IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P49841 | Q15910 | 1 | phosphorylation | down-regulates activity | 0.33 | GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo. | SIGNOR-278176 |
P06493 | P11387 | 1 | phosphorylation | up-regulates activity | 0.349 | In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells. | SIGNOR-276157 |
P49768 | P17252 | 0 | phosphorylation | up-regulates activity | 0.264 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249236 |
Q13131 | Q8N5S9 | 0 | phosphorylation | up-regulates | 0.462 | Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli. | SIGNOR-176598 |
P27448 | P30307 | 1 | phosphorylation | down-regulates activity | 0.485 | C-TAK1 protein kinase phosphorylates human Cdc25C on serine 216 and promotes 14-3-3 protein binding. Phosphorylation of serine 21 6 promotes 1 4-3-3 binding to Cdc25C and is inhibitory to Cdc25C function. | SIGNOR-250176 |
Q16665 | Q8NHM5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271567 |
P12931 | P04629 | 1 | phosphorylation | up-regulates activity | 0.292 | Direct phosphorylation of TrkA by Src family kinases has been demonstrated in vitro, and our studies suggest that Src may lead to selective activation of TrkA. | SIGNOR-279291 |
P01100 | P59595 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260726 |
Q99941 | P11021 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.448 | Accordingly, N-terminal fragments of each ATF6 isoform (N-ATF6α and N-ATF6β) were overexpressed in HeLa cells and the effects on GRP78 induction were assessed. When expressed at similar levels, N-ATF6α conferred ∼200-fold greater GRP78 promoter activation than N-ATF6β. | SIGNOR-261566 |
Q9P289 | Q9Y4P1 | 1 | phosphorylation | up-regulates activity | 0.2 | ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. | SIGNOR-275833 |
P51608 | O00548 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1 | SIGNOR-264674 |
P04062 | Q9NR19 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276552 |
P38936 | P11309 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.481 | Pim-2 phosphorylation of p21(cip1/waf1) enhances its stability and inhibits cell proliferation in hct116 cellshere we demonstrate that like pim-1, pim-2 also phosphorylates the cell cycle inhibitor p21(cip1/waf1) (p21) on thr145 in vitro and in vivo | SIGNOR-164642 |
P15173 | O43257 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.259 | We show that the srcap subunit named znhit1 or p18hamlet, which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. We also show that p18hamlet is required for h2a.z accumulation into this genomic region and for subsequent muscle gene transcriptional activation. | SIGNOR-165613 |
P10636 | Q9H992 | 0 | ubiquitination | down-regulates activity | 0.2 | We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein. | SIGNOR-278655 |
P61586 | Q13459 | 0 | gtpase-activating protein | down-regulates activity | 0.774 | 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-260509 |
Q07812 | O43464 | 1 | relocalization | up-regulates | 0.313 | Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi | SIGNOR-88590 |
P51151 | O60664 | 1 | null | up-regulates activity | 0.591 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253089 |
Q9BUZ4 | Q9HAU4 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.361 | TRAF4 acts as an E3 ubiquitin ligase to ubiquitinate the K119 site of Smurf2 through the K48 ubiquitin chain and degrade Smurf2. | SIGNOR-278617 |
Q00535 | P42858 | 1 | phosphorylation | up-regulates | 0.447 | Huntingtin is an antiapoptotic proteinwe show here that huntingtin is phosphorylated by the cyclin-dependent kinase 5 (cdk5) at serines 1181 and 1201. Phosphorylation can be induced by dna damage in vitro and in vivo. The state of huntingtin phosphorylation is a crucial regulator of neuronal cell death. Absence of phosphorylation of huntingtin at serines 1181 and 1201 confers toxic properties to wild-type huntingtin in a p53-dependent manner in striatal neurons and accelerates neuronal death induced by dna damage. | SIGNOR-156840 |
Q05513 | P41594 | 1 | phosphorylation | up-regulates activity | 0.37 | Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839. | SIGNOR-249284 |
Q01974 | Q9ULK5 | 1 | phosphorylation | down-regulates activity | 0.59 | In support of this, ror2 mutants abolish Vangl2 activity gradient and localization, and ror2; vangl2 double mutants phenocopy the wnt5a limb phenotype (Gao et al., 2011).4.6.|This process is mediated by its receptor Ror2, which in turn phosphorylates Vangl2 and induces asymmetric localization of Vangl2, propagating an activity gradient of Vangl2 in the proximal direction (Gao et al., 2011). | SIGNOR-280111 |
Q15784 | Q92886 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.278 | Based on these results, we concluded that the transactivation of the NDRF gene by ngn1 is mediated through the E4 box, suggesting that the E4 box and its binding bHLH protein(s) may play an important role in the transcriptional regulation of the NDRF gene. | SIGNOR-266235 |
Q96A00 | O75116 | 0 | phosphorylation | up-regulates activity | 0.413 | A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP.| CPI-17 can be also directly phosphorylated at Thr38 residue by MYPT1-associated kinase [222], by PAK, which is downstream of Rac and/or Cdc42 cascade [223], by Rho-associated coiled-coil kinase (ROCK) [224] and by PKN [225]. | SIGNOR-96696 |
P08833 | P17483 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | These data showed that Hox genes selectively activate the transcription of theIGFBP-1 | SIGNOR-261636 |
Q06124 | Q99683 | 1 | dephosphorylation | up-regulates | 0.367 | Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively. | SIGNOR-184604 |
P08670 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.27 | Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced secretion by neutrophils. | SIGNOR-278922 |
Q15139 | P19174 | 1 | phosphorylation | down-regulates activity | 0.404 | Thus, phosphorylation of PLC-gamma 1 by PKC or PKA at serine 1248 may modulate the interaction of PLC-gamma 1 with the protein tyrosine kinase or the protein tyrosine phosphatase; this altered interaction may, at least in part, be responsible for the decreased tyrosine phosphorylation of PLC-gamma 1 seen in PMA- and forskolin-treated Jurkat cells. | SIGNOR-248846 |
Q13127 | O60741 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Levels of NRSF and its physical binding to the Hcn1 gene were augmented after SE, resulting in repression of HCN1 expression and HCN1-mediated currents (I(h) ), and reduced I(h) -dependent resonance in hippocampal CA1 pyramidal cell dendrites. | SIGNOR-268970 |
P37231 | O00327 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.399 | Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms. | SIGNOR-268026 |
P29590 | Q13164 | 0 | phosphorylation | down-regulates activity | 0.474 | Big MAP kinase 1 (BMK1) also phosphorylates PML at two sites : S403 and T409.|Mutational analysis demonstrated that BMK1 drives suppression of PML directly through its phosphorylation. | SIGNOR-279074 |
P61244 | Q16539 | 0 | phosphorylation | down-regulates | 0.627 | Mxi2 phosphorylates max both in vitro and in vivo. Phosphorylation by mxi2 may affect the ability of max to oligomerize with itself and its partners, bind dna, or regulate gene expression. | SIGNOR-26511 |
P04637 | Q9H0F5 | 0 | ubiquitination | down-regulates activity | 0.363 | Here we demonstrate that RNF38 is a functional ubiquitin protein ligase (E3). We show that RNF38 isoform 1 is localized to the nucleus by a bipartite nuclear localization sequence (NLS). We confirm that RNF38 is a binding partner of p53 and demonstrate that RNF38 can ubiquitinate p53 in vitro and in vivo. Finally, we show that overexpression of RNF38 in HEK293T cells results in relocalization of p53 to discrete foci associated with PML nuclear bodies. | SIGNOR-272130 |
Q5S007 | P17612 | 0 | phosphorylation | down-regulates activity | 0.406 | Furthermore, our work establishes S1444 as a PKA-regulated 14-3-3 docking site.Strikingly, 14-3-3 binding to phospho-S1444 decreased LRRK2 kinase activity in vitro. | SIGNOR-237444 |
Q07912 | Q9Y5X1 | 1 | phosphorylation | up-regulates | 0.505 | We have previously shown that sh3px1, phosphorylated by ack2 (activated cdc42-associated tyrosine kinase 2), regulates the degradation of egf (epidermal growth factor) receptor. | SIGNOR-142569 |
O15379 | P49841 | 0 | phosphorylation | up-regulates activity | 0.285 | Given that pharmacological inhibition of GSK3beta inhibits HDAC3 neurotoxicity, we explored the possibility that HDAC3 was directly phosphorylated by GSK3beta.|HDAC3 is directly phosphorylated by GSK3\u03b2, suggesting that the neuronal death-promoting action of GSK3\u03b2 could be mediated through HDAC3 phosphorylation. | SIGNOR-278400 |
P06241 | O43294 | 1 | phosphorylation | up-regulates activity | 0.34 | Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5. | SIGNOR-262875 |
Q7Z6I6 | P60953 | 1 | gtpase-activating protein | down-regulates activity | 0.458 | 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-260487 |
Q01813 | O15294 | 0 | glycosylation | down-regulates activity | 0.257 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267583 |
Q15750 | Q01974 | 1 | phosphorylation | down-regulates | 0.278 | Tak1 (tgf-beta activated kinase 1), a map3k, interacts with ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich (stp) domain | SIGNOR-180566 |
P26378 | O14672 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure | SIGNOR-266865 |
P46934 | P43405 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.291 | The latent membrane protein (LMP) 2A of Epstein-Barr virus (EBV) is implicated in the maintenance of viral latency and appears to function in part by inhibiting B-cell receptor (BCR) signaling. LMP2A enhances Lyn and Syk ubiquitination in vivo in a fashion that depends on the activity of Nedd4 family members and correlates with destabilization of the Lyn tyrosine kinase. These results suggest that LMP2A serves as a molecular scaffold to recruit both B-cell tyrosine kinases and C2/WW/Hect domain E3 protein-ubiquitin ligases. | SIGNOR-272581 |
Q92900 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.368 | Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage. | SIGNOR-278911 |
P18848 | O43781 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop. | SIGNOR-275453 |
P40763 | P08581 | 0 | phosphorylation | up-regulates activity | 0.706 | It has been reported that c-Met can activate STAT3 at the endosome and phosphorylated STAT3 induced by c-Met is colocalized with EEA1, an early endosome marker. | SIGNOR-280041 |
P21802 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.622 | In forming this heterotetrameric complex Grb2 inhibits both the dephosphorylation of FGFR2 by Shp2 and the phosphorylation of Shp2 by FGFR2 (XREF_FIG, respectively).|Knockdown of Grb2 elevates Shp2 phosphorylation (XREF_FIG), strongly suggesting that the inability of Shp2 to interact directly with the receptor in the presence of Grb2 prevents FGFR2 kinase activity toward Shp2. | SIGNOR-277030 |
O60313 | Q96E52 | 0 | cleavage | up-regulates activity | 0.604 | YME1L cleaves OPA1 at S2 and S3 site to transform into L-OPA1 to induce fusion when cells are faced with increased oxidative phosphorylation, whereas OMA1 cleaves OPA1 at an S1 site to transform into S-OPA1, resulting in the fragmented response to cellular stress, mitochondrial dysfunction, or deletion of YME1L | SIGNOR-274139 |
P63000 | Q5VT97 | 0 | gtpase-activating protein | down-regulates activity | 0.402 | 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-260522 |
P23527 | Q14493 | 0 | 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-265379 |
Q92974 | Q14012 | 0 | phosphorylation | up-regulates activity | 0.389 | In this study, we found that CaMKI phosphorylated GEF-H1 at Thr103, which is located close to the C1 domain. | SIGNOR-279359 |
O96013 | O43426 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. | SIGNOR-263024 |
P06748 | Q9P275 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.39 | USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation. | SIGNOR-272290 |
Q14164 | P46937 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.44 | Virus-activated kinase IKKɛ phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response. | SIGNOR-277355 |
Q92934 | O75582 | 0 | phosphorylation | down-regulates activity | 0.344 | Phosphorylation of Bad at Ser112 in response to growth factors or cytokines is generally linked to cell survival. Knockdown of MSK1 suppressed Bad phosphorylation after calcium ionophore A23187 treatment in neuronal cells | SIGNOR-262990 |
P31749 | Q8IYJ3 | 1 | phosphorylation | down-regulates quantity | 0.355 | By mutagenesis analysis and subsequent immunoprecipitation (IP), we established that Akt phosphorylates JFC1 at serine 241. Phosphorylation did not alter the ability of JFC1 to bind to Rab27a. Instead, phosphorylation by Akt dramatically decreased when JFC1 was bound to Rab27a. Finally, we show that as a consequence of in vivo phosphorylation, JFC1 dissociates from the membrane, promoting JFC1 redistribution to the cytosol. | SIGNOR-273540 |
P17612 | P09874 | 1 | phosphorylation | up-regulates activity | 0.2 | In the presence of cAMP, recombinant PKA directly phosphorylated recombinant PARP1 on serines 465 (in the automodification domain) and 782 and 785 (both in the catalytic domain). | SIGNOR-276652 |
P18846 | O75676 | 0 | phosphorylation | up-regulates | 0.615 | Msk1 and msk2 directly phosphorilate and activate transcription factors such as creb1, atf1. | SIGNOR-116252 |
Q99523 | P67870 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Phosphorylation of Ser-825 is required for insulin to induce Sort1 in AML12 cells. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation. | SIGNOR-273636 |
P28482 | Q96PH1 | 1 | phosphorylation | up-regulates | 0.325 | These results suggest that the mek/erk1/2 pathway is necessary but not sufficient to regulate the pma-dependent activation of nox5. | SIGNOR-171847 |
Q9UJU2 | P49674 | 0 | phosphorylation | down-regulates | 0.268 | Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays. | SIGNOR-134497 |
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 |
P12004 | Q149N8 | 0 | ubiquitination | up-regulates | 0.553 | We provide evidence that similar to rad5, shprh physically interacts with the human rad6rad18 and mms2ubc13 protein complexes, and importantly, we show that it exhibits an ubiquitin ligase activity and mediates mms2ubc13-dependent polyubiquitylation of pcna. Thus, shprh is a functional homolog of rad5. | SIGNOR-187757 |
P27361 | P35568 | 1 | phosphorylation | down-regulates activity | 0.707 | Rin beta-cells exposed to high glucose exhibited increased c-jun n-terminal kinase (jnk) and erk1/2 activity, which was associated with increased irs-1 phosphorylation at serine (ser)(307) and ser(612), respectively, that inhibits coupling of irs-1 to the insulin receptor and is upstream of the inhibition of irs-1 tyrosine phosphorylation. | SIGNOR-123177 |
P45983 | Q12968 | 1 | phosphorylation | down-regulates | 0.837 | Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin | SIGNOR-118220 |
P49448 | Q9Y6E7 | 0 | glycosylation | down-regulates activity | 0.508 | We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity. | SIGNOR-268559 |
P28482 | O60716 | 1 | phosphorylation | down-regulates activity | 0.27 | Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation. | SIGNOR-277505 |
Q6UXX9 | Q9ULV1 | 1 | ubiquitination | down-regulates quantity | 0.313 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260117 |
O43524 | Q14680 | 0 | phosphorylation | down-regulates quantity | 0.362 | Further analysis indicated that FOXO1 and FOXO3, two known transcriptional regulators of p21, were phosphorylated by MELK and thus be involved in the induction of p21 after MELK inhibition.|Our findings revealed that siRNA mediated MELK knockdown increased protein levels of FOXO1 and FOXO3, which might increase p21 transcriptional level in a p53 independent manner. | SIGNOR-279375 |
P14598 | P28482 | 0 | phosphorylation | up-regulates | 0.45 | Erk1/2 are the kinases involved in p47phox_ phosphorylation on ser345 in gm-csfprimed human neutrophils._ Phosphorylation of ser345 is required for the priming of nadph oxidase activity in neutrophil-like cells | SIGNOR-147170 |
Q8IZD9 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.656 | 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-260548 |
O15054 | Q15306 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.422 | JMJD3 seems to function by controlling expression of the transcription factor IRF4, which in turn is required for M2 polarization of macrophages in vitro and in vivo. Although this pathway is strongly supported by genetic. | SIGNOR-249540 |
P41221 | Q8NBF1 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.248 | GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A | SIGNOR-269040 |
P29597 | P08575 | 0 | dephosphorylation | down-regulates activity | 0.407 | CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling|these results show that CD45 dephosphorylates functionally important tyrosine residues. It should be noted that, as with our phosphatase assays in vitro, Tyr 1022 and Tyr 1023 of JAK1, Tyr 1007 and Tyr 1008 of JAK2, and Tyr 1054 and Tyr 1055 of Tyk2 are indeed hyperphosphorylated in cd45-deficient cells | SIGNOR-248357 |
Q13114 | P0C6X7-PRO_0000037311 | 0 | deubiquitination | down-regulates activity | 0.2 | Overexpressing PLPro of SARS-CoV or MERS-CoV significantly reduced the expression of IFN-β and proinflammatory cytokines in MDA5-stimulated 293T cells (83).Also, SARS-CoVPLPro catalyzed deubiquitination of TNF-receptor-associated factor3 (TRAF3) and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist (63). The deubiquitinating activity of SARS-CoV PLPro also suppressed a constitutively active phosphomimetic IRF3, suggesting its involvement in the postactivation signaling of IRF3 | SIGNOR-260246 |
P05771 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.258 | 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-275442 |
Q13114 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.2 | We identified a direct interaction between SHP‐1 and TRAF3; the association between these two proteins resulted in diminished recruitment of CK1ε to TRAF3 and inhibited its K63‐linked ubiquitination; SHP‐1 inhibited K63‐linked ubiquitination of TRAF3 by promoting dephosphorylation at Tyr116 and Tyr446. | SIGNOR-277527 |
P78426 | P52945 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.503 | In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1. | SIGNOR-255542 |
P28482 | Q12772 | 1 | phosphorylation | up-regulates | 0.358 | Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity. | SIGNOR-123045 |
P08047 | P08243 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 Activate Transcription Driven by the AS Promoter | SIGNOR-268019 |
P49815 | Q96BR1 | 0 | phosphorylation | up-regulates activity | 0.434 | SGK3 phosphorylates six sites on TSC2 to activate mTORC1 in an AKT-independent manner. | SIGNOR-279284 |
P16298 | P21333 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.2 | Filamin is a phosphoprotein that organizes actin filaments into networks. We report that a purified C-terminal recombinant region of filamin is a suitable substrate for calcineurin |Mutagenesis analysis showed that a dephosphorylation step occurred in Ser 2152, which was previously shown to provide resistance to calpain cleavage when endogenous PKA is activated. In contrast, phosphorylation of Ser 2152 was recently reported to be necessary for membrane dynamic changes. In this regard, we found that CsA protects filamin in platelets from calpain degradation. | SIGNOR-248362 |
P00533 | O15455 | 1 | phosphorylation | up-regulates activity | 0.426 | Although both the ErbB1 and the ErbB2 isoforms of EGFR can bind to activated TLR3, functionally, only ErbB1 can trigger TLR3 signaling.|There is a high degree of specificity of the targets of the two PTKs, EGFR and Src | SIGNOR-278932 |
Q05655 | Q9H6E5 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCdelta associates with and directly phosphorylates Star-PAP. | SIGNOR-279385 |
P51170 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.36 | Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4. | SIGNOR-249448 |
P30304 | Q8NG66 | 0 | phosphorylation | down-regulates | 0.417 | Nek11 regulates cdc25a degradation and the ir-induced g2/m checkpointincubation of wild-type cdc25a with nek11 led to a marked increase in phosphorylation of ser 82 and 88 as detected with the phosphospecific antibody recognizing these sites | SIGNOR-187867 |
Q9UQC2 | P31749 | 0 | phosphorylation | down-regulates | 0.699 | Pkb constitutively associates with gab2, phosphorylates gab2 on a consensus phosphorylation site, ser159, in vitro and inhibits gab2 tyrosine phosphorylation. | SIGNOR-252468 |
Q13554 | Q9UBS5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | ERK1/2 and CaMKIIβ mediated phosphorylation of GABAB1 at serine 867 (S867) and threonine 872 (T872). We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1. | SIGNOR-277851 |
Q96P20 | Q9HAT8 | 0 | ubiquitination | up-regulates activity | 0.2 | Pellino2 promotes ubiquitination of NLRP3.|We now demonstrate that Pellino2 can promote increased production of mature bioactive IL-1beta by facilitating activation of the NLRP3 inflammasome. | SIGNOR-278525 |
P53779 | P63104 | 1 | phosphorylation | down-regulates | 0.2 | Jnk phosphorylates 14-3-3zetaat ser-184 and 14-3-3sigmaat ser-190 | SIGNOR-124009 |
Q14315 | P17252 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.338 | We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKCα. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells. In vitro kinase assays combined with LC-MS confirmed hFLNc-S2233 as a substrate of Akt, whereas PKCα preferentially targeted S2236. | SIGNOR-262617 |
P31749 | P17542 | 1 | phosphorylation | down-regulates | 0.374 | Akt phosphorylates tal1 oncoprotein and inhibits its repressor activity. / our results show that akt specifically phosphorylates thr90 of the tal1 protein within its transactivation domain in vitro and in vivo. | SIGNOR-252479 |
P52565 | Q8TEB7 | 0 | polyubiquitination | up-regulates quantity by stabilization | 0.266 | We found that RhoGDIα and RhoGDIβ are ubiquitin E3 substrates of GRAIL. GRAIL uses nonlysine 48-ubiquitin linkage in polyubiquitinating RhoGDI. GRAIL was subsequently demonstrated to bind and ubiquitinate RhoGDI, although GRAIL-mediated ubiquitination of RhoGDI did not result in proteosomal degradation. Our data suggest that ubiquitination of RhoGDI by GRAIL does not result in proteolytic degradation. In fact, GRAIL activity appeared to increase RhoGDI stability. | SIGNOR-271622 |
P84243 | O60341 | 0 | demethylation | up-regulates activity | 0.2 | Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. | SIGNOR-264509 |
Q4FZB7 | Q8N140 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here we show that, when over-expressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. The novel inhibitor of differentiation Eid3 is an FRG1/Suv4-20h1 target involved in the myogenic defects caused by FRG1 over-expression. Eid3 is down-regulated upon muscle differentiation and behaves as a myogenic inhibitor gene. | SIGNOR-266640 |
P30530 | P04626 | 1 | phosphorylation | down-regulates activity | 0.316 | Blockade of Axl function abrogated phosphorylation of ERBB2 (Her-2 and neu) at the Tyr877 residue, indicative of receptor crosstalk.|We have demonstrated that either pharmacological or genetic inhibition of Axl function abrogates phosphorylation of ERBB2 at the critical Tyr877 residue and sensitizes OE33 cells to lapatinib in vitro. | SIGNOR-280193 |
Q9Y297 | P84022 | 1 | ubiquitination | down-regulates | 0.389 | An e3 ubiquitin ligase complex roc1-scffbw1a consisting of roc1, skp1, cullin1, and fbw1a (also termed trcp1) induces ubiquitination of smad3. | SIGNOR-108237 |
Q13351 | P19784 | 0 | phosphorylation | up-regulates activity | 0.343 | Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41 | SIGNOR-241365 |
P31749 | Q7Z6J0 | 1 | phosphorylation | down-regulates | 0.394 | We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac, as does phosphomimetic s304d and s304e mutation of posh. | SIGNOR-252501 |
Q92823 | P54762 | 0 | phosphorylation | up-regulates activity | 0.411 | EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase. | SIGNOR-262862 |
Q16512 | O95863 | 1 | phosphorylation | up-regulates | 0.2 | Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functionswe found for the first time that pak1 promotes transcription repression activity of snail from e-cadherin, occludin, and aromatase promoters. Pak1 regulates the repressor activity of snail by phosphorylating on ser(246). Pak1 phosphorylation of snail supports snail's accumulation in the nucleus as well as its repressor functions. | SIGNOR-135609 |
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