IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q8NG66 | P30304 | 1 | 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 |
Q13616 | P46527 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.642 | Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2 | SIGNOR-102725 |
P50750 | P10275 | 1 | phosphorylation | up-regulates activity | 0.537 | AR S81 phosphorylation by CDK9 is tightly linked to chromatin binding and transcriptional activation. | SIGNOR-279456 |
P19235 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.459 | In vivo interaction between EPO-R and PTP1B suggested that PTP1B dephosphorylates the EPO-R intracellularly.|Protein tyrosine phosphatase 1B participates in the down-regulation of erythropoietin receptor signalling. | SIGNOR-276994 |
P12931 | Q9UK17 | 1 | phosphorylation | up-regulates activity | 0.337 | These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels. | SIGNOR-276393 |
P21333 | Q13153 | 0 | phosphorylation | up-regulates | 0.789 | In flna, the pak1-binding site involves tandem repeat 23 in the carboxyl terminus and phosphorylation takes place on serine 2152. | SIGNOR-92065 |
P35612 | P17252 | 0 | phosphorylation | down-regulates | 0.2 | We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta. | SIGNOR-139870 |
Q00987 | Q8N726 | 0 | relocalization | down-regulates activity | 0.765 | We propose that p14(arf) increases the binding of p53-mdm2 complexes to chromatin, thereby limiting the access of protein deacetylases to p53. | SIGNOR-192697 |
P08670 | P17252 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.284 | We reported that stoichiometric phosphorylation by either cAMP-dependent protein kinase or protein kinase C induces disassembly of vimentin filaments. In the present work, we attempted to identify the sites of vimentin phosphorylated by each protein kinase. Sequential analysis of the purified phosphopeptides, together with the known primary sequence, revealed that Ser-8, Ser-9, Ser-20, Ser-25, Ser-33, and Ser-41 were specifically phosphorylated by protein kinase C, whereas Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. | SIGNOR-248880 |
P27361 | P02686 | 1 | phosphorylation | down-regulates | 0.502 | Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The identification of myelin basic protein (phosphorylation at -pro-arg-thr-pro-) as a substrate for the erk kinases (fig. 1) demonstrates that there are other determinants important for substrate recognition than those present in the originally identified consensus sequence. | SIGNOR-143481 |
P46937 | P06493 | 0 | phosphorylation | up-regulates activity | 0.425 | Our evidence suggested that these YAP sites (Ser138, Thr143, and Ser367) were CDK1 phosphorylation sites.|These data demonstrate that the YAP phosphorylation sites Ser138, Thr143, and Ser367 are important for proper mitosis and cytokinesis. | SIGNOR-276587 |
Q00535 | Q86YT6 | 1 | phosphorylation | up-regulates activity | 0.325 | Similar to the mechanism of PAR-1 regulation of Mib in neurogenesis, CDK5 phosphorylation is proposed to enhance Mib1 ligase activity leading to destabilization.|The cyclin dependent kinase 5 (CDK5) enriched in neurons phosphorylates Mib1 and suppresses the inhibitory effects of Mib1 on neurite morphology. | SIGNOR-280217 |
P24941 | Q6PKG0 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity. | SIGNOR-279015 |
Q86WV1 | P08575 | 0 | dephosphorylation | up-regulates activity | 0.361 | Mutational analysis demonstrated the pivotal role of Tyr-232 in SKAP55 in the association with CD45. In Jurkat cells, anti-CD3 antibody stimulation promoted SKAP55 tyrosine phosphorylation and translocation from the cytoplasm to the membrane. Overexpression of SKAP55 in these cells induced transcriptional activation of the IL-2 promoter, while mutant SKAP55-Y232F totally suppressed the promoter activity. Furthermore, overexpression of SKAP55-Y232F also caused the tyrosine hyperphosphorylation of Fyn with a decreased kinase activity. Thus, SKAP55 is an essential adapter to couple CD45 with the Src family kinases for dephosphorylation and, thus, positively regulates TCR signaling. | SIGNOR-248360 |
P10275 | O15393 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.575 | The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator. | SIGNOR-253687 |
Q9BTA9 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. Knockdown of WAC compromises Plk1 activity and delays mitotic entry. | SIGNOR-265035 |
O95747 | P55017 | 1 | phosphorylation | up-regulates | 0.388 | We demonstrate that the spak and osr1 kinases that are activated by wnk1 phosphorylate human ncc at three conserved residues (thr46, thr55 and thr60) / our results also indicate that phosphorylation of thr60 plays the most crucial role in triggering the activation of ncc in hek293 cells and its mutation also inhibits phosphorylation of the adjacent thr46 and thr55 sites. | SIGNOR-160833 |
P28482 | O94811 | 1 | phosphorylation | down-regulates activity | 0.354 | Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP. | SIGNOR-262928 |
Q8NG31 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.2 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant). | SIGNOR-165502 |
P49841 | P36956 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.485 | Importantly, we demonstrate that the mature form of endogenous SREBP1 is phosphorylated on Ser-434. Glycogen synthase kinase-3 phosphorylates Ser-434, and the phosphorylation of this residue is attenuated in response to insulin signaling. Interestingly, phosphorylation of Ser-434 promotes the glycogen synthase kinase-3-dependent phosphorylation of Thr-426 and Ser-430 and destabilizes SREBP1. | SIGNOR-236667 |
O15126 | P00533 | 0 | phosphorylation | up-regulates activity | 0.335 | In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation | SIGNOR-262857 |
Q8IUE6 | Q86Y13 | 0 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271758 |
Q96S53 | Q9Y281 | 1 | phosphorylation | down-regulates activity | 0.321 | Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin | SIGNOR-246711 |
Q9Y458 | P14921 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | TBX22 is an X-linked gene, which encodes a T-box-containing transcription factor. Loss-of-function mutation in the X-linked TBX22 promoter disrupts an ETS-1 binding site and leads to cleft palate. We first link the transcription factor ETS-1 to TBX22 pathway during embryonic palatogenesis. | SIGNOR-265565 |
Q93008 | P19544 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. | SIGNOR-275614 |
P06493 | Q14790 | 1 | phosphorylation | down-regulates | 0.361 | In this study, we demonstrate that procaspase-8 is phosphorylated in mitotic cells by cdk1na interference-mediated silencing of cyclin b1 or treatment with the cdk1 inhibitor ro-3306 enhances the fas-mediated activation and processing of procaspase-8 in mitotic cells/cyclin b1 on ser-387 | SIGNOR-168446 |
Q02750 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.287 | This study indicates that mTORC1, MEK1, p38 and DYRK2 induce HSF1 activity to a similar level but phosphorylate HSF1 primarily at S326 as well as S363, a known inhibitory site [71,72], S221, also thought to be an inhibitory site [70], or at S241 and S344, which are two novel phosphorylation sites with unknown function.|While AKT1, mTORC1, MEK1, p38 and DYRK2 can all activate HSF1, the current study indicates that activity of only AKT1 and mTORC1 maintains a strong association with HSF1 activity in tumours (Fig. 4). | SIGNOR-279208 |
P01106 | Q99608 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.265 | Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cystin did so more modestly. | SIGNOR-253381 |
Q9BV47 | P11362 | 1 | dephosphorylation | down-regulates activity | 0.2 | NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells | SIGNOR-277104 |
Q86VP3 | Q13489 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.286 | Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. | SIGNOR-272852 |
Q12955 | Q92823 | 0 | relocalization | up-regulates quantity | 0.721 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266720 |
Q9HCI7 | Q16778 | 1 | monoubiquitination | down-regulates activity | 0.2 | MSL1/2 ubiquitylates histone H2B on K 34. Importantly, only mono-ubiquitylation of H2B by MSL1/2 was detected in cells (data not shown), suggesting that MSL1/2, like RNF20/RNF40, was mainly a mono-ubiquitylase under physiological conditions.the MOF-MSL complex functions to promote both H4 K16ac and H2B K34ub. H2B K34ub, in turn, promotes H2B K120ub, H3 K4me3 and K79me2 to facilitate transcription elongation. | SIGNOR-271976 |
Q9BZK7 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | In addition, we describe that the functions and the specificity of these two highly- related exchange factors is tightly regulated by signal-induced phosphorylation events at the level of target gene promoters, as exemplified by the role of TBLR1 phosphorylation at Ser 123 by PKCδ upon retinoic acid or estrogen stimulation. | SIGNOR-260903 |
O00141 | Q99759 | 1 | phosphorylation | down-regulates activity | 0.2 | Inhibition of mitogen-activated kinase kinase kinase 3 activity through phosphorylation by the serum- and glucocorticoid-induced kinase 2 | SIGNOR-101216 |
Q13627 | Q07820 | 1 | phosphorylation | up-regulates quantity | 0.2 | Furthermore, DYRK1A likely directly bound and phosphorylated Mcl-1, thereby enhancing Mcl-1 protein stability and contributing to the development of acquired resistance to Bcl-2 inhibitors.|DYRK1A upregulates Mcl-1 expression in NSCLC cells.|We demonstrated that DYRK1A suppression by siRNA or harmine decreased the phosphorylation of Mcl-1 at Ser159/Thr163. | SIGNOR-279704 |
P08047 | P06493 | 0 | phosphorylation | up-regulates | 0.463 | Moreover, we showed that sp1 is a novel mitotic substrate of cdk1/cyclin b1 and is phosphorylated by it at thr 739 before the onset of mitosis. | SIGNOR-163738 |
P37231 | P27361 | 0 | relocalization | down-regulates activity | 0.398 | The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform | SIGNOR-179407 |
Q96J02 | Q15583 | 1 | ubiquitination | up-regulates activity | 0.2 | Based on these observations, we suggest that a mechanism of protein stabilization might account for the accumulation of TGIF protein in response to TNF-alpha signaling.Next, we used three different approaches to investigate the possibility that Itch could contribute to the ability of TNF-alpha to promote TGIF stabilization.|We also employed the experimental strategy combining the detection of monoubiquitinated and polyubiquitinated TGIF and found that mutation of K259 not only compromised monoubiquitination of TGIF by Itch but also enhanced its polyubiquitination. | SIGNOR-278817 |
Q92917 | P17612 | 0 | phosphorylation | up-regulates activity | 0.307 | PKA phosphorylates GPKOW at S27 and T316 in vitro. GPKOWs ability to bind RNA is sensitive to mutations of its PKA phosphorylation sites. | SIGNOR-266309 |
Q99558 | P19634 | 1 | phosphorylation | up-regulates activity | 0.307 | The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.|We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1. | SIGNOR-279632 |
P78563 | P31749 | 0 | phosphorylation | down-regulates activity | 0.2 | AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively | SIGNOR-276194 |
Q8NEZ5 | Q00987 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis|we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation. | SIGNOR-273440 |
O43426 | P29323 | 0 | phosphorylation | down-regulates | 0.57 | Ephb2 causes tyrosine phosphorylation in the proline-rich domain of synaptojanin 1, and inhibits both the interaction with endophilin and the 5'-phosphatase activity of synaptojanin 1 | SIGNOR-135274 |
Q14938 | Q9Y6N7 | 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-268907 |
Q8IWA4 | P05771 | 0 | phosphorylation | down-regulates activity | 0.2 | Here we report that βIIPKC accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria in heart failure. | SIGNOR-273826 |
Q5T0T0 | P08195 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Taken together, these findings demonstrate that MARCH8 directly ubiquitinates CD98, and this likely leads to its routing to late endosomes for degradation. | SIGNOR-272755 |
P06239 | P60484 | 1 | phosphorylation | up-regulates | 0.374 | Thus, y240a and y315a are involved in the ability of mmac/pten to dephosphorylate ptdins and regulate tumor cell growth in vitro and in vivo. | SIGNOR-116499 |
P06213 | P0DP25 | 1 | phosphorylation | down-regulates | 0.375 | The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-266336 |
P12277 | P60709 | 1 | relocalization | up-regulates quantity | 0.292 | In summary, data presented here strongly suggest that locally generated ATP is an important regulator for actin-based cytoskeletal dynamics involved in cell extension and motility and that CK-B is a controlling enzyme in the compartmentalization of ATP availability. CK-B co-localizes with cortical actin and facilitates spreading of astrocytes | SIGNOR-265791 |
Q9H267 | P18433 | 0 | dephosphorylation | down-regulates activity | 0.2 | Here, we report that VPS33B, a host protein involved in vesicle trafficking, is dephosphorylated by PtpA leading to a block of phagosome maturation by M. tuberculosis.|These data suggest that M. tuberculosis PtpA inhibits phagosome maturation.To assess the role of VPS33B in phagosome maturation, we attenuated the expression of endogenous VPS33B expression in THP-1 cells using a siRNA based approach. | SIGNOR-277015 |
Q9HCE7 | Q99717 | 1 | ubiquitination | down-regulates | 0.769 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-195663 |
Q14790 | P55957 | 1 | cleavage | up-regulates activity | 0.879 | Caspase-8 cleaves bid at aspartic acid residue 60 (asp60) cleavage of bid by casp8 releases its potent proapoptotic activity | SIGNOR-59655 |
Q9NRM7 | P61981 | 1 | phosphorylation | up-regulates | 0.331 | Phosphorylation of 14-3-3_ on s59 by lats2. Ser(58) phosphorylation and lys(49) acetylation of 14-3-3_ occur in a coordinated time-dependent manner to regulate 14-3-3_ homodimerization. 14-3-3_ ser(58) phosphorylation is required for star interactions under control conditions, | SIGNOR-205247 |
Q99717 | Q9UNE7 | 0 | ubiquitination | down-regulates | 0.343 | In ad-dition, some proteins (e.g. Chip, carboxyl terminus of hsc70-interacting protein) inhibit the signaling activi-ties of smad1/5 by recruiting smad1/5 from the functional r-/co-smad complex and further pro-moting the ubiquitination and degradation of smad1/5 in a chaperone-independent manne | SIGNOR-195690 |
P07108 | Q05655 | 0 | phosphorylation | up-regulates | 0.2 | Acyl coenzyme a-binding protein (acbp) is phosphorylated following protein kinase c activation. | SIGNOR-160393 |
Q70Z35 | Q13153 | 0 | phosphorylation | down-regulates activity | 0.367 | P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. | SIGNOR-277181 |
O00555 | P43146 | 0 | null | up-regulates activity | 0.2 | DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. | SIGNOR-268293 |
Q14934 | P35354 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.282 | NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration | SIGNOR-264027 |
Q13131 | P05091 | 1 | phosphorylation | up-regulates activity | 0.2 | Further studies demonstrate that in the absence of LDLR, AMPK phosphorylates ALDH2 at threonine 356 and enables its nuclear translocation. Nuclear ALDH2 interacts with HDAC3 and represses transcription of a lysosomal proton pump protein ATP6V0E2, critical for maintaining lysosomal function, autophagy, and degradation of oxidized low-density lipid protein. | SIGNOR-271863 |
P45983 | P31947 | 1 | phosphorylation | down-regulates | 0.338 | Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-187. | SIGNOR-124016 |
P35499 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.279 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253460 |
P10275 | P28482 | 0 | phosphorylation | down-regulates | 0.511 | Map kinase-dependent phosphorylation at ar ser-515 was supported by the decrease in intensity of the slower migrating 23-kda band after treatment with both egf and increasing concentrations of the map kinase inhibitor, u0126 | SIGNOR-178718 |
P53355 | Q9UN36 | 1 | phosphorylation | up-regulates activity | 0.273 | DAPK1 phosphorylates and activates N-myc downstream-regulated gene 2 (NDRG2), resulting in increased tau phosphorylation via a reduction in Pin1 expression ( xref ; xref ). | SIGNOR-279983 |
P36956 | Q8NBP7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.427 | Expression of nuclear forms of sterol-regulatory element binding protein-1 (SREBP-1) and SREBP-2 dramatically increased the promoter activity of PCSK9. | SIGNOR-255222 |
Q5T447 | P04049 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | By western blot, we observed robust degradation of endogenous native CRAF in untransformed HEK293 cells treated with control siRNA 24 hr after the addition of AUY922, but this was substantially reduced in cells in which HECTD3 was knocked down, confirming that endogenous CRAF is a bona fide degradation target of HECTD3 | SIGNOR-272328 |
O60469 | O00410 | 0 | relocalization | up-regulates activity | 0.2 | DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs. | SIGNOR-264273 |
Q15109 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.2 | RAGE is phosphorylated at Serine 376 and Serine 389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. | SIGNOR-278907 |
P16333 | P19525 | 0 | phosphorylation | down-regulates activity | 0.2 | In these assays, we observed that GST\u2013Nck-1 was clearly phosphorylated by GST\u2013PKR while GST was not ( Fig. 4 , upper panels). | SIGNOR-279039 |
Q969H0 | Q14258 | 0 | ubiquitination | down-regulates activity | 0.264 | This newly stabilized TRIM25 then directly ubiquitinates Lys412 of FBXW7α, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex involved in Myc ubiquitination, thereby stabilizing Myc. | SIGNOR-277457 |
Q05655 | P13498 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro | SIGNOR-260892 |
Q9Y4K3 | O75385 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.548 | AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. | SIGNOR-273000 |
Q8WTT2 | Q14469 | 0 | transcriptional regulation | down-regulates quantity | 0.2 | The expression level of FAD24 is inversely associated with that of HES1 in porcine MSCs after adipogenic induction. Enforced overexpression of HES1 in MSCs during the early stage of adipogenesis significantly repressed the transcription of FAD24 (P < 0.01) and the other pro-adipogenic genes | SIGNOR-253059 |
Q9HC98 | P40763 | 1 | phosphorylation | up-regulates activity | 0.332 | Our data also show that NEK6 interacts with STAT3, an oncogenic transcription factor, and phosphorylates STAT3 on Ser(727), which is important for transcriptional activation. These results demonstrate that NEK6 interacts with and phosphorylates STAT3, an event that could play an important role in oncogenesis. For the maximal activation of STAT3 signaling, phosphorylation of both Tyr705 and Ser727 is required. Phosphorylation of Tyr705 induces dimerization, nuclear translocation, and DNA binding of the STAT3 protein, whereas phosphorylation of Ser727 is important for transcriptional activation. | SIGNOR-273902 |
Q14493 | Q9BTM1 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265412 |
Q13523 | Q9Y2Y9 | 1 | phosphorylation | down-regulates | 0.342 | Using yeast two-hybrid screening of a human thymus cdna library, prp4, a serine/threonine protein kinase, was identified as a klf13-binding protein...coexpression of prp4 and klf13 increases nuclear localization of klf13 and ccl5 transcription. | SIGNOR-154951 |
Q9ULT6 | Q13467 | 1 | ubiquitination | down-regulates quantity | 0.515 | 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-260118 |
O75914 | P04049 | 1 | phosphorylation | up-regulates | 0.556 | The protein kinase pak3 positively regulates raf-1 activity through phosphorylation of serine 338. | SIGNOR-62043 |
Q9H992 | Q15051 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH7 induces K48 ubiquitination of NPHP5 and protein degradation, while BBS11 triggers K63 ubiquitination and protein delocalization.|Unlike the catalytically inactive mutant , wild type MARCH7 was able to trigger NPHP5 ubiquitination (XREF_FIG). | SIGNOR-278585 |
Q9Y463 | P24385 | 1 | phosphorylation | down-regulates | 0.41 | Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells | SIGNOR-150126 |
Q04206 | Q9H000 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.341 | MKRN2 promotes p65 ubiquitination and degradation through RING finger domain. | SIGNOR-278591 |
O14920 | P25963 | 1 | phosphorylation | down-regulates activity | 0.922 | Tak1 become activated and then phosphorilates and activates ikk2 which in turn now phosphorylates ikba, marking it for k48-ubiquitination and proteasomal degradation | SIGNOR-235400 |
Q8NB16 | Q06418 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6). | SIGNOR-274120 |
P07948 | P35354 | 1 | phosphorylation | up-regulates activity | 0.385 | We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro. | SIGNOR-276643 |
Q02880 | Q13315 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.411 | Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26. | SIGNOR-277510 |
O60346 | P48729 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.309 | We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity. | SIGNOR-276262 |
Q96DR7 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.585 | 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-260545 |
Q8IUQ4 | O75525 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.473 | We found that SIAH1 bound to an octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation. | SIGNOR-272671 |
Q5TZA2 | P24941 | 0 | phosphorylation | down-regulates | 0.2 | Finally, phosphorylation of tax1bp2 at serine-763 by cyclin-dependent kinase (cdk)2 abolished the tax1bp2-mediated p38 activation and tumor-suppressive activity, indicating that tax1bp2 can adapt cdk2 signaling to the p38/p53/p21 pathway. | SIGNOR-197593 |
Q13315 | O95999 | 1 | phosphorylation | up-regulates activity | 0.468 | Upon DNA damage, ATM phosphorylates the residue T91 of BCL10, promoting binding of BCL10 to RNF8 and simultaneously presenting UBC13 to RNF8.|When cells were pre-treated with different PIKK inhibitors, the ATM specific inhibitor KU55933 efficiently reduced etoposide induced focus formation of BCL10, whereas pretreatment of cells with NU6027, an ATR specific inhibitor, or NU7026, a DNA-PKcs-specific inhibitor, did not compromise etoposide induced focus formation of BCL10 (XREF_FIG). | SIGNOR-278392 |
O96013 | Q15796 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.339 | In addition, PAK4 phosphorylates Smad2 on Ser465, leading to the degradation of Smad2 through ubiquitin-proteasome-dependent pathway under hepatocyte growth factor (HGF) stimulation. | SIGNOR-279084 |
Q13535 | Q14191 | 1 | phosphorylation | down-regulates quantity | 0.794 | Importantly, ATR-mediated phosphorylation targets Werner syndrome protein for ubiquitination and degradation.|WRN is phosphorylated at serine 1141 by ATR in response to replication-associated DSBs A. WRN is heavily phosphorylated at S1141 in response to CPT treatment of cells. | SIGNOR-278159 |
Q96B36 | O43781 | 0 | phosphorylation | down-regulates | 0.34 | When dyrk3 is active, it allows stress granule dissolution, releasing mtorc1 for signaling and promoting its activity by directly phosphorylating the mtorc1 inhibitor pras40 | SIGNOR-201002 |
P03956 | P02461 | 1 | cleavage | down-regulates quantity by destabilization | 0.35 | In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4. | SIGNOR-272339 |
P31749 | O14492 | 1 | phosphorylation | up-regulates activity | 0.4 | This study identifies APS as a novel physiological substrate for PKB and the first serine phosphorylation site on APS | SIGNOR-252557 |
P15923 | Q9P286 | 0 | phosphorylation | up-regulates activity | 0.2 | The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation | SIGNOR-275653 |
Q14774 | P05412 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261623 |
Q99608 | P01106 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.265 | Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cystin did so more modestly. | SIGNOR-253381 |
Q99814 | Q9UGL1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | 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-271578 |
P84243 | P06241 | 0 | phosphorylation | down-regulates activity | 0.2 | Here we provide evidence that fyn kinase, a member of the src kinase family, is involved in the uvb-induced phosphorylation of histone h3 at serine 10 | SIGNOR-130274 |
Q13469 | Q9Y625 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.354 | NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. | SIGNOR-264021 |
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