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
Q00653	Q99576	binding	down-regulates activity	0.327	GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits.	SIGNOR-253298
Q9UQB3	Q00535	phosphorylation	up-regulates activity	0.327	Cdk5 mediated delta-catenin phosphorylation regulates delta-catenin subcellular localization into two distinct pools : a cytoplasmic or intraneurite state as well as a pool that is localized to the membrane.\|Cdk5 phosphorylates delta-catenin on serines 300 and 357.	SIGNOR-279323
Q9UKX2	Q14814	transcriptional regulation	up-regulates quantity by expression	0.327	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238712
Q13769	P17252	phosphorylation	up-regulates	0.327	We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling.	SIGNOR-126572
O75553	Q93034	polyubiquitination	down-regulates quantity by destabilization	0.327	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-272140
P42658	Q9UBC3	transcriptional regulation	down-regulates quantity by repression	0.327	Dnmt3b was responsible for transcriptional silencing of Dpp6 gene as depletion of Dnmt3b resulted in increased mRNA and protein expression of Dpp6.	SIGNOR-268963
P49840	P05771	phosphorylation	down-regulates	0.327	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115718
P08237	P01106	transcriptional regulation	up-regulates quantity	0.327	C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.	SIGNOR-259988
P42226	P18031	dephosphorylation	down-regulates activity	0.327	Phosphorylated STAT6 may also serve as a cytoplasmic substrate for PTP1B since overexpression of PTP1B leads to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B deficiency increases IL-4-induced STAT6 signaling in B-cells.	SIGNOR-277122
Q8N122	Q9UBE8	phosphorylation	down-regulates activity	0.327	NLK inhibits mTORC1 lysosomal localization and thereby suppresses mTORC1 activation. Mechanistically, NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment.	SIGNOR-273908
P13796	P17612	phosphorylation	up-regulates	0.327	Phosphorylation on ser5 increases the f-actin-binding activity of l-plastin and promotes its targeting to sites of actin assembly in cells. L-plastin phosphorylation require protein kinase a.	SIGNOR-146287
Q13105	Q7Z6Z7	ubiquitination	down-regulates quantity by destabilization	0.327	Previously, we reported that K48 linked polyubiquitination of Miz1 by Mule triggers its proteasomal degradation, thereby relieving Miz1 suppression on TNF induced JNK activation and apoptosis.	SIGNOR-278697
P35222	Q04912	phosphorylation	up-regulates activity	0.327	Ron and beta-catenin associate and Ron kinase activity leads to tyrosine phosphorylation of beta-catenin.\|We also show that tyrosine residues 654 and 670 of beta-catenin are important in mediating Ron induced beta-catenin transcriptional activation and cell growth.	SIGNOR-279376
Q9Y237	P68400	phosphorylation	down-regulates activity	0.326	As proved by MALDI-TOF mass spectrometry and MS/MS fragmentation, hPar14 is phosphorylated at Ser19 in vitro and in vivo. In human HeLa cells the protein is most likely modified by casein kinase 2 (CK2). \|In contrast to wild-type hPar14, the in vitro DNA-binding affinity of the Glu19 mutant is strongly reduced, suggesting that only the dephosphorylated protein is the active DNA-binding form of hPar14 in the nucleus.	SIGNOR-265753
P62256	P17542	transcriptional regulation	up-regulates quantity by expression	0.326	Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.\|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.	SIGNOR-269000
Q05397	P51452	dephosphorylation	down-regulates activity	0.326	Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.\|In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin.	SIGNOR-277033
P37275	P52954	transcriptional regulation	up-regulates quantity by expression	0.326	Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively	SIGNOR-266054
Q9UBK2	Q99608	binding	up-regulates quantity by stabilization	0.326	Necdin binds and stabilizes PGC-1α\|Necdin strongly stabilizes PGC-1α by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration.	SIGNOR-253390
Q9Y6K1	P42229	transcriptional regulation	up-regulates quantity	0.326	… these data suggest that STAT5A positively regulates levels of DNMT3A, resulting in inactivation of tumor suppressor genes by epigenetic mechanisms in AML cells	SIGNOR-255631
Q49MG5	O14965	phosphorylation	up-regulates	0.326	Asap is a novel substrate of the oncogenic mitotic kinase aurora-a: phosphorylation on ser625 is essential to spindle formation and mitosis.	SIGNOR-158210
Q86UR1	P28482	phosphorylation	down-regulates	0.326	These results demonstrated a critical role of noxa1 phosphorylation on ser-282 and ser-172 in preventing nox1 hyperactivation through the decrease of noxa1 interaction to nox1 and rac1.	SIGNOR-163659
P51812	P06241	phosphorylation	up-regulates	0.326	Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529.	SIGNOR-160048
Q16665	P09467	binding	down-regulates activity	0.326	FBP1, but not FBP2, suppresses HIF-1a activity by directly binding to its inhibitory domain.	SIGNOR-267590
Q14005	P68400	phosphorylation	up-regulates activity	0.326	We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. \| Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.	SIGNOR-250905
Q9UNN5	P68400	phosphorylation	down-regulates activity	0.326	We previously identified the Fas-associated factor FAF1 as an in vitro substrate of protein kinase CK2 and determined Ser289 and Ser291 as phosphorylation sites.\|Therefore we assume that CK2‐mediated FAF1 phosphorylation influences the nuclear localization of FAF1 \| it implies that the major function of FAF1 might not be in the cytoplasm as an interacting partner of Fas.	SIGNOR-250864
Q9Y6Q9	Q16877	phosphorylation	up-regulates activity	0.326	PFKFB4, a regulatory enzyme that synthesizes an allosteric stimulator of glycolysis2, was found to be a robust stimulator of SRC-3 that co-activates estrogen receptor (ER). PFKFB4 phosphorylates SRC-3 at serine 857 (S857) enhancing its transcriptional activity, whereas either suppression of PFKFB4 or ectopic expression of a phosphorylation-deficient SRC-3 mutant S857A (SRC-3S857A) significantly abolishes SRC-3-mediated transcriptional output	SIGNOR-267269
P48730	Q6ZRV2	binding	up-regulates quantity	0.326	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273768
O75822	P68400	phosphorylation	up-regulates activity	0.326	CK2 phosphorylates the eIF3j subunit at Ser127. CK2-phosphorylation of eIF3j triggers its association with the eIF3 complex.	SIGNOR-266402
O14503	P63279	polyubiquitination	down-regulates quantity by destabilization	0.326	Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9.	SIGNOR-272579
Q03933	Q13618	ubiquitination	down-regulates quantity by destabilization	0.326	Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2	SIGNOR-239129
P01160	Q15327	transcriptional regulation	down-regulates quantity by repression	0.326	In vitro calpain-mediated degradation assays, coupled to reporter gene analysis in transfected HeLa cells, strongly suggested that this mutation enhances both the stability of the ANKRD1/CARP protein and its transcriptional repression activity upon the cardiac-specific atrial natriuretic factor (ANF) promoter.	SIGNOR-253647
P21817	P17612	phosphorylation	up-regulates activity	0.326	PKA-mediated hyperphosphorylation of a conserved serine, Ser-2843 in skeletal RyR and Ser-2809 in cardiac RyR, results in an aberrant SR function during heart failure. hyperphosphorylated RyRs are leaky and therefore lead to a reduced SR Ca2+ load and impaired contractile function in heart failure	SIGNOR-250078
Q9UJM3	O14757	phosphorylation	down-regulates activity	0.326	Our results suggest that Chk1 phosphorylates Mig-6 on Ser 251, resulting in the inhibition of Mig-6, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1.	SIGNOR-276411
Q93084	P14921	transcriptional regulation	up-regulates quantity by expression	0.326	Ets-1 was able to transactivate the SERCA3 promoter in MoBr 204 as cotransfection of an Ets-1 expression vector increased the activity of the −97/+301-Luc construct by 6-fold.	SIGNOR-261601
Q92777	P17612	phosphorylation	down-regulates activity	0.326	Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I	SIGNOR-250059
Q8IXH7	Q05086	ubiquitination	down-regulates quantity by destabilization	0.326	In this paper, we identify here trihydrophobin 1 (TH1), an integral subunit of the human negative transcription elongation factor (NELF) complex, as a novel E6-AP interaction protein and a target of E6-AP-mediated degradation. Overexpression of E6-AP results in degradation of TH1 in a dose-dependent manner, whereas knock-down of endogenous E6-AP elevates the TH1 protein level.	SIGNOR-271404
Q05639	P15056	phosphorylation	down-regulates quantity by destabilization	0.326	Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf.	SIGNOR-276406
P12755	Q9HAZ2	binding	up-regulates	0.326	Biochemical analysis demonstrated that mel1 interacts with ski and inhibits tgf-_ signaling by stabilizing the inactive smad3-ski complex on the promoter of tgf-_ target genes.	SIGNOR-182529
P20333	Q9HAU4	ubiquitination	up-regulates activity	0.326	However, co-transfection of Smurf2, but not Smurf2-C/A, drastically increased the potential of TNF-R2 to induce JNK phosphorylation.\|In conclusion, these results indicate that Smurf2 is able to ubiquitinate TNF-R2, which is further enhanced by the TRAF2-mediated targeting of Smurf2 to TNF-R2.	SIGNOR-278716
P36888	Q13191	ubiquitination	down-regulates activity	0.326	Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.	SIGNOR-260106
Q14005	P19784	phosphorylation	up-regulates activity	0.326	We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. \| Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.	SIGNOR-251009
Q9Y6K9	Q9H6Z9	binding	down-regulates activity	0.326	Here we report that EGLN3, but not EGLN1 or -2, interacts with and inhibits K63-linked ubiquitination of IKKγ. The effect appears to be related to inhibition of IKKγ ubiquitination mediated by cIAP1 rather than to stimulation of IKKγ deubiquitination by the deubiquitinases A20 and CYLD (cylindromatosis). EGLN3 does not affect the protein levels of cIAP1 or its E2 ubiquitin-conjugating enzymes UbcH5 and Ubc13. EGLN3 hydroxylase activity is not responsible for its effect on IKKγ ubiquitination and NF-κB signaling. Instead, interaction with IKKγ is required for the ability of EGLN3 to inhibit IKKγ ubiquitination and IKK-NF-κB signaling.	SIGNOR-262005
P49915	P19474	ubiquitination	down-regulates	0.326	Cytoplasmic sequestration of gmps requires ubiquitylation by trim21, a ubiquitin ligase associated with autoimmune disease.	SIGNOR-204478
P53041	Q03113	binding	up-regulates activity	0.326	In this study, we show that active forms of Gna12 and Gna13 specifically interact with PP5 through its TPR domain and activate its phosphatase activity about 2.5-fold.	SIGNOR-278080
P53041	Q14344	binding	up-regulates activity	0.326	In this study, we show that active forms of G12 and G13 specifically interact with PP5 through its TPR domain and activate its phosphatase activity about 2.5-fold. Active forms of G12 and G13 also enhance the arachidonic acid-stimulated PP5 phosphatase activity about 2.5-fold.	SIGNOR-278081
Q05397	Q6ZMU5	ubiquitination	down-regulates quantity by destabilization	0.326	Because RING disrupted MG53 mutants (C14A and DeltaR) did not induce FAK ubiquitination and degradation, the RING domain was determined to be required for MG53 induced FAK ubiquitination.	SIGNOR-278648
P17676	Q9UQM7	phosphorylation	up-regulates activity	0.326	These studies implicate Ser276 of CIEBPP as the major in vim phosphorylation site for CaMKII. \| Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.	SIGNOR-250617
Q8TD08	P18031	dephosphorylation	down-regulates	0.326	Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20%	SIGNOR-142981
P52945	O43791	ubiquitination	down-regulates quantity	0.326	Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation.	SIGNOR-268859
P54198	P24941	phosphorylation	up-regulates activity	0.326	Hira bound to and was phosphorylated by cyclin a- and e-cdk2 in vitrohira became phosphorylated on threonine 555 in s phase when cyclin-cdk2 kinases are active.ectopic expression of hira in cells caused arrest in s phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle.	SIGNOR-105548
P35637	P00519	phosphorylation	down-regulates activity	0.325	Abl kinase-mediated FUS Tyr526 phosphorylation alters nucleocytoplasmic FUS localization in FTLD-FUS.	SIGNOR-280168
Q06609	P15374	deubiquitination	up-regulates activity	0.325	Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. \| UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.\|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3.	SIGNOR-275908
P26927	P03952	cleavage	up-regulates activity	0.325	Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. human kallikrein cleaved only at Arg483–Val484, the cleavage site for formation of a- and b-chains.	SIGNOR-256511
P46019	P17612	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267410
P38606	P25490	transcriptional regulation	up-regulates quantity by expression	0.325	We investigated the relationship between transcription factor YY1 and ATP6V1A, and found that mRNA expression of YY1 had significant correlation with that of ATP6V1A. To validate that YY1 transcriptionally regulates ATP6V1A, we discovered that the ATP6V1A core promoter region contains three YY1 binding sites. Moreover, RNAi-mediated knockdown of YY1 in GC cells significantly decreased ATP6V1A mRNA and protein expression, while YY1 overexpression increased ATP6V1A expression level.	SIGNOR-260635
Q9UKX2	Q02078	transcriptional regulation	up-regulates quantity by expression	0.325	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238703
P04062	P19484	transcriptional regulation	up-regulates quantity by expression	0.325	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276551
Q9Y4D1	P12931	phosphorylation	up-regulates activity	0.325	Our findings reveal a novel mechanism by which reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulates actin dynamics and lung cancer invasiveness.\|PTPN3 suppresses lung cancer cell invasiveness by counteracting Src mediated DAAM1 activation and actin polymerization.	SIGNOR-280128
Q9NQB0	Q8WVD3	polyubiquitination	down-regulates quantity by destabilization	0.325	Here, we show that NARF induces the ubiquitylation of TCF/LEF in vitro and in vivo, and functions as an E3 ubiquitin-ligase that specifically cooperates with the E2 conjugating enzyme E2-25K. We found that NLK augmented NARF binding and ubiquitylation of TCF/LEF, and this required NLK kinase activity. The ubiquitylated TCF/LEF was subsequently degraded by the proteasome.	SIGNOR-271593
Q99683	Q5S007	phosphorylation	up-regulates activity	0.325	LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site.	SIGNOR-277251
P16220	Q15796	binding	up-regulates	0.325	We demonstrate that human smad2 and smad4, two essential smad proteins involved in mediating tgf-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator creb binding protein (cbp). This interaction is specific in that it requires ligand (tgf-beta) activation and is mediated by the transcriptional activation domains of the smad proteins.	SIGNOR-59462
P06241	P17706	dephosphorylation	down-regulates	0.325	Previously, we reported that sfks can serve as bona fide substrates for tcptp and that tcptp dephosphorylates the y418 activation loop autophosphorylation site (corresponding to y394 in lck and y417 in fyn) to inactivate sfks	SIGNOR-177113
P46020	P22612	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267415
P48736	P21860	binding	up-regulates	0.325	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146870
Q96JC1	P37173	binding	up-regulates activity	0.325	TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling.	SIGNOR-261374
Q03933	P35227	sumoylation	down-regulates activity	0.325	MEL-18, in contrast to the polycomb protein PC2/CBX4, in which SUMO E3 activity stimulates sumoylation of certain proteins, actually functions like an anti-SUMO E3 protein, interacting with both HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity and thereby decreasing sumoylation of a target protein, in this case that of HSF2. sumoylation of HSF2 is up-regulated during mitosis and is important for the interaction of this factor with a subunit of the condensin complex during the bookmarking process	SIGNOR-226245
Q13330	O75364	binding	up-regulates activity	0.325	we found that the MTA1/DJ1 complex is required for optimum stimulation of the TH expression by paired like homeodomain transcription factor (Pitx3) homeodomain transcription factor and that the MTA1/DJ1 complex is recruited to the TH gene chromatin via the direct interaction of MTA1 with Pitx3.	SIGNOR-239770
Q8WXX7	O15409	transcriptional regulation	up-regulates quantity by expression	0.325	By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.	SIGNOR-266832
Q9UQD0	Q96PU5	ubiquitination	down-regulates quantity by destabilization	0.325	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253461
Q92905	O15111	phosphorylation	down-regulates activity	0.325	Overexpression of IKKalpha or IKKbeta leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro.	SIGNOR-275507
Q9NZQ7	O43791	ubiquitination	down-regulates quantity	0.325	Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumor-infiltrating lymphocytes (TILs) in mouse tumors and in primary human prostate cancer specimens.	SIGNOR-274978
Q86YT6	Q00535	phosphorylation	up-regulates activity	0.325	Similar to the mechanism of PAR-1 regulation of Mib in neurogenesis, CDK5 phosphorylation is proposed to enhance Mib1 ligase activity leading to destabilization.\|The cyclin dependent kinase 5 (CDK5) enriched in neurons phosphorylates Mib1 and suppresses the inhibitory effects of Mib1 on neurite morphology.	SIGNOR-280217
P07948	Q16827	dephosphorylation	down-regulates activity	0.325	Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.\|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib.	SIGNOR-277144
Q9UKW4	P12931	phosphorylation	up-regulates	0.325	Activation of rac1 and the exchange factor vav3 are involved in npm-alk signaling in anaplastic large cell lymphomas.	SIGNOR-159240
Q16665	Q9P0U3	desumoylation	up-regulates	0.325	Sumo-specific protease 1 is essential for stabilization of hif1alpha during hypoxia / our results support a model in which sumoylated hif1_ is unstable but can be stabilized when sumo is removed by senp1	SIGNOR-158891
P23769	O60216	relocalization	down-regulates activity	0.325	Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity.	SIGNOR-261513
O15524	P29350	binding	up-regulates	0.325	All together, our results indicate that shp-1 inhibits prlr and epor signaling by recruitment and targeting of socs-1 to jak2, highlighting a new mechanism of shp-1 regulation of cytokine-receptor signaling.	SIGNOR-118572
P10721	Q9NX45	transcriptional regulation	up-regulates quantity by expression	0.325	Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression.	SIGNOR-266206
Q96RI1	P17252	phosphorylation	up-regulates	0.325	Phosphorylation of farnesoid x receptor by protein kinase c promotes its transcriptional activity. pkcalpha phosphorylates in vitro fxr in its dna-binding domain on s135 and s154.	SIGNOR-180537
Q92888	O60674	phosphorylation	up-regulates	0.325	We found that angiotensin ii activates arhgef1 through a previously undescribed mechanism in which jak2 phosphorylates tyr738 of arhgef1	SIGNOR-163557
P46019	P22612	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267414
Q14653	Q9BYM8	polyubiquitination	down-regulates quantity by destabilization	0.325	Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. We transfected 293 cells with expression plasmids for Flag-IRF3, HA-ubiquitin, and HA-RBCK1. Coimmunoprecipitation and western blot analysis indicated that RBCK1 significantly polyubiquitinated IRF3 (Figure 4D).	SIGNOR-271737
P46019	P22694	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267412
P08183	O94952	binding	down-regulates quantity by destabilization	0.325	Here we demonstrate that a ubiquitin E3-ligase, FBXO21, targets the multidrug resistance transporter, ABCB1, also known as P-glycoprotein (P-gp), for proteasomal degradation.Purified in vitro translated FLAG-tagged P-gp along with E2 (UbcH5c), E3 ligase FBXO21, Cul1, Skp1, Roc1 purified from Sf-9 insect cells were incubated in vitro.	SIGNOR-272422
P46020	P22694	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267413
Q9H4G4	P51617	phosphorylation	up-regulates activity	0.325	We found that TIRAP-MyD88 dependent kinase IRAK1 phosphorylated GAPR-1 at Serine 58 site. The phosphorylation of GAPR-1 promoted its interaction with TRAM-TRIF dependent inhibitor TMED7, and impaired TMED7-mediated disruption of the TRAM-TRIF complex to trigger IFN-β and the IL10 secretion.	SIGNOR-262887
Q17RY0	P28482	phosphorylation	up-regulates activity	0.325	Our results indicate that CPEB4 activation is driven by ERK2- and Cdk1 mediated hyperphosphorylation of at least 12 residues in the intrinsically disordered NTD.\|We concluded that, in interphase, unphosphorylated CPEB4 phase separates into liquid like droplets that recruit mRNAs but are inactive for cytoplasmic polyadenylation and translation, whereas in M-phase, CPEB4 is phosphorylated by ERK2 and Cdk1 and recovers its monomeric form, which can drive the cytoplasmic polyadenylation of target mRNAs.	SIGNOR-280021
Q96PH1	P28482	phosphorylation	up-regulates	0.325	These results suggest that the mek/erk1/2 pathway is necessary but not sufficient to regulate the pma-dependent activation of nox5.	SIGNOR-171847
Q04206	Q15034	ubiquitination	down-regulates quantity by destabilization	0.325	Our data so far suggest that HERC3 reduces NF-kappaB transcriptional activity by binding to the proteasome and delivering RelA for degradation.\|We show that HERC3 mediates ubiquitination of RelA on two distinct lysine residues, K195 and K315.	SIGNOR-278546
Q9UNZ2	P06493	phosphorylation	down-regulates activity	0.325	Now, we have found that p47, which mainly localizes to the nucleus during interphase, is phosphorylated on serine-140 by cdc2 at mitosis. The phosphorylated p47 does not bind to golgi membranes.	SIGNOR-102350
O60282	Q9Y3R0	binding	up-regulates activity	0.324	HAP1 and GRIP1 are kinesin-1 adaptors that have been implicated individually in the transport of vesicular cargoes in the dendrites of neurons. We find that HAP1a and GRIP1 form a protein complex in the brain, and co-operate to activate the kinesin-1 subunit KIF5C in vitro	SIGNOR-264061
P17302	P17706	dephosphorylation	up-regulates	0.324	Tc-ptp dephosphorylates cx43 residues y247 and y265, dephosphorylation maintained cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-src-mediated phosphorylation of cx43.	SIGNOR-205101
Q15643	P06400	binding	down-regulates	0.324	The wild-type rb is able to interact with the rb-binding domain of trip230 / rb represses trip230-mediated activation of tr-regulated transcription.	SIGNOR-50266
Q9UKT4	P12931	phosphorylation	up-regulates	0.324	We found that emi1 stability was regulated by phosphorylation and mutation of tyrosine 142 reduced the stability. Our data suggested bcr-abl-induced emi1 phosphorylation might be mediated by src kinase.	SIGNOR-167529
O43526	P17252	phosphorylation	up-regulates activity	0.324	Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. \| These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process.	SIGNOR-249209
P51674	P17252	phosphorylation	up-regulates activity	0.324	In summary, a CNS neuron-specific membrane glycoprotein, M6a, could act as a novel NGF-gated Ca2+ channel through the phosphorylation with PKC and augments [Ca2+]i in M6a-S cells.	SIGNOR-263163
Q07954	P17612	phosphorylation	up-regulates activity	0.324	LRP phosphorylation is mediated by PKA at residue serine 76 of its cytoplasmic tail and that this phosphorylation contributes to receptor-mediated endocytosis.	SIGNOR-250000
Q9HC16	P17612	phosphorylation	up-regulates	0.324	Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.	SIGNOR-181526
Q15011	Q7Z6J0	ubiquitination	up-regulates activity	0.324	Upon TG induced ER calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the ER .\|Upon thapsigargin-induced endoplasmic reticulum calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the endoplasmic reticulum .	SIGNOR-278779
P37173	Q13347	binding	up-regulates	0.324	Another receptor-associated protein is trip-1, which interacts with and is phosphorylated by tbrii and contains five wd-40 repeats. The association of wd-40 repeat proteins may then allow them to play a role in signaling by the serine/threonine kinase receptors.	SIGNOR-60700

Q00653

Q99576

0

binding

down-regulates activity

0.327

GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits.

SIGNOR-253298

Q9UQB3

Q00535

0

phosphorylation

up-regulates activity

0.327

Cdk5 mediated delta-catenin phosphorylation regulates delta-catenin subcellular localization into two distinct pools : a cytoplasmic or intraneurite state as well as a pool that is localized to the membrane.|Cdk5 phosphorylates delta-catenin on serines 300 and 357.

SIGNOR-279323

Q9UKX2

Q14814

0

transcriptional regulation

up-regulates quantity by expression

0.327

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238712

Q13769

P17252

0

phosphorylation

up-regulates

0.327

We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling.

SIGNOR-126572

O75553

Q93034

0

polyubiquitination

down-regulates quantity by destabilization

0.327

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-272140

P42658

Q9UBC3

0

transcriptional regulation

down-regulates quantity by repression

0.327

Dnmt3b was responsible for transcriptional silencing of Dpp6 gene as depletion of Dnmt3b resulted in increased mRNA and protein expression of Dpp6.

SIGNOR-268963

P49840

P05771

0

phosphorylation

down-regulates

0.327

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115718

P08237

P01106

0

transcriptional regulation

up-regulates quantity

0.327

C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.

SIGNOR-259988

P42226

P18031

0

dephosphorylation

down-regulates activity

0.327

Phosphorylated STAT6 may also serve as a cytoplasmic substrate for PTP1B since overexpression of PTP1B leads to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B deficiency increases IL-4-induced STAT6 signaling in B-cells.

SIGNOR-277122

Q8N122

Q9UBE8

0

phosphorylation

down-regulates activity

0.327

NLK inhibits mTORC1 lysosomal localization and thereby suppresses mTORC1 activation. Mechanistically, NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment.

SIGNOR-273908

P13796

P17612

0

phosphorylation

up-regulates

0.327

Phosphorylation on ser5 increases the f-actin-binding activity of l-plastin and promotes its targeting to sites of actin assembly in cells. L-plastin phosphorylation require protein kinase a.

SIGNOR-146287

Q13105

Q7Z6Z7

0

ubiquitination

down-regulates quantity by destabilization

0.327

Previously, we reported that K48 linked polyubiquitination of Miz1 by Mule triggers its proteasomal degradation, thereby relieving Miz1 suppression on TNF induced JNK activation and apoptosis.

SIGNOR-278697

P35222

Q04912

0

phosphorylation

up-regulates activity

0.327

Ron and beta-catenin associate and Ron kinase activity leads to tyrosine phosphorylation of beta-catenin.|We also show that tyrosine residues 654 and 670 of beta-catenin are important in mediating Ron induced beta-catenin transcriptional activation and cell growth.

SIGNOR-279376

Q9Y237

P68400

0

phosphorylation

down-regulates activity

0.326

As proved by MALDI-TOF mass spectrometry and MS/MS fragmentation, hPar14 is phosphorylated at Ser19 in vitro and in vivo. In human HeLa cells the protein is most likely modified by casein kinase 2 (CK2). |In contrast to wild-type hPar14, the in vitro DNA-binding affinity of the Glu19 mutant is strongly reduced, suggesting that only the dephosphorylated protein is the active DNA-binding form of hPar14 in the nucleus.

SIGNOR-265753

P62256

P17542

0

transcriptional regulation

up-regulates quantity by expression

0.326

Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.

SIGNOR-269000

Q05397

P51452

0

dephosphorylation

down-regulates activity

0.326

Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.|In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin.

SIGNOR-277033

P37275

P52954

0

transcriptional regulation

up-regulates quantity by expression

0.326

Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively

SIGNOR-266054

Q9UBK2

Q99608

0

binding

up-regulates quantity by stabilization

0.326

Necdin binds and stabilizes PGC-1α|Necdin strongly stabilizes PGC-1α by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration.

SIGNOR-253390

Q9Y6K1

P42229

0

transcriptional regulation

up-regulates quantity

0.326

… these data suggest that STAT5A positively regulates levels of DNMT3A, resulting in inactivation of tumor suppressor genes by epigenetic mechanisms in AML cells

SIGNOR-255631

Q49MG5

O14965

0

phosphorylation

up-regulates

0.326

Asap is a novel substrate of the oncogenic mitotic kinase aurora-a: phosphorylation on ser625 is essential to spindle formation and mitosis.

SIGNOR-158210

Q86UR1

P28482

0

phosphorylation

down-regulates

0.326

These results demonstrated a critical role of noxa1 phosphorylation on ser-282 and ser-172 in preventing nox1 hyperactivation through the decrease of noxa1 interaction to nox1 and rac1.

SIGNOR-163659

P51812

P06241

0

phosphorylation

up-regulates

0.326

Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529.

SIGNOR-160048

Q16665

P09467

0

binding

down-regulates activity

0.326

FBP1, but not FBP2, suppresses HIF-1a activity by directly binding to its inhibitory domain.

SIGNOR-267590

Q14005

P68400

0

phosphorylation

up-regulates activity

0.326

We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.

SIGNOR-250905

Q9UNN5

P68400

0

phosphorylation

down-regulates activity

0.326

We previously identified the Fas-associated factor FAF1 as an in vitro substrate of protein kinase CK2 and determined Ser289 and Ser291 as phosphorylation sites.|Therefore we assume that CK2‐mediated FAF1 phosphorylation influences the nuclear localization of FAF1 | it implies that the major function of FAF1 might not be in the cytoplasm as an interacting partner of Fas.

SIGNOR-250864

Q9Y6Q9

Q16877

0

phosphorylation

up-regulates activity

0.326

PFKFB4, a regulatory enzyme that synthesizes an allosteric stimulator of glycolysis2, was found to be a robust stimulator of SRC-3 that co-activates estrogen receptor (ER). PFKFB4 phosphorylates SRC-3 at serine 857 (S857) enhancing its transcriptional activity, whereas either suppression of PFKFB4 or ectopic expression of a phosphorylation-deficient SRC-3 mutant S857A (SRC-3S857A) significantly abolishes SRC-3-mediated transcriptional output

SIGNOR-267269

P48730

Q6ZRV2

0

binding

up-regulates quantity

0.326

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

SIGNOR-273768

O75822

P68400

0

phosphorylation

up-regulates activity

0.326

CK2 phosphorylates the eIF3j subunit at Ser127. CK2-phosphorylation of eIF3j triggers its association with the eIF3 complex.

SIGNOR-266402

O14503

P63279

0

polyubiquitination

down-regulates quantity by destabilization

0.326

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

SIGNOR-272579

Q03933

Q13618

0

ubiquitination

down-regulates quantity by destabilization

0.326

Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2

SIGNOR-239129

P01160

Q15327

0

transcriptional regulation

down-regulates quantity by repression

0.326

In vitro calpain-mediated degradation assays, coupled to reporter gene analysis in transfected HeLa cells, strongly suggested that this mutation enhances both the stability of the ANKRD1/CARP protein and its transcriptional repression activity upon the cardiac-specific atrial natriuretic factor (ANF) promoter.

SIGNOR-253647

P21817

P17612

0

phosphorylation

up-regulates activity

0.326

PKA-mediated hyperphosphorylation of a conserved serine, Ser-2843 in skeletal RyR and Ser-2809 in cardiac RyR, results in an aberrant SR function during heart failure. hyperphosphorylated RyRs are leaky and therefore lead to a reduced SR Ca2+ load and impaired contractile function in heart failure

SIGNOR-250078

Q9UJM3

O14757

0

phosphorylation

down-regulates activity

0.326

Our results suggest that Chk1 phosphorylates Mig-6 on Ser 251, resulting in the inhibition of Mig-6, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1.

SIGNOR-276411

Q93084

P14921

0

transcriptional regulation

up-regulates quantity by expression

0.326

Ets-1 was able to transactivate the SERCA3 promoter in MoBr 204 as cotransfection of an Ets-1 expression vector increased the activity of the −97/+301-Luc construct by 6-fold.

SIGNOR-261601

Q92777

P17612

0

phosphorylation

down-regulates activity

0.326

Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I

SIGNOR-250059

Q8IXH7

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.326

In this paper, we identify here trihydrophobin 1 (TH1), an integral subunit of the human negative transcription elongation factor (NELF) complex, as a novel E6-AP interaction protein and a target of E6-AP-mediated degradation. Overexpression of E6-AP results in degradation of TH1 in a dose-dependent manner, whereas knock-down of endogenous E6-AP elevates the TH1 protein level.

SIGNOR-271404

Q05639

P15056

0

phosphorylation

down-regulates quantity by destabilization

0.326

Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf.

SIGNOR-276406

P12755

Q9HAZ2

0

binding

up-regulates

0.326

Biochemical analysis demonstrated that mel1 interacts with ski and inhibits tgf-_ signaling by stabilizing the inactive smad3-ski complex on the promoter of tgf-_ target genes.

SIGNOR-182529

P20333

Q9HAU4

0

ubiquitination

up-regulates activity

0.326

However, co-transfection of Smurf2, but not Smurf2-C/A, drastically increased the potential of TNF-R2 to induce JNK phosphorylation.|In conclusion, these results indicate that Smurf2 is able to ubiquitinate TNF-R2, which is further enhanced by the TRAF2-mediated targeting of Smurf2 to TNF-R2.

SIGNOR-278716

P36888

Q13191

0

ubiquitination

down-regulates activity

0.326

Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.

SIGNOR-260106

Q14005

P19784

0

phosphorylation

up-regulates activity

0.326

We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.

SIGNOR-251009

Q9Y6K9

Q9H6Z9

0

binding

down-regulates activity

0.326

Here we report that EGLN3, but not EGLN1 or -2, interacts with and inhibits K63-linked ubiquitination of IKKγ. The effect appears to be related to inhibition of IKKγ ubiquitination mediated by cIAP1 rather than to stimulation of IKKγ deubiquitination by the deubiquitinases A20 and CYLD (cylindromatosis). EGLN3 does not affect the protein levels of cIAP1 or its E2 ubiquitin-conjugating enzymes UbcH5 and Ubc13. EGLN3 hydroxylase activity is not responsible for its effect on IKKγ ubiquitination and NF-κB signaling. Instead, interaction with IKKγ is required for the ability of EGLN3 to inhibit IKKγ ubiquitination and IKK-NF-κB signaling.

SIGNOR-262005

P49915

P19474

0

ubiquitination

down-regulates

0.326

Cytoplasmic sequestration of gmps requires ubiquitylation by trim21, a ubiquitin ligase associated with autoimmune disease.

SIGNOR-204478

P53041

Q03113

0

binding

up-regulates activity

0.326

In this study, we show that active forms of Gna12 and Gna13 specifically interact with PP5 through its TPR domain and activate its phosphatase activity about 2.5-fold.

SIGNOR-278080

P53041

Q14344

0

binding

up-regulates activity

0.326

In this study, we show that active forms of G12 and G13 specifically interact with PP5 through its TPR domain and activate its phosphatase activity about 2.5-fold. Active forms of G12 and G13 also enhance the arachidonic acid-stimulated PP5 phosphatase activity about 2.5-fold.

SIGNOR-278081

Q05397

Q6ZMU5

0

ubiquitination

down-regulates quantity by destabilization

0.326

Because RING disrupted MG53 mutants (C14A and DeltaR) did not induce FAK ubiquitination and degradation, the RING domain was determined to be required for MG53 induced FAK ubiquitination.

SIGNOR-278648

P17676

Q9UQM7

0

phosphorylation

up-regulates activity

0.326

These studies implicate Ser276 of CIEBPP as the major in vim phosphorylation site for CaMKII. | Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.

SIGNOR-250617

Q8TD08

P18031

0

dephosphorylation

down-regulates

0.326

Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20%

SIGNOR-142981

P52945

O43791

0

ubiquitination

down-regulates quantity

0.326

Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation.

SIGNOR-268859

P54198

P24941

0

phosphorylation

up-regulates activity

0.326

Hira bound to and was phosphorylated by cyclin a- and e-cdk2 in vitrohira became phosphorylated on threonine 555 in s phase when cyclin-cdk2 kinases are active.ectopic expression of hira in cells caused arrest in s phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle.

SIGNOR-105548

P35637

P00519

0

phosphorylation

down-regulates activity

0.325

Abl kinase-mediated FUS Tyr526 phosphorylation alters nucleocytoplasmic FUS localization in FTLD-FUS.

SIGNOR-280168

Q06609

P15374

0

deubiquitination

up-regulates activity

0.325

Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. | UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3.

SIGNOR-275908

P26927

P03952

0

cleavage

up-regulates activity

0.325

Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. human kallikrein cleaved only at Arg483–Val484, the cleavage site for formation of a- and b-chains.

SIGNOR-256511

P46019

P17612

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267410

P38606

P25490

0

transcriptional regulation

up-regulates quantity by expression

0.325

We investigated the relationship between transcription factor YY1 and ATP6V1A, and found that mRNA expression of YY1 had significant correlation with that of ATP6V1A. To validate that YY1 transcriptionally regulates ATP6V1A, we discovered that the ATP6V1A core promoter region contains three YY1 binding sites. Moreover, RNAi-mediated knockdown of YY1 in GC cells significantly decreased ATP6V1A mRNA and protein expression, while YY1 overexpression increased ATP6V1A expression level.

SIGNOR-260635

Q9UKX2

Q02078

0

transcriptional regulation

up-regulates quantity by expression

0.325

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238703

P04062

P19484

0

transcriptional regulation

up-regulates quantity by expression

0.325

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276551

Q9Y4D1

P12931

0

phosphorylation

up-regulates activity

0.325

Our findings reveal a novel mechanism by which reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulates actin dynamics and lung cancer invasiveness.|PTPN3 suppresses lung cancer cell invasiveness by counteracting Src mediated DAAM1 activation and actin polymerization.

SIGNOR-280128

Q9NQB0

Q8WVD3

0

polyubiquitination

down-regulates quantity by destabilization

0.325

Here, we show that NARF induces the ubiquitylation of TCF/LEF in vitro and in vivo, and functions as an E3 ubiquitin-ligase that specifically cooperates with the E2 conjugating enzyme E2-25K. We found that NLK augmented NARF binding and ubiquitylation of TCF/LEF, and this required NLK kinase activity. The ubiquitylated TCF/LEF was subsequently degraded by the proteasome.

SIGNOR-271593

Q99683

Q5S007

0

phosphorylation

up-regulates activity

0.325

LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site.

SIGNOR-277251

P16220

Q15796

0

binding

up-regulates

0.325

We demonstrate that human smad2 and smad4, two essential smad proteins involved in mediating tgf-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator creb binding protein (cbp). This interaction is specific in that it requires ligand (tgf-beta) activation and is mediated by the transcriptional activation domains of the smad proteins.

SIGNOR-59462

P06241

P17706

0

dephosphorylation

down-regulates

0.325

Previously, we reported that sfks can serve as bona fide substrates for tcptp and that tcptp dephosphorylates the y418 activation loop autophosphorylation site (corresponding to y394 in lck and y417 in fyn) to inactivate sfks

SIGNOR-177113

P46020

P22612

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267415

P48736

P21860

0

binding

up-regulates

0.325

Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.

SIGNOR-146870

Q96JC1

P37173

0

binding

up-regulates activity

0.325

TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling.

SIGNOR-261374

Q03933

P35227

0

sumoylation

down-regulates activity

0.325

MEL-18, in contrast to the polycomb protein PC2/CBX4, in which SUMO E3 activity stimulates sumoylation of certain proteins, actually functions like an anti-SUMO E3 protein, interacting with both HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity and thereby decreasing sumoylation of a target protein, in this case that of HSF2. sumoylation of HSF2 is up-regulated during mitosis and is important for the interaction of this factor with a subunit of the condensin complex during the bookmarking process

SIGNOR-226245

Q13330

O75364

0

binding

up-regulates activity

0.325

we found that the MTA1/DJ1 complex is required for optimum stimulation of the TH expression by paired like homeodomain transcription factor (Pitx3) homeodomain transcription factor and that the MTA1/DJ1 complex is recruited to the TH gene chromatin via the direct interaction of MTA1 with Pitx3.

SIGNOR-239770

Q8WXX7

O15409

0

transcriptional regulation

up-regulates quantity by expression

0.325

By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.

SIGNOR-266832

Q9UQD0

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.325

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253461

Q92905

O15111

0

phosphorylation

down-regulates activity

0.325

Overexpression of IKKalpha or IKKbeta leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro.

SIGNOR-275507

Q9NZQ7

O43791

0

ubiquitination

down-regulates quantity

0.325

Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumor-infiltrating lymphocytes (TILs) in mouse tumors and in primary human prostate cancer specimens.

SIGNOR-274978

Q86YT6

Q00535

0

phosphorylation

up-regulates activity

0.325

Similar to the mechanism of PAR-1 regulation of Mib in neurogenesis, CDK5 phosphorylation is proposed to enhance Mib1 ligase activity leading to destabilization.|The cyclin dependent kinase 5 (CDK5) enriched in neurons phosphorylates Mib1 and suppresses the inhibitory effects of Mib1 on neurite morphology.

SIGNOR-280217

P07948

Q16827

0

dephosphorylation

down-regulates activity

0.325

Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib.

SIGNOR-277144

Q9UKW4

P12931

0

phosphorylation

up-regulates

0.325

Activation of rac1 and the exchange factor vav3 are involved in npm-alk signaling in anaplastic large cell lymphomas.

SIGNOR-159240

Q16665

Q9P0U3

0

desumoylation

up-regulates

0.325

Sumo-specific protease 1 is essential for stabilization of hif1alpha during hypoxia / our results support a model in which sumoylated hif1_ is unstable but can be stabilized when sumo is removed by senp1

SIGNOR-158891

P23769

O60216

0

relocalization

down-regulates activity

0.325

Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity.

SIGNOR-261513

O15524

P29350

0

binding

up-regulates

0.325

All together, our results indicate that shp-1 inhibits prlr and epor signaling by recruitment and targeting of socs-1 to jak2, highlighting a new mechanism of shp-1 regulation of cytokine-receptor signaling.

SIGNOR-118572

P10721

Q9NX45

0

transcriptional regulation

up-regulates quantity by expression

0.325

Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression.

SIGNOR-266206

Q96RI1

P17252

0

phosphorylation

up-regulates

0.325

Phosphorylation of farnesoid x receptor by protein kinase c promotes its transcriptional activity. pkcalpha phosphorylates in vitro fxr in its dna-binding domain on s135 and s154.

SIGNOR-180537

Q92888

O60674

0

phosphorylation

up-regulates

0.325

We found that angiotensin ii activates arhgef1 through a previously undescribed mechanism in which jak2 phosphorylates tyr738 of arhgef1

SIGNOR-163557

P46019

P22612

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267414

Q14653

Q9BYM8

0

polyubiquitination

down-regulates quantity by destabilization

0.325

Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. We transfected 293 cells with expression plasmids for Flag-IRF3, HA-ubiquitin, and HA-RBCK1. Coimmunoprecipitation and western blot analysis indicated that RBCK1 significantly polyubiquitinated IRF3 (Figure 4D).

SIGNOR-271737

P46019

P22694

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267412

P08183

O94952

0

binding

down-regulates quantity by destabilization

0.325

Here we demonstrate that a ubiquitin E3-ligase, FBXO21, targets the multidrug resistance transporter, ABCB1, also known as P-glycoprotein (P-gp), for proteasomal degradation.Purified in vitro translated FLAG-tagged P-gp along with E2 (UbcH5c), E3 ligase FBXO21, Cul1, Skp1, Roc1 purified from Sf-9 insect cells were incubated in vitro.

SIGNOR-272422

P46020

P22694

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267413

Q9H4G4

P51617

0

phosphorylation

up-regulates activity

0.325

We found that TIRAP-MyD88 dependent kinase IRAK1 phosphorylated GAPR-1 at Serine 58 site. The phosphorylation of GAPR-1 promoted its interaction with TRAM-TRIF dependent inhibitor TMED7, and impaired TMED7-mediated disruption of the TRAM-TRIF complex to trigger IFN-β and the IL10 secretion.

SIGNOR-262887

Q17RY0

P28482

0

phosphorylation

up-regulates activity

0.325

Our results indicate that CPEB4 activation is driven by ERK2- and Cdk1 mediated hyperphosphorylation of at least 12 residues in the intrinsically disordered NTD.|We concluded that, in interphase, unphosphorylated CPEB4 phase separates into liquid like droplets that recruit mRNAs but are inactive for cytoplasmic polyadenylation and translation, whereas in M-phase, CPEB4 is phosphorylated by ERK2 and Cdk1 and recovers its monomeric form, which can drive the cytoplasmic polyadenylation of target mRNAs.

SIGNOR-280021

Q96PH1

P28482

0

phosphorylation

up-regulates

0.325

These results suggest that the mek/erk1/2 pathway is necessary but not sufficient to regulate the pma-dependent activation of nox5.

SIGNOR-171847

Q04206

Q15034

0

ubiquitination

down-regulates quantity by destabilization

0.325

Our data so far suggest that HERC3 reduces NF-kappaB transcriptional activity by binding to the proteasome and delivering RelA for degradation.|We show that HERC3 mediates ubiquitination of RelA on two distinct lysine residues, K195 and K315.

SIGNOR-278546

Q9UNZ2

P06493

0

phosphorylation

down-regulates activity

0.325

Now, we have found that p47, which mainly localizes to the nucleus during interphase, is phosphorylated on serine-140 by cdc2 at mitosis. The phosphorylated p47 does not bind to golgi membranes.

SIGNOR-102350

O60282

Q9Y3R0

0

binding

up-regulates activity

0.324

HAP1 and GRIP1 are kinesin-1 adaptors that have been implicated individually in the transport of vesicular cargoes in the dendrites of neurons. We find that HAP1a and GRIP1 form a protein complex in the brain, and co-operate to activate the kinesin-1 subunit KIF5C in vitro

SIGNOR-264061

P17302

P17706

0

dephosphorylation

up-regulates

0.324

Tc-ptp dephosphorylates cx43 residues y247 and y265, dephosphorylation maintained cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-src-mediated phosphorylation of cx43.

SIGNOR-205101

Q15643

P06400

0

binding

down-regulates

0.324

The wild-type rb is able to interact with the rb-binding domain of trip230 / rb represses trip230-mediated activation of tr-regulated transcription.

SIGNOR-50266

Q9UKT4

P12931

0

phosphorylation

up-regulates

0.324

We found that emi1 stability was regulated by phosphorylation and mutation of tyrosine 142 reduced the stability. Our data suggested bcr-abl-induced emi1 phosphorylation might be mediated by src kinase.

SIGNOR-167529

O43526

P17252

0

phosphorylation

up-regulates activity

0.324

Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. | These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process.

SIGNOR-249209

P51674

P17252

0

phosphorylation

up-regulates activity

0.324

In summary, a CNS neuron-specific membrane glycoprotein, M6a, could act as a novel NGF-gated Ca2+ channel through the phosphorylation with PKC and augments [Ca2+]i in M6a-S cells.

SIGNOR-263163

Q07954

P17612

0

phosphorylation

up-regulates activity

0.324

LRP phosphorylation is mediated by PKA at residue serine 76 of its cytoplasmic tail and that this phosphorylation contributes to receptor-mediated endocytosis.

SIGNOR-250000

Q9HC16

P17612

0

phosphorylation

up-regulates

0.324

Here we show that pka binds and specifically phosphorylates a3g at thr32 in vitro and in vivo. This phosphorylation event reduces the binding of a3g to vif and its subsequent ubiquitination and degradation, and thus promotes a3g antiviral activity.

SIGNOR-181526

Q15011

Q7Z6J0

0

ubiquitination

up-regulates activity

0.324

Upon TG induced ER calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the ER .|Upon thapsigargin-induced endoplasmic reticulum calcium store depletion, POSH promotes Herp lys-63-linked polyubiquitination, which in turn promotes the redistribution of Herp to the endoplasmic reticulum .

SIGNOR-278779

P37173

Q13347

0

binding

up-regulates

0.324

Another receptor-associated protein is trip-1, which interacts with and is phosphorylated by tbrii and contains five wd-40 repeats. The association of wd-40 repeat proteins may then allow them to play a role in signaling by the serine/threonine kinase receptors.

SIGNOR-60700