GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P27816	P06493	phosphorylation	down-regulates activity	0.497	We have shown that MAP4 is phosphorylated in vivo in mitotic HeLa cells at eight sites. Five of these were phosphorylated by p34cdc2 kinase. Two of the five p34cdc2 kinase phosphorylation sites were shown to be Ser696 and Ser787 in the proline-rich region. Mutation of Ser787 to Glu strikingly reduced the MAP4's MT-polymerization activity, while Glu-mutation at Ser696 did not. These results suggest that Ser787 could be the critical phosphorylation site causing MTs to be dynamic at mitosis.	SIGNOR-277459
O00238	P36894	binding	up-regulates	0.497	Using several complementary approaches, we investigated the formation of homomeric and heteromeric complexes between the two known bmp type i receptors	SIGNOR-75649
P38398	P06493	phosphorylation	up-regulates	0.497	However, shrna-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated s phase cell-cycle arrest and the phosphorylation of a subset of atr/atm targets after dna damage. Loss of dna damage-induced checkpoint control was caused by a reduction in formation of brca1-containing foci. Mutation of brca1 at s1497 and s1189/s1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of brca1-containing foci.	SIGNOR-72087
P63092	Q13639	binding	up-regulates activity	0.497	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-256769
Q5VWQ8	P31749	phosphorylation	down-regulates activity	0.497	DAB2IP can be phosphorylated by RIP1 on Ser 604 within the PER domain, and by AKT1 on Ser 847 within the proline-rich domain. Although RIP1-mediated phosphorylation is stimulatory,40 a recent study reported that AKT-mediated phosphorylation inhibits DAB2IP functions	SIGNOR-254780
P84022	O43541	binding	down-regulates activity	0.497	Smad6 and smad7, can prevent tgfb signaling by interacting either with the receptor or with smad2 and smad3	SIGNOR-64071
Q05397	P08581	phosphorylation	up-regulates	0.497	Met-mediated fak phosphorylation could further activate fak. Indeed, we found that met phosphorylates fak at its known phosphorylation sites, including tyr-576 and tyr-577, both of which are located in the activating loop within the catalytic domain	SIGNOR-147199
Q92529	Q15303	relocalization	up-regulates	0.497	Like erbb1, erbb4 recruits grb2, shc and stat5.	SIGNOR-147850
P15172	Q99750	binding	down-regulates activity	0.497	We demonstrate that I-mf inhibits the transactivation activity of the MyoD family and represses myogenesis. I-mf associates with MyoD family members and retains them in the cytoplasm by masking their nuclear localization signals.	SIGNOR-240436
Q13224	P53355	phosphorylation	up-regulates activity	0.497	DAPK1 Activation Enhances the NR1 and NR2B Channel Conductance.\|Thus, an activated DAPK1 enhances NR1 and NR2B receptor channel conductance by phosphorylating NR2B subunit at Ser 1303.	SIGNOR-278397
P50542	Q13315	phosphorylation	up-regulates activity	0.497	Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.	SIGNOR-262792
P04637	O75182	binding	down-regulates activity	0.497	The present study shows that under bleomycin-induced stress, expression of Sin3B gets up-regulated and it gets recruited by p53 at its target promoters. Knockdown of Sin3B leads to impaired negative regulation of p53 target genes and thus exemplifies Sin3B as a critical player in down-regulation of p53 subset target genes.	SIGNOR-266776
Q8IWU2	Q00535	phosphorylation	up-regulates	0.497	Here, we demonstrate that lmtk2 is phosphorylated on serine-1418 (lmtk2ser ) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate pp1cthr __	SIGNOR-195329
P84085	O43150	gtpase-activating protein	up-regulates activity	0.497	Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro.	SIGNOR-269707
P23458	Q8NI17	binding	up-regulates	0.497	Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.	SIGNOR-161342
Q13671	Q12967	binding	up-regulates activity	0.497	Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.	SIGNOR-220923
P24941	P28482	phosphorylation	up-regulates	0.497	In addition to its role in stimulating cyclin d1 expression and nuclear translocation of cdk2, erk regulates thr-160 phosphorylation of cdk2-cyclin e.	SIGNOR-94003
P27540	Q14190	binding	up-regulates activity	0.497	We demonstrate that both SIM1 and SIM2 can heterodimerize via their helix-loop-helix·PAS regions with ARNT, but not with AHR, and that they do not form homodimers. Furthermore, SIM1 may have a dual role, both negatively affecting AHR·ARNT binding to the XRE and also acting in concert with ARNT as a novel DNA-binding heterodimer.	SIGNOR-240808
Q00613	P45983	phosphorylation	down-regulates activity	0.497	JNK is activated by heat shock and phosphorylates HSF-1 on serine 363. JNK Phosphorylation of HSF-1 Leads to Reduction in Its Transcriptional Activity	SIGNOR-250119
Q9UI95	Q96JM3	binding	up-regulates activity	0.497	Here, we report a novel regulator for accurate chromosome segregation, chromosome alignment-maintaining phosphoprotein (CAMP). We identified CAMP as a MAD2L2-interacting protein. Spindle localization of MAD2L2 was abrogated by CAMP depletion (Supplementary Figure S2A)	SIGNOR-264904
P27986	Q9Y6W8	binding	up-regulates activity	0.497	ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling.	SIGNOR-272539
Q6NUQ1	Q9P2Y5	binding	up-regulates activity	0.497	We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity	SIGNOR-265028
P35222	P41225	binding	down-regulates	0.497	Two additional sox proteins, xsox17alfa and xsox3, likewise bind to beta-catenin and inhibit its tcf-mediated signaling activity.	SIGNOR-72039
Q13158	O14733	phosphorylation	down-regulates activity	0.497	The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells	SIGNOR-123164
Q99490	P31749	phosphorylation	up-regulates	0.497	In addition, we have found that activated akt can bind and phosphorylate ggap2 at serine 629, which enhances gtp binding by ggap2.	SIGNOR-183543
Q9UI95	Q92733	relocalization	up-regulates	0.496	We found that the human papillary renal cell carcinoma-associated proteinprccinteracts with the cell cycle control proteinmad2b, and translocates this protein to the nucleus where it exerts its mitotic checkpoint function.	SIGNOR-126516
P46527	P12931	phosphorylation	down-regulates	0.496	Src regulates p27 stability through phosphorylation of p27 at tyrosine 74 and tyrosine 88. Our data indicate that phosphorylation by src impairs the cdk2 inhibitory action of p27	SIGNOR-152839
Q9C0H9	P12931	phosphorylation	up-regulates activity	0.496	Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins.	SIGNOR-263196
O14757	Q9NRD1	binding	down-regulates quantity by destabilization	0.496	Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 and, in turn, terminates the checkpoint.	SIGNOR-271879
P63096	P35346	binding	up-regulates activity	0.496	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-256690
O60291	P51668	binding	up-regulates activity	0.496	Our in vivo and in vitro ubiquitylation studies demonstrate that the binding of TSG101 to Mahogunin targets the substrate TSG101 for ubiquitylation by Mahogunin E3 ligase in cooperation with its cognate E2 enzyme Ubc5a	SIGNOR-271637
Q07817	P24941	phosphorylation	up-regulates activity	0.496	Our findings show that Cdk2 phosphorylation of Bcl-xL at Ser73, but not the Bcl-xL cleavage products, is necessary and sufficient to induce cell death.	SIGNOR-278242
O14757	P67775	dephosphorylation	down-regulates activity	0.496	Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit\|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo.	SIGNOR-248615
Q92530	Q9H2K2	ADP-ribosylation	down-regulates quantity by destabilization	0.496	We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.	SIGNOR-263386
Q01094	O15379	binding	up-regulates	0.496	Furthermore, smad7 caused hdac-1 bind to e2f-1 to form a ternary complex on chromosomal dna containing an e2f-binding motif and leading to repression in the activity of the e2f target genes.	SIGNOR-199961
Q13002	Q6TDP4	binding	down-regulates quantity by destabilization	0.496	Here, we report that actinfilin is able to bind to GluR6, a kainate-type glutamate receptor subunit, and target GluR6 for degradation. Like many members of its protein family, actinfilin acts as a substrate adaptor, binding Cullin 3 (Cul3) and linking GluR6 to the E3 ubiquitin-ligase complex. Together our data demonstrate that actinfilin acts as a scaffold, linking GluR6 to the Cul3 ubiquitin ligase to provide a novel mechanism for kainate receptor degradation.	SIGNOR-271612
P24385	P01106	transcriptional regulation	up-regulates quantity by expression	0.496	C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation	SIGNOR-102731
Q02750	P06493	phosphorylation	down-regulates	0.496	P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well	SIGNOR-36116
P16220	Q9Y243	phosphorylation	up-regulates	0.496	When overexpressed in serum-stimulated cells, akt/pkb potently induced ser-133 phosphorylation of creb and promoted recruitment of cbp.	SIGNOR-62257
Q13490	Q13489	binding	up-regulates activity	0.496	Ligand-stimulated aggregation of receptor complexes causes recruitment of multiple traf2 trimers, which in turn leads to cIAP1 or cIAP2 dimerization.	SIGNOR-199088
Q05397	P35968	null	up-regulates activity	0.496	Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation	SIGNOR-261945
Q9C0K0	Q9UPW6	transcriptional regulation	down-regulates quantity	0.495	Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development	SIGNOR-268931
P46060	P06493	phosphorylation	up-regulates	0.495	Here, we show that rangap1 is phosphorylated on residues t409, s428, and s442. Phosphorylation occurs before nuclear envelope breakdown and is maintained throughout mitosis . Alternatively, phosphorylated rangap1 may recruit specific sumo target proteins to ranbp2's catalytic domain.	SIGNOR-123520
P04637	Q7Z6Z7	ubiquitination	down-regulates quantity by destabilization	0.495	HUWE1 directly binds and ubiquitinates p53 to target it for proteasomal degradation, independently of MDM2 [ xref ].	SIGNOR-278547
P05412	Q969H0	binding	down-regulates quantity by destabilization	0.495	We report that in neurons the stability of c-Jun is regulated by the E3 ligase SCF(Fbw7), which ubiquitinates phosphorylated c-Jun and facilitates c-Jun degradation.	SIGNOR-272950
P49327	P36956	transcriptional regulation	up-regulates quantity by expression	0.495	Ultimately, both the AKT and MAPK transduction pathways regulate FASN expression through the modulation of expression of sterol regulatory element-binding protein (SREBP)-1c, which binds to regulatory elements in the FASN promoter. Proto-oncogene FBI-1 (Pokemon), a transcription factor of the bric--brac tramtrack broad complex/pox viruses and zinc fingers (BTB/POZ) domain family, interacts directly with SREBP-1c through its DNA-binding domain to synergistically activate the transcription of FASN	SIGNOR-242884
P50148	P21728	binding	up-regulates activity	0.495	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-257335
P60953	Q8WZ64	gtpase-activating protein	down-regulates activity	0.495	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-260455
P19105	Q13177	phosphorylation	up-regulates activity	0.495	In this study we report that gamma-PAK, which is activated by the GTP-binding proteins Cdc42 and Rac, catalyses phosphorylation of intact non-muscle myosin II and isolated recombinant RLC. Phosphopeptide maps and phosphoamino acid analysis revealed that gamma-PAK phosphorylates Ser-19 but does not phosphorylate Thr-18.Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization.	SIGNOR-263020
O75581	P98082	binding	down-regulates	0.495	Wnt stimulation induces the casein kinase 2 (ck2)-dependent phosphorylation of lrp6 at s1579, promoting its binding to dab2 and internalization with clathrin.	SIGNOR-196925
Q9BY41	P17612	phosphorylation	down-regulates	0.494	Negative regulation of histone deacetylase 8 activity by cyclic amp-dependent protein kinase athe pka phosphoacceptor site of hdac8 is ser(39)	SIGNOR-120643
P20749	P31749	phosphorylation	up-regulates quantity by stabilization	0.494	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277358
P41235	P27361	phosphorylation	down-regulates activity	0.494	Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4\u03b1.\|Here we have demonstrated that ERK1 is able to phosphorylate HNF4\u03b1 at several serine and threonine residues.	SIGNOR-279070
P24941	Q8TDN4	binding	down-regulates activity	0.494	Our study also showed that Cables1 increases the level of p21 and decreases the level of pRb, but does not affect the other cell cycle-related proteins we studied. Induction of apoptosis by Cables1, which occurs partially through inhibiting Cdk2 activity and upregulating p21, is prevented by Akt phosphorylation and 14-3-3 binding.	SIGNOR-276759
Q12778	Q9HCP0	phosphorylation	down-regulates activity	0.494	Phosphorylation of Ser319 forms a consensus sequence for phosphorylation by CK1, allowing it to phosphorylate Ser322, which in turn primes the CK1-catalysed phosphorylation of Ser325 \| Multisite phosphorylation of the region containing Ser319, Ser322, Ser325 and Ser329 provides a signal for the nuclear exclusion of FKHR	SIGNOR-250822
P63092	P34998	binding	up-regulates activity	0.494	Previous studies have indicated that CRHR could couple to multiple Galpha proteins including Gs, Gi, and Gq/11 and then go on to induce changes in AC activity and activation of PLC-beta3	SIGNOR-268617
Q9Y243	P62714	dephosphorylation	down-regulates activity	0.494	Overexpression of BTBD10 increased phosphorylation levels of Akts at both Thr(308) and Ser(473) while the reduction of the endogenous BTBD10 level resulted in a decrease in the phosphorylation levels of Akts. In vitro analysis indicated that BTBD10 bound to protein phosphatase 2A (PP2A) and inhibited dephosphorylation of Akts by PP2A.	SIGNOR-248611
P63096	P08908	binding	up-regulates activity	0.494	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-256693
P03372	Q15418	phosphorylation	up-regulates	0.494	Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii.	SIGNOR-34113
P42261	P17612	phosphorylation	up-regulates activity	0.494	Phosphorylation of Ser-845 on GluR1 by PKA potentiates its response to glutamate.	SIGNOR-249987
P16144	Q9Y490	binding	up-regulates activity	0.494	Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.	SIGNOR-257627
P01111	Q5VWQ8	gtpase-activating protein	down-regulates activity	0.494	The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.	SIGNOR-254747
Q12888	O75925	sumoylation	up-regulates	0.494	Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation.	SIGNOR-162156
P30304	Q9Y297	ubiquitination	up-regulates	0.494	Scfb-trcp has recently been shown to degrade phosphorylated cdc25a in the s and g2 phases.	SIGNOR-128436
P13612	P17612	phosphorylation	up-regulates activity	0.494	PKA phosphorylationin vitro blocks the binding of the alpha4 tail to paxillin. A mutation that mimics alpha4 phosphorylation disrupts paxillin binding and promotes cell spreading	SIGNOR-110119
Q6UUV9	P57059	phosphorylation	down-regulates	0.494	These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.	SIGNOR-147669
Q99704	Q13882	phosphorylation	down-regulates activity	0.494	BRK downregulates Dok1 via proteasomal degradation.\|BRK phosphorylates Dok1 at tyrosine 362.	SIGNOR-278301
Q9Y618	Q96EB6	null	up-regulates	0.494	In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.	SIGNOR-253506
P03951	P00748	cleavage	up-regulates activity	0.494	Activation of factor XI in plasma is dependent on factor XII \| Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided.	SIGNOR-263519
Q9H3F6	Q13618	binding	up-regulates activity	0.494	BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.	SIGNOR-264234
Q6P1J9	Q06124	dephosphorylation	up-regulates activity	0.494	We found in this work that SHP2 dephosphorylates parafibromin and Cdc73, a component of the nuclear RNA polymerase II associated factor (PAF) complex, which can function as a tumor suppressor or oncoprotein in a context dependent manner.	SIGNOR-277036
P08069	P42345	phosphorylation	up-regulates activity	0.494	Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.\|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR.	SIGNOR-280044
P98170	O15392	binding	up-regulates	0.494	Formation of a survivin-xiap complex promotes increased xiap stability against ubiquitination/proteasomal destruction and synergistic apoptosis	SIGNOR-126367
Q01094	P50613	phosphorylation	down-regulates	0.493	These results suggest that tfiih-mediated phosphorylation of e2f-1 plays a role in triggering e2f-1 degradation during s phase. here we show that the e2f-1 activation domain interacts with a kinase activity which phosphorylates two sites, ser403 and thr433, within the activation domain.	SIGNOR-69776
O15534	Q9UKB1	ubiquitination	down-regulates	0.493	We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1	SIGNOR-137758
P36507	P67775	dephosphorylation	down-regulates	0.493	In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a.	SIGNOR-166652
Q9BXL7	Q92918	phosphorylation	up-regulates activity	0.493	HPK1 interacts with CARMA1 in a TCR stimulation-dependent manner and phosphorylates the linker region of CARMA1. Interestingly, the putative HPK1 phosphorylation sites in CARMA1 are different from known PKC consensus sites. Mutations of residues S549, S551, and S552 in CARMA1 abrogated phosphorylation of a CARMA1-linker construct by HPK1 in vitro.	SIGNOR-276259
P13569	Q13131	phosphorylation	down-regulates activity	0.493	AMPK phosphorylates CFTR¬†in vitro¬†at two essential serines (Ser737and Ser768) in the R domain, formerly identified as "inhibitory" PKA sites.\|Interestingly two of these sites, namely Ser737 and Ser768, have been identified as “inhibitory” R domain sites, i.e. when mutated to alanines they augment the open probability of CFTR relative to wild type\|Our present results suggest that it might be AMPK rather than PKA that is phosphorylating Ser737 and Ser768 under baseline conditions	SIGNOR-259858
P31946	Q05655	phosphorylation	down-regulates	0.493	We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.	SIGNOR-138612
Q8TEW0	Q7KZI7	phosphorylation	up-regulates	0.493	Gab1 brings par1 and par3 into a transient complex, stimulating par3 phosphorylation by par1	SIGNOR-198742
P49768	Q969H0	binding	down-regulates quantity by destabilization	0.493	SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production SEL-10 protein is a homologue of yeast Cdc4, a member of the SCF (Skp1-Cdc53/CUL1-F-box protein) E2-E3 ubiquitin ligase family. In this study, we show that human SEL-10 interacts with PS1 and enhances PS1 ubiquitination, thus altering cellular levels of unprocessed PS1 and its N- and C-terminal fragments. These observations suggest that SEL-10 mediated ubiquitination of PS1-CTF and PS1-NTF leads to their degradation.	SIGNOR-272600
Q93034	Q8WXH5	binding	up-regulates activity	0.493	SOCS7 promotes Dab1 polyubiquitylation and degradation. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1.	SIGNOR-272141
P26599	Q8IY67	binding	up-regulates activity	0.493	Raver1 was identified in two-hybrid screens by its interactions with the cytoskeletal proteins actinin and vinculin, and was also found to interact with PTB \|\| Here we show that raver1 is able to promote the smooth muscle-specific alternative splicing of TM by enhancing PTB-mediated repression of exon 3. This suggests a novel mechanism for PTB-mediated splicing repression involving recruitment of raver1 as a potent splicing co-repressor.	SIGNOR-272475
P17096	Q9H2X6	phosphorylation	down-regulates	0.493	Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.	SIGNOR-158620
P50750	P35813	dephosphorylation	down-regulates activity	0.493	Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function	SIGNOR-248490
P63096	Q99500	binding	up-regulates	0.493	Edg-3 and edg-5 couple not only to gibut also to gqand g13	SIGNOR-70713
Q13635	P98164	binding	up-regulates quantity	0.493	LRP2 Promotes SHH Activity in Neurogenic Niches of the Developing and Adult Brain. In the RDVM, LRP2 forms a co-receptor complex with PTCH1 facilitating SHH binding and internalization of SHH/PTCH1 complexes, a prerequisite for pathway activation (Fig. 3B).	SIGNOR-265257
Q14524	Q13557	phosphorylation	down-regulates	0.492	A stable interaction between ?(C)-camkii and the intracellular loop between domains 1 and 2 of na(v)1.5 was observed. This region was also phosphorylated by ?(C)-camkii, specifically at the ser-516 and thr-594 sites.Wild-type (wt) and phosphomutant hna(v)1.5 were co-expressed with gfp-?(C)-camkii in hek293 cells, and i(na) was recorded. As observed in myocytes, camkii shifted wt i(na) availability to a more negative membrane potential and enhanced accumulation of i(na) into an intermediate inactivated state, but these effects were abolished by mutating either of these sites to non-phosphorylatable ala residues.	SIGNOR-197058
P23025	Q13535	phosphorylation	up-regulates activity	0.492	ATR mediated phosphorylation of XPA on S196 enhances cAMP-mediated optimization of NER, and is promoted by SIRT1-mediated deacetylation of XPA on K63, K67 and K215.	SIGNOR-258985
P63096	Q9H228	binding	up-regulates activity	0.492	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-256676
P19367	P12931	phosphorylation	down-regulates activity	0.492	Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its K m and increases its V max by disrupting its dimer formation.\|Mechanistically, c-Src-mediated Y732 phosphorylation disrupts HK1 dimer formation, alters its enzyme kinetics and eventually enhances enzymatic activity ( ).	SIGNOR-278209
Q9Y3Z3	P06493	phosphorylation	down-regulates	0.492	Cyclin a2/cdk1 phosphorylates samhd1 at the threonine 592 residue both in vitro and in vivo. Phosphorylation of samhd1 thr592 correlates with loss of its ability to restrict hiv-1.	SIGNOR-201913
P26678	P17612	phosphorylation	up-regulates activity	0.492	Phospholamban (PLB) can be phosphorylated at Ser(16) by cyclic AMP-dependent protein kinase. phosphorylation of Ser(16) is sufficient for mediating the maximal cardiac responses to beta-adrenergic stimulation.	SIGNOR-250030
O94761	Q8IWV7	binding	up-regulates	0.492	The isolated recql4, assayed as a complex with ubr1 and ubr2, exhibited dna-stimulated atpase activity but was inactive as either dna helicase or dna translocase / the discovery, in the present work, that these ub ligases, ubr1 and ubr2, interact with the putative helicase recql4 (fig. 2), and that recql4 is a long-lived, non-ubiquitylated protein in hela cells	SIGNOR-128169
P04035	Q9UKV5	ubiquitination	down-regulates quantity by destabilization	0.492	Gp78 mediates the sterol regulated ubiquitination of HMGCR.	SIGNOR-278622
Q99816	O60291	monoubiquitination	up-regulates activity	0.492	In the present study, we identified the first substrate of the Mahogunin E3 ubiquitin–protein ligase: TSG101, a key component of the endosomal sorting ESCRT machinery.We find that Mahogunin interacts with the ubiquitin E2 variant (UEV) domain of TSG101 via its PSAP motif and that it catalyzes monoubiquitylation of TSG101 both in vivo and in vitro. Consistent with the results of the biochemical characterization and subcellular localization studies of Mahogunin, our functional studies provide direct evidence that Mahogunin plays an essential role in regulation of endosome-to-lysosome trafficking. We found that siRNA-mediated depletion of Mahogunin in HeLa cells causes enlargement and clustering of EEA1-positive endosomes and LAMP2-positive late endosomes/lysosomes (Figure 8B) and inhibits the endosomal trafficking of internalized EGF–EGFR complexes to lysosomes for degradation (Figures 9 and and10,10, A and B). These results are strikingly similar to the phenotypes that resulted from depletion of TSG101	SIGNOR-271635
O96017	P53350	phosphorylation	up-regulates	0.492	Plk1 overexpression enhances phosphorylation of chk2 at thr-68.	SIGNOR-96637
O00418	Q13131	phosphorylation	down-regulates activity	0.492	AMPK can phosphorylate three sites in eEF2 kinase in vitro. Of these, Ser-398 appears to be more efficiently phosphorylated than either Ser-78 or Ser-366. Ser-78 and Ser-366 do not appear to be phosphorylated by AMPK within cells. Ser-366 serves to decrease the activity of eEF2 kinase	SIGNOR-250314
P19438	P28799	binding	down-regulates	0.492	Collectively, these findings demonstrate that pgrn is a ligand of tnfr, an antagonist of tnf signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice.	SIGNOR-172684
P50148	Q9HB89	binding	up-regulates activity	0.492	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-256751

P27816

P06493

0

phosphorylation

down-regulates activity

0.497

We have shown that MAP4 is phosphorylated in vivo in mitotic HeLa cells at eight sites. Five of these were phosphorylated by p34cdc2 kinase. Two of the five p34cdc2 kinase phosphorylation sites were shown to be Ser696 and Ser787 in the proline-rich region. Mutation of Ser787 to Glu strikingly reduced the MAP4's MT-polymerization activity, while Glu-mutation at Ser696 did not. These results suggest that Ser787 could be the critical phosphorylation site causing MTs to be dynamic at mitosis.

SIGNOR-277459

O00238

P36894

0

binding

up-regulates

0.497

Using several complementary approaches, we investigated the formation of homomeric and heteromeric complexes between the two known bmp type i receptors

SIGNOR-75649

P38398

P06493

0

phosphorylation

up-regulates

0.497

However, shrna-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated s phase cell-cycle arrest and the phosphorylation of a subset of atr/atm targets after dna damage. Loss of dna damage-induced checkpoint control was caused by a reduction in formation of brca1-containing foci. Mutation of brca1 at s1497 and s1189/s1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of brca1-containing foci.

SIGNOR-72087

P63092

Q13639

0

binding

up-regulates activity

0.497

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-256769

Q5VWQ8

P31749

0

phosphorylation

down-regulates activity

0.497

DAB2IP can be phosphorylated by RIP1 on Ser 604 within the PER domain, and by AKT1 on Ser 847 within the proline-rich domain. Although RIP1-mediated phosphorylation is stimulatory,40 a recent study reported that AKT-mediated phosphorylation inhibits DAB2IP functions

SIGNOR-254780

P84022

O43541

0

binding

down-regulates activity

0.497

Smad6 and smad7, can prevent tgfb signaling by interacting either with the receptor or with smad2 and smad3

SIGNOR-64071

Q05397

P08581

0

phosphorylation

up-regulates

0.497

Met-mediated fak phosphorylation could further activate fak. Indeed, we found that met phosphorylates fak at its known phosphorylation sites, including tyr-576 and tyr-577, both of which are located in the activating loop within the catalytic domain

SIGNOR-147199

Q92529

Q15303

0

relocalization

up-regulates

0.497

Like erbb1, erbb4 recruits grb2, shc and stat5.

SIGNOR-147850

P15172

Q99750

0

binding

down-regulates activity

0.497

We demonstrate that I-mf inhibits the transactivation activity of the MyoD family and represses myogenesis. I-mf associates with MyoD family members and retains them in the cytoplasm by masking their nuclear localization signals.

SIGNOR-240436

Q13224

P53355

0

phosphorylation

up-regulates activity

0.497

DAPK1 Activation Enhances the NR1 and NR2B Channel Conductance.|Thus, an activated DAPK1 enhances NR1 and NR2B receptor channel conductance by phosphorylating NR2B subunit at Ser 1303.

SIGNOR-278397

P50542

Q13315

0

phosphorylation

up-regulates activity

0.497

Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.

SIGNOR-262792

P04637

O75182

0

binding

down-regulates activity

0.497

The present study shows that under bleomycin-induced stress, expression of Sin3B gets up-regulated and it gets recruited by p53 at its target promoters. Knockdown of Sin3B leads to impaired negative regulation of p53 target genes and thus exemplifies Sin3B as a critical player in down-regulation of p53 subset target genes.

SIGNOR-266776

Q8IWU2

Q00535

0

phosphorylation

up-regulates

0.497

Here, we demonstrate that lmtk2 is phosphorylated on serine-1418 (lmtk2ser ) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate pp1cthr __

SIGNOR-195329

P84085

O43150

0

gtpase-activating protein

up-regulates activity

0.497

Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro.

SIGNOR-269707

P23458

Q8NI17

0

binding

up-regulates

0.497

Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.

SIGNOR-161342

Q13671

Q12967

0

binding

up-regulates activity

0.497

Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.

SIGNOR-220923

P24941

P28482

0

phosphorylation

up-regulates

0.497

In addition to its role in stimulating cyclin d1 expression and nuclear translocation of cdk2, erk regulates thr-160 phosphorylation of cdk2-cyclin e.

SIGNOR-94003

P27540

Q14190

0

binding

up-regulates activity

0.497

We demonstrate that both SIM1 and SIM2 can heterodimerize via their helix-loop-helix·PAS regions with ARNT, but not with AHR, and that they do not form homodimers. Furthermore, SIM1 may have a dual role, both negatively affecting AHR·ARNT binding to the XRE and also acting in concert with ARNT as a novel DNA-binding heterodimer.

SIGNOR-240808

Q00613

P45983

0

phosphorylation

down-regulates activity

0.497

JNK is activated by heat shock and phosphorylates HSF-1 on serine 363. JNK Phosphorylation of HSF-1 Leads to Reduction in Its Transcriptional Activity

SIGNOR-250119

Q9UI95

Q96JM3

0

binding

up-regulates activity

0.497

Here, we report a novel regulator for accurate chromosome segregation, chromosome alignment-maintaining phosphoprotein (CAMP). We identified CAMP as a MAD2L2-interacting protein. Spindle localization of MAD2L2 was abrogated by CAMP depletion (Supplementary Figure S2A)

SIGNOR-264904

P27986

Q9Y6W8

0

binding

up-regulates activity

0.497

ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling.

SIGNOR-272539

Q6NUQ1

Q9P2Y5

0

binding

up-regulates activity

0.497

We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity

SIGNOR-265028

P35222

P41225

0

binding

down-regulates

0.497

Two additional sox proteins, xsox17alfa and xsox3, likewise bind to beta-catenin and inhibit its tcf-mediated signaling activity.

SIGNOR-72039

Q13158

O14733

0

phosphorylation

down-regulates activity

0.497

The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells

SIGNOR-123164

Q99490

P31749

0

phosphorylation

up-regulates

0.497

In addition, we have found that activated akt can bind and phosphorylate ggap2 at serine 629, which enhances gtp binding by ggap2.

SIGNOR-183543

Q9UI95

Q92733

0

relocalization

up-regulates

0.496

We found that the human papillary renal cell carcinoma-associated proteinprccinteracts with the cell cycle control proteinmad2b, and translocates this protein to the nucleus where it exerts its mitotic checkpoint function.

SIGNOR-126516

P46527

P12931

0

phosphorylation

down-regulates

0.496

Src regulates p27 stability through phosphorylation of p27 at tyrosine 74 and tyrosine 88. Our data indicate that phosphorylation by src impairs the cdk2 inhibitory action of p27

SIGNOR-152839

Q9C0H9

P12931

0

phosphorylation

up-regulates activity

0.496

Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins.

SIGNOR-263196

O14757

Q9NRD1

0

binding

down-regulates quantity by destabilization

0.496

Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 and, in turn, terminates the checkpoint.

SIGNOR-271879

P63096

P35346

0

binding

up-regulates activity

0.496

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-256690

O60291

P51668

0

binding

up-regulates activity

0.496

Our in vivo and in vitro ubiquitylation studies demonstrate that the binding of TSG101 to Mahogunin targets the substrate TSG101 for ubiquitylation by Mahogunin E3 ligase in cooperation with its cognate E2 enzyme Ubc5a

SIGNOR-271637

Q07817

P24941

0

phosphorylation

up-regulates activity

0.496

Our findings show that Cdk2 phosphorylation of Bcl-xL at Ser73, but not the Bcl-xL cleavage products, is necessary and sufficient to induce cell death.

SIGNOR-278242

O14757

P67775

0

dephosphorylation

down-regulates activity

0.496

Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo.

SIGNOR-248615

Q92530

Q9H2K2

0

ADP-ribosylation

down-regulates quantity by destabilization

0.496

We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.

SIGNOR-263386

Q01094

O15379

0

binding

up-regulates

0.496

Furthermore, smad7 caused hdac-1 bind to e2f-1 to form a ternary complex on chromosomal dna containing an e2f-binding motif and leading to repression in the activity of the e2f target genes.

SIGNOR-199961

Q13002

Q6TDP4

0

binding

down-regulates quantity by destabilization

0.496

Here, we report that actinfilin is able to bind to GluR6, a kainate-type glutamate receptor subunit, and target GluR6 for degradation. Like many members of its protein family, actinfilin acts as a substrate adaptor, binding Cullin 3 (Cul3) and linking GluR6 to the E3 ubiquitin-ligase complex. Together our data demonstrate that actinfilin acts as a scaffold, linking GluR6 to the Cul3 ubiquitin ligase to provide a novel mechanism for kainate receptor degradation.

SIGNOR-271612

P24385

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.496

C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation

SIGNOR-102731

Q02750

P06493

0

phosphorylation

down-regulates

0.496

P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well

SIGNOR-36116

P16220

Q9Y243

0

phosphorylation

up-regulates

0.496

When overexpressed in serum-stimulated cells, akt/pkb potently induced ser-133 phosphorylation of creb and promoted recruitment of cbp.

SIGNOR-62257

Q13490

Q13489

0

binding

up-regulates activity

0.496

Ligand-stimulated aggregation of receptor complexes causes recruitment of multiple traf2 trimers, which in turn leads to cIAP1 or cIAP2 dimerization.

SIGNOR-199088

Q05397

P35968

0

null

up-regulates activity

0.496

Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation

SIGNOR-261945

Q9C0K0

Q9UPW6

0

transcriptional regulation

down-regulates quantity

0.495

Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development

SIGNOR-268931

P46060

P06493

0

phosphorylation

up-regulates

0.495

Here, we show that rangap1 is phosphorylated on residues t409, s428, and s442. Phosphorylation occurs before nuclear envelope breakdown and is maintained throughout mitosis . Alternatively, phosphorylated rangap1 may recruit specific sumo target proteins to ranbp2's catalytic domain.

SIGNOR-123520

P04637

Q7Z6Z7

0

ubiquitination

down-regulates quantity by destabilization

0.495

HUWE1 directly binds and ubiquitinates p53 to target it for proteasomal degradation, independently of MDM2 [ xref ].

SIGNOR-278547

P05412

Q969H0

0

binding

down-regulates quantity by destabilization

0.495

We report that in neurons the stability of c-Jun is regulated by the E3 ligase SCF(Fbw7), which ubiquitinates phosphorylated c-Jun and facilitates c-Jun degradation.

SIGNOR-272950

P49327

P36956

0

transcriptional regulation

up-regulates quantity by expression

0.495

Ultimately, both the AKT and MAPK transduction pathways regulate FASN expression through the modulation of expression of sterol regulatory element-binding protein (SREBP)-1c, which binds to regulatory elements in the FASN promoter. Proto-oncogene FBI-1 (Pokemon), a transcription factor of the bric--brac tramtrack broad complex/pox viruses and zinc fingers (BTB/POZ) domain family, interacts directly with SREBP-1c through its DNA-binding domain to synergistically activate the transcription of FASN

SIGNOR-242884

P50148

P21728

0

binding

up-regulates activity

0.495

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-257335

P60953

Q8WZ64

0

gtpase-activating protein

down-regulates activity

0.495

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-260455

P19105

Q13177

0

phosphorylation

up-regulates activity

0.495

In this study we report that gamma-PAK, which is activated by the GTP-binding proteins Cdc42 and Rac, catalyses phosphorylation of intact non-muscle myosin II and isolated recombinant RLC. Phosphopeptide maps and phosphoamino acid analysis revealed that gamma-PAK phosphorylates Ser-19 but does not phosphorylate Thr-18.Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization.

SIGNOR-263020

O75581

P98082

0

binding

down-regulates

0.495

Wnt stimulation induces the casein kinase 2 (ck2)-dependent phosphorylation of lrp6 at s1579, promoting its binding to dab2 and internalization with clathrin.

SIGNOR-196925

Q9BY41

P17612

0

phosphorylation

down-regulates

0.494

Negative regulation of histone deacetylase 8 activity by cyclic amp-dependent protein kinase athe pka phosphoacceptor site of hdac8 is ser(39)

SIGNOR-120643

P20749

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.494

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277358

P41235

P27361

0

phosphorylation

down-regulates activity

0.494

Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4\u03b1.|Here we have demonstrated that ERK1 is able to phosphorylate HNF4\u03b1 at several serine and threonine residues.

SIGNOR-279070

P24941

Q8TDN4

0

binding

down-regulates activity

0.494

Our study also showed that Cables1 increases the level of p21 and decreases the level of pRb, but does not affect the other cell cycle-related proteins we studied. Induction of apoptosis by Cables1, which occurs partially through inhibiting Cdk2 activity and upregulating p21, is prevented by Akt phosphorylation and 14-3-3 binding.

SIGNOR-276759

Q12778

Q9HCP0

0

phosphorylation

down-regulates activity

0.494

Phosphorylation of Ser319 forms a consensus sequence for phosphorylation by CK1, allowing it to phosphorylate Ser322, which in turn primes the CK1-catalysed phosphorylation of Ser325 | Multisite phosphorylation of the region containing Ser319, Ser322, Ser325 and Ser329 provides a signal for the nuclear exclusion of FKHR

SIGNOR-250822

P63092

P34998

0

binding

up-regulates activity

0.494

Previous studies have indicated that CRHR could couple to multiple Galpha proteins including Gs, Gi, and Gq/11 and then go on to induce changes in AC activity and activation of PLC-beta3

SIGNOR-268617

Q9Y243

P62714

0

dephosphorylation

down-regulates activity

0.494

Overexpression of BTBD10 increased phosphorylation levels of Akts at both Thr(308) and Ser(473) while the reduction of the endogenous BTBD10 level resulted in a decrease in the phosphorylation levels of Akts. In vitro analysis indicated that BTBD10 bound to protein phosphatase 2A (PP2A) and inhibited dephosphorylation of Akts by PP2A.

SIGNOR-248611

P63096

P08908

0

binding

up-regulates activity

0.494

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-256693

P03372

Q15418

0

phosphorylation

up-regulates

0.494

Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii.

SIGNOR-34113

P42261

P17612

0

phosphorylation

up-regulates activity

0.494

Phosphorylation of Ser-845 on GluR1 by PKA potentiates its response to glutamate.

SIGNOR-249987

P16144

Q9Y490

0

binding

up-regulates activity

0.494

Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.

SIGNOR-257627

P01111

Q5VWQ8

0

gtpase-activating protein

down-regulates activity

0.494

The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.

SIGNOR-254747

Q12888

O75925

0

sumoylation

up-regulates

0.494

Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation.

SIGNOR-162156

P30304

Q9Y297

0

ubiquitination

up-regulates

0.494

Scfb-trcp has recently been shown to degrade phosphorylated cdc25a in the s and g2 phases.

SIGNOR-128436

P13612

P17612

0

phosphorylation

up-regulates activity

0.494

PKA phosphorylationin vitro blocks the binding of the alpha4 tail to paxillin. A mutation that mimics alpha4 phosphorylation disrupts paxillin binding and promotes cell spreading

SIGNOR-110119

Q6UUV9

P57059

0

phosphorylation

down-regulates

0.494

These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.

SIGNOR-147669

Q99704

Q13882

0

phosphorylation

down-regulates activity

0.494

BRK downregulates Dok1 via proteasomal degradation.|BRK phosphorylates Dok1 at tyrosine 362.

SIGNOR-278301

Q9Y618

Q96EB6

0

null

up-regulates

0.494

In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.

SIGNOR-253506

P03951

P00748

0

cleavage

up-regulates activity

0.494

Activation of factor XI in plasma is dependent on factor XII | Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided.

SIGNOR-263519

Q9H3F6

Q13618

0

binding

up-regulates activity

0.494

BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.

SIGNOR-264234

Q6P1J9

Q06124

0

dephosphorylation

up-regulates activity

0.494

We found in this work that SHP2 dephosphorylates parafibromin and Cdc73, a component of the nuclear RNA polymerase II associated factor (PAF) complex, which can function as a tumor suppressor or oncoprotein in a context dependent manner.

SIGNOR-277036

P08069

P42345

0

phosphorylation

up-regulates activity

0.494

Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR.

SIGNOR-280044

P98170

O15392

0

binding

up-regulates

0.494

Formation of a survivin-xiap complex promotes increased xiap stability against ubiquitination/proteasomal destruction and synergistic apoptosis

SIGNOR-126367

Q01094

P50613

0

phosphorylation

down-regulates

0.493

These results suggest that tfiih-mediated phosphorylation of e2f-1 plays a role in triggering e2f-1 degradation during s phase. here we show that the e2f-1 activation domain interacts with a kinase activity which phosphorylates two sites, ser403 and thr433, within the activation domain.

SIGNOR-69776

O15534

Q9UKB1

0

ubiquitination

down-regulates

0.493

We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1

SIGNOR-137758

P36507

P67775

0

dephosphorylation

down-regulates

0.493

In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a.

SIGNOR-166652

Q9BXL7

Q92918

0

phosphorylation

up-regulates activity

0.493

HPK1 interacts with CARMA1 in a TCR stimulation-dependent manner and phosphorylates the linker region of CARMA1. Interestingly, the putative HPK1 phosphorylation sites in CARMA1 are different from known PKC consensus sites. Mutations of residues S549, S551, and S552 in CARMA1 abrogated phosphorylation of a CARMA1-linker construct by HPK1 in vitro.

SIGNOR-276259

P13569

Q13131

0

phosphorylation

down-regulates activity

0.493

AMPK phosphorylates CFTR¬†in vitro¬†at two essential serines (Ser737and Ser768) in the R domain, formerly identified as "inhibitory" PKA sites.|Interestingly two of these sites, namely Ser737 and Ser768, have been identified as “inhibitory” R domain sites, i.e. when mutated to alanines they augment the open probability of CFTR relative to wild type|Our present results suggest that it might be AMPK rather than PKA that is phosphorylating Ser737 and Ser768 under baseline conditions

SIGNOR-259858

P31946

Q05655

0

phosphorylation

down-regulates

0.493

We provide a mechanism for these observations through the phosphorylation of 14-3-3 by ikk and pkc on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.

SIGNOR-138612

Q8TEW0

Q7KZI7

0

phosphorylation

up-regulates

0.493

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

SIGNOR-198742

P49768

Q969H0

0

binding

down-regulates quantity by destabilization

0.493

SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production SEL-10 protein is a homologue of yeast Cdc4, a member of the SCF (Skp1-Cdc53/CUL1-F-box protein) E2-E3 ubiquitin ligase family. In this study, we show that human SEL-10 interacts with PS1 and enhances PS1 ubiquitination, thus altering cellular levels of unprocessed PS1 and its N- and C-terminal fragments. These observations suggest that SEL-10 mediated ubiquitination of PS1-CTF and PS1-NTF leads to their degradation.

SIGNOR-272600

Q93034

Q8WXH5

0

binding

up-regulates activity

0.493

SOCS7 promotes Dab1 polyubiquitylation and degradation. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1.

SIGNOR-272141

P26599

Q8IY67

0

binding

up-regulates activity

0.493

Raver1 was identified in two-hybrid screens by its interactions with the cytoskeletal proteins actinin and vinculin, and was also found to interact with PTB || Here we show that raver1 is able to promote the smooth muscle-specific alternative splicing of TM by enhancing PTB-mediated repression of exon 3. This suggests a novel mechanism for PTB-mediated splicing repression involving recruitment of raver1 as a potent splicing co-repressor.

SIGNOR-272475

P17096

Q9H2X6

0

phosphorylation

down-regulates

0.493

Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.

SIGNOR-158620

P50750

P35813

0

dephosphorylation

down-regulates activity

0.493

Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function

SIGNOR-248490

P63096

Q99500

0

binding

up-regulates

0.493

Edg-3 and edg-5 couple not only to gibut also to gqand g13

SIGNOR-70713

Q13635

P98164

0

binding

up-regulates quantity

0.493

LRP2 Promotes SHH Activity in Neurogenic Niches of the Developing and Adult Brain. In the RDVM, LRP2 forms a co-receptor complex with PTCH1 facilitating SHH binding and internalization of SHH/PTCH1 complexes, a prerequisite for pathway activation (Fig. 3B).

SIGNOR-265257

Q14524

Q13557

0

phosphorylation

down-regulates

0.492

A stable interaction between ?(C)-camkii and the intracellular loop between domains 1 and 2 of na(v)1.5 was observed. This region was also phosphorylated by ?(C)-camkii, specifically at the ser-516 and thr-594 sites.Wild-type (wt) and phosphomutant hna(v)1.5 were co-expressed with gfp-?(C)-camkii in hek293 cells, and i(na) was recorded. As observed in myocytes, camkii shifted wt i(na) availability to a more negative membrane potential and enhanced accumulation of i(na) into an intermediate inactivated state, but these effects were abolished by mutating either of these sites to non-phosphorylatable ala residues.

SIGNOR-197058

P23025

Q13535

0

phosphorylation

up-regulates activity

0.492

ATR mediated phosphorylation of XPA on S196 enhances cAMP-mediated optimization of NER, and is promoted by SIRT1-mediated deacetylation of XPA on K63, K67 and K215.

SIGNOR-258985

P63096

Q9H228

0

binding

up-regulates activity

0.492

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-256676

P19367

P12931

0

phosphorylation

down-regulates activity

0.492

Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its K m and increases its V max by disrupting its dimer formation.|Mechanistically, c-Src-mediated Y732 phosphorylation disrupts HK1 dimer formation, alters its enzyme kinetics and eventually enhances enzymatic activity ( ).

SIGNOR-278209

Q9Y3Z3

P06493

0

phosphorylation

down-regulates

0.492

Cyclin a2/cdk1 phosphorylates samhd1 at the threonine 592 residue both in vitro and in vivo. Phosphorylation of samhd1 thr592 correlates with loss of its ability to restrict hiv-1.

SIGNOR-201913

P26678

P17612

0

phosphorylation

up-regulates activity

0.492

Phospholamban (PLB) can be phosphorylated at Ser(16) by cyclic AMP-dependent protein kinase. phosphorylation of Ser(16) is sufficient for mediating the maximal cardiac responses to beta-adrenergic stimulation.

SIGNOR-250030

O94761

Q8IWV7

0

binding

up-regulates

0.492

The isolated recql4, assayed as a complex with ubr1 and ubr2, exhibited dna-stimulated atpase activity but was inactive as either dna helicase or dna translocase / the discovery, in the present work, that these ub ligases, ubr1 and ubr2, interact with the putative helicase recql4 (fig. 2), and that recql4 is a long-lived, non-ubiquitylated protein in hela cells

SIGNOR-128169

P04035

Q9UKV5

0

ubiquitination

down-regulates quantity by destabilization

0.492

Gp78 mediates the sterol regulated ubiquitination of HMGCR.

SIGNOR-278622

Q99816

O60291

0

monoubiquitination

up-regulates activity

0.492

In the present study, we identified the first substrate of the Mahogunin E3 ubiquitin–protein ligase: TSG101, a key component of the endosomal sorting ESCRT machinery.We find that Mahogunin interacts with the ubiquitin E2 variant (UEV) domain of TSG101 via its PSAP motif and that it catalyzes monoubiquitylation of TSG101 both in vivo and in vitro. Consistent with the results of the biochemical characterization and subcellular localization studies of Mahogunin, our functional studies provide direct evidence that Mahogunin plays an essential role in regulation of endosome-to-lysosome trafficking. We found that siRNA-mediated depletion of Mahogunin in HeLa cells causes enlargement and clustering of EEA1-positive endosomes and LAMP2-positive late endosomes/lysosomes (Figure 8B) and inhibits the endosomal trafficking of internalized EGF–EGFR complexes to lysosomes for degradation (Figures 9 and and10,10, A and B). These results are strikingly similar to the phenotypes that resulted from depletion of TSG101

SIGNOR-271635

O96017

P53350

0

phosphorylation

up-regulates

0.492

Plk1 overexpression enhances phosphorylation of chk2 at thr-68.

SIGNOR-96637

O00418

Q13131

0

phosphorylation

down-regulates activity

0.492

AMPK can phosphorylate three sites in eEF2 kinase in vitro. Of these, Ser-398 appears to be more efficiently phosphorylated than either Ser-78 or Ser-366. Ser-78 and Ser-366 do not appear to be phosphorylated by AMPK within cells. Ser-366 serves to decrease the activity of eEF2 kinase

SIGNOR-250314

P19438

P28799

0

binding

down-regulates

0.492

Collectively, these findings demonstrate that pgrn is a ligand of tnfr, an antagonist of tnf signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice.

SIGNOR-172684

P50148

Q9HB89

0

binding

up-regulates activity

0.492

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-256751