GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
O43852	P38435	1	binding	down-regulates activity	0.401	Results are presented that demonstrate that the endoplasmic reticulum chaperone protein calumenin is associated with gamma-carboxylase and inhibits its activity.	SIGNOR-265910
P37840	P63027	1	binding	down-regulates quantity	0.401	The normal function of the small presynaptic protein α-synuclein (α-syn) is of exceptional interest, not only in the context of neurodegeneration, but also as a cytosolic regulator of neurotransmission. we show that α-syn-VAMP2 interactions are necessary for α-syn-induced synaptic attenuation. Our data connect divergent views and suggest a unified model of α-syn function. the data indicate that α-syn–VAMP2 binding is essential for α-syn function and advocate an “interlocking model” where α-syn multimers on the SV surface interact with VAMP2 on adjacent SVs, helping to maintain physiologic SV clustering.	SIGNOR-264104
P06239	Q9BZS1	1	phosphorylation	down-regulates	0.401	Lck phosphorylated tyr-342 of foxp3 by immunoprecipitation and in vitro kinase assay, and the replacement of tyr-342 with phenylalanine (y342f) abolished the ability to suppress mmp9 expression.	SIGNOR-203089
Q8WYB5	Q13950	1	binding	up-regulates	0.401	Moz and morf both interact with runx2 / while morf does not acetylate runx2, its sm domain potentiates runx2-dependent transcriptional activation.	SIGNOR-117335
P46934	Q9Y4G8	1	ubiquitination	down-regulates quantity	0.401	In line with the previous result (XREF_FIG), overexpression of NEDD4-1 reduced the level of CNrasGEF significantly (XREF_FIG).\|NEDD4-1 ubiquitinates CNrasGEF in glioma cells.	SIGNOR-278705
P68400	P12830	1	phosphorylation	up-regulates activity	0.401	Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion. \| Under these conditions, phosphorylation of the E-cadherin double mutant S853A/S855A was reduced by 25% as compared with wt E-cadherin. \| Expression of the E-cadherin double mutant S853A/S855A in NIH3T3 cells expressing Wnt-1 reduces cell-cell adhesion.	SIGNOR-250840
P49407	Q14940	1	relocalization	down-regulates activity	0.401	Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs)	SIGNOR-275505
Q9BZK7	P20749	1	ubiquitination	down-regulates	0.401	We also defined the e3 ligase tblr1 as a protein involved in bcl-3 degradation	SIGNOR-166111
O75843	P46934	2	binding	up-regulates activity	0.401	Gamma2-Adaptin is a putative member of the clathrin adaptor protein family with unknown physiological function. We previously reported that gamma2-adaptin acts as a ubiquitin receptor by virtue of its ubiquitin-interacting motif. Here we demonstrate that this motif mediates a specific physical interaction with the ubiquitin ligase Nedd4 and promotes ubiquitination of gamma2-adaptin. These antibodies clearly recognized the 96 kDa form, thus demonstrating that a fraction of γ2-adaptin is modified by monoubiquitination (Fig. 1C). Thus, binding of γ2-adaptin to Nedd4 is not necessary for its membrane association.Accordingly, one possible function of γ2-adaptin may be to act as an adaptor for Nedd4, recruiting it to membrane compartments for subsequent ubiquitination.	SIGNOR-272636
P00519	P15498	1	phosphorylation	up-regulates	0.401	Thus, the c-terminal tail of vav serves as a direct substrate of bcr-abl in vitro.	SIGNOR-114091
Q8IWU2	P13569	1	phosphorylation	down-regulates activity	0.401	The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.\|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.	SIGNOR-278227
P03956	P08123	1	cleavage	down-regulates quantity by destabilization	0.401	In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.	SIGNOR-272337
P25116	P08754	1	binding	up-regulates activity	0.401	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-256875
Q9UNH5	P04637	1	dephosphorylation	down-regulates activity	0.401	The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53\|. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315)\|Earlier studies showed that Ser315 phosphorylation increases the sequence-specific DNA binding capacity of p53, suggesting that Ser315 phosphorylation is an activating modification	SIGNOR-248828
Q13490	P06730	1	ubiquitination	down-regulates quantity by destabilization	0.401	We found that endogenous eIF4E was ubiquitinated by cIAP1, and ubiquitinated eIF4E accumulated upon MG132 treatment.	SIGNOR-278741
P28328	P28288	1	ubiquitination	up-regulates activity	0.401	PEX5 and PMP70 are ubiquitinated by PEX2 during amino acid starvation.	SIGNOR-278708
O15524	P51617	1	binding	down-regulates	0.401	Coimmunoprecipitation analyses demonstrated association of socs-1 with irak...This Finding suggests that socs-1 might suppress myd88-dependent signal pathways at least by binding to irak	SIGNOR-95528
P31749	Q16584	1	phosphorylation	down-regulates	0.4	Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation.	SIGNOR-252592
Q16891	Q9BXM7	1	binding	up-regulates activity	0.4	MIC60 Is Crucial for Parkin Recruitment and Transiently Interacts with PINK1	SIGNOR-266301
Q06787	Q9Y566	1	post transcriptional regulation	up-regulates quantity	0.4	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.	SIGNOR-262109
Q00987	O43463	1	ubiquitination	down-regulates quantity by destabilization	0.4	A recent report showed that the p53 inducible E3 ligase MDM2 causes SUV39H1 degradation.\|Furthermore, it was reported that MDM2 can ubiquitinate and degrade SUV39H1.	SIGNOR-278631
O43791	P35226	1	binding	up-regulates activity	0.4	Here, we describe an E3 ubiquitin ligase consisting of SPOP and CULLIN3 that is able to ubiquitinate the PcG protein BMI1 and the variant histone MACROH2A1. To investigate whether BMI1 can form a complex with SPOP and CULLIN3 in vivo, we reconstituted the complex in 293HEK cells. We find that BMI1 readily immunoprecipitates both hemagglutinin (HA)-SPOP and CULLIN3, and, conversely, CULLIN3 immunoprecipitates BMI1 (Fig. 2a). Complex formation depends on the presence of SPOP, in accordance with BMI1 binding to the MATH domain of SPOP (Fig. 1b) and previously published data showing SPOP–CULLIN interaction by means of the BTB/POZ domain of SPOP (30).	SIGNOR-272658
O43603	P50148	1	binding	up-regulates activity	0.4	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-257020
P06241	Q16236	1	phosphorylation	down-regulates quantity	0.4	Fyn phosphorylates Nrf2 Y568, resulting in nuclear export and degradation of Nrf2.\|Fyn phosphorylates Nrf2Y568 resulting in nuclear export and degradation of Nrf2.	SIGNOR-278358
P31749	O14492	1	phosphorylation	up-regulates activity	0.4	This study identifies APS as a novel physiological substrate for PKB and the first serine phosphorylation site on APS	SIGNOR-252557
Q99542	P16112	1	cleavage	down-regulates quantity by destabilization	0.4	Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)\|In this study we investigated the ability of MMP-19 and MMP-20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well-described MMP cleavage site between residues Asn(341) and Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.	SIGNOR-266978
Q9UBI6	P42336	1	binding	up-regulates	0.4	We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein)coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin.	SIGNOR-141795
P16520	P42336	1	binding	up-regulates	0.4	Expression of the g__ sequestrant, _-transducin, inhibits both ras activation and membrane translocation of _-arrestin1, suggesting that g__ dimers from g_i2 and g_q activate different effectors to coordinately regulate the pi 3-kinase/akt pathway. , these data indicate that _-thrombin stimulates rapid pi 3-kinase activity and akt phosphorylation by the g__ dimers released from a ptx-sensitive g protein.	SIGNOR-120264
Q9UBY5	Q14344	1	binding	up-regulates	0.4	Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.	SIGNOR-198547
P16333	P00519	2	binding	down-regulates activity	0.4	We also show that overexpression of nck could repress the phosphorylation of cbl by abl in vivo. Studies with nck mutants suggested that the nck sh2 domain is responsible for inhibiting the activity of abl toward both cbl and nck itself, most likely by competing with the abl sh2 for tyrosine-phosphorylated binding sites	SIGNOR-109672
P17612	P07949	1	phosphorylation	down-regulates	0.4	Furthermore, we find that activation of protein kinase a (pka) by forskolin reduces the recruitment of shp2 to ret and negatively affects ligand-mediated neurite outgrowth. In agreement with this, mutation of ser(696), a known pka phosphorylation site in ret, enhances shp2 binding to the receptor and eliminates the effect of forskolin on ligand-induced outgrowth.	SIGNOR-167349
P43119	P50148	1	binding	up-regulates activity	0.4	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-257078
Q92729	P35222	1	dephosphorylation	down-regulates activity	0.4	Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating \u03b2-catenin and reducing the activation of \u03b2-catenin signaling.	SIGNOR-277095
Q9UBI6	P17612	1	binding	down-regulates	0.4	As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp.	SIGNOR-152615
P62714	Q00987	1	dephosphorylation	up-regulates activity	0.4	cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells	SIGNOR-248593
Q13315	Q09472	1	phosphorylation	up-regulates	0.4	Atm mediates phosphorylation of p300 in response to dna damageexpression of nonphosphorylatable serine to alanine form of p300 (s106a) destabilized both p300 and nbs1 proteins, after dna damage	SIGNOR-165567
Q13153	O95863	1	phosphorylation	up-regulates	0.4	Pak1 regulates the repressor activity of snail by phosphorylating on ser(246). Pak1 phosphorylation of snail supports snail's accumulation in the nucleus as well as its repressor functions.	SIGNOR-135605
P29275	P50148	1	binding	up-regulates activity	0.4	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-257365
Q8IYK4	P08123	1	glycosylation	up-regulates activity	0.4	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-261157
Q00535	O60229	1	phosphorylation	up-regulates activity	0.4	We then demonstrated that Cdk5 phosphorylates Kalirin 7 on Thr 1590 , increasing its GEF activity slightly and changing its solubility properties.	SIGNOR-279603
P15172	P38936	1	transcriptional regulation	up-regulates	0.4	P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells	SIGNOR-251574
P49841	P38936	1	phosphorylation	down-regulates quantity by destabilization	0.4	Glycogen synthase kinase 3beta phosphorylates p21waf1/cip1 for proteasomal degradation after uv irradiationhere, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (gsk-3beta) is required for its degradation in response to uv irradiation	SIGNOR-152941
P00519	P16333	2	phosphorylation	up-regulates	0.4	Activated c-abl reduces the amplitude of mitogen-activated protein kinases (erk1/2, jnks and p38) activation in a dose-dependent manner by a negative feedback mechanism. By analysis of the adaptor proteins nck1 and grb2 mutants we further show that the negative loop on p38 is mediated by c-abl phosphorylation at tyrosine 105 of the adaptor protein nck1	SIGNOR-196043
Q8IUQ4	P49757	1	ubiquitination	down-regulates	0.4	We report that siah-1 interacts directly with and promotes the degradation of the cell fate regulator numb.	SIGNOR-113469
Q86UT6	Q15366	1	binding	up-regulates activity	0.4	Moreover, poly(rC) binding protein 2 (PCBP2) interacts with NLRX1 to participate in the NLRX1-induced degradation of MAVS and the inhibition of antiviral responses during HCV infection.	SIGNOR-260359
Q13315	Q8IW19	1	phosphorylation	up-regulates activity	0.4	We show that APLF undergoes ATM dependent hyperphosphorylation following IR and that APLF is directly phosphorylated by ATM in vitro.	SIGNOR-279492
P00533	P11171	1	phosphorylation	down-regulates	0.4	The phosphorylation site has been localized to the 8-kda domain, which has one tyrosine, tyrosine-418. The 8-kda region is required for the assembly of the spectrin/actin complex, and phosphorylation by egfr reduced the ability of protein 4.1 to promote the assembly of the spectrin/actin/protein 4.1 ternary complex	SIGNOR-20452
Q86TM6	O15354	1	polyubiquitination	down-regulates quantity by destabilization	0.4	We demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R.	SIGNOR-272631
Q04724	O95343	1	binding	up-regulates activity	0.4	Biochemical and mutational analysis shows that the Six domain of both SIX3 and SIX6 strongly interact with the QD domain of TLE1 and AES. TLE1 over-expression induces an enlargement of the eye field and reinforcesSIX3/SIX6 capability of initiating retina formation	SIGNOR-234595
Q14164	P42224	1	phosphorylation	up-regulates	0.4	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154775
P17612	Q9NXR1	1	phosphorylation	up-regulates	0.4	Here, we demonstrate that disc1 and pde4 modulate nde1 phosphorylation by camp-dependent protein kinase a (pka) and identify a novel pka substrate site on nde1 at threonine-131 (t131).Since phosphorylated t131 is detectable at multiple subcellular locations (centrosome, nucleus, postsynaptic density, proximal axon), there is potential for disc1/pde4 to influence several important brain processes that critically depend on the nde1/ndel1/lis1 comple	SIGNOR-174410
Q6IQ23	Q86UF1	1	binding	up-regulates activity	0.4	Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11.	SIGNOR-261250
P49841	Q14494	1	phosphorylation	down-regulates	0.4	Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (nrf1) and inhibits pro-survival function of nrf1	SIGNOR-193450
P48454	Q92934	1	dephosphorylation	up-regulates activity	0.399	Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD\|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.	SIGNOR-248529
Q02156	P40763	1	phosphorylation	up-regulates	0.399	Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation.	SIGNOR-143832
P17612	P29474	1	phosphorylation	up-regulates	0.399	Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.	SIGNOR-112371
P05129	Q13224	1	phosphorylation	up-regulates activity	0.399	These results indicate that PKC can directly phosphorylate S1303 and S1323 in the NR2B C terminus, leading to enhanced currents through NMDA receptor channels.	SIGNOR-249085
Q5BJH7	P08908	1	relocalization	up-regulates activity	0.399	Together, our results provide strong evidence that Yif1B is a member of the ER/Golgi trafficking machinery, which plays a key role in specific targeting of 5-HT(1A)R to the neuronal dendrites. This finding opens up new pathways for the study of 5-HT(1A)R regulation by partner proteins and for the development of novel antidepressant drugs.\|We confirmed 5-HT(1A)R-Yif1B interaction by glutathione S-transferase pull-down experiments using rat brain extracts and transfected cell lines.	SIGNOR-268299
P11802	Q13761	1	phosphorylation	down-regulates	0.399	Our findings demonstrate that the cell cycle proteins cyclin d1 and cdk4 induce runx2 and runx3 phosphorylation, ubiquitylation and proteasomal degradation.	SIGNOR-185120
P06239	Q8IWV1	1	phosphorylation	up-regulates activity	0.399	Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.	SIGNOR-273528
Q9Y5X4	P20393	1	binding	up-regulates	0.399	All four proteins, nr2e3, nr1d1, nrl and crx, could be co-immunoprecipitated from the bovine retinal nuclear extract, suggesting their existence in a multi-protein transcriptional regulatory complex in vivo.	SIGNOR-125661
P00519	P11387	1	phosphorylation	up-regulates activity	0.399	This study demonstrates that ABL1-dependent phosphorylation up-regulates topo I activity. The ABL1 SH3 domain bound directly to the N-terminal region of topo I. The results demonstrate that ABL1 phosphorylated topo I at Tyr268 in core subdomain II.	SIGNOR-260775
Q07687	P28360	2	binding	down-regulates activity	0.399	We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.	SIGNOR-240918
Q06710	P07202	1	transcriptional regulation	up-regulates quantity by expression	0.399	TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.	SIGNOR-267277
P17252	P13569	1	phosphorylation	up-regulates activity	0.399	Direct amino acid sequencing and peptide mapping of CF-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by PKA and PKG, and serines 686 and 790 were phosphorylated by PKC.	SIGNOR-248849
Q99986	Q12888	1	phosphorylation	up-regulates	0.399	The kinase vrk1 is activated by dna double strand breaks induced by ionizing radiation (ir) and specifically phosphorylates 53bp1 in serum-starved cells./ Vrk1 knockdown resulted in the defective formation of 53bp1 foci in response to ir both in number and size	SIGNOR-197625
Q13315	P27707	1	phosphorylation	up-regulates activity	0.399	Here we report that ATM phosphorylation of dCK on Serine 74 is essential to activate the G2/M checkpoint in response to DNA damage.\|Together, these results indicate that the dCK-Cdk1 interaction is enhanced in response to DNA damage and that ATM mediated dCK Serine 74 phosphorylation is required for the interaction.	SIGNOR-278221
P28360	Q07687	2	binding	down-regulates activity	0.399	We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.	SIGNOR-240929
P00533	O14828	1	phosphorylation	up-regulates activity	0.399	In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation	SIGNOR-262858
Q13131	Q16875	1	phosphorylation	up-regulates	0.399	Ipfk-2 was phosphorylated on the homologous serine (ser-461) and activated by ampk in vitro.	SIGNOR-89760
Q07021	P02747	1	binding	down-regulates activity	0.399	Previous studies have shown that gC1qR inhibits aggregated IgG-mediated complement activation by binding to the gC1q site on C1q, thereby preventing IgG from binding to the gh’s (28), suggesting that the binding sites for gC1qR and IgG on C1q may be identical or at least overlapping.	SIGNOR-263404
P12931	P52565	1	phosphorylation	down-regulates	0.399	We show here that src kinase binds and phosphorylates rhogdi both in vitro and in vivo at tyr156. analysis of rho gtpase-rhogdi complexes using in vitro assays of complexation and in vivo by coimmunoprecipitation analysis indicates that src-mediated phosphorylation of tyr156 causes a dramatic decrease in the ability of rhogdi to form a complex with rhoa, rac1, or cdc42.	SIGNOR-149282
Q9Y371	P22681	1	binding	up-regulates	0.399	Cbl rapidly recruits cin85 (cbl-interacting protein of 85k;ref. 6) and endophilins (regulatory components of clathrin-coated vesicles) to form a complex with activated egf receptors, thus controlling receptor internalization.	SIGNOR-115826
Q13469	P05231	1	transcriptional regulation	up-regulates quantity by expression	0.399	The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. \|Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries.	SIGNOR-251731
P36508	P20226	1	binding	down-regulates activity	0.399	We identified ZNF76 as a novel transcriptional repressor that targets TBP. ZNF76 interacts with TBP through both its N and C termini. ZNF76 targets TBP for transcriptional repression.	SIGNOR-224650
O14904	O15146	1	binding	up-regulates	0.399	we provide evidence that wnt9a and wnt11 bind directly to the extracellular domain of musk, to induce musk dimerization and subsequent tyrosine phosphorylation of the kinase	SIGNOR-195975
Q96EP1	Q14807	1	ubiquitination	down-regulates quantity by destabilization	0.399	Chfr ubiquitinates Kif22 and promotes its degradation.	SIGNOR-271469
P11229	P63096	1	binding	up-regulates activity	0.399	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-256735
Q9UGL1	O00257	1	binding	up-regulates activity	0.399	Our results clearly showed that the PcG protein hPc2 interacted with the N-terminus of JARID1B both in vivo and in vitro. It is interesting that the C-terminus of hPc2 was essential for the interaction and transcriptional co-repression.	SIGNOR-226447
P00519	P17676	1	phosphorylation	up-regulates	0.399	The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells	SIGNOR-186423
Q9UQB9	O75410	1	phosphorylation	up-regulates activity	0.399	Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. although the patho-physiological meaning of TACC1 phosphorylation by Aurora-C in normal and in malignant somatic cells remains to be fully investigated, our observations suggest that Aurora-C has a role in the later stage of mitosis, when an interaction with TACC1 may be relevant for the correct progression of the cell cycle.	SIGNOR-262663
P84022	P26367	1	binding	down-regulates activity	0.399	The paired domain of Pax6 interacts with the MH1 domain of Smad3. Smad3 prevents Pax6 paired domain from binding DNA	SIGNOR-251875
P00533	Q13315	1	phosphorylation	up-regulates activity	0.399	Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks.	SIGNOR-276872
Q96PU5	Q12809	1	ubiquitination	down-regulates quantity by destabilization	0.399	As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.\|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface.	SIGNOR-278771
P17706	Q02790	1	dephosphorylation	down-regulates	0.399	We have documented that a cellular protein that binds the immunosuppressant drug fk506, termed the fk506-binding protein (fkbp52), interacts with the single-stranded d sequence within the aav inverted terminal repeats, inhibits viral second-strand dna synthesis, and consequently limits high-efficiency transgene expression. Deliberate overexpression of the murine wild-type (wt) tc-ptp gene, but not that of a cysteine-to-serine (c-s) mutant, caused tyrosine dephosphorylation of fkbp52, leading to efficient viral second-strand dna synthesis and resulting in a significant increase in aav-mediated transduction efficiency in hela cells in vitro.	SIGNOR-97794
Q9H2X6	Q06413	1	phosphorylation	down-regulates activity	0.399	HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.	SIGNOR-279192
P00533	O43639	1	binding	up-regulates	0.399	Growth factor binding to receptor protein tyrosine kinases (r-ptks)1 induces their dimerization and trans-phosphorylation, creating docking sites for proteins containing sh2 and ptb protein interaction domains. Nck binds to the pdgf and egfr receptors (figure 3c).	SIGNOR-64731
P37231	O00327	1	transcriptional regulation	up-regulates quantity by expression	0.399	Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms.	SIGNOR-268026
P98170	P60953	1	ubiquitination	down-regulates quantity	0.398	As XIAP can directly ubiquitinate Cdc42, we tested if the RING domain of XIAP is required for modulating the protein levels of Cdc42 in vivo .\|We then investigated the molecular mechanisms behind XIAP mediated Cdc42 degradation.	SIGNOR-278799
Q5H8A4	Q8TEQ8	1	binding	up-regulates quantity by stabilization	0.398	We show that the human homolog of Gpi7p, termed hGPI7, binds to and is stabilized by PIG-F and that hGPI7 competes with PIG-O for binding to PIG-F. PIG-F Binds to and Stabilizes hGPI7 and PIG-O Independently. These results are consistent with the hypothesis that overexpression of hGPI7 decreases the biosynthetic activity of PIG-O by decreasing the available PIG-F, thereby destabilizing PIG-O.	SIGNOR-261359
Q9NP71	Q9H5J4	1	transcriptional regulation	up-regulates quantity by expression	0.398	In this study, we clearly show that mouse and human Elovl6 are direct targets of ChREBP.	SIGNOR-267945
P27361	P37231	1	relocalization	down-regulates activity	0.398	The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform	SIGNOR-179407
Q9UQM7	Q14524	1	phosphorylation	up-regulates activity	0.398	Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate‚Äìactivated protein kinase (AMPK)‚Äìdependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).\|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. \| Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5	SIGNOR-275772
P19784	Q13547	1	phosphorylation	up-regulates activity	0.398	Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified. Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1.	SIGNOR-250999
P26022	P08603	1	binding	up-regulates activity	0.398	Our findings identify PTX3 as a unique FH ligand in that it can bind both of the two hot-spots of FH, namely SCR7 and SCR19-20 and indicate that PTX3 participates in the localization of functionally active FH. PTX3 binds FH without interfering with its complement inhibitory function. Therefore PTX3 may contribute to focusing FH regulatory action, prevent excessive complement activation, and thus exert an important function in the control of inflammation in response to tissue injury.	SIGNOR-252140
Q12834	Q5XUX0	1	binding	down-regulates quantity by destabilization	0.398	Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.	SIGNOR-277378
Q9NZL9	Q9Y2X7	1	binding	up-regulates activity	0.398	We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens. MAT2B and GIT1 require each other to activate MEK1/ERK and increase growth.	SIGNOR-261244
Q13418	Q96C90	1	phosphorylation	up-regulates activity	0.398	We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.\|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin	SIGNOR-265741
P49841	Q13485	1	phosphorylation	down-regulates quantity by destabilization	0.398	In the presence of FGF, Wnt potentiates TGF-β signaling by preventing Smad4 GSK3 phosphorylations that inhibit a transcriptional activation domain located in the linker region.	SIGNOR-276440
P11802	Q92879	1	phosphorylation	up-regulates activity	0.398	These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.	SIGNOR-262735

O43852

P38435

1

binding

down-regulates activity

0.401

Results are presented that demonstrate that the endoplasmic reticulum chaperone protein calumenin is associated with gamma-carboxylase and inhibits its activity.

SIGNOR-265910

P37840

P63027

1

binding

down-regulates quantity

0.401

The normal function of the small presynaptic protein α-synuclein (α-syn) is of exceptional interest, not only in the context of neurodegeneration, but also as a cytosolic regulator of neurotransmission. we show that α-syn-VAMP2 interactions are necessary for α-syn-induced synaptic attenuation. Our data connect divergent views and suggest a unified model of α-syn function. the data indicate that α-syn–VAMP2 binding is essential for α-syn function and advocate an “interlocking model” where α-syn multimers on the SV surface interact with VAMP2 on adjacent SVs, helping to maintain physiologic SV clustering.

SIGNOR-264104

P06239

Q9BZS1

1

phosphorylation

down-regulates

0.401

Lck phosphorylated tyr-342 of foxp3 by immunoprecipitation and in vitro kinase assay, and the replacement of tyr-342 with phenylalanine (y342f) abolished the ability to suppress mmp9 expression.

SIGNOR-203089

Q8WYB5

Q13950

1

binding

up-regulates

0.401

Moz and morf both interact with runx2 / while morf does not acetylate runx2, its sm domain potentiates runx2-dependent transcriptional activation.

SIGNOR-117335

P46934

Q9Y4G8

1

ubiquitination

down-regulates quantity

0.401

In line with the previous result (XREF_FIG), overexpression of NEDD4-1 reduced the level of CNrasGEF significantly (XREF_FIG).|NEDD4-1 ubiquitinates CNrasGEF in glioma cells.

SIGNOR-278705

P68400

P12830

1

phosphorylation

up-regulates activity

0.401

Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion. | Under these conditions, phosphorylation of the E-cadherin double mutant S853A/S855A was reduced by 25% as compared with wt E-cadherin. | Expression of the E-cadherin double mutant S853A/S855A in NIH3T3 cells expressing Wnt-1 reduces cell-cell adhesion.

SIGNOR-250840

P49407

Q14940

1

relocalization

down-regulates activity

0.401

Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs)

SIGNOR-275505

Q9BZK7

P20749

1

ubiquitination

down-regulates

0.401

We also defined the e3 ligase tblr1 as a protein involved in bcl-3 degradation

SIGNOR-166111

O75843

P46934

2

binding

up-regulates activity

0.401

Gamma2-Adaptin is a putative member of the clathrin adaptor protein family with unknown physiological function. We previously reported that gamma2-adaptin acts as a ubiquitin receptor by virtue of its ubiquitin-interacting motif. Here we demonstrate that this motif mediates a specific physical interaction with the ubiquitin ligase Nedd4 and promotes ubiquitination of gamma2-adaptin. These antibodies clearly recognized the 96 kDa form, thus demonstrating that a fraction of γ2-adaptin is modified by monoubiquitination (Fig. 1C). Thus, binding of γ2-adaptin to Nedd4 is not necessary for its membrane association.Accordingly, one possible function of γ2-adaptin may be to act as an adaptor for Nedd4, recruiting it to membrane compartments for subsequent ubiquitination.

SIGNOR-272636

P00519

P15498

1

phosphorylation

up-regulates

0.401

Thus, the c-terminal tail of vav serves as a direct substrate of bcr-abl in vitro.

SIGNOR-114091

Q8IWU2

P13569

1

phosphorylation

down-regulates activity

0.401

The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.

SIGNOR-278227

P03956

P08123

1

cleavage

down-regulates quantity by destabilization

0.401

In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.

SIGNOR-272337

P25116

P08754

1

binding

up-regulates activity

0.401

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-256875

Q9UNH5

P04637

1

dephosphorylation

down-regulates activity

0.401

The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53|. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315)|Earlier studies showed that Ser315 phosphorylation increases the sequence-specific DNA binding capacity of p53, suggesting that Ser315 phosphorylation is an activating modification

SIGNOR-248828

Q13490

P06730

1

ubiquitination

down-regulates quantity by destabilization

0.401

We found that endogenous eIF4E was ubiquitinated by cIAP1, and ubiquitinated eIF4E accumulated upon MG132 treatment.

SIGNOR-278741

P28328

P28288

1

ubiquitination

up-regulates activity

0.401

PEX5 and PMP70 are ubiquitinated by PEX2 during amino acid starvation.

SIGNOR-278708

O15524

P51617

1

binding

down-regulates

0.401

Coimmunoprecipitation analyses demonstrated association of socs-1 with irak...This Finding suggests that socs-1 might suppress myd88-dependent signal pathways at least by binding to irak

SIGNOR-95528

P31749

Q16584

1

phosphorylation

down-regulates

0.4

Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation.

SIGNOR-252592

Q16891

Q9BXM7

1

binding

up-regulates activity

0.4

MIC60 Is Crucial for Parkin Recruitment and Transiently Interacts with PINK1

SIGNOR-266301

Q06787

Q9Y566

1

post transcriptional regulation

up-regulates quantity

0.4

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.

SIGNOR-262109

Q00987

O43463

1

ubiquitination

down-regulates quantity by destabilization

0.4

A recent report showed that the p53 inducible E3 ligase MDM2 causes SUV39H1 degradation.|Furthermore, it was reported that MDM2 can ubiquitinate and degrade SUV39H1.

SIGNOR-278631

O43791

P35226

1

binding

up-regulates activity

0.4

Here, we describe an E3 ubiquitin ligase consisting of SPOP and CULLIN3 that is able to ubiquitinate the PcG protein BMI1 and the variant histone MACROH2A1. To investigate whether BMI1 can form a complex with SPOP and CULLIN3 in vivo, we reconstituted the complex in 293HEK cells. We find that BMI1 readily immunoprecipitates both hemagglutinin (HA)-SPOP and CULLIN3, and, conversely, CULLIN3 immunoprecipitates BMI1 (Fig. 2a). Complex formation depends on the presence of SPOP, in accordance with BMI1 binding to the MATH domain of SPOP (Fig. 1b) and previously published data showing SPOP–CULLIN interaction by means of the BTB/POZ domain of SPOP (30).

SIGNOR-272658

O43603

P50148

1

binding

up-regulates activity

0.4

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-257020

P06241

Q16236

1

phosphorylation

down-regulates quantity

0.4

Fyn phosphorylates Nrf2 Y568, resulting in nuclear export and degradation of Nrf2.|Fyn phosphorylates Nrf2Y568 resulting in nuclear export and degradation of Nrf2.

SIGNOR-278358

P31749

O14492

1

phosphorylation

up-regulates activity

0.4

This study identifies APS as a novel physiological substrate for PKB and the first serine phosphorylation site on APS

SIGNOR-252557

Q99542

P16112

1

cleavage

down-regulates quantity by destabilization

0.4

Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)|In this study we investigated the ability of MMP-19 and MMP-20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well-described MMP cleavage site between residues Asn(341) and Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.

SIGNOR-266978

Q9UBI6

P42336

1

binding

up-regulates

0.4

We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein)coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin.

SIGNOR-141795

P16520

P42336

1

binding

up-regulates

0.4

Expression of the g__ sequestrant, _-transducin, inhibits both ras activation and membrane translocation of _-arrestin1, suggesting that g__ dimers from g_i2 and g_q activate different effectors to coordinately regulate the pi 3-kinase/akt pathway. , these data indicate that _-thrombin stimulates rapid pi 3-kinase activity and akt phosphorylation by the g__ dimers released from a ptx-sensitive g protein.

SIGNOR-120264

Q9UBY5

Q14344

1

binding

up-regulates

0.4

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

SIGNOR-198547

P16333

P00519

2

binding

down-regulates activity

0.4

We also show that overexpression of nck could repress the phosphorylation of cbl by abl in vivo. Studies with nck mutants suggested that the nck sh2 domain is responsible for inhibiting the activity of abl toward both cbl and nck itself, most likely by competing with the abl sh2 for tyrosine-phosphorylated binding sites

SIGNOR-109672

P17612

P07949

1

phosphorylation

down-regulates

0.4

Furthermore, we find that activation of protein kinase a (pka) by forskolin reduces the recruitment of shp2 to ret and negatively affects ligand-mediated neurite outgrowth. In agreement with this, mutation of ser(696), a known pka phosphorylation site in ret, enhances shp2 binding to the receptor and eliminates the effect of forskolin on ligand-induced outgrowth.

SIGNOR-167349

P43119

P50148

1

binding

up-regulates activity

0.4

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-257078

Q92729

P35222

1

dephosphorylation

down-regulates activity

0.4

Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating \u03b2-catenin and reducing the activation of \u03b2-catenin signaling.

SIGNOR-277095

Q9UBI6

P17612

1

binding

down-regulates

0.4

As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp.

SIGNOR-152615

P62714

Q00987

1

dephosphorylation

up-regulates activity

0.4

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

SIGNOR-248593

Q13315

Q09472

1

phosphorylation

up-regulates

0.4

Atm mediates phosphorylation of p300 in response to dna damageexpression of nonphosphorylatable serine to alanine form of p300 (s106a) destabilized both p300 and nbs1 proteins, after dna damage

SIGNOR-165567

Q13153

O95863

1

phosphorylation

up-regulates

0.4

Pak1 regulates the repressor activity of snail by phosphorylating on ser(246). Pak1 phosphorylation of snail supports snail's accumulation in the nucleus as well as its repressor functions.

SIGNOR-135605

P29275

P50148

1

binding

up-regulates activity

0.4

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-257365

Q8IYK4

P08123

1

glycosylation

up-regulates activity

0.4

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-261157

Q00535

O60229

1

phosphorylation

up-regulates activity

0.4

We then demonstrated that Cdk5 phosphorylates Kalirin 7 on Thr 1590 , increasing its GEF activity slightly and changing its solubility properties.

SIGNOR-279603

P15172

P38936

1

transcriptional regulation

up-regulates

0.4

P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells

SIGNOR-251574

P49841

P38936

1

phosphorylation

down-regulates quantity by destabilization

0.4

Glycogen synthase kinase 3beta phosphorylates p21waf1/cip1 for proteasomal degradation after uv irradiationhere, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (gsk-3beta) is required for its degradation in response to uv irradiation

SIGNOR-152941

P00519

P16333

2

phosphorylation

up-regulates

0.4

Activated c-abl reduces the amplitude of mitogen-activated protein kinases (erk1/2, jnks and p38) activation in a dose-dependent manner by a negative feedback mechanism. By analysis of the adaptor proteins nck1 and grb2 mutants we further show that the negative loop on p38 is mediated by c-abl phosphorylation at tyrosine 105 of the adaptor protein nck1

SIGNOR-196043

Q8IUQ4

P49757

1

ubiquitination

down-regulates

0.4

We report that siah-1 interacts directly with and promotes the degradation of the cell fate regulator numb.

SIGNOR-113469

Q86UT6

Q15366

1

binding

up-regulates activity

0.4

Moreover, poly(rC) binding protein 2 (PCBP2) interacts with NLRX1 to participate in the NLRX1-induced degradation of MAVS and the inhibition of antiviral responses during HCV infection.

SIGNOR-260359

Q13315

Q8IW19

1

phosphorylation

up-regulates activity

0.4

We show that APLF undergoes ATM dependent hyperphosphorylation following IR and that APLF is directly phosphorylated by ATM in vitro.

SIGNOR-279492

P00533

P11171

1

phosphorylation

down-regulates

0.4

The phosphorylation site has been localized to the 8-kda domain, which has one tyrosine, tyrosine-418. The 8-kda region is required for the assembly of the spectrin/actin complex, and phosphorylation by egfr reduced the ability of protein 4.1 to promote the assembly of the spectrin/actin/protein 4.1 ternary complex

SIGNOR-20452

Q86TM6

O15354

1

polyubiquitination

down-regulates quantity by destabilization

0.4

We demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R.

SIGNOR-272631

Q04724

O95343

1

binding

up-regulates activity

0.4

Biochemical and mutational analysis shows that the Six domain of both SIX3 and SIX6 strongly interact with the QD domain of TLE1 and AES. TLE1 over-expression induces an enlargement of the eye field and reinforcesSIX3/SIX6 capability of initiating retina formation

SIGNOR-234595

Q14164

P42224

1

phosphorylation

up-regulates

0.4

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154775

P17612

Q9NXR1

1

phosphorylation

up-regulates

0.4

Here, we demonstrate that disc1 and pde4 modulate nde1 phosphorylation by camp-dependent protein kinase a (pka) and identify a novel pka substrate site on nde1 at threonine-131 (t131).Since phosphorylated t131 is detectable at multiple subcellular locations (centrosome, nucleus, postsynaptic density, proximal axon), there is potential for disc1/pde4 to influence several important brain processes that critically depend on the nde1/ndel1/lis1 comple

SIGNOR-174410

Q6IQ23

Q86UF1

1

binding

up-regulates activity

0.4

Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11.

SIGNOR-261250

P49841

Q14494

1

phosphorylation

down-regulates

0.4

Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (nrf1) and inhibits pro-survival function of nrf1

SIGNOR-193450

P48454

Q92934

1

dephosphorylation

up-regulates activity

0.399

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.

SIGNOR-248529

Q02156

P40763

1

phosphorylation

up-regulates

0.399

Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation.

SIGNOR-143832

P17612

P29474

1

phosphorylation

up-regulates

0.399

Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.

SIGNOR-112371

P05129

Q13224

1

phosphorylation

up-regulates activity

0.399

These results indicate that PKC can directly phosphorylate S1303 and S1323 in the NR2B C terminus, leading to enhanced currents through NMDA receptor channels.

SIGNOR-249085

Q5BJH7

P08908

1

relocalization

up-regulates activity

0.399

Together, our results provide strong evidence that Yif1B is a member of the ER/Golgi trafficking machinery, which plays a key role in specific targeting of 5-HT(1A)R to the neuronal dendrites. This finding opens up new pathways for the study of 5-HT(1A)R regulation by partner proteins and for the development of novel antidepressant drugs.|We confirmed 5-HT(1A)R-Yif1B interaction by glutathione S-transferase pull-down experiments using rat brain extracts and transfected cell lines.

SIGNOR-268299

P11802

Q13761

1

phosphorylation

down-regulates

0.399

Our findings demonstrate that the cell cycle proteins cyclin d1 and cdk4 induce runx2 and runx3 phosphorylation, ubiquitylation and proteasomal degradation.

SIGNOR-185120

P06239

Q8IWV1

1

phosphorylation

up-regulates activity

0.399

Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.

SIGNOR-273528

Q9Y5X4

P20393

1

binding

up-regulates

0.399

All four proteins, nr2e3, nr1d1, nrl and crx, could be co-immunoprecipitated from the bovine retinal nuclear extract, suggesting their existence in a multi-protein transcriptional regulatory complex in vivo.

SIGNOR-125661

P00519

P11387

1

phosphorylation

up-regulates activity

0.399

This study demonstrates that ABL1-dependent phosphorylation up-regulates topo I activity. The ABL1 SH3 domain bound directly to the N-terminal region of topo I. The results demonstrate that ABL1 phosphorylated topo I at Tyr268 in core subdomain II.

SIGNOR-260775

Q07687

P28360

2

binding

down-regulates activity

0.399

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

SIGNOR-240918

Q06710

P07202

1

transcriptional regulation

up-regulates quantity by expression

0.399

TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.

SIGNOR-267277

P17252

P13569

1

phosphorylation

up-regulates activity

0.399

Direct amino acid sequencing and peptide mapping of CF-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by PKA and PKG, and serines 686 and 790 were phosphorylated by PKC.

SIGNOR-248849

Q99986

Q12888

1

phosphorylation

up-regulates

0.399

The kinase vrk1 is activated by dna double strand breaks induced by ionizing radiation (ir) and specifically phosphorylates 53bp1 in serum-starved cells./ Vrk1 knockdown resulted in the defective formation of 53bp1 foci in response to ir both in number and size

SIGNOR-197625

Q13315

P27707

1

phosphorylation

up-regulates activity

0.399

Here we report that ATM phosphorylation of dCK on Serine 74 is essential to activate the G2/M checkpoint in response to DNA damage.|Together, these results indicate that the dCK-Cdk1 interaction is enhanced in response to DNA damage and that ATM mediated dCK Serine 74 phosphorylation is required for the interaction.

SIGNOR-278221

P28360

Q07687

2

binding

down-regulates activity

0.399

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

SIGNOR-240929

P00533

O14828

1

phosphorylation

up-regulates activity

0.399

In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation

SIGNOR-262858

Q13131

Q16875

1

phosphorylation

up-regulates

0.399

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

SIGNOR-89760

Q07021

P02747

1

binding

down-regulates activity

0.399

Previous studies have shown that gC1qR inhibits aggregated IgG-mediated complement activation by binding to the gC1q site on C1q, thereby preventing IgG from binding to the gh’s (28), suggesting that the binding sites for gC1qR and IgG on C1q may be identical or at least overlapping.

SIGNOR-263404

P12931

P52565

1

phosphorylation

down-regulates

0.399

We show here that src kinase binds and phosphorylates rhogdi both in vitro and in vivo at tyr156. analysis of rho gtpase-rhogdi complexes using in vitro assays of complexation and in vivo by coimmunoprecipitation analysis indicates that src-mediated phosphorylation of tyr156 causes a dramatic decrease in the ability of rhogdi to form a complex with rhoa, rac1, or cdc42.

SIGNOR-149282

Q9Y371

P22681

1

binding

up-regulates

0.399

Cbl rapidly recruits cin85 (cbl-interacting protein of 85k;ref. 6) and endophilins (regulatory components of clathrin-coated vesicles) to form a complex with activated egf receptors, thus controlling receptor internalization.

SIGNOR-115826

Q13469

P05231

1

transcriptional regulation

up-regulates quantity by expression

0.399

The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. |Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries.

SIGNOR-251731

P36508

P20226

1

binding

down-regulates activity

0.399

We identified ZNF76 as a novel transcriptional repressor that targets TBP. ZNF76 interacts with TBP through both its N and C termini. ZNF76 targets TBP for transcriptional repression.

SIGNOR-224650

O14904

O15146

1

binding

up-regulates

0.399

we provide evidence that wnt9a and wnt11 bind directly to the extracellular domain of musk, to induce musk dimerization and subsequent tyrosine phosphorylation of the kinase

SIGNOR-195975

Q96EP1

Q14807

1

ubiquitination

down-regulates quantity by destabilization

0.399

Chfr ubiquitinates Kif22 and promotes its degradation.

SIGNOR-271469

P11229

P63096

1

binding

up-regulates activity

0.399

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-256735

Q9UGL1

O00257

1

binding

up-regulates activity

0.399

Our results clearly showed that the PcG protein hPc2 interacted with the N-terminus of JARID1B both in vivo and in vitro. It is interesting that the C-terminus of hPc2 was essential for the interaction and transcriptional co-repression.

SIGNOR-226447

P00519

P17676

1

phosphorylation

up-regulates

0.399

The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells

SIGNOR-186423

Q9UQB9

O75410

1

phosphorylation

up-regulates activity

0.399

Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. although the patho-physiological meaning of TACC1 phosphorylation by Aurora-C in normal and in malignant somatic cells remains to be fully investigated, our observations suggest that Aurora-C has a role in the later stage of mitosis, when an interaction with TACC1 may be relevant for the correct progression of the cell cycle.

SIGNOR-262663

P84022

P26367

1

binding

down-regulates activity

0.399

The paired domain of Pax6 interacts with the MH1 domain of Smad3. Smad3 prevents Pax6 paired domain from binding DNA

SIGNOR-251875

P00533

Q13315

1

phosphorylation

up-regulates activity

0.399

Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks.

SIGNOR-276872

Q96PU5

Q12809

1

ubiquitination

down-regulates quantity by destabilization

0.399

As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface.

SIGNOR-278771

P17706

Q02790

1

dephosphorylation

down-regulates

0.399

We have documented that a cellular protein that binds the immunosuppressant drug fk506, termed the fk506-binding protein (fkbp52), interacts with the single-stranded d sequence within the aav inverted terminal repeats, inhibits viral second-strand dna synthesis, and consequently limits high-efficiency transgene expression. Deliberate overexpression of the murine wild-type (wt) tc-ptp gene, but not that of a cysteine-to-serine (c-s) mutant, caused tyrosine dephosphorylation of fkbp52, leading to efficient viral second-strand dna synthesis and resulting in a significant increase in aav-mediated transduction efficiency in hela cells in vitro.

SIGNOR-97794

Q9H2X6

Q06413

1

phosphorylation

down-regulates activity

0.399

HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.

SIGNOR-279192

P00533

O43639

1

binding

up-regulates

0.399

Growth factor binding to receptor protein tyrosine kinases (r-ptks)1 induces their dimerization and trans-phosphorylation, creating docking sites for proteins containing sh2 and ptb protein interaction domains. Nck binds to the pdgf and egfr receptors (figure 3c).

SIGNOR-64731

P37231

O00327

1

transcriptional regulation

up-regulates quantity by expression

0.399

Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms.

SIGNOR-268026

P98170

P60953

1

ubiquitination

down-regulates quantity

0.398

As XIAP can directly ubiquitinate Cdc42, we tested if the RING domain of XIAP is required for modulating the protein levels of Cdc42 in vivo .|We then investigated the molecular mechanisms behind XIAP mediated Cdc42 degradation.

SIGNOR-278799

Q5H8A4

Q8TEQ8

1

binding

up-regulates quantity by stabilization

0.398

We show that the human homolog of Gpi7p, termed hGPI7, binds to and is stabilized by PIG-F and that hGPI7 competes with PIG-O for binding to PIG-F. PIG-F Binds to and Stabilizes hGPI7 and PIG-O Independently. These results are consistent with the hypothesis that overexpression of hGPI7 decreases the biosynthetic activity of PIG-O by decreasing the available PIG-F, thereby destabilizing PIG-O.

SIGNOR-261359

Q9NP71

Q9H5J4

1

transcriptional regulation

up-regulates quantity by expression

0.398

In this study, we clearly show that mouse and human Elovl6 are direct targets of ChREBP.

SIGNOR-267945

P27361

P37231

1

relocalization

down-regulates activity

0.398

The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform

SIGNOR-179407

Q9UQM7

Q14524

1

phosphorylation

up-regulates activity

0.398

Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate‚Äìactivated protein kinase (AMPK)‚Äìdependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5

SIGNOR-275772

P19784

Q13547

1

phosphorylation

up-regulates activity

0.398

Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified. Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1.

SIGNOR-250999

P26022

P08603

1

binding

up-regulates activity

0.398

Our findings identify PTX3 as a unique FH ligand in that it can bind both of the two hot-spots of FH, namely SCR7 and SCR19-20 and indicate that PTX3 participates in the localization of functionally active FH. PTX3 binds FH without interfering with its complement inhibitory function. Therefore PTX3 may contribute to focusing FH regulatory action, prevent excessive complement activation, and thus exert an important function in the control of inflammation in response to tissue injury.

SIGNOR-252140

Q12834

Q5XUX0

1

binding

down-regulates quantity by destabilization

0.398

Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.

SIGNOR-277378

Q9NZL9

Q9Y2X7

1

binding

up-regulates activity

0.398

We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens. MAT2B and GIT1 require each other to activate MEK1/ERK and increase growth.

SIGNOR-261244

Q13418

Q96C90

1

phosphorylation

up-regulates activity

0.398

We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin

SIGNOR-265741

P49841

Q13485

1

phosphorylation

down-regulates quantity by destabilization

0.398

In the presence of FGF, Wnt potentiates TGF-β signaling by preventing Smad4 GSK3 phosphorylations that inhibit a transcriptional activation domain located in the linker region.

SIGNOR-276440

P11802

Q92879

1

phosphorylation

up-regulates activity

0.398

These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.

SIGNOR-262735