IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P42229 | P52333 | 0 | phosphorylation | up-regulates | 0.854 | For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated. | SIGNOR-182817 |
Q13444 | P08631 | 0 | phosphorylation | up-regulates | 0.355 | Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling. | SIGNOR-112919 |
P29597 | Q8N6P7 | 2 | binding | up-regulates | 0.542 | Il-22 activates jak1 and tyk2 | SIGNOR-90165 |
Q13490 | P06730 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.401 | We found that endogenous eIF4E was ubiquitinated by cIAP1, and ubiquitinated eIF4E accumulated upon MG132 treatment. | SIGNOR-278741 |
P48357 | O60674 | 2 | binding | up-regulates activity | 0.774 | Janus kinase 2 (JAK2) is associated with LEPRb and autophosphorylates in response to leptin. JAK2 also phosphorylates LEPRb, STAT3, and multiple other downstream molecules. | SIGNOR-263491 |
P38936 | Q9H0Z9 | 0 | post transcriptional regulation | up-regulates quantity by stabilization | 0.318 | Here, we found that RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript. | SIGNOR-275391 |
Q92997 | Q92837 | 2 | binding | up-regulates | 0.454 | These results indicate that cki epsilon-dependent phosphorylation of dvl enhances the formation of a complex of dvl-1 with frat-1 and that this complex leads to the activation of the wnt signaling pathway. | SIGNOR-97877 |
P31431 | O43184 | 2 | binding | up-regulates | 0.466 | The adam12 cysteine-rich domain (radam12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers beta(1) integrin-dependent cell spreading, stress fiber assembly, and focal adhesion formation. | SIGNOR-96931 |
P08670 | P05771 | 0 | phosphorylation | up-regulates quantity | 0.2 | PKCbeta induces vimentin phosphorylation in MCP-1-activated human monocytes. | SIGNOR-278984 |
P10826 | P19793 | 2 | binding | up-regulates | 0.682 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins. | SIGNOR-16519 |
P00533 | Q99675 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | CGRRF1 ubiquitinates EGFR through K48-linked ubiquitination, which leads to proteasome degradation. | SIGNOR-272220 |
P34947 | P61073 | 1 | phosphorylation | down-regulates quantity | 0.459 | Conversely, GRK5 knock-down in cells with low WIP1 expression inhibited CXCR4 phosphorylation, increased cell membrane expression of CXCR4, and promoted medulloblastoma growth.|Transfection of GRK5 into D556-WIP1 cells increased Ser339 phosphorylation of CXCR4 and reduced proliferation. | SIGNOR-279740 |
P39748 | P06493 | 0 | phosphorylation | down-regulates activity | 0.446 | Phosphorylation of human fen1 by cyclin-dependent kinase modulates its role in replication fork regulation.As a functional consequence of phosphorylation by cdk1-cyclin a in vitro, endo- and exonuclease activities of fen1 are reduced whereas its dna binding is not affected. | SIGNOR-103535 |
O75581 | P43250 | 0 | phosphorylation | up-regulates activity | 0.345 | In contrast to the GRK5 and GRK6 stimulated activity of wild-type LRP6, the LRP6 M5 mutant failed to respond to the expression of GRK5 or GRK6 (XREF_FIG C) by increased TOPflash reporter activity, indicating that PPPSP motifs are indispensable for GRK5- and GRK6 mediated LRP6 activation.|Our findings that GRK5 and GRK6 phosphorylate the single membrane-spanning receptor LRP6 on defined serine/threonine sites ( i.e. serine 1490) within proline-rich PPPSP motifs and thereby activate LRP6 are important and interesting in two respects. | SIGNOR-279412 |
Q14938 | O75093 | 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-268906 |
P01106 | P15884 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.371 | Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription. | SIGNOR-253324 |
Q8NEB9 | P60484 | 2 | binding | up-regulates | 0.665 | Direct positive regulation of pten by the p85 subunit of phosphatidylinositol 3-kinase.Thus p85 regulates both p110-pi3k and pten-phosphatase enzymes through direct interaction | SIGNOR-164075 |
Q96GD4 | Q69YH5 | 1 | phosphorylation | down-regulates activity | 0.446 | This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin. | SIGNOR-274001 |
Q9Y294 | Q14676 | 2 | binding | up-regulates activity | 0.311 | Chk1 activated by ataxia telangiectasia mutated (ATM) kinase on DNA breaks in G1 promotes NHEJ through direct phosphorylation of ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with the repair protein MDC1 and thus enhances MDC1's interaction with ATM and the stable localization of ATM at DNA breaks. | SIGNOR-277621 |
P38936 | P45983 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.672 | The stress-activated protein kinases p38 alpha and jnk1 stabilize p21(cip1) by phosphorylation.|p38 alpha and JNK1 phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at Ser(130) in vitro. | SIGNOR-89440 |
P41743 | 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-251635 |
Q86U44 | P28482 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.273 | Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex. | SIGNOR-265948 |
P35346 | P09471 | 2 | binding | up-regulates activity | 0.28 | 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-256969 |
P05412 | P45983 | 0 | phosphorylation | up-regulates activity | 0.907 | JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain. | SIGNOR-250122 |
P06241 | Q12913 | 1 | phosphorylation | up-regulates activity | 0.366 | We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1-catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin. | SIGNOR-276372 |
O15357 | P12931 | 0 | phosphorylation | up-regulates | 0.535 | Ship2 could be phosphorylated in vitro by recombinant src kinase and tyrosines 986-987 in the npxy motif of ship2 appear to be the major sites of phosphorylation for src both in vitro and in vivo. | SIGNOR-92935 |
P53350 | O60563 | 1 | phosphorylation | down-regulates activity | 0.379 | Further analysis indicated that Plk1 could phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. | SIGNOR-276501 |
Q06124 | P62993 | 2 | binding | up-regulates activity | 0.737 | SHP-2 is thus a positive regulator of ERK by leptin receptors, and both the adaptor function and the phosphatase activity of SHP-2 are critical for this regulation. Based on these data, we conclude that tyrosinephosphorylation of SHP-2 is a mediator of ERK activation viaTyr-985. This is likely to occur via Grb-2 binding to SHP-2 atthe C terminus followed by activation of the Ras-Raf pathwayas suggested for other signaling systems (55, 56) and morerecently for the leptin receptor (33). | SIGNOR-263498 |
Q06124 | Q14289 | 1 | dephosphorylation | down-regulates activity | 0.725 | We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. |We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM..... 1) RAFTK is a substrate of SHP2 in vitro and 2) dephosphorylation of RAFTK by SHP2 inhibits its kinase activity. | SIGNOR-277084 |
P27361 | Q15418 | 1 | phosphorylation | up-regulates activity | 0.718 | Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3. | SIGNOR-102648 |
P23467 | P27361 | 1 | dephosphorylation | up-regulates | 0.432 | When cells are stimulated with various ligands such as growth factors, hormones, neurotransmitters, or tumor promoters, erk1/2 is activated through dualphosphorylation at the -ptepy-motif. Subsequently, p-erk1/2 translocates into the nucleus and phosphorylates elk-1, thereby acting as a transcription factor for cell proliferationthese data indicate that sa-p-erk1/2 might not only be regulated by mkp such as rvhr, but also by pp1 and ptp as well | SIGNOR-103165 |
Q12778 | P35558 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.428 | Phosphorylated foxo1 is inactive and retained in the cytosol. Mkp-3 mediated dephosphorylation activates foxo1 and subsequentially promotes its nuclear translocation and binding to the promoters of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (pepck) and glucose-6-phosphatase (g6pase). | SIGNOR-197200 |
Q9Y5F8 | Q9Y5H9 | 2 | 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-265689 |
Q9UHD2 | O15379 | 1 | phosphorylation | up-regulates activity | 0.2 | The feedback of activation of HDAC3 by TBK1 was able to further enhance IFN production and IFN-STAT activation.|We found that HDAC3 could be phosphorylated by TBK1. | SIGNOR-279662 |
Q8NEB9 | Q14457 | 2 | binding | up-regulates activity | 0.936 | The beclin 1-vps34 interaction regulates autophagy. | SIGNOR-184521 |
P53350 | Q8TD19 | 1 | phosphorylation | up-regulates activity | 0.611 | We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1. | SIGNOR-273888 |
Q05901 | P25054 | 2 | binding | up-regulates activity | 0.2 | Treatment of muscle cells with neural agrin causes tyrosine phosphorylation of the AChR β subunit and induces AChR clustering by promoting anchoring of the receptor protein to postsynaptic cytoskeleton. Regulation of acetylcholine receptor clustering by the tumor suppressor APC. By showing a direct requirement for APC in AChR clustering, our present study suggests that the Wnt/β-catenin pathway may crosstalk with the agrin signaling cascade during the formation of mammalian neuromuscular junction. | SIGNOR-264261 |
P17612 | P48436 | 1 | phosphorylation | up-regulates | 0.465 | We find that activation of camp-dependent protein kinase a (pka) induces phosphorylation of sox9 on its two s64 and s181 pka sites, and its nuclear localization by enhancing sox9 binding to the nucleocytoplasmic transport protein importin beta. | SIGNOR-137085 |
P10721 | P35232 | 1 | phosphorylation | up-regulates activity | 0.2 | In this study, we showed that c-Kit associates with PHB to upregulate phospho-PHB in the lipid raft of the plasma membrane.|c-Kit phosphorylates PHB at the Tyr259 residue. | SIGNOR-278362 |
P35499 | P61328 | 2 | binding | down-regulates activity | 0.255 | 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-253432 |
P22681 | Q8TBZ2 | 1 | monoubiquitination | up-regulates activity | 0.298 | We moreover found that AMAP1 is monoubiquitinated, rather than polyubiquitinated, by virtue of Cbl and provide evidence that the ability of AMAP1 to be monoubiquitinated is important for its involvement in invasion. | SIGNOR-272627 |
P16104 | O60934 | 2 | binding | up-regulates | 0.2 | Nbs1 physically interacts with ?-H2ax to form nuclear foci at dna damage sites. The inhibition of this interaction by introduction of anti-?-H2ax antibody into cells abolishes nbs1 foci formation in response to dna damage. | SIGNOR-133020 |
Q13464 | O14649 | 1 | phosphorylation | down-regulates | 0.2 | Task1 channels contain two putative rho kinase phosphorylation sites, ser(336) and ser(393) . Mutation of ser(393) rendered task1 channels insensitive to et(a) - or et(b)-mediated current inhibition. In contrast, removal of ser(336) selectively attenuated et(a) -dependent task1 regulation without affecting the et(b) pathway. | SIGNOR-176025 |
O14965 | O95239 | 1 | phosphorylation | up-regulates activity | 0.419 | We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C). | SIGNOR-265993 |
P35222 | O00512 | 2 | binding | up-regulates | 0.938 | The transcriptional activity of beta-catenin depends on bcl-9. Bcl-9 functions in targeting beta-catenin to the nucleus and thus increases the transcriptional activity of beta-catenin | SIGNOR-126059 |
Q9H1Y0 | Q8IZQ1 | 2 | binding | up-regulates quantity | 0.598 | Alfy is recruited to intracellular inclusions and scaffolds a complex between p62(SQSTM1)-positive proteins and the autophagic effectors Atg5, Atg12, Atg16L and LC3. Alfy directly interacts with Atg5 and can be found in a complex with Atg5, Atg12 and Atg16L | SIGNOR-266791 |
Q13546 | Q9NYJ8 | 2 | binding | up-regulates activity | 0.864 | TNF_ induced the polyubiquitination of RIP and the association of polyubiquitinated RIP with TAB2. | SIGNOR-128406 |
Q8NB16 | P34972 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Under hyperglycemic conditions, high glucose induced CB2R internalization in a β-arrestin 2-dependent manner; thereafter, MLKL (mixed lineage kinase domain-like), but not receptor-interacting protein kinase 1 or 3, phosphorylated CB2R at serine 352 and promoted CB2R degradation by ubiquitin modification. CB2R transcriptionally repressed necroptosis through interaction with BACH2; in turn, MLKL formed a negative feedback to phosphorylate CB2R. | SIGNOR-274121 |
Q92915 | P35499 | 2 | binding | down-regulates activity | 0.26 | 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-253433 |
P68400 | P27986 | 1 | phosphorylation | up-regulates activity | 0.246 | Protein kinase CK2 phosphorylates p85α on Ser608 when p85α is free but not when it is complexed with p110α. | SIGNOR-276005 |
P31269 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.323 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260025 |
P41252 | P18848 | 0 | 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-269427 |
P04626 | P19174 | 2 | binding | up-regulates | 0.649 | Activated egfr binds the sh2 domain of phospholipase c-gamma (plc-gamma), activating plc-gamma-mediated downstream signaling. | SIGNOR-20815 |
Q8IZQ1 | Q9H1Y0 | 2 | binding | up-regulates quantity | 0.598 | Alfy is recruited to intracellular inclusions and scaffolds a complex between p62(SQSTM1)-positive proteins and the autophagic effectors Atg5, Atg12, Atg16L and LC3. Alfy directly interacts with Atg5 and can be found in a complex with Atg5, Atg12 and Atg16L | SIGNOR-266791 |
Q8IYK4 | P02461 | 1 | glycosylation | up-regulates activity | 0.404 | Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues. | SIGNOR-261158 |
P53350 | Q8TEP8 | 1 | phosphorylation | up-regulates activity | 0.608 | In the presence of AurA binding, Plk1 preferentially phosphorylates and interacts with the T44 motif of Cep192 through the “self-priming and binding” mechanism | SIGNOR-266405 |
P00441 | P10415 | 2 | binding | up-regulates activity | 0.507 | Familial amyotrophic lateral sclerosis (ALS)-linked mutations in the copper-zinc superoxide dismutase (SOD1) gene cause motor neuron death in about 3% of ALS cases. While the wild-type (wt) protein is anti-apoptotic, mutant SOD1 promotes apoptosis.|We now demonstrate that both wt and mutant SOD1 bind the anti-apoptotic protein Bcl-2, providing evidence of a direct link between SOD1 and an apoptotic pathway. This interaction is evident in vitro and in vivo in mouse and human spinal cord.|These findings provide new insights into the anti-apoptotic function of SOD1 and suggest that entrapment of Bcl-2 by large SOD1 aggregates may deplete motor neurons of this anti-apoptotic protein. | SIGNOR-262799 |
P30304 | P24941 | 2 | dephosphorylation | up-regulates activity | 0.83 | The phosphatase activity of Cdc25A is necessary for Cdk2 activation, most likely due to dephosphorylation on Tyr-15 and Thr-14 of Cdk2. | SIGNOR-248481 |
P63000 | P53602 | 0 | 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 |
O00401 | O43516 | 2 | binding | up-regulates activity | 0.933 | Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP-WIP complex. | SIGNOR-261880 |
P09471 | P47900 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257185 |
Q15208 | P30304 | 1 | phosphorylation | down-regulates quantity | 0.247 | Here, we demonstrate that the depletion of serine-threonine kinase 38 (STK38) prevents the DNA-damage-induced degradation of CDC25A and subsequent G2 arrest, and that STK38 directly phosphorylates CDC25A at Ser-76, resulting in CDC25A's degradation. | SIGNOR-279488 |
Q15853 | P78347 | 2 | binding | up-regulates activity | 0.347 | TFII-I has been shown to interact with USF and to associate with either E-box elements or initiator sequences to activate gene transcription | SIGNOR-268537 |
P13807 | Q13627 | 0 | phosphorylation | down-regulates activity | 0.267 | DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity. | SIGNOR-260632 |
O95453 | Q7Z2W4 | 2 | binding | up-regulates activity | 0.414 | We provide evidence indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA exosome to degrade the RNA body from the 3′ end. | SIGNOR-261296 |
P17612 | Q13936 | 1 | phosphorylation | up-regulates activity | 0.498 | These findings reveal an essential role for _1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes | SIGNOR-251709 |
O00712 | P41221 | 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-268883 |
Q13444 | P06239 | 0 | phosphorylation | up-regulates | 0.349 | Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling. | SIGNOR-112931 |
Q15139 | Q15139 | 2 | phosphorylation | up-regulates | 0.2 | Activation of the serine/threonine kinase, protein kinase d (pkd/pkc mu) via a phorbol ester/pkc-dependent pathway involves phosphorylation events. the second autophosphorylation site (ser(203)) lies in that region of the regulatory domain | SIGNOR-78676 |
Q96SN8 | P05067 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | The APPcyt is phosphorylated at Thr668 in vivo specifically in the brain. Cyclin‐dependent kinase 5 (Cdk5), a unique member of the Cdk family that is implicated in central nervous system development, participates in this phosphorylation. | In the present study, we demonstrate that APP phosphorylated at Thr668 is less vulnerable to cytoplasmic cleavage by caspase-3 and caspase-8. | SIGNOR-260818 |
Q96RG2 | P61964 | 1 | phosphorylation | up-regulates activity | 0.307 | Pask directly interacts with and phosphorylates Wdr5 at Ser49.|We therefore believe that differentiation cues act, at least in part, to drive the myogenic transcriptional program via Pask activation and phosphorylation of Wdr5. | SIGNOR-278266 |
P52735 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates | 0.761 | Vav2 activates rac1 / vav2 is an exchange factor for rho family gtpases. | SIGNOR-81645 |
Q6PML9 | P49757 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation. | SIGNOR-113704 |
P11171 | P00533 | 0 | phosphorylation | down-regulates | 0.4 | The phosphorylation site has been localized to the 8-kda domain, which has one tyrosine, tyrosine-418. The 8-kda region is required for the assembly of the spectrin/actin complex, and phosphorylation by egfr reduced the ability of protein 4.1 to promote the assembly of the spectrin/actin/protein 4.1 ternary complex | SIGNOR-20452 |
O76064 | Q96AP0 | 1 | polyubiquitination | up-regulates quantity by stabilization | 0.2 | The Rnf8 RING-finger domain is essential for Tpp1 stability and retention at telomeres. Rnf8 physically interacts with Tpp1 to generate Ubc13-dependent Lys63 polyubiquitin chains that stabilize Tpp1 at telomeres. The conserved Tpp1 residue Lys233 is important for Rnf8-mediated Tpp1 ubiquitylation and localization to telomeres. | SIGNOR-272722 |
P00533 | Q16512 | 0 | 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 |
Q9UEW8 | Q9H4A3 | 0 | phosphorylation | up-regulates | 0.446 | Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1). | SIGNOR-151671 |
O60341 | Q9H3R0 | 2 | binding | up-regulates activity | 0.2 | JMJD2C was found to be co-localized with AR and LSD1 in the epithelium of prostate carcinoma and normal prostate cells. For the detailed mechanism, JMJD2C, AR and LSD1 assembled on the chromatin to remove the methyl groups from mono-, di- and trimethylated H3K9. Importantly, JMJD2C specifically removed the demethylation of the trimethyl H3K9 marks and modulated the transcriptional activity of AR. Moreover, JMJD2C cooperated with LSD1 and activated AR-mediated gene expression via decreasing H3K9me3 at the promoter of AR targeting genes KLK2 and PSA. | SIGNOR-263880 |
Q5VWQ8 | Q13309 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.267 | DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1 | SIGNOR-254775 |
Q96J92 | O95198 | 2 | binding | down-regulates quantity by destabilization | 0.519 | We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. | SIGNOR-272118 |
Q9BXM7 | O60260 | 1 | phosphorylation | up-regulates | 0.2 | We show that human pink1 is specifically activated by mitochondrial membrane potential (??m) depolarization, enabling it to phosphorylate parkin at ser(65). We further show that phosphorylation of parkin at ser(65) leads to marked activation of its e3 ligase activity that is prevented by mutation of ser(65) or inactivation of pink1. | SIGNOR-197976 |
Q9HCE7 | Q13243 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.262 | K125 was also the major site of SRSF5 ubiquitylation mediated by Smurf1.|Smurf1 targets SRSF5 for degradation upon low glucose | SIGNOR-278665 |
P04083 | Q96QT4 | 0 | phosphorylation | up-regulates | 0.544 | Trpm7 was responsible for phosphorylation of the serine 5 (ser5) residue [29]. In 2009, the study focused on an association between anxa1 and trpm7 confirmed the presence of a trpm7/annexin a1/mg2_+ complex, suggesting a novel pathway in bradykinin signaling, dependent on pkc and c-src [30]. Even though that pathway is not fully characterized, the same team that discovered the ser5 phosphorylation of anxa1 also reported crucial relevance of this modification for anxa1 membrane binding and especially for the interaction between annexin a1 and its known partner, the calcium binding protein s100a11 | SIGNOR-202804 |
Q9H4B4 | P04637 | 1 | phosphorylation | up-regulates activity | 0.706 | Upon exposure of cells to hydrogen peroxide (h(2)o(2)) phosphorylation of p53 was rapidly induced in human fibroblast gm00637, and this phosphorylation occurred on serine 9, serine 15, serine 20, but not on serine 392. In addition, h(2)o(2)-induced phosphorylation of p53 was followed by induction of p21, suggesting functional activation of p53. Ectopic expression of a plk3 dominant negative mutant, plk3(k52r), in gm00637 cells suppressed h(2)o(2)-induced serine 20 phosphorylation. Taken together, our studies strongly suggest that the oxidative stress-induced activation of p53 is at least in part mediated by plk3. | SIGNOR-109239 |
Q05655 | Q9Y6H6 | 1 | phosphorylation | up-regulates activity | 0.2 | Currents mediated by the complex formed by KCNQ1 and the mutant KCNE3-S82A β-subunit (mutation of the site for PKCdelta-promoted phosphorylation and modulation of the activity of KCNE3) showed rapid run-down and insensitivity to E2. | SIGNOR-275964 |
P04626 | P06493 | 1 | phosphorylation | down-regulates | 0.274 | Phosphorylation on tyrosine-15 of p34(cdc2) by erbb2 inhibits p34(cdc2) activation and is involved in resistance to taxol-induced apoptosis | SIGNOR-88671 |
Q8NCW0 | O75581 | 2 | binding | down-regulates | 0.639 | Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to block wnt/beta-catenin signalling. Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of the wnt receptor lrp6 from the plasma membrane. | SIGNOR-88894 |
Q8N4C6 | O60674 | 2 | binding | down-regulates | 0.242 | We showed that jak2 directly phosphorylates the n-terminus ofnineinwhile the c-terminus ofnineininhibits jak2 kinase activity in vitro. | SIGNOR-205581 |
P31749 | Q99683 | 1 | phosphorylation | down-regulates activity | 0.729 | Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1 akt decreased ask1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus akt site at serine 83 of ask1. | SIGNOR-252465 |
Q16649 | P04150 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.296 | GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription | SIGNOR-268051 |
Q9NPA3 | Q13085 | 2 | binding | up-regulates activity | 0.375 | Recently, we reported the discovery that MIG12, a 183 amino acid protein, binds to ACC1 and ACC2, which induces polymerization and subsequently increases the enzymatic activity of the protein | SIGNOR-267111 |
Q09472 | P04637 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.912 | P53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300. | SIGNOR-271418 |
P36952 | Q13547 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.413 | We found that maspin is selectively upregulated in IFIXα-expressing cells and involved in anti-invasive activity of IFIXα. We also present evidence indicating that IFIXα downregulates histone deacetylase 1 (HDAC1), which is possibly involved in the silencing of the maspin gene in human breast cancer cells. To confirm these results, we performed a luciferase assay using a maspin-promoter-luciferase plasmid. The results showed that HDAC1 overexpression suppressed the activity of the maspin promoter (Figure 3C). Therefore, our results suggest that IFIXα enhances maspin expression through the downregulation of HDAC1. | SIGNOR-268494 |
Q9P253 | Q9NYY3 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | VPS18 Ubiquitylates SNK in Vitro and in Vivo. The ubiquitylation of proteins by hVPS18 was selectively mediated by UbcH4. | SIGNOR-271550 |
Q8WV28 | Q9NRF2 | 0 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK. | SIGNOR-268446 |
Q9H0H3 | Q13541 | 2 | binding | down-regulates quantity by destabilization | 0.408 | We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination. | SIGNOR-272049 |
P40763 | Q13233 | 0 | phosphorylation | up-regulates activity | 0.291 | Phosphorylation of s727 induces pin1 binding which increases transcription. Pin1 binding increases stat3 interaction with p300 and dna. | SIGNOR-236346 |
O75674 | P06241 | 0 | phosphorylation | up-regulates activity | 0.434 | Tyr-457, located in the presumed Src SH2 binding site, is the predominant tyrosine residue that is phosphorylated by Fyn.Fyn can phosphorylate Srcasm, and association of these molecules relies on cooperative binding between the SH2 and SH3 domains of Fyn and corresponding canonical binding sites in Srcasm. Srcasm is capable of interacting with Grb2 and the regulatory subunit of phosphoinositide 3-kinase, p85, in a phosphorylation-dependent manner. The evidence suggests that Srcasm may help promote Src family kinase signaling in cells. | SIGNOR-251185 |
Q9HAZ1 | Q13285 | 1 | phosphorylation | up-regulates activity | 0.2 | Immunoblotting analyses showed that the phosphorylation status of NR5A1 at Ser203 was attenuated by the CLK1/4 inhibitor. | SIGNOR-274117 |
Q9Y2I6 | Q96GD4 | 0 | phosphorylation | up-regulates | 0.252 | Importantly, nlp is characterized as a novel substrate of aurora b and can be phosphorylated by aurora b. The specific phosphorylation sites are mapped at ser-185, ser-448, and ser-585. The phosphorylation at ser-448 and ser-585 is likely required for nlp association with aurora b and localization at midbody. Meanwhile, the phosphorylation at ser-185 is vital to nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability. | SIGNOR-168053 |
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