GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q13315	P54132	1	phosphorylation	up-regulates	0.775	Mitotic phosphorylation of blm was partially dependent on atm, and phosphorylation sites on blm were identified. A phosphospecific antibody against one of these sites (thr-99) revealed radiation-induced phosphorylation, which was defective in ataxia-telangiectasia cells. These data suggest that atm and blm function together in recognizing abnormal dna structures by direct interaction and that these phosphorylation sites in blm are important for radiosensitivity status but not for sce frequency.	SIGNOR-88010
P52735	P00533	2	binding	up-regulates	0.592	Oligomerization of receptor protein tyrosine kinases such as the epidermal growth factor receptor (egfr) by their cognate ligands leads to activation of the receptor.We Demonstrate that vav-2 is phosphorylated on tyrosine residues in response to egf and associates with the egfr in vivo.	SIGNOR-73874
P20226	P28360	2	binding	down-regulates activity	0.397	Msx-1 is a potent transcriptional repressor and that this activity is independent of its DNA binding function. Here we show that Msx-1 interacts directly with the TATA binding protein (TBP) but not with several other general transcription factors. This interaction is mediated by the Msx-1 homeodomain, specifically through residues in the N-terminal arm. These same N-terminal arm residues are required for repression by Msx-1, suggesting a functional relationship between TBP association and transcriptional repression.	SIGNOR-240401
P05019	P20823	0	transcriptional regulation	up-regulates quantity by expression	0.301	Growth hormone induces insulin-like growth factor-I gene transcription by a synergistic action of STAT5 and HNF-1α	SIGNOR-251720
Q9Y6Q9	P48730	0	phosphorylation	up-regulates	0.284	In this study, we show that both eralpha and aib1 are substrates for ck1delta in vitro, and identify a novel aib1 phosphorylation site (s601) targeted by ck1delta, significant for the co-activator function of aib1.	SIGNOR-184946
Q9P0K8	Q9HC98	0	phosphorylation	up-regulates activity	0.2	Additionally, we found that NEK6 phosphorylated FOXJ2 at Thr23 and Ser254 ( xref , lanes 3 and 5), and NCOA5 at Ser21 and Ser151 ( xref , lanes 3 and 4).	SIGNOR-278965
P17612	P63252	1	phosphorylation	down-regulates activity	0.2	PKA consensus site S425 required for PKA-mediated effects on Kir2.1 channels. PKA activation reduced outward IK1 for heteromeric Kir2.1 WT+V227F channels after 2 hours of PKA activation.	SIGNOR-276267
Q9UQM7	Q05469	1	phosphorylation	down-regulates	0.2	Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.	SIGNOR-58251
O60462	Q13214	2	binding	up-regulates activity	0.59	Further examination of the composition of the functional Sema3B receptor revealed that, unlike Sema3A, which signals exclusively using the NP1 receptor, Sema3B utilizes both NP1 and NP2 for signal transduction.	SIGNOR-261816
P32019	P20339	2	binding	up-regulates activity	0.447	We report that Rab5 acts at the plasma membrane, downstream of ruffling, to promote macropinosome sealing and scission. Rab5 is recruited to plasmalemmal circular ruffles before macropinosome closure. Rab5 effectors Inpp5b, OCRL and APPL1 localize to macropinocytic cups and vesicles, and are required for macropinosome sealing. The mammalian 5-phosphatases Inpp5b and OCRL, which can degrade PtdIns(4,5)P2, are both Rab5-associating effectors implicated in endocytosis and macropinocytosis	SIGNOR-277770
O14757	P49593	0	dephosphorylation	down-regulates activity	0.2	As a result, inactivation of Chk1 by POPX2 leads to impaired G1S checkpoint activation and cells are able to proceed from G1 to S phase despite DNA damage.\|We also determined that POPX2 can dephosphorylate Chk1Ser317 and -Ser345 and is a potential regulator of Chk1 function in the cell.	SIGNOR-276988
O15297	P16104	1	dephosphorylation	down-regulates	0.2	Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-h2ax and suppresses dna double strand break repair. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (wip1) also dephosphorylates gamma-h2ax at serine 139 in vitro and in vivo.	SIGNOR-163693
Q9H0A0	P09874	1	acetylation	up-regulates quantity by stabilization	0.2	MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1.	SIGNOR-273715
Q14493	P16104	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265405
O14965	Q8NHV4	1	phosphorylation	up-regulates activity	0.557	Microtubule nucleation during central spindle assembly requires NEDD1 phosphorylation on serine 405 by Aurora A\| In the absence of Aurora A, the HURP (also known as DLGAP5) and NEDD1 proteins that are involved in nucleation of microtubules fail to concentrate in the midzone.	SIGNOR-272965
Q6PKG0	P24941	0	phosphorylation	up-regulates activity	0.2	CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity.	SIGNOR-279015
P49841	P12830	1	phosphorylation	up-regulates activity	0.558	Phosphorylation of the E-cadherin Cytoplasmic Domain by CKII and GSK-3β Increases the Binding to β-catenin. pre-phosphorylation by CKII at Ser-855 and/or Ser-853 of E-cadherin is required before GSK-3β can phosphorylate at Ser-849.	SIGNOR-251225
P48200	P40337	0	ubiquitination	down-regulates quantity by destabilization	0.359	We show here that IRP2 can interact with pVHL in co-transfection/co-immunoprecipitation assays. Furthermore, pVHL is able to promote the ubiquitination and the decay of transfected IRP2.	SIGNOR-271421
P23458	P15260	2	phosphorylation	up-regulates	0.703	Interferon gamma activation of stat1alpha requires both jak1 and jak2 as well as tyrosine phosphorylation of the alpha chain of the ifngamma receptor.	SIGNOR-29866
Q14571	Q96K19	0	polyubiquitination	down-regulates activity	0.331	In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound.	SIGNOR-271914
Q5FBB7	O14965	0	phosphorylation	up-regulates activity	0.2	Loss of INCENP/Aurora B in Mitosis Correlates with Delocalization of MEI-S332\|MEI-S332 Is Phosphorylated by Aurora B In Vitro\|Of these, MEI-S332S124,125,126A was a poor substrate for Aurora B kinase in vitro	SIGNOR-252046
Q8N1W1	Q05397	0	phosphorylation	up-regulates activity	0.459	Importantly, FAK promotes p190RhoGEF tyrosine phosphorylation and enhances activation of RhoA ( ).\|Importantly, FAK promotes p190RhoGEF tyrosine phosphorylation and enhances activation of RhoA.	SIGNOR-279271
P17676	P00519	0	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
Q9Y4P8	Q676U5	2	binding	up-regulates quantity	0.733	WIPI1 assists WIPI2 in recruiting ATG16L for LC3 lipidation. WIPI1-WIPI2 heterodimer may function more efficiently in ATG16L complex recruitment.	SIGNOR-268478
P46937	O95835	0	phosphorylation	down-regulates quantity by destabilization	0.84	We show that YAP is phosphorylated by Lats on Ser 381 in one of the HXRXXS motifs, and this phosphorylation provides the priming signal for CK1delta/epsilon to phosphorylate a phosphodegron in YAP. The phosphorylated phosphodegron recruits beta-TRCP, leading to YAP ubiquitination and degradation under conditions of elevated Hippo pathway activity, such as cell contact inhibition	SIGNOR-218034
P68400	P05549	1	phosphorylation	up-regulates	0.307	Ck2 phosphorylates ap-2_ and increases its transcriptional activity	SIGNOR-175130
P00740	P08709	2	cleavage	up-regulates activity	0.55	The factor VII zymogen is cleaved at arginine 152 by a variety of proteases, including thrombin, factor IXa, factor Xa, and factor VIIa–tissue factor to produce the serine protease factor VIIa.	SIGNOR-263522
O14744	O60674	0	phosphorylation	down-regulates	0.693	Oncogenic jak2 kinases phosphorylate prmt5 in_vivo phosphorylation of prmt5 by jak2v617f greatly impairs its methyltransferase activity	SIGNOR-171994
Q969H0	Q16204	2	binding	down-regulates	0.367	Fbxw7 interacts with and targets ccdc6 for ubiquitin-mediated proteasomal degradation	SIGNOR-199279
O43148	P52292	2	binding	down-regulates activity	0.412	KPNA2 Inhibits RNMT Activity\|We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor.	SIGNOR-265502
O60684	P46531	1	relocalization	up-regulates	0.2	Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of nicd and thus are directly involved in notch signaling.	SIGNOR-165343
Q14689	P00441	2	binding	up-regulates activity	0.2	DIP2a is associated with SOD in the mitochondria of mouse brain. DIP2a knockout inhibited SOD activity. In this paper, we analyzed the interacting proteins of DIP2A by mass spectrum analysis and found that DIP2A was correlated with superoxide dismutase (SOD), SOD1 and SOD2. Knockout of DIP2A decreased SOD activity and increased the level of ROS in the mouse brain.	SIGNOR-266591
Q6KC79	Q13185	2	binding	up-regulates activity	0.436	The heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus.	SIGNOR-264524
P22736	O60858	0	ubiquitination	down-regulates quantity by destabilization	0.2	These results suggest that Trim13 activity mediates Nur77 ubiquitination, leading to its degradation.	SIGNOR-278564
Q9BXH1	Q07812	1	relocalization	up-regulates	0.49	Puma promotes bax translocation by both by directly interacting with bax and by competitive binding to bcl-x(l) in uv-induced apoptosis.	SIGNOR-185671
Q00613	P68400	0	phosphorylation	up-regulates activity	0.37	Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.	SIGNOR-250898
P38398	P11802	0	phosphorylation	down-regulates	0.665	In particular, we have identified ser 632 of brca1 as a cyclin d1/cdk4 phosphorylation site in vitro. Using chromatin immunoprecipitation assays, we observed that the inhibition of cyclin d1/cdk4 activity resulted in increased brca1 dna binding at particular promoters in vivo.	SIGNOR-153450
P29350	P15498	1	dephosphorylation	down-regulates activity	0.576	SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.	SIGNOR-277171
P00519	Q8IWL8	1	phosphorylation	up-regulates activity	0.2	STH interacts with tau and Abl, and Abl phosphorylates STH on its single tyrosine residue.	SIGNOR-279353
Q13315	P41236	1	phosphorylation	down-regulates	0.2	Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.	SIGNOR-160648
P13807	Q9UQK1	2	binding	up-regulates	0.851	In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)	SIGNOR-271733
Q15418	P23588	1	phosphorylation	up-regulates	0.529	S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function.	SIGNOR-123993
P78549	P06493	0	phosphorylation	up-regulates activity	0.33	The main cell cycle kinase Cdk1 directly phosphorylates and activates the trehalase Nth1 to trigger the flux of storage carbohydrates into central carbon metabolism.	SIGNOR-278916
Q05586	P17252	0	phosphorylation	up-regulates activity	0.417	Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.	SIGNOR-263177
P52564	O43318	0	phosphorylation	up-regulates activity	0.764	The activity of tak1 to phosphorylate mkk6, which activates the jnk-p38 kinase pathway, is directly regulated by k63-linked polyubiquitination	SIGNOR-109497
P04637	P40337	2	binding	up-regulates quantity by stabilization	0.452	Here we found that pVHL directly associates with and stabilizes p53 by suppressing Mdm2-mediated ubiquitination and nuclear export of p53.	SIGNOR-256594
P09471	P34969	2	binding	up-regulates activity	0.297	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-257256
Q9NZ94	P58400	2	binding	up-regulates activity	0.84	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264147
P06400	Q13131	0	phosphorylation	down-regulates	0.2	Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site.	SIGNOR-184052
Q9H063	P42345	0	phosphorylation	down-regulates	0.712	The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly.	SIGNOR-165795
Q12857	Q02535	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268873
O43318	P61006	1	phosphorylation	up-regulates activity	0.252	In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. \|Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.\|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease	SIGNOR-260266
Q04721	A0PJZ3	2	binding	up-regulates	0.322	We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum.	SIGNOR-177717
Q07817	O14920	0	phosphorylation	down-regulates quantity	0.339	We present evidence for a signaling network that involves phosphorylation and reduction of Bcl-xL by IKKbeta, and subsequent activation of caspases, which can cleave Htt.\|We propose that IKKbeta reduces Bcl-xL levels by phosphorylation (XREF_FIG), a modification known to promote Bcl-xL degradation .	SIGNOR-279529
Q9NRH2	Q15831	0	phosphorylation	up-regulates activity	0.367	We demonstrate that LKB1 activates SNRK by phosphorylating the T‐loop residue (Thr173)	SIGNOR-260824
P14921	P27361	0	phosphorylation	up-regulates	0.672	We found that hgf/sf activates the erk1 map kinase, leading to the phosphorylation of the threonine 38 residue of ets1	SIGNOR-116494
P36956	Q13131	0	phosphorylation	down-regulates activity	0.36	Ampk was recently found to phosphorylate a conserved serine near the cleavage site within srebp1, suppressing its activation	SIGNOR-176497
Q9BYB0	O14490	0	relocalization	up-regulates activity	0.2	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264588
O14522	P40763	1	dephosphorylation	down-regulates activity	0.516	Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T\|Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.	SIGNOR-263981
O43474	P53350	0	phosphorylation	up-regulates quantity by stabilization	0.249	We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization.	SIGNOR-277463
P61026	Q5S007	0	phosphorylation	down-regulates activity	0.33	To investigate whether the phosphorylation of Rab10 by LRRK2 is direct, we performed an in vitro kinase assay using recombinant components. Notably, we found that both wt and LRRK2-G2019S, but neither kinase inactive D1994A mutant nor small molecule-inhibited LRRK2, efficiently phosphorylated Rab10, proving a direct kinase-substrate relationship (Figure 2C). Furthermore, incubation of Rab10 with LRRK2 followed by tryptic digestion and MS analysis unambiguously identified T73 as the major phosphorylation site (Figure 2—figure supplement 1B)\|In pathogenic conditions, in which LRRK2 is hyperactive, RabGTPases have strongly diminished affinities for GDIs.	SIGNOR-261277
Q8IZI9	Q8IU57	2	binding	up-regulates	0.849	Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha.	SIGNOR-96243
Q96RE7	O43829	2	binding	up-regulates activity	0.288	NAC1 potentiated ZF5 mediated repression in Gal4-DBD fusion transient assays. GST pulldown assays further confirmed proteinprotein interactions between these proteins and NAC1.	SIGNOR-226443
P49840	Q9Y4H4	1	phosphorylation	down-regulates quantity by destabilization	0.2	Co-immunoprecipitation of endogenous GPSM3 and 14-3-3 proteins from the human monocytic cell line THP-1 suggests basal phosphorylation of GPSM3 at serine 35 as potentially mediated by GSK3alpha. The GPSM3/14-3-3 interaction is seen to stabilize GPSM3 from degradation and also support the nuclear exclusion of both proteins.	SIGNOR-264863
P42336	Q5VWQ8	2	binding	down-regulates activity	0.2	DAB2IP inhibits the PI3K–AKT axis by directly interacting with both proteins, reducing phosphorylation and activation of AKT. The GAP activity of DAB2IP can further enforce inhibition of the PI3K–AKT axis by reducing Ras-dependent activation of PI3K p110α subunit.	SIGNOR-254750
Q12857	Q13562	1	transcriptional regulation	up-regulates quantity	0.284	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268890
P40763	Q8TD84	2	binding	up-regulates activity	0.2	Our findings now further suggest that STAT3 and the adaptor protein SH2D2A interact with tyrosine‐containing motifs within the DSCAM/L1 ICDs. The SH2 domains of both STAT3 and SH2D2A are known to bind to phosphorylated tyrosine residues in the context of such motifs. Thus, the interactions between DSCAMs and SH2‐domain containing proteins seem to play a central and conserved role in Dscam signaling in the context of dynamic changes of tyrosine‐phosphorylation levels.	SIGNOR-264278
P17612	O76054	1	phosphorylation	up-regulates activity	0.2	These results suggest that phosphorylation of SPF by PKA is a dynamic process and that, in the absence of PKA activity, SPF is rapidly inactivated.Thus, phosphorylation of SPF at Ser-289 appears necessary for maximal stimulation of squalene monooxygenase activity in vitro and absolutely required for the stimulation of cholesterol synthesis in cell culture.	SIGNOR-276027
Q9UQB8	Q7KZI7	0	phosphorylation	down-regulates activity	0.462	Par1b directly phosphorylates IRSp53 on S366 in cell lysates and stimulates phosphorylation on S453/3/5 via an indirect mechanism.\|These data are consistent with a scenario in which Par1b phosphorylation inhibits IRSp53 function.	SIGNOR-278411
Q07820	P45983	0	phosphorylation	up-regulates	0.526	We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.	SIGNOR-92597
Q03113	P43115	2	binding	up-regulates activity	0.25	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-257203
P32239	O95837	2	binding	up-regulates activity	0.453	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-257363
Q9UPY5	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.424	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. NFE2L2 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy	SIGNOR-279867
P12830	P35221	2	binding	up-regulates	0.686	Additionally, the E-cadherin associated protein _-catenin regulates YAP directly by sequestering YAP/14-3-3 complexes in the cytoplasm.	SIGNOR-203468
P35372	P04843	2	binding	up-regulates	0.252	Ribophorin i (rpni), a component of the oligosaccharide transferase complex, could directly interact with mor. Rpni can be shown to participate in mor export by the intracellular retention of the receptor after small interfering rna knockdown of endogenous rpni.	SIGNOR-184651
Q9NQ66	P62873	2	binding	down-regulates	0.483	These results indicate that g-protein beta gamma subunits constitute a mechanism by which g-protein mediate a rapid and transient plc- beta 1.	SIGNOR-44369
P47900	Q14344	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257442
Q13285	P49675	1	transcriptional regulation	up-regulates quantity by expression	0.472	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271788
P49137	Q14134	1	phosphorylation	up-regulates activity	0.307	ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC.	SIGNOR-273675
P13807	Q96RG2	0	phosphorylation	down-regulates activity	0.508	Recombinant human PASK (hPASK) phosphorylates purified muscle glycogen synthase, causing robust inactivation. Furthermore, hPASK interacts directly with glycogen synthase when expressed in cultured cells and this interaction and the phosphorylation of glycogen synthase by human PASK (hPASK) are inhibited by glycogen.	SIGNOR-245866
Q13555	P00533	1	phosphorylation	down-regulates activity	0.362	The mechanism of desensitization of kinase activity can be accounted for, in part, by the EGF-stimulated phosphorylation of the receptor at Ser1046/7, a substrate for the multifunctional calmodulin-dependent protein kinase II in vitro. Mutation of Ser1046/7 by replacement with Ala residues blocks desensitization of the EGF receptor protein-tyrosine kinase activity.	SIGNOR-250694
P46937-3	P12931	0	phosphorylation	up-regulates activity	0.632	We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation.	SIGNOR-274025
Q8N122	Q9UPZ9	0	phosphorylation	up-regulates	0.2	Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division.	SIGNOR-196198
O14757	P30291	1	phosphorylation	up-regulates	0.611	Chk1 also phosphorylates and stabilizes wee1.	SIGNOR-163164
P50148	P32245	2	binding	up-regulates activity	0.25	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-257336
Q05639	P45983	0	phosphorylation	down-regulates quantity by destabilization	0.374	Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome.	SIGNOR-276492
Q9UBF6	Q16665	1	ubiquitination	down-regulates activity	0.2	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271450
Q92838	Q9HAV5	2	binding	up-regulates	0.678	Identification of the major product of the eda gene (ectodysplasin a), a protein belonging to a group of tnf ligands, and molecular cloning of the cdna, encoding its receptor (edar), a member of the tnf receptor family, are presented. The role of an alternative eda receptor, localised on the x chromosome (xedar) in the developmental control of the differentiation of skin appendages, is discussed.	SIGNOR-90040
Q8TEQ8	Q5H8A4	2	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
P51531	Q12824	2	binding	up-regulates activity	0.924	The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.	SIGNOR-65181
Q9H3N8	P63096	2	binding	up-regulates activity	0.516	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-256672
P51692	P18031	0	dephosphorylation	down-regulates activity	0.676	A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b	SIGNOR-248429
P12931	P10721	1	phosphorylation	up-regulates activity	0.386	C-src phosphorylates tyr900 in the second part of the kinase domain of c-kit.	SIGNOR-103999
Q9UI33	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.288	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-253462
Q86WV6	Q9UK80	0	deubiquitination	down-regulates activity	0.2	In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I	SIGNOR-273671
O43248	O15550	0	transcriptional regulation	up-regulates quantity by expression	0.302	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260026
P23528	P53667	0	phosphorylation	down-regulates	0.814	Our results suggest that limk1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis	SIGNOR-159885
Q07666	P28482	0	phosphorylation	up-regulates	0.666	In support of this assumption, purified gst_sam68 protein was phosphorylated by recombinant erk2we found that sam68 mutated in ser 58, thr 71 and thr 84 showed the same extent of impairment in induced exon inclusion as did sam68 mutated in all s/tp sites	SIGNOR-96414
P53350	Q16143	1	phosphorylation	down-regulates activity	0.318	Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.	SIGNOR-176079
P11362	P54764	0	phosphorylation	up-regulates activity	0.402	EphA4 and FGFR1 heterodimer promotes FGFR1 signaling in glioma cell line.\|Ligand stimulation of EphA4 stimulates FGFR1 phosphorylation and signaling.	SIGNOR-280007

Q13315

P54132

1

phosphorylation

up-regulates

0.775

Mitotic phosphorylation of blm was partially dependent on atm, and phosphorylation sites on blm were identified. A phosphospecific antibody against one of these sites (thr-99) revealed radiation-induced phosphorylation, which was defective in ataxia-telangiectasia cells. These data suggest that atm and blm function together in recognizing abnormal dna structures by direct interaction and that these phosphorylation sites in blm are important for radiosensitivity status but not for sce frequency.

SIGNOR-88010

P52735

P00533

2

binding

up-regulates

0.592

Oligomerization of receptor protein tyrosine kinases such as the epidermal growth factor receptor (egfr) by their cognate ligands leads to activation of the receptor.We Demonstrate that vav-2 is phosphorylated on tyrosine residues in response to egf and associates with the egfr in vivo.

SIGNOR-73874

P20226

P28360

2

binding

down-regulates activity

0.397

Msx-1 is a potent transcriptional repressor and that this activity is independent of its DNA binding function. Here we show that Msx-1 interacts directly with the TATA binding protein (TBP) but not with several other general transcription factors. This interaction is mediated by the Msx-1 homeodomain, specifically through residues in the N-terminal arm. These same N-terminal arm residues are required for repression by Msx-1, suggesting a functional relationship between TBP association and transcriptional repression.

SIGNOR-240401

P05019

P20823

0

transcriptional regulation

up-regulates quantity by expression

0.301

Growth hormone induces insulin-like growth factor-I gene transcription by a synergistic action of STAT5 and HNF-1α

SIGNOR-251720

Q9Y6Q9

P48730

0

phosphorylation

up-regulates

0.284

In this study, we show that both eralpha and aib1 are substrates for ck1delta in vitro, and identify a novel aib1 phosphorylation site (s601) targeted by ck1delta, significant for the co-activator function of aib1.

SIGNOR-184946

Q9P0K8

Q9HC98

0

phosphorylation

up-regulates activity

0.2

Additionally, we found that NEK6 phosphorylated FOXJ2 at Thr23 and Ser254 ( xref , lanes 3 and 5), and NCOA5 at Ser21 and Ser151 ( xref , lanes 3 and 4).

SIGNOR-278965

P17612

P63252

1

phosphorylation

down-regulates activity

0.2

PKA consensus site S425 required for PKA-mediated effects on Kir2.1 channels. PKA activation reduced outward IK1 for heteromeric Kir2.1 WT+V227F channels after 2 hours of PKA activation.

SIGNOR-276267

Q9UQM7

Q05469

1

phosphorylation

down-regulates

0.2

Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.

SIGNOR-58251

O60462

Q13214

2

binding

up-regulates activity

0.59

Further examination of the composition of the functional Sema3B receptor revealed that, unlike Sema3A, which signals exclusively using the NP1 receptor, Sema3B utilizes both NP1 and NP2 for signal transduction.

SIGNOR-261816

P32019

P20339

2

binding

up-regulates activity

0.447

We report that Rab5 acts at the plasma membrane, downstream of ruffling, to promote macropinosome sealing and scission. Rab5 is recruited to plasmalemmal circular ruffles before macropinosome closure. Rab5 effectors Inpp5b, OCRL and APPL1 localize to macropinocytic cups and vesicles, and are required for macropinosome sealing. The mammalian 5-phosphatases Inpp5b and OCRL, which can degrade PtdIns(4,5)P2, are both Rab5-associating effectors implicated in endocytosis and macropinocytosis

SIGNOR-277770

O14757

P49593

0

dephosphorylation

down-regulates activity

0.2

As a result, inactivation of Chk1 by POPX2 leads to impaired G1S checkpoint activation and cells are able to proceed from G1 to S phase despite DNA damage.|We also determined that POPX2 can dephosphorylate Chk1Ser317 and -Ser345 and is a potential regulator of Chk1 function in the cell.

SIGNOR-276988

O15297

P16104

1

dephosphorylation

down-regulates

0.2

Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-h2ax and suppresses dna double strand break repair. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (wip1) also dephosphorylates gamma-h2ax at serine 139 in vitro and in vivo.

SIGNOR-163693

Q9H0A0

P09874

1

acetylation

up-regulates quantity by stabilization

0.2

MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1.

SIGNOR-273715

Q14493

P16104

1

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265405

O14965

Q8NHV4

1

phosphorylation

up-regulates activity

0.557

Microtubule nucleation during central spindle assembly requires NEDD1 phosphorylation on serine 405 by Aurora A| In the absence of Aurora A, the HURP (also known as DLGAP5) and NEDD1 proteins that are involved in nucleation of microtubules fail to concentrate in the midzone.

SIGNOR-272965

Q6PKG0

P24941

0

phosphorylation

up-regulates activity

0.2

CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity.

SIGNOR-279015

P49841

P12830

1

phosphorylation

up-regulates activity

0.558

Phosphorylation of the E-cadherin Cytoplasmic Domain by CKII and GSK-3β Increases the Binding to β-catenin. pre-phosphorylation by CKII at Ser-855 and/or Ser-853 of E-cadherin is required before GSK-3β can phosphorylate at Ser-849.

SIGNOR-251225

P48200

P40337

0

ubiquitination

down-regulates quantity by destabilization

0.359

We show here that IRP2 can interact with pVHL in co-transfection/co-immunoprecipitation assays. Furthermore, pVHL is able to promote the ubiquitination and the decay of transfected IRP2.

SIGNOR-271421

P23458

P15260

2

phosphorylation

up-regulates

0.703

Interferon gamma activation of stat1alpha requires both jak1 and jak2 as well as tyrosine phosphorylation of the alpha chain of the ifngamma receptor.

SIGNOR-29866

Q14571

Q96K19

0

polyubiquitination

down-regulates activity

0.331

In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound.

SIGNOR-271914

Q5FBB7

O14965

0

phosphorylation

up-regulates activity

0.2

Loss of INCENP/Aurora B in Mitosis Correlates with Delocalization of MEI-S332|MEI-S332 Is Phosphorylated by Aurora B In Vitro|Of these, MEI-S332S124,125,126A was a poor substrate for Aurora B kinase in vitro

SIGNOR-252046

Q8N1W1

Q05397

0

phosphorylation

up-regulates activity

0.459

Importantly, FAK promotes p190RhoGEF tyrosine phosphorylation and enhances activation of RhoA ( ).|Importantly, FAK promotes p190RhoGEF tyrosine phosphorylation and enhances activation of RhoA.

SIGNOR-279271

P17676

P00519

0

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

Q9Y4P8

Q676U5

2

binding

up-regulates quantity

0.733

WIPI1 assists WIPI2 in recruiting ATG16L for LC3 lipidation. WIPI1-WIPI2 heterodimer may function more efficiently in ATG16L complex recruitment.

SIGNOR-268478

P46937

O95835

0

phosphorylation

down-regulates quantity by destabilization

0.84

We show that YAP is phosphorylated by Lats on Ser 381 in one of the HXRXXS motifs, and this phosphorylation provides the priming signal for CK1delta/epsilon to phosphorylate a phosphodegron in YAP. The phosphorylated phosphodegron recruits beta-TRCP, leading to YAP ubiquitination and degradation under conditions of elevated Hippo pathway activity, such as cell contact inhibition

SIGNOR-218034

P68400

P05549

1

phosphorylation

up-regulates

0.307

Ck2 phosphorylates ap-2_ and increases its transcriptional activity

SIGNOR-175130

P00740

P08709

2

cleavage

up-regulates activity

0.55

The factor VII zymogen is cleaved at arginine 152 by a variety of proteases, including thrombin, factor IXa, factor Xa, and factor VIIa–tissue factor to produce the serine protease factor VIIa.

SIGNOR-263522

O14744

O60674

0

phosphorylation

down-regulates

0.693

Oncogenic jak2 kinases phosphorylate prmt5 in_vivo phosphorylation of prmt5 by jak2v617f greatly impairs its methyltransferase activity

SIGNOR-171994

Q969H0

Q16204

2

binding

down-regulates

0.367

Fbxw7 interacts with and targets ccdc6 for ubiquitin-mediated proteasomal degradation

SIGNOR-199279

O43148

P52292

2

binding

down-regulates activity

0.412

KPNA2 Inhibits RNMT Activity|We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor.

SIGNOR-265502

O60684

P46531

1

relocalization

up-regulates

0.2

Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of nicd and thus are directly involved in notch signaling.

SIGNOR-165343

Q14689

P00441

2

binding

up-regulates activity

0.2

DIP2a is associated with SOD in the mitochondria of mouse brain. DIP2a knockout inhibited SOD activity. In this paper, we analyzed the interacting proteins of DIP2A by mass spectrum analysis and found that DIP2A was correlated with superoxide dismutase (SOD), SOD1 and SOD2. Knockout of DIP2A decreased SOD activity and increased the level of ROS in the mouse brain.

SIGNOR-266591

Q6KC79

Q13185

2

binding

up-regulates activity

0.436

The heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus.

SIGNOR-264524

P22736

O60858

0

ubiquitination

down-regulates quantity by destabilization

0.2

These results suggest that Trim13 activity mediates Nur77 ubiquitination, leading to its degradation.

SIGNOR-278564

Q9BXH1

Q07812

1

relocalization

up-regulates

0.49

Puma promotes bax translocation by both by directly interacting with bax and by competitive binding to bcl-x(l) in uv-induced apoptosis.

SIGNOR-185671

Q00613

P68400

0

phosphorylation

up-regulates activity

0.37

Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.

SIGNOR-250898

P38398

P11802

0

phosphorylation

down-regulates

0.665

In particular, we have identified ser 632 of brca1 as a cyclin d1/cdk4 phosphorylation site in vitro. Using chromatin immunoprecipitation assays, we observed that the inhibition of cyclin d1/cdk4 activity resulted in increased brca1 dna binding at particular promoters in vivo.

SIGNOR-153450

P29350

P15498

1

dephosphorylation

down-regulates activity

0.576

SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.

SIGNOR-277171

P00519

Q8IWL8

1

phosphorylation

up-regulates activity

0.2

STH interacts with tau and Abl, and Abl phosphorylates STH on its single tyrosine residue.

SIGNOR-279353

Q13315

P41236

1

phosphorylation

down-regulates

0.2

Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.

SIGNOR-160648

P13807

Q9UQK1

2

binding

up-regulates

0.851

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

SIGNOR-271733

Q15418

P23588

1

phosphorylation

up-regulates

0.529

S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function.

SIGNOR-123993

P78549

P06493

0

phosphorylation

up-regulates activity

0.33

The main cell cycle kinase Cdk1 directly phosphorylates and activates the trehalase Nth1 to trigger the flux of storage carbohydrates into central carbon metabolism.

SIGNOR-278916

Q05586

P17252

0

phosphorylation

up-regulates activity

0.417

Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.

SIGNOR-263177

P52564

O43318

0

phosphorylation

up-regulates activity

0.764

The activity of tak1 to phosphorylate mkk6, which activates the jnk-p38 kinase pathway, is directly regulated by k63-linked polyubiquitination

SIGNOR-109497

P04637

P40337

2

binding

up-regulates quantity by stabilization

0.452

Here we found that pVHL directly associates with and stabilizes p53 by suppressing Mdm2-mediated ubiquitination and nuclear export of p53.

SIGNOR-256594

P09471

P34969

2

binding

up-regulates activity

0.297

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-257256

Q9NZ94

P58400

2

binding

up-regulates activity

0.84

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264147

P06400

Q13131

0

phosphorylation

down-regulates

0.2

Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site.

SIGNOR-184052

Q9H063

P42345

0

phosphorylation

down-regulates

0.712

The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly.

SIGNOR-165795

Q12857

Q02535

1

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268873

O43318

P61006

1

phosphorylation

up-regulates activity

0.252

In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease

SIGNOR-260266

Q04721

A0PJZ3

2

binding

up-regulates

0.322

We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum.

SIGNOR-177717

Q07817

O14920

0

phosphorylation

down-regulates quantity

0.339

We present evidence for a signaling network that involves phosphorylation and reduction of Bcl-xL by IKKbeta, and subsequent activation of caspases, which can cleave Htt.|We propose that IKKbeta reduces Bcl-xL levels by phosphorylation (XREF_FIG), a modification known to promote Bcl-xL degradation .

SIGNOR-279529

Q9NRH2

Q15831

0

phosphorylation

up-regulates activity

0.367

We demonstrate that LKB1 activates SNRK by phosphorylating the T‐loop residue (Thr173)

SIGNOR-260824

P14921

P27361

0

phosphorylation

up-regulates

0.672

We found that hgf/sf activates the erk1 map kinase, leading to the phosphorylation of the threonine 38 residue of ets1

SIGNOR-116494

P36956

Q13131

0

phosphorylation

down-regulates activity

0.36

Ampk was recently found to phosphorylate a conserved serine near the cleavage site within srebp1, suppressing its activation

SIGNOR-176497

Q9BYB0

O14490

0

relocalization

up-regulates activity

0.2

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264588

O14522

P40763

1

dephosphorylation

down-regulates activity

0.516

Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T|Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.

SIGNOR-263981

O43474

P53350

0

phosphorylation

up-regulates quantity by stabilization

0.249

We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization.

SIGNOR-277463

P61026

Q5S007

0

phosphorylation

down-regulates activity

0.33

To investigate whether the phosphorylation of Rab10 by LRRK2 is direct, we performed an in vitro kinase assay using recombinant components. Notably, we found that both wt and LRRK2-G2019S, but neither kinase inactive D1994A mutant nor small molecule-inhibited LRRK2, efficiently phosphorylated Rab10, proving a direct kinase-substrate relationship (Figure 2C). Furthermore, incubation of Rab10 with LRRK2 followed by tryptic digestion and MS analysis unambiguously identified T73 as the major phosphorylation site (Figure 2—figure supplement 1B)|In pathogenic conditions, in which LRRK2 is hyperactive, RabGTPases have strongly diminished affinities for GDIs.

SIGNOR-261277

Q8IZI9

Q8IU57

2

binding

up-regulates

0.849

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

SIGNOR-96243

Q96RE7

O43829

2

binding

up-regulates activity

0.288

NAC1 potentiated ZF5 mediated repression in Gal4-DBD fusion transient assays. GST pulldown assays further confirmed proteinprotein interactions between these proteins and NAC1.

SIGNOR-226443

P49840

Q9Y4H4

1

phosphorylation

down-regulates quantity by destabilization

0.2

Co-immunoprecipitation of endogenous GPSM3 and 14-3-3 proteins from the human monocytic cell line THP-1 suggests basal phosphorylation of GPSM3 at serine 35 as potentially mediated by GSK3alpha. The GPSM3/14-3-3 interaction is seen to stabilize GPSM3 from degradation and also support the nuclear exclusion of both proteins.

SIGNOR-264863

P42336

Q5VWQ8

2

binding

down-regulates activity

0.2

DAB2IP inhibits the PI3K–AKT axis by directly interacting with both proteins, reducing phosphorylation and activation of AKT. The GAP activity of DAB2IP can further enforce inhibition of the PI3K–AKT axis by reducing Ras-dependent activation of PI3K p110α subunit.

SIGNOR-254750

Q12857

Q13562

1

transcriptional regulation

up-regulates quantity

0.284

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268890

P40763

Q8TD84

2

binding

up-regulates activity

0.2

Our findings now further suggest that STAT3 and the adaptor protein SH2D2A interact with tyrosine‐containing motifs within the DSCAM/L1 ICDs. The SH2 domains of both STAT3 and SH2D2A are known to bind to phosphorylated tyrosine residues in the context of such motifs. Thus, the interactions between DSCAMs and SH2‐domain containing proteins seem to play a central and conserved role in Dscam signaling in the context of dynamic changes of tyrosine‐phosphorylation levels.

SIGNOR-264278

P17612

O76054

1

phosphorylation

up-regulates activity

0.2

These results suggest that phosphorylation of SPF by PKA is a dynamic process and that, in the absence of PKA activity, SPF is rapidly inactivated.Thus, phosphorylation of SPF at Ser-289 appears necessary for maximal stimulation of squalene monooxygenase activity in vitro and absolutely required for the stimulation of cholesterol synthesis in cell culture.

SIGNOR-276027

Q9UQB8

Q7KZI7

0

phosphorylation

down-regulates activity

0.462

Par1b directly phosphorylates IRSp53 on S366 in cell lysates and stimulates phosphorylation on S453/3/5 via an indirect mechanism.|These data are consistent with a scenario in which Par1b phosphorylation inhibits IRSp53 function.

SIGNOR-278411

Q07820

P45983

0

phosphorylation

up-regulates

0.526

We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.

SIGNOR-92597

Q03113

P43115

2

binding

up-regulates activity

0.25

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-257203

P32239

O95837

2

binding

up-regulates activity

0.453

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-257363

Q9UPY5

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.424

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. NFE2L2 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy

SIGNOR-279867

P12830

P35221

2

binding

up-regulates

0.686

Additionally, the E-cadherin associated protein _-catenin regulates YAP directly by sequestering YAP/14-3-3 complexes in the cytoplasm.

SIGNOR-203468

P35372

P04843

2

binding

up-regulates

0.252

Ribophorin i (rpni), a component of the oligosaccharide transferase complex, could directly interact with mor. Rpni can be shown to participate in mor export by the intracellular retention of the receptor after small interfering rna knockdown of endogenous rpni.

SIGNOR-184651

Q9NQ66

P62873

2

binding

down-regulates

0.483

These results indicate that g-protein beta gamma subunits constitute a mechanism by which g-protein mediate a rapid and transient plc- beta 1.

SIGNOR-44369

P47900

Q14344

2

binding

up-regulates activity

0.2

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

SIGNOR-257442

Q13285

P49675

1

transcriptional regulation

up-regulates quantity by expression

0.472

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271788

P49137

Q14134

1

phosphorylation

up-regulates activity

0.307

ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC.

SIGNOR-273675

P13807

Q96RG2

0

phosphorylation

down-regulates activity

0.508

Recombinant human PASK (hPASK) phosphorylates purified muscle glycogen synthase, causing robust inactivation. Furthermore, hPASK interacts directly with glycogen synthase when expressed in cultured cells and this interaction and the phosphorylation of glycogen synthase by human PASK (hPASK) are inhibited by glycogen.

SIGNOR-245866

Q13555

P00533

1

phosphorylation

down-regulates activity

0.362

The mechanism of desensitization of kinase activity can be accounted for, in part, by the EGF-stimulated phosphorylation of the receptor at Ser1046/7, a substrate for the multifunctional calmodulin-dependent protein kinase II in vitro. Mutation of Ser1046/7 by replacement with Ala residues blocks desensitization of the EGF receptor protein-tyrosine kinase activity.

SIGNOR-250694

P46937-3

P12931

0

phosphorylation

up-regulates activity

0.632

We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation.

SIGNOR-274025

Q8N122

Q9UPZ9

0

phosphorylation

up-regulates

0.2

Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division.

SIGNOR-196198

O14757

P30291

1

phosphorylation

up-regulates

0.611

Chk1 also phosphorylates and stabilizes wee1.

SIGNOR-163164

P50148

P32245

2

binding

up-regulates activity

0.25

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-257336

Q05639

P45983

0

phosphorylation

down-regulates quantity by destabilization

0.374

Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome.

SIGNOR-276492

Q9UBF6

Q16665

1

ubiquitination

down-regulates activity

0.2

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271450

Q92838

Q9HAV5

2

binding

up-regulates

0.678

Identification of the major product of the eda gene (ectodysplasin a), a protein belonging to a group of tnf ligands, and molecular cloning of the cdna, encoding its receptor (edar), a member of the tnf receptor family, are presented. The role of an alternative eda receptor, localised on the x chromosome (xedar) in the developmental control of the differentiation of skin appendages, is discussed.

SIGNOR-90040

Q8TEQ8

Q5H8A4

2

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

P51531

Q12824

2

binding

up-regulates activity

0.924

The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.

SIGNOR-65181

Q9H3N8

P63096

2

binding

up-regulates activity

0.516

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-256672

P51692

P18031

0

dephosphorylation

down-regulates activity

0.676

A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b

SIGNOR-248429

P12931

P10721

1

phosphorylation

up-regulates activity

0.386

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

SIGNOR-103999

Q9UI33

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.288

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-253462

Q86WV6

Q9UK80

0

deubiquitination

down-regulates activity

0.2

In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I

SIGNOR-273671

O43248

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.302

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260026

P23528

P53667

0

phosphorylation

down-regulates

0.814

Our results suggest that limk1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis

SIGNOR-159885

Q07666

P28482

0

phosphorylation

up-regulates

0.666

In support of this assumption, purified gst_sam68 protein was phosphorylated by recombinant erk2we found that sam68 mutated in ser 58, thr 71 and thr 84 showed the same extent of impairment in induced exon inclusion as did sam68 mutated in all s/tp sites

SIGNOR-96414

P53350

Q16143

1

phosphorylation

down-regulates activity

0.318

Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.

SIGNOR-176079

P11362

P54764

0

phosphorylation

up-regulates activity

0.402

EphA4 and FGFR1 heterodimer promotes FGFR1 signaling in glioma cell line.|Ligand stimulation of EphA4 stimulates FGFR1 phosphorylation and signaling.

SIGNOR-280007