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
Q92793	P04637	1	acetylation	up-regulates activity	0.912	C-terminal acetylation of p53 by p300/CBP and PCAF promotes an open conformation of p53 by preventing the occlusion of the DNA binding domain by the C-terminal tail. This enhances p53 transcriptional activity, leading to growth arrest and/or apoptosis	SIGNOR-261495
P52907	P68400	0	phosphorylation	up-regulates	0.2	We demonstrate that ser9 of cpalpha is phosphorylated by protein kinase ck2 in vitro, that cpalpha is phosphorylated in vivo. Finally, we demonstrate that ckip-1 and ck2 inhibit the activity of actin capping protein at the barbed ends of actin filaments.	SIGNOR-135422
P48729	A6ND36	2	binding	up-regulates quantity	0.373	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-273745
P01308	P06213	2	binding	up-regulates activity	0.934	Our previous studies indicated that amino acid residues 240-250 in the cysteine-rich region of the human insulin receptor alpha-subunit constitute a site in which insulin binds.	SIGNOR-23001
Q02224	O14965	0	phosphorylation	down-regulates activity	0.48	Aurora A also phosphorylates and inhibits the centromere-associated kinesin CENP-E involved in efficient chromosome congression ( xref ; xref ).	SIGNOR-280187
Q99570	P20339	2	binding	up-regulates activity	0.422	Vps34 PI 3-kinase activity18 is stimulated by complex formation with the protein kinase Vps15\|Rab5GTP binds Vps15, enhancing Vps34 activity	SIGNOR-260708
P17612	Q16613	1	phosphorylation	up-regulates activity	0.32	AANAT1–207 was phosphorylated in vitro at both PKA sites, Thr-31 and Ser-205. regulation is achieved by binding to 14-3-3, which structurally modulates the substrate binding sites, leading to measurable effects on the affinity of AANAT for its substrates with an accompanying increase in activity at low substrate concentrations.	SIGNOR-250324
P06681	P48740	0	cleavage	up-regulates activity	0.537	The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase	SIGNOR-263420
O14757	Q04206	1	phosphorylation	up-regulates activity	0.454	Here we demonstrate that ARF induces the ATR- and Chk1-dependent phosphorylation of the RelA transactivation domain at threonine 505, a site required for ARF-dependent repression of RelA transcriptional activity.	SIGNOR-280225
Q9C0F0	P10828	2	binding	down-regulates activity	0.2	We determined that ASXL3 depletion augments the ligand-induced transcriptional activities of LXRα and TRβ, which were repressed by ASXL3 overexpression. The ligand-dependent interactions of ASXL3 with LXRα and TRβ were demonstrated by the GST pull-down and immunoprecipitation analyses. We confirmed that ASXL3 suppresses the expression of LXRα target genes through its recruitment to the LXR-response elements.	SIGNOR-266766
O96017	Q13535	0	phosphorylation	up-regulates activity	0.86	Atm- and rad3-related also phosphorylates thr68 in addition to thr26 and ser50, which are not phosphorylated to a significant extent by atm in vitro.Substitution of thr68 with ala reduced the extent of phosphorylation and activation of chk2 in response to ir	SIGNOR-81442
P10071	P17612	0	phosphorylation	down-regulates quantity	0.468	Ci/gli zinc finger proteins mediate the transcriptional effects of hedgehog protein signals. In drosophila, ci action as transcriptional repressor or activator is contingent upon hedgehog-regulated, pka-dependent proteolytic processingall six pka phosphorylation sites are required for processing of gli3.	SIGNOR-75359
P49841	Q9H0Z9	1	phosphorylation	down-regulates	0.2	Here, we showed that rnpc1 is phosphorylated at ser195 by glycogen synthase kinase 3 (gsk3). We also provided evidence that ser195 phosphorylation converts rnpc1 from a repressor to an activator of p53.	SIGNOR-203011
Q13283	Q53GL7	0	post translational modification	up-regulates activity	0.2	Further, we pinpoint the core SG component, G3BP1, as a PARP10 substrate and find that PARP10 regulates SG assembly driven by both G3BP1 and its modeled mechanism. Intriguingly, while PARP10 only adds a single ADP-ribose unit to proteins, G3BP1 is PARylated, suggesting its potential role as a scaffold for protein recruitment. PARP10 knockdown alters the SG core composition, notably decreasing translation factor presence.	SIGNOR-273727
Q676U5	Q9Y239	2	binding	up-regulates activity	0.681	By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.	SIGNOR-252406
Q13188	Q9Y243	0	phosphorylation	down-regulates	0.271	Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation.	SIGNOR-164306
P53350	Q8N3U4	1	dephosphorylation	down-regulates activity	0.737	Two phosphorylation sites in Scc1 (Thr144 and Thr312) match the consensus proposed by Nakajima et al. [24]. These two sites, in addition to one in Scc1 (Ser454) and three in SA2 (Thr1109, Ser1137, and Ser1224) conform with the consensus proposed by Barr et al. [25]. These findings are consistent with the possibility that at least some of the sites in Scc1 and SA2 are directly phosphorylated by Plk1.\|Phosphorylation of SA2 Is Essential for the Dissociation of Cohesin from Chromosomes during Prophase and Prometaphase	SIGNOR-275534
Q92995	Q14457	2	deubiquitination	up-regulates quantity by stabilization	0.53	Similarly, the overexpression of USP13 reduced the levels of ubiquitinated Beclin1 which was inhibited by spautin-1 (Figure 4E)	SIGNOR-260295
P63096	O00398	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-256726
P52630	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.263	GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation.	SIGNOR-276761
Q92547	Q9UPP1	2	binding	up-regulates quantity by stabilization	0.2	TopBP1 Interacts with PHF8 through residue R1314 of TopBP1. Importantly, PHF8 regulates TopBP1 protein level by preventing its ubiquitination and degradation mediated by the E3 ligase UBR5.	SIGNOR-273657
P38936	Q9BV68	0	polyubiquitination	down-regulates quantity by destabilization	0.331	E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation.We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner.	SIGNOR-272033
P60484	Q13882	1	dephosphorylation	down-regulates activity	0.416	PTEN inhibits PTK6 activity and downstream signaling in prostate cancer cells.\|Using an in vitro phosphatase assay, we observed that PTEN was able to dephosphorylate PTK6 at tyrosine residue 342 in a dose dependent manner.	SIGNOR-276975
Q02410	O14936	2	binding	up-regulates activity	0.851	Interaction with Munc18 increases Mint1 binding to CASK.	SIGNOR-264041
P14780	P01033	2	binding	down-regulates activity	0.807	Tissue inhibitor of metalloproteinase (TIMP-1) is an inhibitor of MMP-9 that binds to MMP-9 precursors and to the active form.	SIGNOR-278116
P21860	P04626	2	binding	up-regulates	0.588	Although ErbB-2 binds no known ligand, when recruited into heterodimers it increases ligand binding affinity	SIGNOR-99569
P16471	P01241	2	binding	up-regulates	0.777	Hprl does not bind to the hgh receptor, but hgh binds to both the hghr and hprlr, and mutagenesis studies have shown that the receptor-binding sites on hgh overlap.	SIGNOR-35575
Q05397	A6NI28	1	phosphorylation	up-regulates activity	0.309	FAK and Src Mediated Phosphorylation of GRAF3 at Y376 Promotes Allosteric Activation.	SIGNOR-280097
P00533	Q96FA3	2	phosphorylation	up-regulates activity	0.2	EGFR is positively correlated with PELI1 expression in breast cancers, and its activation led to the phosphorylation of PELI1 at Tyr154 and Thr264, which subsequently activated its E3 ubiquitin ligase.	SIGNOR-277874
P27361	Q15831	1	phosphorylation	down-regulates activity	0.39	Directly and/or through the activation of p90RSK, ERK phosphorylates LKB-1 at Ser325 and Ser428. The phosphorylation of LKB-1 causes the dissociation of LKB-1 from AMPK, resulting in the impaired activation of AMPK.	SIGNOR-209880
P07949	P29353	2	binding	up-regulates	0.656	We have shown that the sh2 domain of the adaptor protein shc coimmunoprecipitates with all the ret.	SIGNOR-36902
P25098	P25025	1	phosphorylation	down-regulates activity	0.2	Upon activation, GRK2 phosphorylates CXCR2 and causes receptor desensitization and internalization, leading to down-regulation of neutrophil chemotaxis	SIGNOR-260647
P19784	Q01105-2	1	phosphorylation	down-regulates	0.259	Ckii-mediated phosphorylation at ser9 hinders nuclear import of set	SIGNOR-200802
P38484	O60674	2	binding	up-regulates activity	0.7	In the classical model of IFNgamma signaling, dimeric IFNgamma cross-links the IFNGR1 receptor subunit that results in allosteric changes in receptor cytoplasmic domain. This results in movement of JAK2 from receptor subunit IFNGR2 to IFNGR1. The JAKs autophosphorylate and then phosphorylate IFNGR1 cytoplasmic domain. This results in binding, phosphorylation, and dimer formation of STAT1_. The dimeric STAT1_ dissociates from receptor and undergoes nuclear translocation via an intrinsic NLS for specific gene activation	SIGNOR-249504
Q07912	P31749	1	phosphorylation	up-regulates activity	0.427	Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation.	SIGNOR-252446
O95714	Q9Y2K6	1	ubiquitination	down-regulates quantity	0.372	HERC2 promotes USP20 degradation.\|Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase.	SIGNOR-278692
Q15561	P29279	1	transcriptional regulation	up-regulates quantity by expression	0.2	The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter	SIGNOR-277686
P04637	O60285	0	phosphorylation	up-regulates	0.547	Here we showed that in the presence of wild-type lkb1, nuak1 directly interacts with and phosphorylates p53 in vitro and in vivo.	SIGNOR-172008
P63000	Q15311	0	gtpase-activating protein	down-regulates activity	0.582	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260513
Q7Z6Z7	Q86YD1	1	ubiquitination	down-regulates quantity	0.2	Our data suggest that HUWE1 can ubiquitinate PTOV1 in vitro and depletion of HUWE1 in cells increases the stability of PTOV1 S36A protein in the nucleus.\|Our data suggest that depletion of HUWE1 elevates PTOV1 protein levels, which, in turn, promote the expression of cJun, a pro-growth translational target of PTOV1 (18)\n In our model, we propose that HUWE1 mediates the degradation of PTOV1 in the nucleus.	SIGNOR-278755
P63092	Q969V1	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 ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256795
P15056	O00141	0	phosphorylation	down-regulates activity	0.344	Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.\|We observed that SGK inhibits B-Raf activity.	SIGNOR-279110
Q9UQL6	Q13131	0	phosphorylation	down-regulates	0.341	Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs)	SIGNOR-176479
P49840	P17252	0	phosphorylation	down-regulates	0.345	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-115714
P15151	Q86YJ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271530
O96017	P38398	1	phosphorylation	up-regulates	0.787	In this study, we tested the hypothesis that the brca1-mediated regulation of recombination requires the chk2- and atm-dependent phosphorylation sites.	SIGNOR-120575
P23258	P37198	2	binding	up-regulates activity	0.2	Furthermore, we found interactions and co-localization with γ-tubulin and SAS-6. Our results also point to a potential role of Nup62 in targeting gamma-tubulin and SAS-6 to the centrioles.	SIGNOR-261257
Q9BYX4	O14730	0	phosphorylation	down-regulates activity	0.468	RIOK3 mediates phosphorylation of MDA5 Ser-828\|RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and attenuates the innate immune response	SIGNOR-264576
P53667	Q9Y252	0	polyubiquitination	down-regulates quantity by destabilization	0.432	Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons.	SIGNOR-271481
P61586	P17612	0	phosphorylation	down-regulates activity	0.518	PKA phosphorylates RhoA on Ser188. the addition of a negative charge to Ser188 is sufficient to diminish both RhoA activation and activity within the context of a cell.	SIGNOR-250047
P32243	P14653	0	transcriptional regulation	up-regulates quantity by expression	0.274	Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. \| Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively	SIGNOR-261633
Q96G30	P41968	2	binding	down-regulates activity	0.505	We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.	SIGNOR-252367
Q9GZM8	P28482	0	phosphorylation	up-regulates activity	0.287	In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites	SIGNOR-274076
P09488	P10242	0	transcriptional regulation	up-regulates quantity by expression	0.2	Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation	SIGNOR-253975
Q00535	P47989	1	phosphorylation	up-regulates activity	0.2	Finally, threonine 222 of XOR is the critical target site for CDK5 dependent activation of XOR.\|Once we determined CDK5 was necessary for hypoxia induced hyperactivation of XOR, we tested whether CDK5 was sufficient to phosphorylate XOR and induce increased enzymatic activity in a cell free system.	SIGNOR-280221
P01178-PRO_0000020495	P30559	2	binding	up-regulates activity	0.2	The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation.\| The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta.	SIGNOR-268545
Q6ZTQ3	Q13188	2	binding	down-regulates	0.658	When rassf 6 is bound to mst2, rassf 6 inhibits mst2 activity, thus, inhibiting its role in the hippo pathway.	SIGNOR-198463
Q96JK9	Q99466	2	binding	up-regulates	0.867	Whereas maml1 and maml2 functioned efficiently as coactivators with each of the notch receptors to transactivate a notch target hes1 promoter construct, maml3 functioned more efficiently with icn4 than with other forms of icn.	SIGNOR-94103
P06454	P55211	2	binding	down-regulates	0.364	PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation.	SIGNOR-259079
P08581	Q03135	1	phosphorylation	up-regulates activity	0.424	Findings obtained using SNU-449 cells suggested that c-Met positively regulated CAV1 activity.\|Inhibition of c-Met activation abolished phosphorylation of CAV1 on Tyrosine 14.	SIGNOR-279080
P84022	Q9H6Z4	0	relocalization	down-regulates	0.389	Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner	SIGNOR-184608
P31947	P53779	0	phosphorylation	down-regulates	0.2	Here we demonstrate that activated jnk promotes bax translocation to mitochondria through phosphorylation of 14-3-3, a cytoplasmic anchor of bax. Phosphorylation of 14-3-3 led to dissociation of bax from this protein.Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-191	SIGNOR-124005
P47900	P63092	2	binding	up-regulates activity	0.323	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256800
P67775	P23396	1	dephosphorylation	down-regulates	0.427	We identified that pp2a interacts with wild-type rps3, but not with mutants (s6a/t221a) (fig. 8), and that it associates with the n-terminal region of rps3 (fig. 2). From our results presented here, we conclude that pp2a is involved in the dephosphorylation of phosphorylated rps3 by pkc, and that serine 6 on the n-terminal region of rps3 appears to mediate the pp2a recruitment.	SIGNOR-137963
P01112	P15056	2	binding	up-regulates activity	0.878	The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.	SIGNOR-147327
P61328	Q9UI33	2	binding	down-regulates activity	0.264	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253436
P12931	P35228	1	phosphorylation	up-regulates	0.681	We identify human inos residue tyr(1055) as a target for src-mediated phosphorylation. src kinase-mediated phosphorylation stabilizes inducible nitric-oxide synthase in normal cells and cancer cells.	SIGNOR-188974
P33076	P28482	0	phosphorylation	up-regulates	0.432	We show in this study that the nuclear localized form of ciita is a predominantly phosphorylated form of the protein, whereas cytoplasmic ciita is predominantly unphosphorylated. Novel phosphorylation sites were determined to be located within a region that contains serine residues 286, 288, and 293. Double mutations of these residues increased nuclear ciita, indicating that these sites are not required for nuclear import. Erk1/2-mediated phosphorylation of ciita down-regulates ciita activity by priming it for nuclear export, thus providing a means for cells to tightly regulate the extent of antigen presentation.	SIGNOR-160609
Q00526	Q5TKA1	1	phosphorylation	up-regulates	0.2	In this report, we demonstrate that cyclin e1/cdk3 phosphorylates lin-9 on thr-96. Mutating thr-96 to alanine inhibits activation of cyclins a2 and b1 promoters, whereas a phosphomimetic asp mutant strongly activates their promoters and triggers accelerated entry into g2/m phase in 293t cells.	SIGNOR-204529
P04626	Q9UJM3	2	binding	down-regulates activity	0.707	The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2	SIGNOR-252077
Q9GZQ4	P30679	2	binding	up-regulates activity	0.435	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257352
P31946	P78362	2	binding	down-regulates	0.33	14-3-3 interacts with akt-phosphorylated srpk2 and blocks its nuclear translocation. kt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events.	SIGNOR-186767
P36507	P10398	0	phosphorylation	up-regulates	0.754	Active raf phosphorylates mek.	SIGNOR-175142
P36896	O95551	1	phosphorylation	up-regulates activity	0.28	ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.	SIGNOR-262612
P00740	P01008	0	cleavage	down-regulates activity	0.897	Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1	SIGNOR-264140
O94826	P0DMV8	2	binding	up-regulates activity	0.2	The Tom70 receptor is a membrane-localized cochaperone that integrates the Hsp70/Hsp90 chaperones with mitochondrial preprotein targeting and translocation. In mammals, preprotein in the cytosol is associated with both Hsp90 and Hsp70 in a multichaperone complex, and docking of Hsp90 and/or Hsp70 onto Tom70 is essential for preprotein targeting.	SIGNOR-261380
P12931	Q9UKW4	1	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
P34995	P50148	2	binding	up-regulates activity	0.449	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-257083
P38936	Q00534	2	binding	down-regulates	0.864	P21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage.We Have explored the interaction of p21 with the currently known cdks. p21 effectively inhibits cdk2, cdk3, cdk4, and cdk6 kinases	SIGNOR-30030
P49716	P48436	0	transcriptional regulation	down-regulates quantity by repression	0.272	Sox9 directly binds to the promoter regions of c/ebpbeta and c/ebpdelta to suppress their promoter activity, preventing adipocyte differentiation	SIGNOR-184283
Q05655	P35568	1	phosphorylation	down-regulates activity	0.646	Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).	SIGNOR-249267
Q92529-2	Q16620	0	phosphorylation	up-regulates activity	0.755	We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo.	SIGNOR-273917
P27361	P33076	1	phosphorylation	up-regulates	0.341	We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.	SIGNOR-150545
P19174	P10586	0	dephosphorylation	down-regulates	0.2	Here we show that lar reduces the constitutive tyrosine autophosphorylation and kinase activity of ret-men2a but not ret-men2b, accompanying a significant decrease of phosphorylation of phospholipase cgamma, akt, and erk1/2.	SIGNOR-85166
O94822	Q15418	1	ubiquitination	down-regulates activity	0.2	Ltn1 ubiquitylation of RSK1, RSK2, and TWY3 could either result in degradation or impart a regulatory function on target proteins distinct from degradation.	SIGNOR-278757
Q9Y261	P32243	2	binding	down-regulates activity	0.548	Here we show that OTX2 directly associates with LIM1 and HNF-3beta. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression.	SIGNOR-221164
P27361	Q15046	1	phosphorylation	up-regulates	0.2	Lysrs serves as a key signaling molecule in the immune response by regulating gene expression. Lysrs was phosphorylated on serine 207 in a mapk-dependent manner, released from the multisynthetase complex, and translocated into the nucleus.	SIGNOR-186125
P30530	Q14511	1	phosphorylation	up-regulates activity	0.2	Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.\|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling.	SIGNOR-278905
P04040	P42684	0	phosphorylation	up-regulates activity	0.34	C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases	SIGNOR-101306
Q00987	Q8NEZ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis\|we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation.	SIGNOR-273440
O60841	P55010	0	relocalization	up-regulates activity	0.75	eIF5B promotes ribosomal subunit joining, with the help of eIF1A. Upon subunit joining, eIF5B hydrolyzes GTP and is released together with eIF1A. We found that human eIF5 interacts with eIF5B and may help recruit eIF5B to the PIC.	SIGNOR-269122
Q15067	Q2T9J0	0	cleavage	up-regulates activity	0.694	Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β-oxidation. In vitro cleavage of Acox1, Scp2 and prethiolase by recombinant Tysnd1.	SIGNOR-261057
P05556	Q99704	2	binding	down-regulates activity	0.315	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257669
Q8N5Z5	Q9BT92	2	binding	down-regulates quantity by destabilization	0.336	We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis.	SIGNOR-272463
O95271	Q92530	1	ADP-ribosylation	down-regulates quantity by destabilization	0.501	We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.	SIGNOR-263387
Q16539	Q9UK80	1	phosphorylation	up-regulates activity	0.253	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-273670
O15119	Q8N726	1	transcriptional regulation	down-regulates quantity by repression	0.395	TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS	SIGNOR-249603
P60484	P52732	1	dephosphorylation	up-regulates activity	0.455	PTEN significantly reduces EG5 phosphorylation at Thr926 (XREF_FIG), suggesting PTEN may target this EG5 site for dephosphorylation.	SIGNOR-277000
P16234	P01127	2	binding	up-regulates activity	0.718	Pdgf-b activates both pdgfr-alpha and pdgfr-beta	SIGNOR-107397
O15111	P03372	1	phosphorylation	up-regulates activity	0.47	These results demonstrated an estrogen-mediated increase in the phosphorylation of ER\u03b1 at serine residue 118 by IKK\u03b1 ( Figure 5 H, bottom).\|Wt IKKalpha, but not the IKKalpha kinase mutant, increased both estrogen dependent and -independent ERalpha activation.	SIGNOR-279696

Q92793

P04637

1

acetylation

up-regulates activity

0.912

C-terminal acetylation of p53 by p300/CBP and PCAF promotes an open conformation of p53 by preventing the occlusion of the DNA binding domain by the C-terminal tail. This enhances p53 transcriptional activity, leading to growth arrest and/or apoptosis

SIGNOR-261495

P52907

P68400

0

phosphorylation

up-regulates

0.2

We demonstrate that ser9 of cpalpha is phosphorylated by protein kinase ck2 in vitro, that cpalpha is phosphorylated in vivo. Finally, we demonstrate that ckip-1 and ck2 inhibit the activity of actin capping protein at the barbed ends of actin filaments.

SIGNOR-135422

P48729

A6ND36

2

binding

up-regulates quantity

0.373

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-273745

P01308

P06213

2

binding

up-regulates activity

0.934

Our previous studies indicated that amino acid residues 240-250 in the cysteine-rich region of the human insulin receptor alpha-subunit constitute a site in which insulin binds.

SIGNOR-23001

Q02224

O14965

0

phosphorylation

down-regulates activity

0.48

Aurora A also phosphorylates and inhibits the centromere-associated kinesin CENP-E involved in efficient chromosome congression ( xref ; xref ).

SIGNOR-280187

Q99570

P20339

2

binding

up-regulates activity

0.422

Vps34 PI 3-kinase activity18 is stimulated by complex formation with the protein kinase Vps15|Rab5GTP binds Vps15, enhancing Vps34 activity

SIGNOR-260708

P17612

Q16613

1

phosphorylation

up-regulates activity

0.32

AANAT1–207 was phosphorylated in vitro at both PKA sites, Thr-31 and Ser-205. regulation is achieved by binding to 14-3-3, which structurally modulates the substrate binding sites, leading to measurable effects on the affinity of AANAT for its substrates with an accompanying increase in activity at low substrate concentrations.

SIGNOR-250324

P06681

P48740

0

cleavage

up-regulates activity

0.537

The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase

SIGNOR-263420

O14757

Q04206

1

phosphorylation

up-regulates activity

0.454

Here we demonstrate that ARF induces the ATR- and Chk1-dependent phosphorylation of the RelA transactivation domain at threonine 505, a site required for ARF-dependent repression of RelA transcriptional activity.

SIGNOR-280225

Q9C0F0

P10828

2

binding

down-regulates activity

0.2

We determined that ASXL3 depletion augments the ligand-induced transcriptional activities of LXRα and TRβ, which were repressed by ASXL3 overexpression. The ligand-dependent interactions of ASXL3 with LXRα and TRβ were demonstrated by the GST pull-down and immunoprecipitation analyses. We confirmed that ASXL3 suppresses the expression of LXRα target genes through its recruitment to the LXR-response elements.

SIGNOR-266766

O96017

Q13535

0

phosphorylation

up-regulates activity

0.86

Atm- and rad3-related also phosphorylates thr68 in addition to thr26 and ser50, which are not phosphorylated to a significant extent by atm in vitro.Substitution of thr68 with ala reduced the extent of phosphorylation and activation of chk2 in response to ir

SIGNOR-81442

P10071

P17612

0

phosphorylation

down-regulates quantity

0.468

Ci/gli zinc finger proteins mediate the transcriptional effects of hedgehog protein signals. In drosophila, ci action as transcriptional repressor or activator is contingent upon hedgehog-regulated, pka-dependent proteolytic processingall six pka phosphorylation sites are required for processing of gli3.

SIGNOR-75359

P49841

Q9H0Z9

1

phosphorylation

down-regulates

0.2

Here, we showed that rnpc1 is phosphorylated at ser195 by glycogen synthase kinase 3 (gsk3). We also provided evidence that ser195 phosphorylation converts rnpc1 from a repressor to an activator of p53.

SIGNOR-203011

Q13283

Q53GL7

0

post translational modification

up-regulates activity

0.2

Further, we pinpoint the core SG component, G3BP1, as a PARP10 substrate and find that PARP10 regulates SG assembly driven by both G3BP1 and its modeled mechanism. Intriguingly, while PARP10 only adds a single ADP-ribose unit to proteins, G3BP1 is PARylated, suggesting its potential role as a scaffold for protein recruitment. PARP10 knockdown alters the SG core composition, notably decreasing translation factor presence.

SIGNOR-273727

Q676U5

Q9Y239

2

binding

up-regulates activity

0.681

By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.

SIGNOR-252406

Q13188

Q9Y243

0

phosphorylation

down-regulates

0.271

Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation.

SIGNOR-164306

P53350

Q8N3U4

1

dephosphorylation

down-regulates activity

0.737

Two phosphorylation sites in Scc1 (Thr144 and Thr312) match the consensus proposed by Nakajima et al. [24]. These two sites, in addition to one in Scc1 (Ser454) and three in SA2 (Thr1109, Ser1137, and Ser1224) conform with the consensus proposed by Barr et al. [25]. These findings are consistent with the possibility that at least some of the sites in Scc1 and SA2 are directly phosphorylated by Plk1.|Phosphorylation of SA2 Is Essential for the Dissociation of Cohesin from Chromosomes during Prophase and Prometaphase

SIGNOR-275534

Q92995

Q14457

2

deubiquitination

up-regulates quantity by stabilization

0.53

Similarly, the overexpression of USP13 reduced the levels of ubiquitinated Beclin1 which was inhibited by spautin-1 (Figure 4E)

SIGNOR-260295

P63096

O00398

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-256726

P52630

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.263

GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation.

SIGNOR-276761

Q92547

Q9UPP1

2

binding

up-regulates quantity by stabilization

0.2

TopBP1 Interacts with PHF8 through residue R1314 of TopBP1. Importantly, PHF8 regulates TopBP1 protein level by preventing its ubiquitination and degradation mediated by the E3 ligase UBR5.

SIGNOR-273657

P38936

Q9BV68

0

polyubiquitination

down-regulates quantity by destabilization

0.331

E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation.We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner.

SIGNOR-272033

P60484

Q13882

1

dephosphorylation

down-regulates activity

0.416

PTEN inhibits PTK6 activity and downstream signaling in prostate cancer cells.|Using an in vitro phosphatase assay, we observed that PTEN was able to dephosphorylate PTK6 at tyrosine residue 342 in a dose dependent manner.

SIGNOR-276975

Q02410

O14936

2

binding

up-regulates activity

0.851

Interaction with Munc18 increases Mint1 binding to CASK.

SIGNOR-264041

P14780

P01033

2

binding

down-regulates activity

0.807

Tissue inhibitor of metalloproteinase (TIMP-1) is an inhibitor of MMP-9 that binds to MMP-9 precursors and to the active form.

SIGNOR-278116

P21860

P04626

2

binding

up-regulates

0.588

Although ErbB-2 binds no known ligand, when recruited into heterodimers it increases ligand binding affinity

SIGNOR-99569

P16471

P01241

2

binding

up-regulates

0.777

Hprl does not bind to the hgh receptor, but hgh binds to both the hghr and hprlr, and mutagenesis studies have shown that the receptor-binding sites on hgh overlap.

SIGNOR-35575

Q05397

A6NI28

1

phosphorylation

up-regulates activity

0.309

FAK and Src Mediated Phosphorylation of GRAF3 at Y376 Promotes Allosteric Activation.

SIGNOR-280097

P00533

Q96FA3

2

phosphorylation

up-regulates activity

0.2

EGFR is positively correlated with PELI1 expression in breast cancers, and its activation led to the phosphorylation of PELI1 at Tyr154 and Thr264, which subsequently activated its E3 ubiquitin ligase.

SIGNOR-277874

P27361

Q15831

1

phosphorylation

down-regulates activity

0.39

Directly and/or through the activation of p90RSK, ERK phosphorylates LKB-1 at Ser325 and Ser428. The phosphorylation of LKB-1 causes the dissociation of LKB-1 from AMPK, resulting in the impaired activation of AMPK.

SIGNOR-209880

P07949

P29353

2

binding

up-regulates

0.656

We have shown that the sh2 domain of the adaptor protein shc coimmunoprecipitates with all the ret.

SIGNOR-36902

P25098

P25025

1

phosphorylation

down-regulates activity

0.2

Upon activation, GRK2 phosphorylates CXCR2 and causes receptor desensitization and internalization, leading to down-regulation of neutrophil chemotaxis

SIGNOR-260647

P19784

Q01105-2

1

phosphorylation

down-regulates

0.259

Ckii-mediated phosphorylation at ser9 hinders nuclear import of set

SIGNOR-200802

P38484

O60674

2

binding

up-regulates activity

0.7

In the classical model of IFNgamma signaling, dimeric IFNgamma cross-links the IFNGR1 receptor subunit that results in allosteric changes in receptor cytoplasmic domain. This results in movement of JAK2 from receptor subunit IFNGR2 to IFNGR1. The JAKs autophosphorylate and then phosphorylate IFNGR1 cytoplasmic domain. This results in binding, phosphorylation, and dimer formation of STAT1_. The dimeric STAT1_ dissociates from receptor and undergoes nuclear translocation via an intrinsic NLS for specific gene activation

SIGNOR-249504

Q07912

P31749

1

phosphorylation

up-regulates activity

0.427

Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation.

SIGNOR-252446

O95714

Q9Y2K6

1

ubiquitination

down-regulates quantity

0.372

HERC2 promotes USP20 degradation.|Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase.

SIGNOR-278692

Q15561

P29279

1

transcriptional regulation

up-regulates quantity by expression

0.2

The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter

SIGNOR-277686

P04637

O60285

0

phosphorylation

up-regulates

0.547

Here we showed that in the presence of wild-type lkb1, nuak1 directly interacts with and phosphorylates p53 in vitro and in vivo.

SIGNOR-172008

P63000

Q15311

0

gtpase-activating protein

down-regulates activity

0.582

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260513

Q7Z6Z7

Q86YD1

1

ubiquitination

down-regulates quantity

0.2

Our data suggest that HUWE1 can ubiquitinate PTOV1 in vitro and depletion of HUWE1 in cells increases the stability of PTOV1 S36A protein in the nucleus.|Our data suggest that depletion of HUWE1 elevates PTOV1 protein levels, which, in turn, promote the expression of cJun, a pro-growth translational target of PTOV1 (18)\n In our model, we propose that HUWE1 mediates the degradation of PTOV1 in the nucleus.

SIGNOR-278755

P63092

Q969V1

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 ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256795

P15056

O00141

0

phosphorylation

down-regulates activity

0.344

Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.|We observed that SGK inhibits B-Raf activity.

SIGNOR-279110

Q9UQL6

Q13131

0

phosphorylation

down-regulates

0.341

Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs)

SIGNOR-176479

P49840

P17252

0

phosphorylation

down-regulates

0.345

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-115714

P15151

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271530

O96017

P38398

1

phosphorylation

up-regulates

0.787

In this study, we tested the hypothesis that the brca1-mediated regulation of recombination requires the chk2- and atm-dependent phosphorylation sites.

SIGNOR-120575

P23258

P37198

2

binding

up-regulates activity

0.2

Furthermore, we found interactions and co-localization with γ-tubulin and SAS-6. Our results also point to a potential role of Nup62 in targeting gamma-tubulin and SAS-6 to the centrioles.

SIGNOR-261257

Q9BYX4

O14730

0

phosphorylation

down-regulates activity

0.468

RIOK3 mediates phosphorylation of MDA5 Ser-828|RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and attenuates the innate immune response

SIGNOR-264576

P53667

Q9Y252

0

polyubiquitination

down-regulates quantity by destabilization

0.432

Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons.

SIGNOR-271481

P61586

P17612

0

phosphorylation

down-regulates activity

0.518

PKA phosphorylates RhoA on Ser188. the addition of a negative charge to Ser188 is sufficient to diminish both RhoA activation and activity within the context of a cell.

SIGNOR-250047

P32243

P14653

0

transcriptional regulation

up-regulates quantity by expression

0.274

Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. | Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively

SIGNOR-261633

Q96G30

P41968

2

binding

down-regulates activity

0.505

We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.

SIGNOR-252367

Q9GZM8

P28482

0

phosphorylation

up-regulates activity

0.287

In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites

SIGNOR-274076

P09488

P10242

0

transcriptional regulation

up-regulates quantity by expression

0.2

Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation

SIGNOR-253975

Q00535

P47989

1

phosphorylation

up-regulates activity

0.2

Finally, threonine 222 of XOR is the critical target site for CDK5 dependent activation of XOR.|Once we determined CDK5 was necessary for hypoxia induced hyperactivation of XOR, we tested whether CDK5 was sufficient to phosphorylate XOR and induce increased enzymatic activity in a cell free system.

SIGNOR-280221

P01178-PRO_0000020495

P30559

2

binding

up-regulates activity

0.2

The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation.| The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta.

SIGNOR-268545

Q6ZTQ3

Q13188

2

binding

down-regulates

0.658

When rassf 6 is bound to mst2, rassf 6 inhibits mst2 activity, thus, inhibiting its role in the hippo pathway.

SIGNOR-198463

Q96JK9

Q99466

2

binding

up-regulates

0.867

Whereas maml1 and maml2 functioned efficiently as coactivators with each of the notch receptors to transactivate a notch target hes1 promoter construct, maml3 functioned more efficiently with icn4 than with other forms of icn.

SIGNOR-94103

P06454

P55211

2

binding

down-regulates

0.364

PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation.

SIGNOR-259079

P08581

Q03135

1

phosphorylation

up-regulates activity

0.424

Findings obtained using SNU-449 cells suggested that c-Met positively regulated CAV1 activity.|Inhibition of c-Met activation abolished phosphorylation of CAV1 on Tyrosine 14.

SIGNOR-279080

P84022

Q9H6Z4

0

relocalization

down-regulates

0.389

Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner

SIGNOR-184608

P31947

P53779

0

phosphorylation

down-regulates

0.2

Here we demonstrate that activated jnk promotes bax translocation to mitochondria through phosphorylation of 14-3-3, a cytoplasmic anchor of bax. Phosphorylation of 14-3-3 led to dissociation of bax from this protein.Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-191

SIGNOR-124005

P47900

P63092

2

binding

up-regulates activity

0.323

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

SIGNOR-256800

P67775

P23396

1

dephosphorylation

down-regulates

0.427

We identified that pp2a interacts with wild-type rps3, but not with mutants (s6a/t221a) (fig. 8), and that it associates with the n-terminal region of rps3 (fig. 2). From our results presented here, we conclude that pp2a is involved in the dephosphorylation of phosphorylated rps3 by pkc, and that serine 6 on the n-terminal region of rps3 appears to mediate the pp2a recruitment.

SIGNOR-137963

P01112

P15056

2

binding

up-regulates activity

0.878

The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.

SIGNOR-147327

P61328

Q9UI33

2

binding

down-regulates activity

0.264

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253436

P12931

P35228

1

phosphorylation

up-regulates

0.681

We identify human inos residue tyr(1055) as a target for src-mediated phosphorylation. src kinase-mediated phosphorylation stabilizes inducible nitric-oxide synthase in normal cells and cancer cells.

SIGNOR-188974

P33076

P28482

0

phosphorylation

up-regulates

0.432

We show in this study that the nuclear localized form of ciita is a predominantly phosphorylated form of the protein, whereas cytoplasmic ciita is predominantly unphosphorylated. Novel phosphorylation sites were determined to be located within a region that contains serine residues 286, 288, and 293. Double mutations of these residues increased nuclear ciita, indicating that these sites are not required for nuclear import. Erk1/2-mediated phosphorylation of ciita down-regulates ciita activity by priming it for nuclear export, thus providing a means for cells to tightly regulate the extent of antigen presentation.

SIGNOR-160609

Q00526

Q5TKA1

1

phosphorylation

up-regulates

0.2

In this report, we demonstrate that cyclin e1/cdk3 phosphorylates lin-9 on thr-96. Mutating thr-96 to alanine inhibits activation of cyclins a2 and b1 promoters, whereas a phosphomimetic asp mutant strongly activates their promoters and triggers accelerated entry into g2/m phase in 293t cells.

SIGNOR-204529

P04626

Q9UJM3

2

binding

down-regulates activity

0.707

The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2

SIGNOR-252077

Q9GZQ4

P30679

2

binding

up-regulates activity

0.435

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

SIGNOR-257352

P31946

P78362

2

binding

down-regulates

0.33

14-3-3 interacts with akt-phosphorylated srpk2 and blocks its nuclear translocation. kt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events.

SIGNOR-186767

P36507

P10398

0

phosphorylation

up-regulates

0.754

Active raf phosphorylates mek.

SIGNOR-175142

P36896

O95551

1

phosphorylation

up-regulates activity

0.28

ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.

SIGNOR-262612

P00740

P01008

0

cleavage

down-regulates activity

0.897

Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1

SIGNOR-264140

O94826

P0DMV8

2

binding

up-regulates activity

0.2

The Tom70 receptor is a membrane-localized cochaperone that integrates the Hsp70/Hsp90 chaperones with mitochondrial preprotein targeting and translocation. In mammals, preprotein in the cytosol is associated with both Hsp90 and Hsp70 in a multichaperone complex, and docking of Hsp90 and/or Hsp70 onto Tom70 is essential for preprotein targeting.

SIGNOR-261380

P12931

Q9UKW4

1

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

P34995

P50148

2

binding

up-regulates activity

0.449

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-257083

P38936

Q00534

2

binding

down-regulates

0.864

P21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage.We Have explored the interaction of p21 with the currently known cdks. p21 effectively inhibits cdk2, cdk3, cdk4, and cdk6 kinases

SIGNOR-30030

P49716

P48436

0

transcriptional regulation

down-regulates quantity by repression

0.272

Sox9 directly binds to the promoter regions of c/ebpbeta and c/ebpdelta to suppress their promoter activity, preventing adipocyte differentiation

SIGNOR-184283

Q05655

P35568

1

phosphorylation

down-regulates activity

0.646

Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).

SIGNOR-249267

Q92529-2

Q16620

0

phosphorylation

up-regulates activity

0.755

We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo.

SIGNOR-273917

P27361

P33076

1

phosphorylation

up-regulates

0.341

We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.

SIGNOR-150545

P19174

P10586

0

dephosphorylation

down-regulates

0.2

Here we show that lar reduces the constitutive tyrosine autophosphorylation and kinase activity of ret-men2a but not ret-men2b, accompanying a significant decrease of phosphorylation of phospholipase cgamma, akt, and erk1/2.

SIGNOR-85166

O94822

Q15418

1

ubiquitination

down-regulates activity

0.2

Ltn1 ubiquitylation of RSK1, RSK2, and TWY3 could either result in degradation or impart a regulatory function on target proteins distinct from degradation.

SIGNOR-278757

Q9Y261

P32243

2

binding

down-regulates activity

0.548

Here we show that OTX2 directly associates with LIM1 and HNF-3beta. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression.

SIGNOR-221164

P27361

Q15046

1

phosphorylation

up-regulates

0.2

Lysrs serves as a key signaling molecule in the immune response by regulating gene expression. Lysrs was phosphorylated on serine 207 in a mapk-dependent manner, released from the multisynthetase complex, and translocated into the nucleus.

SIGNOR-186125

P30530

Q14511

1

phosphorylation

up-regulates activity

0.2

Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling.

SIGNOR-278905

P04040

P42684

0

phosphorylation

up-regulates activity

0.34

C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases

SIGNOR-101306

Q00987

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis|we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation.

SIGNOR-273440

O60841

P55010

0

relocalization

up-regulates activity

0.75

eIF5B promotes ribosomal subunit joining, with the help of eIF1A. Upon subunit joining, eIF5B hydrolyzes GTP and is released together with eIF1A. We found that human eIF5 interacts with eIF5B and may help recruit eIF5B to the PIC.

SIGNOR-269122

Q15067

Q2T9J0

0

cleavage

up-regulates activity

0.694

Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β-oxidation. In vitro cleavage of Acox1, Scp2 and prethiolase by recombinant Tysnd1.

SIGNOR-261057

P05556

Q99704

2

binding

down-regulates activity

0.315

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257669

Q8N5Z5

Q9BT92

2

binding

down-regulates quantity by destabilization

0.336

We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis.

SIGNOR-272463

O95271

Q92530

1

ADP-ribosylation

down-regulates quantity by destabilization

0.501

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

SIGNOR-263387

Q16539

Q9UK80

1

phosphorylation

up-regulates activity

0.253

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-273670

O15119

Q8N726

1

transcriptional regulation

down-regulates quantity by repression

0.395

TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS

SIGNOR-249603

P60484

P52732

1

dephosphorylation

up-regulates activity

0.455

PTEN significantly reduces EG5 phosphorylation at Thr926 (XREF_FIG), suggesting PTEN may target this EG5 site for dephosphorylation.

SIGNOR-277000

P16234

P01127

2

binding

up-regulates activity

0.718

Pdgf-b activates both pdgfr-alpha and pdgfr-beta

SIGNOR-107397

O15111

P03372

1

phosphorylation

up-regulates activity

0.47

These results demonstrated an estrogen-mediated increase in the phosphorylation of ER\u03b1 at serine residue 118 by IKK\u03b1 ( Figure 5 H, bottom).|Wt IKKalpha, but not the IKKalpha kinase mutant, increased both estrogen dependent and -independent ERalpha activation.

SIGNOR-279696