Q03113

2

binding

up-regulates activity

0.2

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

SIGNOR-257231

P32119

P00519

0

phosphorylation

down-regulates activity

0.284

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-276280

P38936

P24941

2

binding

down-regulates

0.954

Considering that akt1 phosphorylates p21, this dissociation likely results from phosphorylation of p21 and release of cdk2.

SIGNOR-149711

Q16611

Q9NR28

1

relocalization

up-regulates

0.522

Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi

SIGNOR-118905

Q13224

Q00535

0

phosphorylation

down-regulates quantity

0.443

Cdk5 phosphorylates NR2B at Ser1116 and controls surface level expression.|Reduction in Cdk5 activity, as well as disruption of Cdk5-NR2B interactions consistently increased NR2B surface levels and facilitated NMDA mediated synaptic function.

SIGNOR-278265

Q9UHD2

P31749

1

phosphorylation

up-regulates

0.407

Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling.

SIGNOR-252608

P50542

P51668

0

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

Q13131

P49815

1

phosphorylation

up-regulates activity

0.682

However, AMP-activated protein kinase (AMPK), an essential cellular energy sensor, phosphorylates and activates TSC2 [ xref ].

SIGNOR-278981

Q9HA82

P68400

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-273984

Q13568

O14920

0

phosphorylation

up-regulates activity

0.37

Here we present evidence that the kinase IKKbeta phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll like receptors and retinoic acid inducible gene I like receptors.|Recombinant IKK\u03b2 phosphorylated IRF5 at Ser-445 in vitro, and a point mutation of this serine abolished IRF5 activation and cytokine production.

SIGNOR-279466

O14920

Q9H765

2

phosphorylation

up-regulates activity

0.2

We found that ASB8 was phosphorylated at the N-terminal Ser-31 by host IkappaB kinase beta (IKKbeta). In turn, ASB8 facilitated K48-linked ubiquitination and degradation of IKKbeta via the ubiquitin-proteasome pathway, resulting in remarkable inhibition of I-kappa-B-alpha (IkappaBalpha) and of p65 phosphorylation, consequently suppressing NF-kappaB activity.

SIGNOR-272242

O14965

Q9UM11

2

binding

down-regulates quantity by destabilization

0.561

We previously showed that human Aurora-A is turned over through the anaphase promoting complex/cyclosome (APC/C)–ubiquitin–proteasome pathway. The association of two distinct WD40 repeat proteins known as Cdc20 and Cdh1, respectively, sequentially activates the APC/C. The present study shows that Aurora-A degradation is dependent on hCdh1 in vivo, not on hCdc20, and that Aurora-A is targeted for proteolysis through distinct structural features of the destruction box, the KEN box motifs and its kinase activity.

SIGNOR-272610

P12757

Q15797

2

binding

down-regulates

0.482

Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7

SIGNOR-195636

P16885

Q96QT4

0

phosphorylation

up-regulates activity

0.263

We present data indicating that TRPM7 phosphorylates phospholipase C\u03b32 at position Ser1164 in the C2-domain, and at position Thr1045 in the linker between the catalytic region and the C2 domain.

SIGNOR-278460

Q13882

P22681

1

phosphorylation

down-regulates activity

0.488

Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl.

SIGNOR-279348

Q13185

O14965

0

phosphorylation

up-regulates activity

0.363

We report for the first time that during mitotic cell division, heterochromatin protein 1\u03b3 colocalizes and is phosphorylated at serine 83 in G2/M phase by Aurora A.

SIGNOR-280185

P60953

Q12982

2

binding

up-regulates activity

0.709

Cdo-bnip-2-cdc42 complex stimulates cdc42 activation which in turn promotes p38 alpha/beta activity and cell differentiation.

SIGNOR-179861

P17252

P21731-2

1

phosphorylation

down-regulates activity

0.521

These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.

SIGNOR-274092

P04637

P14921

2

binding

down-regulates activity

0.53

We demonstrate that p53 and ets-1 coregulate TXSA in an antagonistic and inter-related manner, with ets-1 being a potent transcriptional activator and p53 inhibiting ets-1-dependent transcription. We show that ets-1 and p53 associate physically in vitro and in vivo and that their interaction, rather than a direct binding of p53 to the TXSA promoter, is required for transcriptional repression of TXSA by wild-type p53.

SIGNOR-254087

P31749

Q12906

1

phosphorylation

up-regulates activity

0.367

Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.

SIGNOR-252512

O96017

P78527

0

phosphorylation

up-regulates

0.59

We have found that dna-pk is the major constituent of an activity present in extracts of mammalian cells that phosphorylates chk2. Our results suggest that hypophosphorylated chk2 can be phosphorylated at thr68 by dna-pk in vitro.

SIGNOR-133384

Q9NSA3

P35222

2

binding

down-regulates

0.816

We identify a novel beta-catenin-interacting protein, icat, that was found to inhibit the interaction of beta-catenin with tcf-4 and represses beta-catenin-tcf-4-mediated transactivation.

SIGNOR-79399

Q16644

Q14457

1

phosphorylation

up-regulates activity

0.425

Taken together, these data indicate that MK2 and MK3 directly phosphorylate Beclin 1 S90 in vitro, and that MK2 like kinase activity also mediates starvation induced Beclin 1 S90 phosphorylation in cultured cells.

SIGNOR-279342

O95837

P28335

2

binding

up-regulates activity

0.435

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-257295

O00230

Q92847

2

binding

up-regulates

0.471

In human tissues cst-14 as well as cst-17 but not ss-14 bind the gh secretagogue receptor (ghs-r).

SIGNOR-91134

O15511

P17252

0

phosphorylation

up-regulates activity

0.2

PKC\u03b1 phosphorylates and activates ARPC5, which organizes the actin net dorsolateral of nucleus.

SIGNOR-280078

P02461

Q8IYK4

0

glycosylation

up-regulates activity

0.404

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261158

Q92574

O43524

0

transcriptional regulation

up-regulates quantity

0.448

FoxO3a binds to and transactivates the TSC1 promoter, indicating a key role for FoxO3a in regulating TSC1 expression. Together, these data demonstrate that FoxO3a regulates glycolysis downstream of Akt through transcriptional control of Tsc1

SIGNOR-259382

Q14653

P01574

1

transcriptional regulation

up-regulates quantity by expression

0.665

Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants

SIGNOR-252257

P02462

Q8NBJ5

0

glycosylation

up-regulates activity

0.402

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261155

P63104

P53779

0

phosphorylation

down-regulates

0.2

Jnk phosphorylates 14-3-3zetaat ser-184 and 14-3-3sigmaat ser-190

SIGNOR-124009

Q9UN36

P53355

0

phosphorylation

up-regulates activity

0.273

DAPK1 phosphorylates and activates N-myc downstream-regulated gene 2 (NDRG2), resulting in increased tau phosphorylation via a reduction in Pin1 expression ( xref ; xref ).

SIGNOR-279983

P35372

P01213

0

chemical activation

up-regulates activity

0.674

Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.

SIGNOR-258414

P25103

P19086

2

binding

up-regulates activity

0.289

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-257316

Q9BZM5

P26718

2

binding

up-regulates

0.586

Here we describe a family of gpi-anchored cell surface proteins that function as ligands for the mouse activating nkg2d receptor. These molecules are encoded by the retinoic acid early inducible (rae-1) and h60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with mhc class i.

SIGNOR-79233

O14757

P30305

1

phosphorylation

down-regulates activity

0.785

Here, we show that cdc25b is phosphorylated by chk1 in vitro on multiple residues, including s230 and s563.We show that the s230-phosphorylated form of cdc25b is located at the centrosome from early s phase until mitosis. Furthermore, mutation of s230 to alanine increases the mitotic-inducing activity of cdc25b

SIGNOR-149898

Q15139

Q8NEB9

1

phosphorylation

up-regulates activity

0.371

PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate formation, and autophagosome formation.|Therefore, PKD phosphorylates Vps34 on multiple sites, including Thr677 within the catalytic domain.

SIGNOR-278495

P15498

P06241

0

phosphorylation

up-regulates

0.636

Study of t cells from a fyn-deficient tcr transgenic mouse also showed that fyn was required for tyrosine phosphorylation and activation of vav induced by both antagonist and agonist peptides.

SIGNOR-82287

Q15768

P54764

2

binding

up-regulates

0.838

Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor

SIGNOR-52621

Q9H300

Q9BXM7

1

cleavage

down-regulates quantity by destabilization

0.613

Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy.

SIGNOR-261364

Q8NFZ4

Q9NQX3

2

binding

up-regulates activity

0.473

Gephyrin is believed to act as a scaffold at inhibitory synapses, in a manner analogous to that of the prototypic excitatory synaptic scaffold, PSD-95. The best-known function of gephyrin is to bring the inhibitory synaptic receptors and to stabilize them at the inhibitory synapses. gephyrin interacts with NL-2 and collybistin, suggesting that it may be critical for the maturation or maintenance of inhibitory synapses.

SIGNOR-264974

P06400

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.667

In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB

SIGNOR-278530

O14746

P49711

0

transcriptional regulation

down-regulates quantity by repression

0.328

CTCF binds the proximal exonic region of hTERT and inhibits its transcription

SIGNOR-253832

Q9Y4I1

P31751

0

phosphorylation

up-regulates activity

0.458

Here we identify an Akt consensus phosphorylation motif in the actin-based motor protein myosin 5a and show that insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact with the actin cytoskeleton.Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface.

SIGNOR-262632

Q13422

P43405

0

phosphorylation

up-regulates

0.404

Syk phoshorylatesikarosat unique c-terminal serine phosphorylation sites s358 and s361, thereby augmenting its nuclear localization and sequence-specific dna binding activity. Mechanistically, we establish that syk-inducedikarosactivation is essential for its nuclear localization and optimal transcription factor function.

SIGNOR-199100

P78352

P00519

0

phosphorylation

up-regulates activity

0.441

Moreover, c-Abl phosphorylates PSD-95 at tyrosine 533.|c-Abl modulates the synaptic contact number and PSD-95 clustering.

SIGNOR-278391

P12931

P84022

1

phosphorylation

up-regulates activity

0.377

Although the role of ERK in mediating phosphorylation of Smad2/3 remains to be investigated, our data indicate that early Smad3 phosphorylation is independent of transient EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas Src mediated chronic EGFR transactivation and ERK1/2 activation involve late Smad3 activation induced by TGF-beta1.|Inhibition of Src not only decreases Smad3 phosphorylation but also decreases phosphorylation dependent nuclear translocation of Smad2/3, suggesting that Src kinase could modulate Smad3 activity.

SIGNOR-279292