IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P37198 | Q6UVJ0 | 1 | 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-261256 |
P12644 | P12644 | 2 | binding | up-regulates | 0.2 | Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is anabsolute requirement for the biological action and interaction with receptors | SIGNOR-236169 |
P49841 | Q9Y5Q3 | 1 | phosphorylation | down-regulates | 0.2 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity. | SIGNOR-159476 |
P03186 | P25963 | 1 | deubiquitination | down-regulates activity | 0.2 | In the current study, we have found that BPLF1 interferes with innate immune activation by targeting multiple intermediates along the TLR signal transduction pathway, including TRAF6, NEMO, and IκBα. BPLF1 can remove ubiquitin tags from proteins in the TLR signaling cascade. This inhibits TLR signaling and decreases the expression of immune response genes. | SIGNOR-266744 |
P09769 | P09769 | 2 | phosphorylation | up-regulates activity | 0.2 | Autophosphorylation of c-Fgr under basal conditions involves Tyr-400 (homologous of c-Src Tyr-416) but not, to any appreciable extent, Tyr-511. Both Tyr-511 and Tyr-400, however, incorporate phosphate if autophosphorylation is performed in the presence of polycationic peptides, such as polylysine, histones H1 and protamines. Such a double phosphorylation induced by polylysine gives rise to an upshifted form of c-Fgr on SDS-PAGE and correlates with a stimulation of catalytic activity instead of a down-regulation | SIGNOR-251143 |
Q14493 | Q6FI13 | 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-265396 |
P17252 | P17252 | 2 | phosphorylation | up-regulates | 0.2 | Pkc is frequently autophosphorylated on two c-terminal sites, the turn motif (thr- 638 in human pkc) and the hydrophobic site (ser-657 in human pkc). Thus, it is becoming clear that autophosphorylation of pkc can be a regulated event and that it has significant impact on pkc function | SIGNOR-127253 |
P05771 | Q9Y5S8 | 1 | phosphorylation | up-regulates activity | 0.2 | Site-directed mutagenesis and isothermal titration calorimetry indicated that protein kinase C-beta1 phosphorylates Nox1 at threonine 429. Moreover, Nox1 threonine 429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly | SIGNOR-264729 |
O75676 | O75676 | 2 | phosphorylation | up-regulates activity | 0.2 | Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196. | SIGNOR-276269 |
Q9Y4B6 | Q7L590 | 1 | binding | down-regulates quantity by destabilization | 0.2 | By screening the known DDB1 interacting proteins, we discovered that VprBP is the substrate recognition subunit that targets Mcm10 for degradation. Hence, these results establish that Cul4-DDB1-VprBP ubiquitin ligase mediates the stress-induced proteolysis of replication factor, Mcm10. | SIGNOR-272046 |
P49840 | Q04206 | 1 | phosphorylation | up-regulates activity | 0.2 | Redundant functions of GSK-3_ and GSK-3_ through phosphorylation of RelA at Thr-254 play a crucial role in early stages of chondrocyte differentiation | SIGNOR-255827 |
Q8TEB1 | Q17RS7 | 1 | binding | down-regulates quantity by destabilization | 0.2 | (WDR23) isoforms differentially ubiquitinate (GEN1). In the presence of the necessary components for a successful ubiquitination reaction (CUL4A-DDB1-WDR23 complex, UBE1, UBE2D1, ubiquitin, and ATP) GEN1 receives the addition of ubiquitin in a time dependent manner. | SIGNOR-272258 |
P30411 | P09471 | 1 | 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-256974 |
P49841 | Q99250 | 1 | phosphorylation | down-regulates activity | 0.2 | Glycogen synthase kinase 3β (GSK3beta) phosphorylates the Nav1.2C-terminal tail at T1966, suppressing Na+ currents and channel trafficking to the plasma membrane | SIGNOR-275748 |
Q13315 | Q504Q3 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52. | SIGNOR-273508 |
Q9UK80 | Q86WV6 | 1 | 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 |
O75385 | P06733 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274029 |
P08047 | Q9UKX5 | 1 | null | up-regulates quantity by expression | 0.2 | We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors. | SIGNOR-253350 |
Q16512 | P00533 | 1 | phosphorylation | down-regulates activity | 0.2 | This identified thr654 in egfr as the pkn1 phosphorylation siteit has been shown that the phosphorylation of egfr at thr654 by pkc reduces the tyrosine kinase activity of the receptor | SIGNOR-174755 |
P42680 | P42680 | 2 | phosphorylation | up-regulates | 0.2 | Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated | SIGNOR-98098 |
P0DMV9 | O15217 | 1 | relocalization | up-regulates activity | 0.2 | Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. |Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation | SIGNOR-264800 |
Q00526 | Q03112 | 1 | phosphorylation | up-regulates activity | 0.2 | The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A. | SIGNOR-273431 |
Q9BYT3 | P32754 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation. | SIGNOR-272958 |
O60548 | P10644 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Elevating the amounts of FOXD2 expression vector up to 12-fold relative to the RIα1b reporter construct demonstrated that maximal induction of the RIα1b promoter by FOXD2 was at least 5.8-fold | SIGNOR-261605 |
P06241 | P31995 | 1 | phosphorylation | up-regulates activity | 0.2 | Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation | SIGNOR-262677 |
O60260 | Q99719 | 1 | ubiquitination | down-regulates quantity | 0.2 | Furthermore, Parkin ubiquitinates and promotes the degradation of CDCrel-1.|Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. | SIGNOR-278711 |
Q04759 | P29474 | 1 | phosphorylation | down-regulates activity | 0.2 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251636 |
Q9HC97 | Q14344 | 1 | 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-257283 |
P49841 | Q9UKT6 | 1 | phosphorylation | up-regulates activity | 0.2 | GSK-3beta phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation.|These results show direct GSK-3beta phosphorylation of TCAP S157 and FBXL21 T33 sites. | SIGNOR-264851 |
Q8TBJ4 | Q8N9B8 | 1 | binding | up-regulates activity | 0.2 | Oncogenic effects of imbalanced PRG3 are mediated via PRG3-RasGEF1 interaction and Ras activation. PRG3 interacts with RasGEF1 in vivo.We could further show that PRG3 executes the binding to RasGEF1 predominantly via its C-terminal domain (CT) and in the consequence causes Ras activation. | SIGNOR-261807 |
P78362 | Q99538 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report that serine-arginine protein kinase 2 (SRPK2) phosphorylates delta-secretase and enhances its enzymatic activity. SRPK2 phosphorylates serine 226 on delta-secretase and accelerates its autocatalytic cleavage, leading to its cytoplasmic translocation and escalated enzymatic activities. | SIGNOR-273569 |
P45984 | P54259 | 1 | phosphorylation | down-regulates activity | 0.2 | Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment, | SIGNOR-102402 |
P05129 | P04083 | 1 | phosphorylation | up-regulates | 0.2 | The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization. | SIGNOR-202788 |
P0DMV8 | Q96M98 | 1 | binding | up-regulates quantity by stabilization | 0.2 | Our in vitro data suggest that CHIP competes with Hsp70 in binding to Parkin, probably via suppression of the ATPase activity of Hsc/Hsp70 (Figure 4E).In fact, it acts as an inhibitory factor that suppresses the ubiquitination of Pael-R mediated by Parkin in vitro, and Hsp70 enhances the efficiency of folding of overexpressed Pael-R in vivo. | SIGNOR-272890 |
O94874 | Q13315 | 2 | ubiquitination | up-regulates activity | 0.2 | UFM1 specific ligase 1 (UFL1), an ufmylation E3 ligase, is important for ATM activation. UFL1 is recruited to double strand breaks by the MRE11/RAD50/NBS1 complex, and monoufmylates histone H4 following DNA damage. | SIGNOR-265073 |
Q15831 | P25116 | 1 | phosphorylation | up-regulates activity | 0.2 | LKB1 phosphorylates PAR-1 at the T408 site xref .|LKB1 thus positively regulates PAR-1 at the postsynapse. | SIGNOR-278992 |
P49841 | P14921 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Here, we show that ETS1 forms a complex with glycogen synthase kinase-3β (GSK3β). Specifically, GSK3β-mediated phosphorylation of ETS1 at threonine 265 and serine 269 promoted protein stability, induced the transcriptional activation of matrix metalloproteinase (MMP)-9, and increased cell migration. | SIGNOR-277560 |
Q6P3R8 | P20248 | 1 | binding | up-regulates activity | 0.2 | NEK5 promotes breast cancer cell proliferation through up-regulation of Cyclin A2 | SIGNOR-273874 |
P07949 | P18848 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We observed that RET physically interacted with and phosphorylated ATF4 at tyrosine and threonine residues. Indeed, RET kinase activity was required to inhibit the ATF4-dependent activation of the NOXA gene because the site-specific substitution mutations that block threonine phosphorylation increased ATF4 stability and activated its targets NOXA and PUMA. | SIGNOR-276448 |
P29279 | O75581 | 1 | binding | up-regulates | 0.2 | Igfbp-4 physically interacted with a wnt receptor, frizzled 8 (frz8), and a wnt co-receptor, low-density lipoprotein receptor-related protein 6 (lrp6), and inhibited the binding of wnt3a to frz8 and lrp6. | SIGNOR-178875 |
O75914 | P19429 | 1 | phosphorylation | down-regulates | 0.2 | In vitro addition of pak3 to skinned rat cardiac fibres increased myofilament ca2+ sensitivity with no change in maximal ca2+-activated force [67]. These effects were associated with pak3-induced phosphorylation of myofilament proteins, including ctni which was phosphorylated at a novel site, ser149, located in the region forming a ca2+-sensitive interaction with the n-terminal regulatory domain of tnc. | SIGNOR-134593 |
Q9UPC5 | P08754 | 1 | 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-256831 |
Q9Y4C0 | Q14118 | 1 | binding | up-regulates activity | 0.2 | The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM. | SIGNOR-265463 |
Q9ULU4 | P30542 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We also confirmed transcriptional coactivator functions of ZMYND8 in ERα-driven reporter assays and on endogenous E2-dependent genes (Figure 5F,G). siRNA knockdown of ZMYND8 showed markedly decreased transcription at the presumptive ERα/Z3 target genes ADORA1 and NAV2, while the classical ERα targets pS2/TFF1 and GREB1 appear to be less affected (Figure 5G), suggesting likely gene-specificity of ZMYND8. | SIGNOR-266208 |
P03206 | Q92985 | 1 | binding | down-regulates activity | 0.2 | We have shown that Epstein-Barr virus (EBV) IE protein Zta (BZLF1) physically interacts with IRF7, inhibiting its ability to activate the IFN-α, IFN-β, and Tap2 promoters | SIGNOR-266643 |
P03209 | Q92985 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs. | SIGNOR-266645 |
P03230 | Q92985 | 1 | sumoylation | down-regulates activity | 0.2 | One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. | SIGNOR-266951 |
P0C725 | Q92985 | 1 | binding | down-regulates activity | 0.2 | EBV LF2 tegument protein specifically interacts with the central inhibitory association domain of IRF7, and this interaction leads to inhibition of the dimerization of IRF7, which suppresses IFN-alpha production and IFN-mediated immunity. | SIGNOR-266632 |
Q13489 | Q13489 | 2 | ubiquitination | down-regulates activity | 0.2 | Ciap1 and ciap2 undergo autoubiquitination and degradation upon binding to the iap antagonist second mitochondrial activator of caspases (smac)/direct iap-binding protein with low pi (diablo), which is released from the mitochondria. | SIGNOR-121880 |
Q96HN2 | P51003 | 1 | binding | down-regulates activity | 0.2 | Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation|In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner. | SIGNOR-268330 |
P31269 | P11309 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells. | SIGNOR-261632 |
P54753 | P46527 | 1 | phosphorylation | down-regulates activity | 0.2 | In accord with this concept are the findings of Vlach et al. , who have studied point mutants of p27 deficient in their interactions with EK2, and have found that T187 phosphorylation of p27 by EK2 requires an interaction of p27 with the cyclin E subunit, while inhibition of the kinase activity requires an additional interaction with the CDK2 subunit.|The question considered here is the theoretical question whether deactivation of p27 by EK2 can produce binary EK2 release, and if so what biochemical kinetic features are required for this behavior. | SIGNOR-279406 |
Q9ULV8 | Q96JA1 | 2 | ubiquitination | down-regulates | 0.2 | Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation | SIGNOR-127292 |
P54646 | Q13393 | 1 | phosphorylation | up-regulates | 0.2 | Ampk-wild type (wt) stimulates pld activity, while ampk-dominant negative (dn) inhibits it. Ampk regulates pld1 activity through phosphorylation of the ser-505 and this phosphorylation is increased by the presence of amp. | SIGNOR-164293 |
Q9UHC7 | P46783 | 1 | ubiquitination | up-regulates activity | 0.2 | We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates. | SIGNOR-272216 |
P55085 | P09471 | 1 | 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-257144 |
P17612 | O95835 | 1 | phosphorylation | up-regulates | 0.2 | Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381. | SIGNOR-236991 |
Q13188 | P00519 | 2 | phosphorylation | down-regulates | 0.2 | Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3 | SIGNOR-181056 |
Q15831 | Q14680 | 1 | phosphorylation | up-regulates | 0.2 | Site-directed mutagenesis indicated that thr167 and ser171, located between the dfg and ape motifs in the activation loop or t-loop, need to be autophosphorylated for melk to be active as a protein kinase (fig. 5). These sites are conserved in all other ampk-related protein kinases (fig. 4a), and the site corresponding to thr167 has been shown to be phosphorylated by protein kinase lkb1 (5). | SIGNOR-141038 |
Q8WV44 | Q02156 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear. | SIGNOR-271668 |
Q9ULU4 | P00533 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported | SIGNOR-262040 |
Q14289 | Q14289 | 2 | phosphorylation | up-regulates | 0.2 | Overexpression of pyk2 alone led to its spontaneous activation and tyrosine phosphorylation, resulting in activation of stat5b, indicated by the reporter gfp-stat5b. These effects were completely dependent upon tyr(402), the autophosphorylation site of pyk2, which allows recruitment of src family members for further activating phosphorylations at other sites on pyk2. | SIGNOR-124339 |
Q02156 | P29353 | 1 | phosphorylation | up-regulates activity | 0.2 | Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc)) was phosphorylated only after TPA stimulation. Phosphorylation of this site together with the intact phosphotyrosine-binding domain was essential for ShcA binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA phosphorylation at this site (and hence, its association with PTP-PEST) was inhibited by a protein kinase C-specific inhibitor and was induced by overexpression of constitutively active mutants of protein kinase Calpha, -epsilon, and -delta isoforms. | SIGNOR-263048 |
P17612 | Q13002 | 1 | phosphorylation | up-regulates activity | 0.2 | GluR6 glutamate receptor, transiently expressed in mammalian cells, is directly phosphorylated by PKA, and that intracellularly applied PKA increases the amplitude of the glutamate response. Site-specific mutagenesis of the serine residue (Ser 684) representing a PKA consensus site completely eliminates PKA-mediated phosphorylation of this site as well as the potentiation of the glutamate response. | SIGNOR-250315 |
O00712 | P41161 | 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-268880 |
P18848 | P07814 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269419 |
P25098 | P05387 | 1 | phosphorylation | up-regulates | 0.2 | The phosphorylation sites in grk2-phosphorylated p2 are identified (s102 and s105) and are identical to the sites known to regulate p2 activity. | SIGNOR-94254 |
Q9P286 | P15923 | 1 | phosphorylation | up-regulates activity | 0.2 | The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation | SIGNOR-275653 |
Q15139 | Q9Y5P4 | 1 | phosphorylation | down-regulates | 0.2 | In this study, we identify cert as a novel in vivo pkd substrate. Phosphorylation on serine 132 by pkd decreases the affinity of cert toward its lipid target phosphatidylinositol 4-phosphate at golgi membranes and reduces ceramide transfer activity | SIGNOR-156500 |
Q9Y5I2 | Q9Y5G9 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265697 |
P24723 | P49841 | 1 | phosphorylation | down-regulates | 0.2 | Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka). | SIGNOR-188585 |
Q14493 | P0DPK5 | 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-265416 |
Q14164 | Q96AQ6 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. | SIGNOR-276618 |
P14373 | A8K0Z3 | 1 | ubiquitination | up-regulates activity | 0.2 | Our mechanistic studies uncovered that K63-linked ubiquitination of WASH K220 by MAGE-L2-TRIM27 is required for endosomal F-actin nucleation and retrograde transport. These results suggest that K63-linked ubiquitination of WASH K220 by TRIM27 is required for WASH function in retrograde transport. | SIGNOR-253514 |
Q8NFU7 | O94813 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9. | SIGNOR-259093 |
Q05655 | Q9BZK7 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition, we describe that the functions and the specificity of these two highly- related exchange factors is tightly regulated by signal-induced phosphorylation events at the level of target gene promoters, as exemplified by the role of TBLR1 phosphorylation at Ser 123 by PKCδ upon retinoic acid or estrogen stimulation. | SIGNOR-260903 |
Q2TAL8 | O95363 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269403 |
Q9Y5I2 | O60330 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265698 |
Q13557 | Q13557 | 2 | phosphorylation | up-regulates | 0.2 | Upon binding of the Ca2+/calmodulin complex to the binding domain of CaMKII, it is activated via autophosphorylation, then remaining active independent of of Ca2+ levels. | SIGNOR-255954 |
P53602 | P63000 | 1 | lipidation | up-regulates activity | 0.2 | Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation. | SIGNOR-265892 |
Q13131 | Q9H0B6 | 1 | phosphorylation | up-regulates | 0.2 | Consistent with phosphorylation of both ser545 and ser582 of klc2 contributing to its 14-3-3 binding, a ser545ala mutant of klc2 could be phosphorylated in vitro by ampk on ser582 | SIGNOR-174681 |
Q8NI29 | P13473 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Here, we report the characterization of FBXO27, a glycoprotein-specific F-box protein that is part of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, and demonstrate that SCFFBXO27 ubiquitinates glycoproteins in damaged lysosomes to regulate autophagic machinery recruitment.We found that the lysosomal protein LAMP2, which is ubiquitinated preferentially on lysosomal damage, enhances autophagic machinery recruitment to damaged lysosomes. Thus, we propose that SCFFBXO27 ubiquitinates glycoproteins exposed upon lysosomal damage to induce lysophagy. | SIGNOR-272323 |
Q9P0L2 | Q13470 | 1 | phosphorylation | down-regulates activity | 0.2 | We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters. | SIGNOR-273866 |
Q14774 | P19419 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261622 |
Q9GZU7 | Q15672 | 1 | dephosphorylation | down-regulates activity | 0.2 | These results indicate that SCP1 is the phosphatase that counter-regulates the MAPK-mediated phosphorylation of S68-Twist1. | SIGNOR-245962 |
Q13131 | Q13131 | 2 | phosphorylation | down-regulates activity | 0.2 | We show that AMPK α-Ser485/491 can be a site for autophosphorylation, which may play a role in limiting AMPK activation in response to energy depletion or other regulators | SIGNOR-256114 |
Q5T0T0 | P08195 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Taken together, these findings demonstrate that MARCH8 directly ubiquitinates CD98, and this likely leads to its routing to late endosomes for degradation. | SIGNOR-272755 |
Q92915 | Q9Y5Y9 | 1 | binding | down-regulates activity | 0.2 | 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-253441 |
Q9UPS6 | Q16695 | 1 | methylation | down-regulates activity | 0.2 | SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. | SIGNOR-265577 |
Q7Z570 | P35638 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269464 |
Q92692 | Q15762 | 1 | binding | up-regulates activity | 0.2 | CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediated cytotoxicity against certain tumors. Here, we have identified the human poliovirus receptor-related (PRR) family members CD155 [poliovirus receptor (PVR)] and CD112 (nectin-2/PRR-2) as the ligands for human CD226. | SIGNOR-261426 |
Q9UPP1 | Q92547 | 1 | 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 |
P35916 | P51812 | 1 | phosphorylation | down-regulates | 0.2 | Upon truncation of this c-terminal stretch, or mutation of the tyr-707 residue alone, autoinhibition is attenuated, and the kinase becomes constitutively active. Based on these findings we propose that phosphorylation of the tyr-707 represents a novel alternative regulatory mechanism for p90rsk activation. | SIGNOR-98708 |
Q02750 | Q02750 | 2 | phosphorylation | up-regulates activity | 0.2 | MEK1 and MEK2 can also be activated by autophosphorylation. Tyrosine 304 may be a candidate for the autophosphorylation site in MEK1. | SIGNOR-251415 |
Q9UNE7 | O60260 | 1 | binding | up-regulates activity | 0.2 | In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6). | SIGNOR-272888 |
P78527 | Q9UBK2 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. | SIGNOR-277911 |
Q05513 | P78563 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we identified ADAR2 as a direct substrate of PKCζ in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCζ/ADAR2 axis regulates miR-200 secretion through RNA editing. | SIGNOR-277391 |
Q4FZB7 | P62805 | 1 | methylation | down-regulates activity | 0.2 | SUV420H1 and SUV420H2 are two highly homologous enzymes that methylate lysine 20 of histone H4 (H4K20), a mark that has been implicated in transcriptional regulation. | SIGNOR-266651 |
Q05655 | O00429 | 1 | phosphorylation | up-regulates | 0.2 | Drp1 was specifically phosphorylated in mitosis by cdk1/cyclin b on ser-585. Exogenous expression of unphosphorylated mutant drp1s585a led to reduced mitotic mitochondrial fragmentation. | SIGNOR-153148 |
Q13131 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.2 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275438 |
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