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 |
|---|---|---|---|---|---|---|---|
P06493 | Q8WUX9 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that recombinant CHMP7 could be directly phosphorylated by CDK1/CCNB1 in vitro and that CDK1-phosphorylation reduced the capacity of CHMP7 to sediment (Figure 4A and B).|We identified direct CDK1 phosphorylation of CHMP7 at Ser3 and Ser441 as a suppressor of both CHMP7\u2019s ability to interact with LEM2 and its ability to assemble, as judged by sedimentation assays. | SIGNOR-279445 |
P49841 | Q9UKT5 | 1 | phosphorylation | up-regulates | 0.2 | Gsk3beta-mediated phosphorylation of fbx4 ser12 during the g1/s transition regulates fbx4 dimerization, which in turn governs fbx4-driven e3 ligase activity. | SIGNOR-171648 |
Q9P1W9 | Q13200 | 1 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273896 |
O15111 | P51608 | 1 | phosphorylation | up-regulates activity | 0.2 | Representative confocal micrographs of 4th day differentiating cultures are shown. (C) IKK\u03b1 promotes MeCP2-dependent BDNF expression.|The characterization of IKK\u03b1-mediated phosphorylation of MeCP2 at Ser421 and other residues and their effects on the activity of MeCP2 is a topic of current work in our laboratory. | SIGNOR-279459 |
Q99835 | P63215 | 1 | binding | up-regulates | 0.2 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-148598 |
P00519 | P00519 | 2 | phosphorylation | up-regulates activity | 0.2 | We demonstrate here that autophosphorylation of ABL1 is intermolecular and stimulates Abl catalytic activity. | SIGNOR-260781 |
Q92600 | O75420 | 1 | binding | up-regulates activity | 0.2 | Through interaction analysis of RQCD1 with full-length or partial proteins of GIGYF1 and GIGYF2, segments corresponding to 620-665th and 667-712th amino acids were identified as potential interacting regions on GIGYF1 and GIGYF2, respectively, with RQCD1. we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2 | SIGNOR-260059 |
P30291 | Q93096 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study , we found that WEE1 phosphorylates PRL1 and promotes PRL1 degradation .|In this study, we demonstrated that WEE1 phosphorylates and inhibits PRL1 to regulate alternative splicing of CYCD1;1 and CYCD3;1 , which may represent a new cell cycle control mechanism. | SIGNOR-278434 |
Q00535 | Q8NER1 | 1 | phosphorylation | up-regulates activity | 0.2 | TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34]. | SIGNOR-278437 |
O15033 | O43236 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists | SIGNOR-267670 |
Q05655 | P51398 | 1 | phosphorylation | up-regulates | 0.2 | Dap3 is phosphorylated by protein kinase cdelta on thr237. Dap3 was originally identified as a pro-apoptotic protein. The mutation of the phosphorylation site thr237 to alanine reversed the cell death caused by the wild-type dap3 | SIGNOR-160488 |
Q9UKE5 | P35240 | 1 | phosphorylation | up-regulates activity | 0.2 | Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3). | SIGNOR-278386 |
P17252 | Q8NF50 | 1 | phosphorylation | down-regulates activity | 0.2 | In response to chemokine stimulation, PKC\u03b1 phosphorylates DOCK8 at its three serine sites, promoting DOCK8 separation from LRCH1 and translocation to the leading edge to guide T cell migration.|Taken our data together, we suggest that PKC\u03b1 phosphorylates DOCK8 at the Ser2077/2082/2087 sites to promote T cell migration. | SIGNOR-279384 |
P25098 | P08913 | 1 | phosphorylation | down-regulates activity | 0.2 | The alpha 2A-adrenergic receptor (alpha 2AAR) undergoes rapid functional desensitization caused by phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK). beta ARK-mediated phosphorylation of alpha 2C10 occurs at Ser-296-299 in the third intracellular loop, and this represents the critical step in rapid agonist-promoted desensitization. | SIGNOR-251440 |
O00712 | Q9HD90 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268898 |
Q9Y5I3 | P05556 | 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. | SIGNOR-265663 |
Q9UBY8 | P67775 | 1 | binding | up-regulates activity | 0.2 | CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8. | SIGNOR-265583 |
P51812 | P16104 | 1 | phosphorylation | up-regulates activity | 0.2 | Herein, we found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates histone H2AX at Ser139 and also at a newly discovered site, Ser16.|Phosphorylated RSK2 and histone H2AX colocalized in the nucleus following EGF treatment, and the phosphorylation of histone H2AX by RSK2 enhanced the stability of histone H2AX and prevented cell transformation induced by EGF. | SIGNOR-279349 |
Q2TAL8 | Q9UGM6 | 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-269411 |
O95390 | P61160 | 1 | binding | up-regulates | 0.2 | Here we demonstrate using genetic and biochemical studies that actriib and its subfamily receptor, actriia, cooperatively mediate the gdf11 signal in patterning the axial vertebrae, and that gdf11 binds to both actriia and actriib, and induces phosphorylation of smad2. | SIGNOR-144147 |
P33981 | Q96PE2 | 1 | phosphorylation | down-regulates activity | 0.2 | Because Mps1 also phosphorylates ARHGEF17, the Mps1\u2013ARHGEF17 complex is short lived and promotes its own dissociation, which in turn releases Mps1 and ARHGEF17 from the kinetochore.|ARHGEF17 and Mps1 interact during mitosis and Mps1 phosphorylates ARHGEF17. | SIGNOR-279352 |
Q9H2X6 | Q15038 | 1 | phosphorylation | down-regulates activity | 0.2 | In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus. | SIGNOR-279335 |
Q9H2X6 | Q9H2X6 | 2 | phosphorylation | up-regulates activity | 0.2 | Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo. | SIGNOR-276601 |
O00141 | Q99835 | 1 | binding | down-regulates | 0.2 | SGK1 is known to inhibit another intrinsic pathway, the Hedgehog pathway, through downregulation of SMO and the GLI transcription factor family | SIGNOR-251673 |
P78368 | Q9Y5P4 | 1 | phosphorylation | down-regulates | 0.2 | These results indicate that ckigamma2 hyperphosphorylates the serine-repeat motif of cert, thereby inactivating cert and down-regulating the synthesis of sphingomyelin. | SIGNOR-182160 |
Q15257 | P31749 | 1 | dephosphorylation | down-regulates | 0.2 | Consistent with previous reports (2830), we found that expression of sv40st, suppression of either pp2a c or b resulted in elevated levels of akt phosphorylation (ser473) | SIGNOR-252607 |
Q7Z419 | P06748 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | NPMc degradation was mediated by the ubiquitin-proteasome pathway involving the IBR-type RING-finger E3 ubiquitin ligase IBRDC2, and genetic correction of FA-A or FA-C lymphoblasts prevented NPMc ubiquitination. As shown in Fig. 4C, knockdown of IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase (21), significantly reduced NPMc ubiquitination and restored NPMc stability in FA-A cells | SIGNOR-271490 |
O75914 | Q99523 | 1 | phosphorylation | down-regulates activity | 0.2 | PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction. | SIGNOR-273719 |
Q15139 | P61073 | 1 | phosphorylation | down-regulates quantity | 0.2 | Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR responsive cells in vitro.|This cascade consisted on a novel BCR dependent pathway in which PI3K-delta phosphorylates PKD, which in turn phosphorylates CXCR4 at Ser 324/325. | SIGNOR-279263 |
Q13882 | P78357 | 1 | phosphorylation | up-regulates activity | 0.2 | As a consequence, Brk stimulates p190 and attenuates p120 functions, leading to RhoA inactivation and Ras activation, respectively.|Brk phosphorylates p190 at the Y (1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120RasGAP (p120). | SIGNOR-279274 |
P25098 | P20941 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of phosducin by GRK2 markedly reduces its G beta gamma binding ability|The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of protein, respectively). | SIGNOR-279411 |
P36888 | Q9NTG7 | 1 | phosphorylation | down-regulates activity | 0.2 | We also hypothesize that, besides activating ACAT1 through Y407 phosphorylation (Fan et al., 2016), FLT3 might simultaneously phosphorylate and regulate SIRT3. Our mutational studies on all of the seven tyrosine sites of SIRT3 revealed that purified rFLT3 directly phosphorylated purified rSIRT3 in an in vitro kinase assay, leading to decreased SIRT3 deacetylase activity that was assessed by ability to deacetylate K413 of mIDH2 (Figure 4H, first three samples in left, middle, and right panels), whereas replacement of Y226 completely abolished inhibition of SIRT3 by FLT3 (Figure 4H, right). | SIGNOR-267631 |
Q5TCX8 | Q02750 | 1 | phosphorylation | up-regulates activity | 0.2 | These experiments showed that MEK1 is phosphorylated by MLK4 on Ser217/221 | SIGNOR-260767 |
P07947 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276185 |
O60260 | Q8IXI1 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. | SIGNOR-272726 |
P68400 | Q15019 | 1 | phosphorylation | down-regulates | 0.2 | Here we show that human septin 2 is phosphorylated in vivo at ser218 by casein kinase ii. Septin 2 binds and hydrolyses gtp. The purified protein has the capacity to polymerize into long filaments when loaded with gtp or gdp. Moreover, we show that the endogenous protein in hela cells, like that produced in insect cells, is phosphorylated by casein kinase ii and that this phosphorylation alters nucleotide binding. | SIGNOR-148010 |
Q05655 | Q96D96 | 1 | phosphorylation | up-regulates activity | 0.2 | HVCN1S is phosphorylated more by PKC-δ than HVCN1L. PKC-δ in vitro kinase assay showing phosphorylation of HVCN1 | SIGNOR-273827 |
P48729 | O60716 | 1 | phosphorylation | up-regulates activity | 0.2 | Moreover, CK1α phosphorylates p120-catenin on Ser268 and Ser269, releasing this protein from the signalosome and facilitating the subsequent phosphorylation of cadherin and the disruption of this cadherin interaction with LRP5/6 | SIGNOR-277893 |
P23458 | Q9NZJ5 | 1 | phosphorylation | up-regulates activity | 0.2 | JAK1 interacts with and phosphorylates PERK. PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation. Similarly, PERK is associated with and phosphorylated by JAK1 at Y585 and Y619 (and possibly other JAKs) during ER stress, resulting in PERK- and JAK1-dependent activation of STAT3. | SIGNOR-276677 |
Q9Y5I2 | Q9Y5G4 | 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-265700 |
Q8NHY2 | Q8NHY2 | 2 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | MTA1 destabilizes COP1 by promoting its autoubiquitination. in addition to polyubiquitination of its substrates, COP1 also catalyzes its autoubiquitination for degradation as a part of an autoregulatory mechanism | SIGNOR-271893 |
Q9BY66 | P68431 | 1 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264308 |
P05771 | Q8NER1 | 2 | phosphorylation | up-regulates activity | 0.2 | PKCβII causes the downregulation of TRPV1 by phosphorylating the channel. The increased threonine phosphorylation was substantially reduced by mutating Thr705, showing that Thr705 is indeed a major PKCβII phosphorylation site. | SIGNOR-276638 |
Q12857 | P29322 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268896 |
P46934 | P60321 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.|To examine whether complex formation of NEDD4 and NDFIP2 promotes NANOS2 ubiquitination in vivo, FLAG tagged NANOS2 was expressed in HEK293 cells with or without MYC-NEDD4 and MYC-NDFIP2. | SIGNOR-278770 |
P52564 | Q9NQU5 | 1 | phosphorylation | up-regulates | 0.2 | Moreover, pak6 was directly activated by mkk6, and mutation of tyrosine 566 in a consensus mkk6 site (threonine-proline-tyrosine, tpy) in the activation loop of the pak6 kinase domain prevented activation by mkk6. | SIGNOR-130975 |
P07711 | P59594 | 1 | cleavage | up-regulates activity | 0.2 | A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection. | SIGNOR-260218 |
P11226 | P59594 | 1 | binding | down-regulates activity | 0.2 | We have demonstrated that MBL selectively binds to SARS-S pseudotyped virus and can inhibit SARS-CoV infection in susceptible cell lines. Our results identified a single N-linked glycosylation site, N330, on S glycoprotein as the target for the specific interactions between MBL and SARS-CoV and provide evidence that the viral interaction with MBL did not affect its interaction with the ACE2 receptor. Binding to MBL did not affect SARS-S interactions with the ACE2 receptor. Furthermore, MBL-mediated inhibition occurred at a step prior to CTSL-mediated activation of SARS-S fusion. Thus, we suggest that the binding of the MBL may interfere with the induction of conformational changes within the S glycoprotein and thus prevent an early, postreceptor-binding event. | SIGNOR-260285 |
P63279 | P59595 | 1 | sumoylation | up-regulates activity | 0.2 | In this study, we identified Ubc9 as a host protein that interacts specifically with SARS-CoV N protein. This interaction was verified both in vivo and in vitro. Furthermore, we showed that, in addition to phosphorylation, the N protein was modified by covalent attachment of SUMO to its lysine 62 residue. Evidence provided demonstrated that sumoylation may promote homo-oligomerization of the protein. | SIGNOR-260263 |
P10912 | Q13163 | 1 | phosphorylation | up-regulates activity | 0.2 | The MEK5-dependent activation of ERK5 promotes binding of the transcription factor SP1 to the promoter of the genes encoding the transcription factors Klf2 and Klf4, leading to their increased abundance. Subsequently, Klf2 and Klf4 bind to the Npnt promoter and induce the production of nephronectin during myoblast fusion | SIGNOR-255452 |
P05771 | P49768 | 1 | phosphorylation | up-regulates activity | 0.2 | 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-249237 |
Q13315 | Q03112 | 1 | phosphorylation | up-regulates activity | 0.2 | To investigate to what extent EVI1 function might be regulated by post-translational modifications we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif. | SIGNOR-273433 |
Q9NR48 | Q16620 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Depletion of ASH1L decreases neurite outgrowth and decreases expression of the gene encoding the neurotrophin receptor TrkB whose signaling pathway is linked to neuronal morphogenesis. | SIGNOR-269058 |
P24752 | P29803 | 1 | acetylation | down-regulates activity | 0.2 | We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1) | SIGNOR-267634 |
P49840 | Q9NZQ7 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. | SIGNOR-277552 |
P17612 | O76054 | 1 | phosphorylation | up-regulates activity | 0.2 | These results suggest that phosphorylation of SPF by PKA is a dynamic process and that, in the absence of PKA activity, SPF is rapidly inactivated.Thus, phosphorylation of SPF at Ser-289 appears necessary for maximal stimulation of squalene monooxygenase activity in vitro and absolutely required for the stimulation of cholesterol synthesis in cell culture. | SIGNOR-276027 |
P18848 | O95750 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Reporter gene analyses using the 5'-promoter region of FGF19 revealed that a functional AARE (amino-acid-response element) was localized in this region, and this site was responsible for inducing its transcription through ATF4 (activating transcription factor 4), which is activated in response to ER stress | SIGNOR-253727 |
O00743 | Q8N884 | 1 | dephosphorylation | down-regulates activity | 0.2 | In this study, we found that PPP6C suppressed phosphorylation of human cGAS (hcGAS) at S435 or mouse cGAS (mcGAS) at S420 in its substrate-binding pocket, thus preventing its binding to GTP and inhibiting the synthesis of cGAMP.|These data suggest that PPP6C inhibits cGAS activity. | SIGNOR-276990 |
Q92914 | Q15858 | 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-253426 |
Q14680 | Q05397 | 1 | phosphorylation | up-regulates activity | 0.2 | As the aforementioned results showed that MELK promotes FAK phosphorylation, and it is well known that FAK is an important regulator of cell migration and invasion, we speculated that MELK could regulate cell migration and invasion via the FAK/Paxillin pathway.|Finally, knockdown of MELK decreased the phosphorylation of the FAK and paxillin, and prevented gastrin stimulated FAK and paxillin phosphorylation. | SIGNOR-279230 |
Q13131 | P14859 | 1 | phosphorylation | down-regulates | 0.2 | Mitosis-specific phosphorylation site in the homeodomain of oct-1 was phosphorylated in vitro by protein kinase a. Pka-mediated phosphorylation event was identified in the cns-specific pou domain protein brn-2/n-oct-3/pou3f2 (nieto et al. 2007). In this case, the modification, at a position homologous to oct1 s385, was found to alter binding specificity for complex dimeric sites. | SIGNOR-53254 |
P16066 | P52961 | 1 | phosphorylation | down-regulates activity | 0.2 | Art1 is a substrate for the kinase Npr1, which phosphorylates Art1 and, thereby, causes its inactivation by limiting its plasma membrane association. | SIGNOR-279239 |
Q8WY64 | Q8WY64 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MIR contains, beside the ERM domain, a RING zinc finger region. The present study shows that the ubiquitin ligase activity of the RING can also be directed towards the protein itself indicating that the degradation of MIR can be regulated by autoubiquitination. | SIGNOR-271480 |
Q13191 | P42226 | 1 | ubiquitination | down-regulates quantity | 0.2 | Having shown that Cbl-b negatively regulates Stat6, we further investigated the mechanism of this regulation by determining whether Cbl-b associates with Stat6.|Our data demonstrate that Stat6 is ubiquitinated at K108 and K398 by Cbl-b, and that Stat6 ubiquitination is a critical post-translational regulatory mechanism for Stat6. | SIGNOR-278806 |
Q05655 | P49715 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We next demonstrated by immunoprecipitation that IL-32\u03b2 interacted with PKC\u03b4 and C/EBP\u03b1, thereby mediating C/EBP\u03b1 Ser-21 phosphorylation by PKC\u03b4. | SIGNOR-279427 |
Q8TDB6 | P62805 | 1 | monoubiquitination | down-regulates activity | 0.2 | Herein, we demonstrate that BBAP selectively monoubiquitylates histone H4 lysine 91 and protects cells exposed to DNA-damaging agents. Disruption of BBAP-mediated monoubiquitylation of histone H4K91 is associated with the loss of chromatin-associated H4K20 methylase, mono- and dimethyl H4K20, and a delay in the kinetics of 53BP1 foci formation at sites of DNA damage. In response to DNA damage, BBAP expression increases and the E3 ligase selectively monoubiquitylates H4K91. Disruption of BBAP-mediated monoubiquitylation of H4K91 is associated with loss of chromatin-associated PR-Set7/Set8 and mono- and dimethyl H4K20, delayed kinetics of 53BP1 foci formation and increased sensitivity to DNA damage. | SIGNOR-271897 |
O43293 | O43293 | 2 | phosphorylation | up-regulates | 0.2 | Mutational analysis showed that phosphorylation of thr180 in the kinase activation t-loop, thr225 in the substrate-binding groove, and thr265 in kinase subdomain x is essential for full zipk autophosphorylation and activity toward exogenous substrates. | SIGNOR-132463 |
Q13188 | P18754 | 1 | phosphorylation | up-regulates | 0.2 | MST2 Phosphorylates RCC1 In Vitro and In Vivo. Using an antibody generated against phospho-S2/11 in RCC1 [18], we found that these two residues were also efficiently phosphorylated by MST1 and MST2 (Figure 2D), further supporting that S2 and/or S11 are genuine MST2 phosphorylation targets. | SIGNOR-263146 |
Q9P289 | Q8TDY4 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545|Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction. | SIGNOR-272238 |
Q6PHR2 | Q6PHR2 | 2 | phosphorylation | up-regulates activity | 0.2 | We show that ULK3 autophosphorylation occurs at four serine residues (Ser-300, Ser-350, Ser-384, and Ser-464) situated outside of the KD | Thus, autophosphorylation of ULK3 may involve conformational changes resulted in exposure of CTD to KD and consequently in generation of the catalytically active kinase. | SIGNOR-260794 |
P17252 | Q6UVK1 | 1 | phosphorylation | up-regulates activity | 0.2 | Protein kinase C (PKC)-alpha phosphorylation of recombinant NG2 cytoplasmic domain and phorbol ester-induced PKC-dependent phosphorylation of full-length NG2 expressed in U251 cells are both blocked by mutation of Thr(2256), identifying this residue as a primary phosphorylation site. PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is therefore a key step for initiating cell polarization and motility. | SIGNOR-263162 |
P16520 | P19174 | 1 | binding | up-regulates | 0.2 | Furthermore, this work suggested that the g subunits released upon gi activation activated phospholipase c (plc- ) to produce inositol 3-phosphate (ip3), which would subsequently increase intracellular ca2+ abundance. | SIGNOR-199135 |
Q13164 | P43354 | 1 | phosphorylation | up-regulates activity | 0.2 | Activation of MEK, which in turns activates ERK5, does enhance the ERK5 induced nurr1 activity, while no increase is observed in the presence of a dn MEK5 or of the unphosphorylated ERK5 AEF, in which amino acids phosphorylated by MEK5 are mutated.|The A/B domain of nurr1 is highly phosphorylated in the presence of ERK5 and mutations of two amino acids in this same domain decrease significantly the ERK5 mediated nurr1 transcriptional response.|These data would suggest once again that the basal activity of ERK5 is responsible for the phosphorylation of nurr1.|As shown in XREF_FIG, nurr1 A/B domain was significantly phosphorylated by ERK5, while the GST protein alone was not a substrate for this kinase. | SIGNOR-279215 |
Q9C0A6 | Q16695 | 1 | methylation | up-regulates activity | 0.2 | SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription. | SIGNOR-264621 |
P01189-PRO_0000024969 | Q01726 | 1 | binding | up-regulates activity | 0.2 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268701 |
P05771 | P68104 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein. | SIGNOR-263167 |
P20962 | Q15788 | 1 | binding | up-regulates activity | 0.2 | Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells. | SIGNOR-268462 |
P18848 | Q6PI48 | 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-269418 |
Q2TAL8 | Q9BW92 | 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-269407 |
P35226 | P35226 | 2 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here, we report that BMI1 autoactivates its own promoter via an E-box present in its promoter. | SIGNOR-245344 |
Q9Y6R4 | Q9Y6R4 | 2 | phosphorylation | up-regulates activity | 0.2 | Gadd45 binding also induced mtk1 dimerization via a dimerization domain containing a coiled-coil motif, which is essential for the trans autophosphorylation of mtk1 at thr-1493 in the kinase activation loop. | SIGNOR-152408 |
P11309 | Q13200 | 1 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273895 |
O75144 | Q9Y6W8 | 1 | binding | up-regulates activity | 0.2 | ICOSL expression is largely restricted to professional antigen-presenting cells (APCs), including B cells [in which ICOSL is regulated by BAFFR and non-canonical NFκB signaling (20)], macrophages, and dendritic cells (DCs) (12, 17, 21, 22), but is also expressed by certain endothelial cells (23) and lung epithelium | SIGNOR-272497 |
P17612 | Q13526 | 1 | phosphorylation | down-regulates activity | 0.2 | Pka and pkc readily phosphorylated pin1 and its ww domain in summary, we have demonstrated that phosphorylation of the pin1 ww domain on ser16 regulates its ability to function as a pser/thr-binding module. |To examine the importance of Ser16 of Pin1, it was mutated to Glu to mimic pSer, and the mutant Pin1S16E failed to bind mitotic phosphoproteins | SIGNOR-112164 |
Q9Y4D8 | P01106 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop. | SIGNOR-267146 |
P25098 | P32245 | 1 | phosphorylation | down-regulates activity | 0.2 | Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor. | SIGNOR-247770 |
Q99835 | P16520 | 1 | binding | up-regulates | 0.2 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling as pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp | SIGNOR-199180 |
Q9Y5I2 | Q9Y5F6 | 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-265705 |
Q5T0W9 | Q8N752 | 1 | binding | up-regulates quantity | 0.2 | 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-273754 |
P42345 | O60260 | 1 | phosphorylation | down-regulates activity | 0.2 | MTOR phosphorylates PARK2 at Ser127 Through biochemical, mutational, and genetic studies, we identified PARK2 as a mTORC1 substrate. mTORC1 phosphorylates PARK2 at Ser127, which blocks its cellular ubiquitination activity, thereby hindering its tumor suppressor effect on eIF4B's stability. | SIGNOR-277586 |
P49841 | O95997 | 1 | phosphorylation | down-regulates activity | 0.2 | Glycogen synthase kinase-3beta (GSK3beta) negatively regulates PTTG1 and human securin protein stability, and GSK3beta inactivation correlates with securin accumulation in breast tumors.|Here, we demonstrate that glycogen synthase kinase-3\u03b2 (GSK3\u03b2) phosphorylates securin to promote its proteolysis via SCF(\u03b2TrCP) E3 ubiquitin ligase. | SIGNOR-279188 |
Q86Z02 | P10242 | 1 | phosphorylation | down-regulates activity | 0.2 | C-Myb appears to be phosphorylated by HIPK1 in its negative regulatory domain as supported by both in vivo and in vitro data. | SIGNOR-279189 |
Q9H2X6 | P06276 | 1 | phosphorylation | down-regulates quantity | 0.2 | As shown in XREF_FIG, HIPK2 overexpression strongly reduced Myc-Che-1 levels, whereas it produced little effect on Che-1 T144A expression.|Notably, we found that HIPK2 phosphorylates a specific residue of Che-1, which is required for its interaction with Pin1 and for its degradation through the proteasome pathway. | SIGNOR-279190 |
Q9H2X6 | P15923 | 1 | phosphorylation | down-regulates activity | 0.2 | This result provides a mechanistic explanation for the context-dependent function of HIPK2 in Wnt signaling | SIGNOR-279193 |
P17252 | Q92934 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of BAD at ser112 and ser136 in the setting of lapatinib treatment was fully restored by PRKACA expression in BT474, SKBr3, and ZR-75-30 cells (XREF_FIG).|We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro apoptotic protein BAD, thereby permitting survival signaling through BCL-XL. | SIGNOR-280080 |
P24723 | Q9BZL6 | 1 | phosphorylation | up-regulates | 0.2 | Thus, pkd2 is likely to be a novel downstream target of specific pkcs upon the stimulation of ags-b cells with gastrin. Our data suggest a two-step mechanism of activation of pkd2 via endogenously produced diacylglycerol and the activation of pkcs. | SIGNOR-89431 |
Q92831 | Q5TEC6 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269624 |
P0C6X7-PRO_0000037311 | Q86WV6 | 1 | binding | down-regulates activity | 0.2 | Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING | SIGNOR-260247 |
P35790 | Q9H6E5 | 1 | phosphorylation | up-regulates activity | 0.2 | Our data indicate that the kinase activities of both the isoforms of CKI -- alpha and epsilon modulate Star-PAP polyadenylation activity and target mRNAs.|Taken together, these data suggest that phosphorylation of Star-PAP by CKI modulates the Star-PAP polyadenylation activity downstream of stimulation by oxidant stress and phosphorylation primes Star-PAP, so that it can be stimulated by PI4,5 P 2. | SIGNOR-279162 |
P41240 | Q00987 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that activated c-Src kinase phosphorylates Y281 and Y302 of Mdm2, resulting in an increase in Mdm2 stability and its association with Ubc12, the E2 enzyme of the neddylating complex. | SIGNOR-279163 |
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