IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q14012 | P46527 | 1 | phosphorylation | up-regulates activity | 0.305 | We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia. | SIGNOR-261194 |
Q96J84 | P06241 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we have characterized Neph1, another SD component, as a novel substrate of SFK. Fyn interacts with and phosphorylates the cytoplasmic domain of Neph1 in vitro and in intact cells. Both tyrosine 637 and 638 of Neph1 are crucial for Neph1-Grb2 binding. | SIGNOR-262746 |
P67775 | P10415 | 1 | dephosphorylation | up-regulates activity | 0.47 | The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A. | SIGNOR-248624 |
Q08499 | P28482 | 0 | phosphorylation | down-regulates | 0.353 | Long pde4d forms are inhibited by erk2 phosphorylation | SIGNOR-77574 |
A1X283 | P12931 | 0 | phosphorylation | up-regulates activity | 0.521 | C-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells|Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation. | SIGNOR-264705 |
P17612 | Q15052 | 1 | phosphorylation | down-regulates activity | 0.2 | ARHGEF6 is a Rho guanine nucleotide exchange factor for Rac1 and constitutively bound to GIT1. NO and PGI2 activate PKG and PKA, respectively and both kinases phosphorylate ARHGEF6 on Ser-684 and possibly on Ser-640. Phosphorylation of ARHGEF6 results in the assembly of a GIT1-ARHGEF6–14-3-3 complex. These changes might contribute to PGI2- and NO-mediated Rac1 inhibition. | SIGNOR-272162 |
P54756 | Q12857 | 0 | 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-268895 |
P57059 | Q53ET0 | 1 | phosphorylation | down-regulates | 0.644 | These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities. | SIGNOR-147707 |
Q92831 | P46531 | 1 | acetylation | up-regulates | 0.602 | In earlier studies, we demonstrated that maml1 enhanced p300 acetyltransferase activity, which increased the acetylation of notch by p300.Acetylation controls notch stability and function in t-cell leukemia. | SIGNOR-199024 |
Q96DT5 | Q92949 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.361 | FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1). | SIGNOR-266931 |
P41240 | P13639 | 1 | phosphorylation | down-regulates quantity | 0.264 | C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2.|In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus. | SIGNOR-279698 |
P04629 | Q92529-2 | 1 | phosphorylation | up-regulates activity | 0.778 | We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo. | SIGNOR-273915 |
P42345 | P53396 | 1 | phosphorylation | up-regulates activity | 0.332 | Biochemical studies indicated that mTOR directly and specifically phosphorylated ACL on Ser 455 in vitro. | SIGNOR-278962 |
P15336 | Q13315 | 0 | phosphorylation | up-regulates | 0.566 | Here, we demonstrate that the protein kinase atm phosphorylates atf2 on serines 490 and 498 following ionizing radiation (ir). dose- and time-dependent phosphorylation of atf2 by atm that results in its rapid colocalization with gamma-h2ax and mrn components into ir-induced foci (irif) | SIGNOR-137619 |
P13498 | P17252 | 0 | 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-260891 |
Q16549 | P41212 | 1 | phosphorylation | down-regulates | 0.2 | In vivo p38-dependent phosphorylation reduced trans-repressional abilities of tel through ets-binding consensus site | SIGNOR-95622 |
P04637 | P53778 | 0 | phosphorylation | up-regulates activity | 0.474 | Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53. | SIGNOR-280026 |
Q05209 | Q14289 | 1 | dephosphorylation | down-regulates activity | 0.544 | Inhibition of the catalytic activity of cell adhesion kinase beta by protein-tyrosine phosphatase-pest-mediated dephosphorylation. / dephosphorylation of tyr402 and tyr579/580 by ptp-pest | SIGNOR-107502 |
Q13370 | P31749 | 0 | phosphorylation | up-regulates | 0.687 | Pde3b is a physiological substrate of akt and that akt-mediated phosphorylation of pde3b on serine-273 is important for insulin-induced activation of pde3b. | SIGNOR-252583 |
O94806 | Q8WUI4 | 1 | phosphorylation | up-regulates activity | 0.2 | Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67]. | SIGNOR-275934 |
Q13371 | P68400 | 0 | phosphorylation | up-regulates | 0.387 | Phosducin-like protein (phlp) is a widely expressed binding partner of the g protein betagamma subunit complex (gbetagamma) that has been recently shown to catalyze the formation of the gbetagamma dimer from its nascent polypeptides. Phosphorylation of phlp at one or more of three consecutive serines (ser-18, ser-19, and ser-20) is necessary for gbetagamma dimer formation and is believed to be mediated by the protein kinase ck2. | SIGNOR-146833 |
P48730 | Q02880 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | 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.CK1 binds with and phosphorylates TOP2β at Ser1130 to promote its degradation by VM-26. | SIGNOR-277509 |
Q9Y4K3 | Q53ET0 | 1 | ubiquitination | down-regulates quantity | 0.307 | Consistently, TRAF6 reduced G6pase gene expression or reporter activity induced by wild-type CRTC1 and CRTC2 but not TRAF6-interaction-defective CRTC1 and CRTC2 (XREF_FIG and XREF_SUPPLEMENTARY).|Indeed, TRAF6, the E3 ubiquitin ligase activated by IL-1beta associates with and ubiquitinates CRTC2. | SIGNOR-278725 |
P10398 | Q15599 | 1 | phosphorylation | up-regulates activity | 0.375 | We also identify A-Raf as a kinase necessary for E3KARP phosphorylation at the G2/M stage of the cell cycle. Phosphorylation of Ser-303 regulates the localization, function, and dynamics of E3KARP | SIGNOR-273503 |
P27361 | P11362 | 1 | phosphorylation | down-regulates | 0.32 | Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling | SIGNOR-200884 |
P17676 | P06702 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Among several known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14 gene (-81), as evidenced by the competitive gel mobility-shift assay.|Thus, it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif, and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells. | SIGNOR-254044 |
P11308 | P48730 | 0 | phosphorylation | down-regulates activity | 0.2 | Interestingly, only CKId, but not other CKI isoforms or CKII could promote ERG degradation under ectopic expression conditions (XREF_FIG).|These results indicate that phosphorylation of ERG by CKIdelta within the SPOP-recognition degron triggers its interaction with SPOP to promote ERG destruction . | SIGNOR-280234 |
P14618 | P45983 | 0 | phosphorylation | up-regulates activity | 0.371 | Active JNK1 specifically activates PKM2 but not PKM1. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365. | SIGNOR-276933 |
P11362 | Q9BV47 | 0 | 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 |
P07949 | Q16539 | 1 | phosphorylation | up-regulates | 0.332 | Dually phosphorylated on thr-180 and tyr-182 by the map2ks map2k3/mkk3, map2k4/mkk4 and map2k6/mkk6 in response to inflammatory citokines, environmental stress or growth factors, which activates the enzyme. | SIGNOR-40493 |
P01106 | Q8N699 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.298 | MT-MC1 is a widely expressed nuclear protein whose overexpression, unlike that of c-Myc targets reported previously, recapitulates multiple c-Myc phenotypes. These include promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation. The MT-MC1 promoter is a direct c-Myc target; it contains two consensus E-box elements, both of which bind c-Myc. | SIGNOR-261736 |
Q7Z6Z7 | O95140 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.42 | AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome | SIGNOR-272978 |
P01106 | Q96RU2 | 0 | deubiquitination | up-regulates | 0.703 | Usp28, an ubiquitin-specific protease, binds to myc through an interaction with fbw7alpha, an f-box protein that is part of an scf-type ubiquitin ligase. Therefore, it stabilizes myc. | SIGNOR-155590 |
Q8TAS1 | Q15637 | 1 | phosphorylation | up-regulates | 0.406 | Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding. | SIGNOR-199797 |
Q16539 | P26651 | 1 | phosphorylation | down-regulates activity | 0.357 | TTP appears to be a p38α/β MAPK target and pretreating skeletal muscle with a p38α/β MAPK inhibitor reduces TTP phosphorylation. | SIGNOR-253596 |
P06493 | P46060 | 1 | phosphorylation | up-regulates | 0.495 | Here, we show that rangap1 is phosphorylated on residues t409, s428, and s442. Phosphorylation occurs before nuclear envelope breakdown and is maintained throughout mitosis . Alternatively, phosphorylated rangap1 may recruit specific sumo target proteins to ranbp2's catalytic domain. | SIGNOR-123520 |
Q9Y297 | P46937 | 1 | ubiquitination | down-regulates | 0.544 | This cascade of phosphorylation allows the binding of scfbetatrcp that promotes the ubiquitination and degradation of yap. | SIGNOR-201138 |
Q16821 | Q15418 | 0 | phosphorylation | up-regulates activity | 0.43 | The protein G(M), which targets protein phosphatase 1 (PP1) to the glycogen particles and sarcoplasmic reticulum (SR) of striated muscles, is known to be phosphorylated at Ser48 and Ser67 in vitro by adenosine 3',5' cyclic monophosphate-dependent protein kinase (PKA) and at Ser48 by MAP kinase-activated protein kinase-1 (MAPKAP-K1, also called p90 RSK). The phosphorylation of Ser48 increases the rate at which the glycogen-associated PP1.G(M) complex dephosphorylates (activates) glycogen synthase, but the phosphorylation of Ser67 has the opposite effect, suppressing the activity of PP1 toward glycogen-bound substrates. | SIGNOR-249036 |
Q96PD2 | P00519 | 0 | phosphorylation | up-regulates activity | 0.2 | SFKs and Abl differentially phosphorylate DCBLD1 and DCBLD2 at distinct tyrosine phosphorylation sites.|We report that Src family kinases and Abl differentially promote the interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while Src family kinases and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of Abl is more pronounced for DCBLD1. 45999997={Domain=45999998 LikeProtein=1399} 45999998="sh2 domain" 45999999="sh2 domain"} | SIGNOR-280167 |
Q8WY64 | P10275 | 1 | ubiquitination | down-regulates quantity | 0.2 | MYLIP knockdown increased AR protein levels whereas CNPY2 knockdown increased MYLIP and reduced AR protein expression levels.|These results showed that the E3 ligase MYLIP could ubiquitinate lysine 845 and 847 residues of AR. | SIGNOR-278766 |
P08047 | P01137 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.296 | MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-β mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-β production | SIGNOR-251740 |
Q92995 | P01106 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.353 | In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation. | SIGNOR-274124 |
P46783 | Q9UHC7 | 0 | ubiquitination | up-regulates activity | 0.2 | We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates. | SIGNOR-272216 |
P01019 | P12821 | 0 | cleavage | up-regulates activity | 0.782 | Angiotensin I-converting enzyme is a zinc metallopeptidase that plays an important role in blood pressure regulation by cleaving the inactive decapeptide angiotensin I to angiotensin II, a potent vasopressor octapeptide. | SIGNOR-253326 |
P28482 | Q16829 | 0 | dephosphorylation | down-regulates | 0.797 | Pyst2 preferentially dephosphorylates and inactivates p42 map kinase in vitro and in vivo | SIGNOR-60871 |
Q8N5S9 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | In vitro, CaMKK is phosphorylated by PKA and this is associated with inhibition of enzyme activity. The major site of phosphorylation is threonine 108, although additional sites are phosphorylated with lower efficiency. | SIGNOR-256115 |
Q9P1Z0 | Q9H2X6 | 0 | phosphorylation | down-regulates activity | 0.379 | The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4. | SIGNOR-262882 |
Q02224 | O14965 | 0 | phosphorylation | down-regulates activity | 0.48 | Aurora A also phosphorylates and inhibits the centromere-associated kinesin CENP-E involved in efficient chromosome congression ( xref ; xref ). | SIGNOR-280187 |
P11309 | P17612 | 0 | phosphorylation | up-regulates activity | 0.266 | In this study, we found that PKCα stabilized and activated PIM-1L by phosphorylation at Ser65. The PIM-1L phosphorylation suppressed sotrastaurin-induced apoptosis. These findings suggest that PKCα promotes cell survival and proliferation by upregulating PIM-1L in acute myeloid leukemia. | SIGNOR-256153 |
P37840 | P34947 | 0 | phosphorylation | down-regulates activity | 0.636 | Grk5 phosphorylated ser-129 of alpha-synuclein at the plasma membrane and induced translocation of phosphorylated alpha-synuclein to the perikaryal area. Grk5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of alpha-synuclein. | SIGNOR-149372 |
Q9Y2K6 | P17612 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.311 | Upon β2AR activation, a specific isoform of the second messenger cAMP-dependent protein kinase A (PKAα) rapidly phosphorylates USP20 on serine 333 located in its unique insertion domain. This phosphorylation of USP20 correlates with a characteristic SDS-PAGE mobility shift of the protein, blocks its deubiquitinase activity, promotes its dissociation from the activated β2AR complex, and facilitates trafficking of the ubiquitinated β2AR to autophagosomes, which fuse with lysosomes to form autolysosomes where receptors are degraded. | SIGNOR-273795 |
Q15306 | Q13568 | 1 | null | down-regulates activity | 0.456 | IL-4-induced c-Myc activity controls a subset of M2-associated genes. IL-4 also induces the M2-polarizing JMJD3-IRF4 axis to inhibit IRF5-mediated M1 polarization. | SIGNOR-249560 |
Q9NZQ7 | Q92905 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.2 | The results suggested that TNF-α upregulates expression of CSN5, which interacts and deubiquitinates PD-L1 for protein stabilization. | SIGNOR-274977 |
Q9NQ66 | P28482 | 0 | phosphorylation | up-regulates activity | 0.398 | coimmunoprecipitation detected a specific association between the activated erk and plc beta1 within the nucleus. In vitro studies revealed that recombinant plc beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by pka. The erk phosphorylation site was mapped to serine 982 this result suggests that erk-evoked phosphorylation of plc beta1 at serine 982 plays a critical role in the activation of the nuclear pi cycle and is also crucial to the mitogenic action of igf-i. | SIGNOR-106561 |
P67809 | P31749 | 0 | phosphorylation | up-regulates | 0.558 | Phosphorylation of yb-1 at the serine 102 residue is required for transcriptional activation of growth-enhancing genes, such as egfr. Herein, we illustrate that activated akt binds to and phosphorylates the yb-1 cold shock domain at ser102 | SIGNOR-252521 |
P12830 | P49674 | 0 | phosphorylation | down-regulates activity | 0.259 | Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846 | SIGNOR-274047 |
P12931 | Q13224 | 1 | phosphorylation | up-regulates activity | 0.559 | We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases | SIGNOR-247180 |
P17252 | P04637 | 1 | phosphorylation | up-regulates activity | 0.437 | Here, we demonstrate that cotransfection of p53 with either PKC alpha or PKC zeta increases p53's transcriptional activity. Mutagenesis of p53 indicates that serine 371 is the major site for phosphorylation by PKC alpha in vitro. | SIGNOR-248999 |
Q96KB5 | Q92769 | 1 | phosphorylation | up-regulates activity | 0.2 | The results of in vitro studies further confirmed the effect of TOPK on HDAC activity by showing that TOPK overexpression significantly up-regulated p-HDAC1 and p-HDAC2, resulting in an increase in the acetylation of histones H3 and H4 in BV2 cells.|These results indicated that TOPK overexpression resulted in the phosphorylation of HDAC1 and HDAC2, which might inactivate them and promote the acetylation of Histone 3 and Histone 4. | SIGNOR-279087 |
Q93045 | P27361 | 0 | phosphorylation | down-regulates activity | 0.352 | SCG10, a growth cone-enriched MT-destabilizing protein, has been recently characterized as an in vitro substrate for various serine/threonine kinases including PKA, MAP kinase, and CDK (19). We have found that SCG10 is phosphorylated in vivo in developing rat brain.| The sites for MAP kinase phosphorylation were identified as Ser-62 and Ser-73 of SCG10|By expressing a series of phosphorylation site mutants, we showed that the MT-destabilizing effect of SCG10 could be modulated. While the nonphosphorylatable mutant showed higher activity than the wild-type protein, the activity of the mutant in which phosphorylation on all four sites was mimicked by an aspartate residue was greatly reduced. These data suggest that the nonphosphorylated state of SCG10 represents the most active form of the protein. | SIGNOR-249115 |
Q9NZP8 | P00738 | 1 | cleavage | up-regulates activity | 0.375 | We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum. This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction. Furthermore, incubation of affinity-purified C1r-LP and proHp led to the cleavage of the latter protein. ProHp appeared to be cleaved at the expected site because substitution of Gly for Arg-161 blocked the reaction. | SIGNOR-256358 |
P10636 | P48730 | 0 | phosphorylation | down-regulates | 0.374 | Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.Here we characterized the contribution of one ck1 isoform, ckidelta, to the phosphorylation of tau at residues ser202/thr205 and ser396/ser404 in human embryonic kidney 293 cells. | SIGNOR-121717 |
O43781 | Q96EB6 | 1 | phosphorylation | up-regulates activity | 0.502 | DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr (522), promoting deacetylation of p53.|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. | SIGNOR-279705 |
O15530 | P51812 | 1 | phosphorylation | up-regulates | 0.655 | We characterize two monoclonal antibodies raised against phosphorylated forms of the n- and c-terminal domain of rsk2 (p-s227 and p-t577, respectively). Using these two antibodies, we show that stress signals, such as uv light, induce phosphorylation and activation of the three rsks. | SIGNOR-70612 |
Q8IUQ4 | P46531 | 1 | relocalization | up-regulates | 0.26 | The overexpression of siah1 causes the re-localization of notch from the cell surface to the cytoplasm and to the nucleus, which is indicative of notch activation | SIGNOR-168460 |
Q05655 | P14598 | 1 | phosphorylation | up-regulates | 0.447 | Pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation. The use of p47phox mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc?, ???, And ?. | SIGNOR-89229 |
P27361 | Q16665 | 1 | phosphorylation | up-regulates | 0.695 | We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_ | SIGNOR-178731 |
Q9HBA0 | P17252 | 0 | phosphorylation | up-regulates activity | 0.38 | We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4. | SIGNOR-260882 |
O60934 | P24941 | 0 | phosphorylation | up-regulates activity | 0.507 | Nbs1 is phosphorylated by Cdk2 on Ser432 in human whole-cell extracts. | SIGNOR-279500 |
Q9UQM7 | P48058 | 1 | phosphorylation | up-regulates | 0.592 | Receptor internalization, altered;intracellular localization | SIGNOR-97546 |
Q15796 | Q9NYA4 | 0 | dephosphorylation | down-regulates | 0.53 | Here we demonstrate that myotubularin-related protein 4 (mtmr4), a fyve domain-containing dual-specificity protein phosphatase (dsp), attenuates tgfbeta signaling by reducing the phosphorylation level of r-smads in early endosomes. | SIGNOR-163031 |
Q13315 | Q04206 | 1 | phosphorylation | down-regulates activity | 0.502 | Interestingly, another group has identified that in the VP-16 induced NF-\u03baB activation, ATM binds to RelA directly and phosphorylates RelA on Ser 547, a post-translational modification that represses a subset of NF-\u03baB-dependent genes ( xref ).|Our findings that ablation of ATM reduces RelA serine 276 phosphorylation, suggests a mechanism for how ROS mediates RelA serine 276 phosphorylation in the TNF pathway (Figure -D). | SIGNOR-279006 |
P61586 | Q07960 | 0 | gtpase-activating protein | down-regulates activity | 0.864 | 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-260458 |
P18848 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | By using mutants of ATF4 we identified serine 215 as the main CK2 phosphorylation site. The ATF4 S215A mutant turned out to be more stable than the wild-type form. | SIGNOR-276425 |
P68400 | P28482 | 0 | phosphorylation | up-regulates | 0.369 | Erk2, which is activated by egfr signaling, directly binds to ck2alpha via the erk2 docking groove and phosphorylates ck2alpha primarily at t360/s362, subsequently enhancing ck2alpha activity | SIGNOR-161855 |
Q92547 | O95071 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.462 | Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks. | SIGNOR-272667 |
Q7Z6Z7 | Q92858 | 1 | ubiquitination | down-regulates quantity | 0.304 | Huwe1 ubiquitinates and degrades Atoh1, and robustly affects development of GNPs that express this transcription factor [ xref ].|This provides further evidence that phosphorylation of Atoh1 affects Huwe1-mediated degradation, and demonstrates that Huwe1 inhibits Atoh1 to affect cellular differentiation in multiple cell types. | SIGNOR-278693 |
P24752 | P11362 | 0 | phosphorylation | up-regulates activity | 0.2 | Treatment with the FGFR1 inhibitor TKI258 in FGFR1-expressing H1299 cells led to decreased Y407 phosphorylation of ACAT1 in the mitochondrial fraction, where both ACAT1 and a fraction of FGFR1 were detected|Inhibition of tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in decreased ACAT1 activity, | SIGNOR-264423 |
P49840 | P01106 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.406 | Similar to c-myc, similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation. | SIGNOR-138596 |
Q16875 | Q13131 | 0 | phosphorylation | up-regulates | 0.399 | Ipfk-2 was phosphorylated on the homologous serine (ser-461) and activated by ampk in vitro. | SIGNOR-89760 |
Q9NRC8 | P22087 | 1 | deacetylation | up-regulates activity | 0.271 | Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206) | SIGNOR-275894 |
Q96D59 | Q07817 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.385 | As an E3 ligase, RNF183 ubiquitinates Bcl-xL, causing its degradation and subsequent apoptosis. | SIGNOR-278595 |
Q13164 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.577 | Furthermore, PKC\u03b6 phosphorylates ERK5, and mutation analysis showed that the preferred site is S486.|PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5 | SIGNOR-280090 |
P63279 | Q92985 | 1 | sumoylation | down-regulates activity | 0.287 | One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. we identified that IRF7 is sumoylated at lysine 452. | SIGNOR-266837 |
Q14493 | P04908 | 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-265397 |
Q5RD31 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.487 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.NFE2L2-mediated upregulation of NQO1 is implicated in promoting resistance to ferroptosis inducers, such as erastin and sorafenib, in HCC cells | SIGNOR-279860 |
Q9Y478 | Q92786 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation. | SIGNOR-277609 |
P49321 | P68400 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. | SIGNOR-273627 |
O60285 | P04637 | 1 | phosphorylation | up-regulates | 0.547 | Here we showed that in the presence of wild-type lkb1, nuak1 directly interacts with and phosphorylates p53 in vitro and in vivo. | SIGNOR-172008 |
P55265 | Q9Y243 | 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-276191 |
P16885 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Phosphorylation at Ser-146 by PKCδ increases p21 stability | SIGNOR-262963 |
Q12923 | P25963 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.442 | Identification of IkappaBalpha as a substrate of Fas-associated phosphatase-1|A full-length FAP-1 protein preferentially dephosphorylates Tyr-42 of IkBa|Moreover, other studies have shown that tyrosine phosphorylation of IkBa on Tyr-42 (which occurs with Fas ligand binging) protected against inducible degradation both in vitro [30] and in vivo [38] | SIGNOR-248712 |
P05019 | P20823 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.301 | Growth hormone induces insulin-like growth factor-I gene transcription by a synergistic action of STAT5 and HNF-1α | SIGNOR-251720 |
P12931 | P17706 | 0 | dephosphorylation | down-regulates | 0.72 | We found that tcptp dephosphorylates and inactivates src family kinases to regulate t cell responses._ | SIGNOR-177116 |
Q9NPA2 | P08253 | 1 | cleavage | up-regulates activity | 0.375 | Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6 matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond. Leukolysin Cleaves ProMMP-2 at Asn66-Leu and Asn109-Tyr. | SIGNOR-256345 |
P01100 | P17612 | 0 | phosphorylation | up-regulates activity | 0.518 | Human c-Fos protein is phosphorylated in vitro by PKA. phosphorylation of Fos occurs at serine residue 362. Modification of the Fos protein by phosphorylation with PKA then allows it to act as a regulator of its own synthesis by downregulating fos gene expression at a transcriptional level | SIGNOR-250356 |
Q92530 | Q9H2K2 | 0 | ADP-ribosylation | down-regulates quantity by destabilization | 0.496 | We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31. | SIGNOR-263386 |
P05412 | Q8IW41 | 0 | phosphorylation | up-regulates activity | 0.383 | Consequently, our study clearly determined that p38 MAP kinase-activated MK5 could trigger the activity of c-Jun through phosphorylation of c-Jun, which then bound to the SNAI1 promoter to promote SNAI1-mediated EMT.It has been reported that altering extracellular responses and intracellular signal transduction, such as enhancing the activity of p38MAPK [48], JNK [49] and eIF4 [39] signaling pathways, leads to carcinogenesis and aggravates metastasis.|Western blot analysis showed that MK5 could promote the phosphorylation of c-Jun S63 site and the expression of SNAI1 (Fig.\u00a05a). | SIGNOR-279422 |
P35228 | P12931 | 0 | phosphorylation | up-regulates | 0.681 | We identify human inos residue tyr(1055) as a target for src-mediated phosphorylation. src kinase-mediated phosphorylation stabilizes inducible nitric-oxide synthase in normal cells and cancer cells. | SIGNOR-188974 |
Q9NX47 | O60260 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MITOL promotes cell survival by degrading Parkin during mitophagy.|Mechanistically, MITOL mediates ubiquitination of Parkin at lysine 220 residue, which promotes its proteasomal degradation, and thereby fine-tunes mitophagy by controlling the quantity of Parkin. | SIGNOR-278554 |
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