IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P62993 | P04626 | 0 | relocalization | up-regulates | 0.85 | All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor | SIGNOR-121968 |
P22888 | P10588 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.302 | Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription. | SIGNOR-266216 |
O75914 | P19429 | 1 | phosphorylation | down-regulates | 0.2 | In vitro addition of pak3 to skinned rat cardiac fibres increased myofilament ca2+ sensitivity with no change in maximal ca2+-activated force [67]. These effects were associated with pak3-induced phosphorylation of myofilament proteins, including ctni which was phosphorylated at a novel site, ser149, located in the region forming a ca2+-sensitive interaction with the n-terminal regulatory domain of tnc. | SIGNOR-134593 |
Q92934 | P22612 | 0 | phosphorylation | down-regulates | 0.434 | Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo. | SIGNOR-81153 |
P12830 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin. | SIGNOR-260893 |
Q13618 | Q99426 | 1 | ubiquitination | down-regulates quantity | 0.245 | Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B. | SIGNOR-268945 |
P53350 | O75122 | 1 | phosphorylation | up-regulates activity | 0.622 | Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore-microtubule attachments.|Finally, we demonstrate that CLASP2 phosphorylation on S1234 and S1255 by Cdk1 and Plk1, respectively, increases with conditions that allow the establishment and stabilization of KT\u2013MT attachments ( xref ). | SIGNOR-278321 |
P40763 | Q9HC98 | 0 | 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 |
O15033 | O75431 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2. | SIGNOR-267674 |
P31645 | Q13976 | 0 | phosphorylation | up-regulates | 0.382 | These results are consistent with the hypothesis that pkg phosphorylates hsert at thr-276 and increases its activity by modifying the substrate permeation pathway formed, in part, by tm5. | SIGNOR-158186 |
P04070 | P12259 | 1 | cleavage | down-regulates activity | 0.601 | The mechanism of inactivation of human factor V and human factor Va by activated protein C|Membrane-bound human factor V (250 nM) is cleaved by APC (2.5 nM) to give M(r) = 200,000, 70,000, 45,000, and 30,000 fragments and an M(r) = 22/20,000 doublet. These fragments are released after four sequential cleavages of the membrane-bound procofactor at Arg306, Arg506, Arg679, and Lys994. | SIGNOR-263629 |
Q15303 | Q92529 | 1 | relocalization | up-regulates | 0.497 | Like erbb1, erbb4 recruits grb2, shc and stat5. | SIGNOR-147850 |
O60331 | P23443 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation. | SIGNOR-277283 |
P17612 | P10071 | 1 | phosphorylation | down-regulates quantity | 0.468 | Ci/gli zinc finger proteins mediate the transcriptional effects of hedgehog protein signals. In drosophila, ci action as transcriptional repressor or activator is contingent upon hedgehog-regulated, pka-dependent proteolytic processingall six pka phosphorylation sites are required for processing of gli3. | SIGNOR-75359 |
P23470 | O60674 | 1 | dephosphorylation | down-regulates activity | 0.287 | Deeper examination shows that JAKs are critically involved in integrin-mediated monocyte adhesion and that PTPRG activation leads to JAK2 dephosphorylation on the critical 1007–1008 phosphotyrosine residues, implying JAK2 inhibition and thus explaining the antiadhesive role of PTPRG. | SIGNOR-254690 |
O60674 | P42229 | 1 | phosphorylation | up-regulates activity | 0.866 | Jak2 kinase induces tyrosine phosphorylation, dimerization, nuclear translocation, and dna binding of a concomitantly expressed stat5 protein | SIGNOR-249507 |
O15350 | Q9NYY3 | 0 | phosphorylation | down-regulates activity | 0.275 | PLK2 inhibits TAp73 translocation to the nucleus.|PLK2 phosphorylated TAp73 at residue Ser48 within the TA domain; phosphorylation of TAp73 was abolished by mutating this residue. | SIGNOR-278218 |
Q9Y385 | Q13490 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.37 | We also found that ubiquitin-ligase (E3), c-IAP1 preferentially interacts with phosphorylated Ube2j1. Moreover, we noticed that phosphorylated Ube2j1 is rapidly degraded by the proteasome during ER stress cell recovery. Taken together, these data suggest that Ube2j1 and its phosphorylation is important for transient ER stress cell recovery and the phosphorylated Ube2j1 is degraded by the proteasome. | SIGNOR-263092 |
P40337 | O96017 | 0 | phosphorylation | up-regulates | 0.455 | We demonstrated that checkpoint kinase-2 (chk2) binds to the beta-domain of pvhl and phosphorylates ser 111 on dna damage. Notably, this modification enhances pvhl-mediated transactivation of p53 by recruiting p300 and tip60 to the chromatin of p53 target gene | SIGNOR-177091 |
Q9Y6D9 | P53350 | 0 | phosphorylation | up-regulates activity | 0.464 | These findings indicate mechanistic roles contributed by protein phosphorylation and Plk1 to the SAC activity of Mad1.Here, we have studied the phosphorylation of Mad1 and mapped using liquid chromatography-tandem mass spectrometry several phosphorylated amino acids in this protein. One phosphorylated residue, Thr680, was characterized to be important for the kinetochore localization of Mad1 and its SAC function. | SIGNOR-276173 |
A8MYZ6 | O00712 | 0 | 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-268881 |
P09874 | P28482 | 0 | phosphorylation | up-regulates | 0.519 | Parp1 phosphorylation by erk1/2 is required for maximal parp-1 activation after dna damage. S372a and t373a mutations impaired parp-1 activation. | SIGNOR-146224 |
Q16611 | P54829 | 0 | dephosphorylation | up-regulates activity | 0.2 | In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multimerisation. | SIGNOR-248542 |
Q16665 | O76061 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.297 | With the ChIP assay, we demonstrated the direct binding of HIF-1alpha to STC2 promoter. These findings support the notion that HIF-1 is a potent stimulator of STC2 expression. Collectively, this is the first report to show that STC2 was aberrantly hypermethylated in human cancer cells. The findings demonstrated that STC2 epigenetic inactivation may interfere with HIF-1 mediated activation of STC2 expression. | SIGNOR-260389 |
P62736 | P01137 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.419 | A TGF-β1 response element that has a sequence different to that known for Smad binding has been identified in the α- SM actin promoter and seems to be essential for expression of α-SM actin in both SM cells 72 and myofibroblasts73 . How TGF-β1 activates expression of α-SM actin through this TGF-β1 control element is, as yet, unknown | SIGNOR-277681 |
Q9H0N0 | O43896 | 0 | relocalization | up-regulates quantity | 0.245 | Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. | SIGNOR-266879 |
Q7Z6M1 | P11717 | 1 | relocalization | up-regulates activity | 0.385 | P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking. | SIGNOR-253090 |
P78527 | Q92831 | 1 | phosphorylation | up-regulates activity | 0.417 | In response to UV-induced DNA damage, DNA-PK phosphorylates and activates PCAF, and activated PCAF is transferred to photo lesion sites and further acetylates RPA1 at K163. | SIGNOR-280092 |
P25774 | P02818 | 1 | cleavage | down-regulates quantity by destabilization | 0.309 | This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42. | SIGNOR-256323 |
Q13541 | P28482 | 0 | phosphorylation | down-regulates activity | 0.659 | The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 |phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding | SIGNOR-249390 |
Q86Y07 | P04406 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation. | SIGNOR-277840 |
P53350 | P49959 | 1 | phosphorylation | down-regulates activity | 0.2 | Plk1 phosphorylates Mre11 at S649.Mre11 phosphorylation at S649/S688 inhibits its binding to dsDNA and antagonizes the ATM signaling. | SIGNOR-265943 |
Q14258 | Q7Z2W4 | 1 | ubiquitination | up-regulates activity | 0.398 | Our data demonstrates that TRIM25 triggers ubiquitination of ZAP and enhances its antiviral activity through inhibition of viral translation, highlighting the importance of cofactors in the mechanisms of broadly antiviral proteins. | SIGNOR-278565 |
P07948 | P14317 | 1 | phosphorylation | up-regulates activity | 0.714 | Lyn and Syk synergistically phosphorylate HS1, and that Tyr-378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis. PMID: 9104825 PMCID: PMC2196252 | SIGNOR-251401 |
Q13107 | Q9ULA0 | 0 | cleavage | down-regulates quantity by destabilization | 0.2 | A further analysis showed that the hydrolysis pathway contributes to DNPEP-mediated degradation of USP4 (Supporting Information Figs. S3A–S3F). The interaction between USP4 and DNPEP was confirmed by coIP assays | SIGNOR-275652 |
Q15910 | P31749 | 0 | phosphorylation | down-regulates activity | 0.594 | Enhancer of zeste homolog 2 (ezh2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone h3. Here, we show that akt phosphorylates ezh2 at serine 21 and suppresses its methyltransferase activity by impeding ezh2 binding to histone h3 | SIGNOR-141043 |
P49841 | Q01518 | 1 | phosphorylation | up-regulates activity | 0.253 | We found that GSK3 phosphorylates S307 and S309 by using inhibitors LiCl. Inhibition of GSK3beta can cause loss of cell polarity as well as accumulation of stress fibers. We propose that GSK3 regulates CAP1 through at least two mechanisms. First, GSK3 (and potentially other kinases) phosphorylate CAP1 at S309 and promote CAP1 localization to the cytosol. Second, phosphorylation at S309 affects protein-protein interactions with actin and cofilin. The loss of this phospho-regulation by GSK3 inhibition is expected to disrupt CAP1 function and actin dynamics. | SIGNOR-264822 |
P27361 | Q12929 | 1 | phosphorylation | down-regulates activity | 0.323 | We further show that the actin barbed-end capping activity of Eps8 is inhibited by brain-derived neurotrophic factor (BDNF) treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation. | SIGNOR-263058 |
Q14194 | P49841 | 0 | phosphorylation | up-regulates | 0.47 | Using in vitro kinase assays and pharmacological inhibition of gsk3 as described above for crmp2 and crmp4, it was found that thr509 (and presumably ser518 and thr514) of human crmp1 is phosphorylated by gsk3, following priming of ser522 by cdk5 | SIGNOR-145999 |
P78509 | O15409 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.365 | By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets. | SIGNOR-266833 |
Q13469 | P35354 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.371 | NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration | SIGNOR-264025 |
Q13233 | O95819 | 0 | phosphorylation | up-regulates | 0.558 | Hpk1 binds and phosphorylates mekk1 directly | SIGNOR-44040 |
Q9NP77 | Q8N3U4 | 1 | dephosphorylation | up-regulates activity | 0.298 | Additional experiments revealed that Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells. Interestingly, depletion or mutational inactivation of Ssu72 phosphatase activity caused the premature resolution of sister chromatid arm cohesion, whereas the overexpression of Ssu72 yielded high resistance to this resolution.|anti‐phospho SA2 serine 1224 | SIGNOR-275531 |
P41594 | P05771 | 0 | phosphorylation | up-regulates activity | 0.354 | Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839. | SIGNOR-249286 |
Q92985 | Q9UHD2 | 0 | phosphorylation | up-regulates activity | 0.768 | In most cell types, IRF7 is phosphorylated and activated by IKK\u03b5 and TBK1 after viral infection.|We found that phosphorylation of IRF7 on Ser477 and Ser479 by IKK\u03b5 or TBK1 is inhibited by ORF45. | SIGNOR-278216 |
Q15172 | P19525 | 0 | phosphorylation | up-regulates | 0.328 | Phosphorylation of serine 28 by pkr promotes mitochondrial localization of b56alpha, because wild-type but not mutant s28a b56alpha promoted mitochondrial pp2a activity. | SIGNOR-181793 |
P11309 | P10275 | 1 | phosphorylation | up-regulates activity | 0.381 | PIM1 phosphorylates the AR and 14-3-3 ζ and coordinates their interaction. PIM1 phosphorylation of the AR and 14-3-3 ζ enhances their interaction and shifts their occupancy on chromatin, resulting in 14-3-3 ζ co-regulation of AR, likely by recruiting other AR co-regulators such as hnRNPK and TRIM28. | SIGNOR-277575 |
Q9UNE7 | Q9Y4K3 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.466 | CHIP promotes TRAF6 ubiquitination and degradation.|These results suggest that CHIP negatively regulates the stability of TRAF6. | SIGNOR-278670 |
P28562 | P45984 | 1 | dephosphorylation | down-regulates | 0.681 | We assayed the relative ability of mkp-2, pac1, and mkp-1 to dephosphorylate erk2 and the other related map kinases, jnk2 and p38. the dual specific phosphatases pac1 and mkp-1 previously have been implicated in the in vivo inactivation of erk or of erk and jnk, respectively. | SIGNOR-40879 |
P27361 | Q15303 | 1 | phosphorylation | down-regulates activity | 0.534 | We also identified Ser-1026 as an ErbB4-specific ERK target site in the CYT-1 region. Moreover, double mutations (Thr-674/Ser-1026 to Ala) significantly upregulated ErbB4 activation, indicating that Thr-674 and Ser-1026 are cooperatively involved in negative feedback regulation. | SIGNOR-277448 |
P23467 | P12931 | 1 | dephosphorylation | down-regulates activity | 0.445 | Collectively, these results suggest that PTPRB inhibits Src activation and down -- regulation of PTPRB activates Src signalling pathway required for cell invasion in A549 cells.|Knockdown of PTPRB increased Src phosphorylation and cell invasion, which was reversed by Src inhibitor PP2. | SIGNOR-277132 |
P18669 | P11362 | 0 | phosphorylation | up-regulates activity | 0.33 | Nevertheless, these data suggest that FGFR1 dependent tyrosine phosphorylation " further " enhances PGAM1 activation.|Phosphorylation of PGAM1 WT by FGFR1 resulted in a significant increase in the amount of bound 2,3-BPG analogue, whereas substitution of PGAM1 Y26 abolished enhanced binding of cofactor in the presence of rFGFR1 (XREF_FIG). | SIGNOR-279175 |
Q14289 | Q86X29 | 1 | phosphorylation | up-regulates activity | 0.2 | Pyk2 enhances LSR and tricellulin localization to tTJs.|Pyk2-dependent phosphorylation of LSR enhances localization of LSR and tricellulin at tricellular tight junctions. | SIGNOR-280101 |
Q96T37 | O95628 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.359 | We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). | SIGNOR-271466 |
P15056 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.294 | To address whether PP1\u03b1 activates B-Raf through these inhibitory sites, we made use of B-Raf protein mutants in which an individual inhibitory site, as well as all four sites (4A), were mutated to alanine.|We confirmed that GST-B-Raf was phosphorylated by ERK2 in vitro xref , mainly on S151 and T753 (Fig.\u00a0 xref ), and found that PP1\u03b1 dephosphorylated B-Raf on both ERK phosphorylation sites (Fig.\u00a0 xref ). | SIGNOR-277160 |
Q8IWR1 | O75367 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Nuclear TRIM59 induces ubiquitination and degradation of the tumor suppressive histone variant macroH2A1, leading to enhanced STAT3 signaling activation and tumorigenicity. | SIGNOR-272931 |
P04637 | Q00535 | 0 | phosphorylation | up-regulates | 0.732 | We show that cdk5 phosphorylates p53 on ser15, ser33 and ser46 cdk5-stabilized p53 protein is transcriptionally active | SIGNOR-156422 |
Q9UGM6 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.246 | 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-269430 |
P35222 | P19784 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.471 | We show that CKII phosphorylates the N-terminal region of beta-catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of beta-catenin and acts synergistically with GSK-3beta in the multi-protein complex that controls the degradation of beta-catenin. | SIGNOR-275993 |
Q13049 | Q9H9R9 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | TRIM32 is an E3 ubiquitin ligase for dysbindin. TRIM32 targets dysbindin for degradation. | SIGNOR-271422 |
P07585 | P08253 | 0 | cleavage | down-regulates quantity by destabilization | 0.695 | Degradation of decorin by matrix metalloproteinases. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues. | SIGNOR-256350 |
Q96M96 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.619 | 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-260554 |
Q9Y2R2 | P22681 | 1 | dephosphorylation | down-regulates | 0.387 | The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state. | SIGNOR-65405 |
P05091 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.281 | Post-translational enhancement of ALDH2 activity can be achieved by serine/threonine phosphorylation by epsilon protein kinase C (epsilonPKC). |e identified S279 as a critical εPKC phosphorylation site in the activation of ALDH2. The critical catalytic site, cysteine 302 (C302) of ALDH2 is susceptible to adduct formation by reactive aldehyde, 4HNE, which readily renders the enzyme inactive. We show that phosphomimetic mutations of T185E, S279E and T412E confer protection of ALDH2 against 4HNE-induced inactivation, indicating that phosphorylation on these three sites by εPKC likely also protects the enzyme against reactive aldehydes. | SIGNOR-271864 |
P45984 | Q96KS0 | 1 | phosphorylation | up-regulates activity | 0.2 | Interestingly, we found that docetaxel induced JNK2 activation increased phosphorylation of PHD1 at Ser 74 and Ser 162 in hypoxic cancer cells (XREF_FIG). | SIGNOR-279077 |
P60953 | P98170 | 0 | ubiquitination | down-regulates quantity | 0.398 | As XIAP can directly ubiquitinate Cdc42, we tested if the RING domain of XIAP is required for modulating the protein levels of Cdc42 in vivo .|We then investigated the molecular mechanisms behind XIAP mediated Cdc42 degradation. | SIGNOR-278799 |
P19174 | P10586 | 0 | dephosphorylation | down-regulates | 0.2 | Here we show that lar reduces the constitutive tyrosine autophosphorylation and kinase activity of ret-men2a but not ret-men2b, accompanying a significant decrease of phosphorylation of phospholipase cgamma, akt, and erk1/2. | SIGNOR-85166 |
Q13761 | P11309 | 0 | phosphorylation | up-regulates quantity | 0.353 | Inhibition of Pim1 kinase prevents peanut allergy by enhancing Runx3 expression and suppressing T (H) 2 and T (H) 17 T-cell differentiation.|Pim1 kinase phosphorylates and stabilizes Runx3 and alters its subcellular localization. | SIGNOR-279547 |
P28482 | Q9UQC2 | 1 | phosphorylation | up-regulates | 0.68 | Phosphorylation of grb2-associated binder 2 on serine 623 by erk mapk regulates its association with the phosphatase shp-2 and decreases stat5 activation.We and others have demonstrated that il-2-induced tyrosine phosphorylation of gab2 and its interaction with its sh2 domain-containing partners, shp-2, p85 pi3k, and crkl (5, 26, 27). we report that pretreatment of kit 225 cells with the mek inhibitor u0126, strongly decreased the characteristic shift of gab2 in response to il-2 and increased gab2/shp-2 association, an effect that could be ascribed to erk phosphorylation of serine 623. | SIGNOR-128727 |
P17931 | P42684 | 0 | phosphorylation | up-regulates | 0.2 | The sh (src homology)3 domains of c-abl/arg bind to a p(80)gppsgp motif of gal3, and tyr79 and tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of gal3. | SIGNOR-163747 |
P67809 | Q15418 | 0 | phosphorylation | up-regulates | 0.543 | We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue. | SIGNOR-182497 |
O60500 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | Binding of _-arrestin2 to the nephrin intracellular domain depended on phosphorylation of nephrin threonine residues 1120 and 1125 by pkc_. | SIGNOR-172056 |
Q96P31 | P12931 | 0 | phosphorylation | up-regulates activity | 0.2 | Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2. | SIGNOR-274008 |
Q96GD4 | Q96CF2 | 1 | phosphorylation | up-regulates | 0.469 | Moreover, we find that the cpc's catalytic subunit, aurora b kinase, phosphorylates one of the three human snf7 paralogues-chmp4c-in its c-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for chmp4c function because their mutation leads to cytokinesis defects. The introduction of the s214a and s215a mutations together with s210a almost completely abolished aurora b phosphorylation | SIGNOR-197967 |
P17612 | Q9NXR1 | 1 | phosphorylation | up-regulates | 0.4 | Here, we demonstrate that disc1 and pde4 modulate nde1 phosphorylation by camp-dependent protein kinase a (pka) and identify a novel pka substrate site on nde1 at threonine-131 (t131).Since phosphorylated t131 is detectable at multiple subcellular locations (centrosome, nucleus, postsynaptic density, proximal axon), there is potential for disc1/pde4 to influence several important brain processes that critically depend on the nde1/ndel1/lis1 comple | SIGNOR-174410 |
P31749 | P51617 | 1 | phosphorylation | down-regulates activity | 0.386 | CaMKKc and Akt overexpression increases IRAK1 phosphorylation at Thr100, and point mutation of this site abrogates the inhibitory effect of Akt on IRAK1-mediated NF-kappaB activation. | SIGNOR-252551 |
Q8NDV7 | Q6PJ69 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.445 | Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. | SIGNOR-272174 |
Q16539 | P19634 | 1 | phosphorylation | up-regulates | 0.571 | Trophic factor withdrawal: p38 mitogen-activated protein kinase activates nhe1, which induces intracellular alkalinization. activated p38 mapk directly phosphorylated the c terminus of nhe1 within a 40-amino-acid region. Analysis by mass spectroscopy identified four phosphorylation sites on nhe1, thr 717, ser 722, ser 725, and ser 728. | SIGNOR-111043 |
P17252 | P16144 | 1 | phosphorylation | down-regulates | 0.531 | Egf stimulates a pkc-?-Dependent pathway that results in the phosphorylation of the ?4 Integrin subunit on serine residues and its redistribution to actin-rich structures together, these results highlight the importance of serine phosphorylation in regulating type ii hemidesmosome disassembly, implicate a cluster of serine residues within the connecting segment of ?4, and argue for a key role for pkc-? In regulating these structures | SIGNOR-124494 |
O15169 | P49674 | 0 | phosphorylation | up-regulates | 0.747 | We conclude that a major role of axin in the wnt is to provide the kinase activity that initiates the betBeta-catenin phosphorylation cascade at s45. This process is mediated by cki, the alfa, delta, or ? Isoform, all detected in association with axin by lc/ms. | SIGNOR-87444 |
Q9H0D6 | O76064 | 0 | ubiquitination | up-regulates activity | 0.2 | Mechanistically, RNF8 interacts with XRN2, which is crucial for transcription termination and R-loop resolution. We report that RNF8 ubiquitylates XRN2 to facilitate its recruitment to R-loop-prone genomic loci and that RNF8 deficiency in BRCA1-mutant breast cancer cells decreases XRN2 occupancy at R-loop-prone sites, thereby promoting R-loop accumulation, transcription-replication collisions, excessive genomic instability, and cancer cell death. | SIGNOR-277195 |
Q13177 | P19105 | 1 | phosphorylation | up-regulates activity | 0.495 | In this study we report that gamma-PAK, which is activated by the GTP-binding proteins Cdc42 and Rac, catalyses phosphorylation of intact non-muscle myosin II and isolated recombinant RLC. Phosphopeptide maps and phosphoamino acid analysis revealed that gamma-PAK phosphorylates Ser-19 but does not phosphorylate Thr-18.Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization. | SIGNOR-263020 |
Q96EB6 | Q96EP1 | 0 | ubiquitination | down-regulates quantity | 0.372 | CHFR binds to and ubiquitylates SIRT1, leading to its proteasomal degradation.|CHFR ubiquitylates and promotes the proteasomal degradation of SIRT1. | SIGNOR-278691 |
P23470 | P00519 | 1 | dephosphorylation | down-regulates activity | 0.341 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254691 |
Q9HBA0 | O00141 | 0 | phosphorylation | up-regulates activity | 0.361 | Recently, we identified that TRPV4 is also one of SGK1 substrate proteins (Fig. . , and the phosphorylation on serine 824 by SGK1 regulates the binding affinity to actin or tubulin [31].|Therefore, we propose the hypothesis that the SGK1 phosphorylation may enhance TRPV4 channel density in the plasma membrane through the dissociation from STIM1, similar with the regulation mechanism of GLUT4 or AQP2 by insulin or vasopressin, respectively , ]. | SIGNOR-279386 |
P11802 | Q14106 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation. | SIGNOR-273602 |
P04083 | P00533 | 0 | phosphorylation | up-regulates | 0.508 | The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].Finally in 2013 caron et al. showed the relevance of y21 phosphorylation for the anxa1 stability. In fact the authors demonstrated that the tyrosine 21 phosphorylation is crucial for anxa1 sumoylation induced by egf | SIGNOR-202776 |
Q96CG3 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | For the activation of signal 2, Akt is involved in TIFA Thr9 phosphorylation, which is essential for TIFA-TIFA homophilic oligomerization. Thr9 phosphorylation-dependent TIFA oligomerization facilitates the higher-order assembly of NLRP3 inflammasome, as indicated by the interaction between TIFA and caspase-1 in the activated ECs. | SIGNOR-273542 |
Q9UIC8 | P67775 | 1 | methylation | up-regulates activity | 0.908 | Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1) | SIGNOR-265749 |
P14384 | P69905 | 1 | cleavage | down-regulates activity | 0.2 | Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity. | SIGNOR-256507 |
O00141 | Q9UN36 | 1 | phosphorylation | up-regulates | 0.395 | Sgk1 phosphorylated ndrg2 at thr330, ser332 and thr348 in vitro. for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, the phosphorylation of thr348 by sgk1 may prime for phosphorylation at ser344 | SIGNOR-129676 |
P62877 | P19838 | 1 | ubiquitination | up-regulates | 0.451 | The scf-betatrcp complex is responsible for the ubiquitination of p100 and p105 following their phosphorylation by ikk. | SIGNOR-106781 |
O14745 | P43250 | 0 | phosphorylation | down-regulates activity | 0.405 | GRK6A phosphorylates NHERF on Ser289, the primary site of constitutive phosphorylation of NHERF in HEK-293 cells. The interaction of NHERF and NHE3 is mediated by the region of NHERF encompassing the second PDZ domain and the tail (25), and it is therefore reasonable that phosphorylation of the serine-rich stretch in the center of this region (including Ser289) might affect the physical interaction of NHERF with NHE3. | SIGNOR-251214 |
O15169 | P48729 | 0 | phosphorylation | up-regulates activity | 0.785 | Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated (Supplementary Figure 3). Three of them (S80, S82, and S473) were also phosphorylated in vitro by CKI and are conserved between axin1 and axin2/conductin.|This suggests that cumulative phosphorylation of axin is required for it to fully downregulate Wnt/beta_catenin signaling. | SIGNOR-249191 |
O14920 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.547 | Monoubiquitylated PKC\u03b5 interacts with a ubiquitin-binding domain in NEMO zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where PKC\u03b5 phosphorylates IKK\u03b2 at Ser177 and activates IKK\u03b2.|These results indicate that PKCepsilon phosphorylates IKKbeta at S177 and activates IKKbeta, which in turn induces PKM2 upregulation. | SIGNOR-278323 |
O15516 | Q7Z5J4 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.479 | RAI1 Transcriptionally Activates CLOCK via an Intron 1 Enhancer Element. data suggest that RAI1 binds, directly or in a complex, to the first intron of CLOCK and enhances its transcriptional activity in vitro, supporting RAI1 as a positive regulator of CLOCK and an important part of the circadian loop of transcription. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others. | SIGNOR-266839 |
P06213 | P09958 | 0 | cleavage | up-regulates activity | 0.283 | Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. | SIGNOR-260365 |
Q9Y4E8 | Q13501 | 1 | deubiquitination | down-regulates activity | 0.26 | SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors. Dissociation of the RNF26/SQSTM1 complex, promoted by the DUB USP15 (yellow), releases target vesicles for (4) fast transport into the cell periphery. | SIGNOR-269829 |
P16104 | P45984 | 0 | phosphorylation | up-regulates | 0.2 | H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk. | SIGNOR-160210 |
P17600 | Q00535 | 0 | phosphorylation | up-regulates | 0.563 | Synapsin i (syni), a major sv phosphoprotein involved in the regulation of sv trafficking and neurotransmitter release, is one of the presynaptic substrates of cdk5, which phosphorylates it in its c-terminal region at ser(549) (site 6) and ser(551) (site 7). Phosphorylation of syni by cdk5 is physiologically regulated and enhances its binding to f-actin. | SIGNOR-78883 |
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