IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P12931 | P00533 | 1 | phosphorylation | up-regulates activity | 0.625 | Revealed that peptides derived from egfr residues y992, y1086, y1101, and y1148 bound directly to the sh2 domain of c-src (figure 8c). These experiments demonstrate that a specific subset of egfr receptor c-src phosphorylation sites are also ligands for the sh2 domain of c-src.Cellular src functions as a co-transducer of transmembrane signals emanating from a variety of growth factor receptors, including egfr | SIGNOR-44251 |
Q96NM4 | Q9UL17 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.294 | We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). | SIGNOR-266097 |
P06493 | Q14CS0 | 1 | phosphorylation | down-regulates activity | 0.2 | At mitosis, Cdc2 kinase phosphorylates p47 on Serine-140 and p37 on Serine-56 and Threonine-59, respectively. The phosphorylated p47 and p37 are unable to bind to Golgi membranes, resulting in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively. | SIGNOR-265041 |
Q6NXT2 | Q9Y4C1 | 0 | demethylation | up-regulates activity | 0.2 | Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. | SIGNOR-276847 |
Q9Y3Q4 | P12931 | 0 | phosphorylation | up-regulates | 0.371 | These results demonstrate that src tyrosine kinase enhances hcn4 currents by shifting their activation to more positive potentials and increasing the whole cell channel conductance as well as speeding the channel kinetics. The tyrosine residue that mediates most of src s actions on hcn4 channels is tyr531. | SIGNOR-158707 |
P48729 | O43524 | 1 | phosphorylation | down-regulates | 0.2 | Casein kinase (ck) 1 mediates the hierarchical phosphorylation of foxo3a at s318 and s321, which like foxo1 (rena et al., 2002 blue right-pointing triangle, 2004 blue right-pointing triangle), is probably to enhance its rate of nuclear export | SIGNOR-163676 |
P23443 | P28482 | 0 | phosphorylation | up-regulates | 0.596 | Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase | SIGNOR-28800 |
O15055 | P49674 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.902 | Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2 | SIGNOR-277419 |
P56545 | P12830 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.381 | Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner | SIGNOR-261578 |
Q99708 | Q13315 | 0 | phosphorylation | down-regulates | 0.828 | Atm phosphorylates ctip at serine residues 664 and 745 our study suggests another dna damage-response pathway in which the signal is transmitted through phosphorylation of ctip by atm, leading to dissociation of the ctip_ctbp repressor complex from brca1, which in turn, activate transcription of gadd45 | SIGNOR-79872 |
Q14164 | Q04864 | 1 | phosphorylation | up-regulates | 0.354 | The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel. | SIGNOR-148620 |
P69892 | Q9H165 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.446 | Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching. | SIGNOR-269066 |
P35222 | P48730 | 0 | phosphorylation | down-regulates | 0.626 | However, ckiepsilon has been recently shown to interact with axin (sakanaka et al. 1999;rubinfeld et al. 2001), and it was proposed that this kinase mediates axin-induced apc phosphorylation, thereby stabilizing the -catenin degradation complex (rubinfeld et al. 2001). We have, therefore, evaluated cki as a candidate s45-kinase in several assays, both in vitro and in vivo. | SIGNOR-87441 |
P35626 | P35372 | 1 | phosphorylation | down-regulates activity | 0.2 | These results demonstrate that the T180A mutation probably blocks GRK3- and arr3-mediated desensitization of MOR by preventing a critical agonist-dependent receptor phosphorylation and suggest a novel GRK3 site of regulation not yet described for other G-protein-coupled receptors | SIGNOR-247915 |
P49841 | Q9Y6H5 | 1 | phosphorylation | down-regulates | 0.487 | Synphilin-1 s556a mutant, which is less phosphorylated by gsk3beta, formed more inclusion bodies than wild type synphilin-1. Mutation analysis showed that ser556 is a major gsk3beta phosphorylation site in synphilin-1 | SIGNOR-140609 |
P78347 | O60341 | 1 | relocalization | up-regulates activity | 0.405 | Moreover, the inhibitory effect of TFII-I on transcription is mediated by its ability to recruit corepressor complexes, including histone deacetylase 3 (HDAC3) (25, 133), histone H3K4-specific demethylase LSD1 (48), and components of the polycomb repressor complex | SIGNOR-268540 |
Q99759 | O00141 | 0 | 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 |
P49815 | O75592 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.356 | We show that Pam associates with E2 ubiquitin conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain. | SIGNOR-278704 |
P35813 | Q15797 | 1 | dephosphorylation | down-regulates | 0.538 | In this study, we have found that ppm1a, a metal ion-dependent protein serine/threonine phosphatase, physically interacts with and dephosphorylates smad1 both in vitro and in vivo. considering the highly conserved nature of the sxs motif in all r-smads, we reasoned that ppm1a might also recognize the sxs motif in the bmp-activated smad1. | SIGNOR-149077 |
P18850 | P35638 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.658 | Apart from ER protein chaperones, ATF6 also induces the expression of CHOP and XBP1, thereby connecting the three UPR branches into an integrated signaling network | SIGNOR-260180 |
P56181 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation | SIGNOR-275593 |
P06493 | Q9BXS6 | 1 | phosphorylation | down-regulates | 0.431 | We report here that cdk1 phosphorylates nusap at threonine 300 and 338 in early mitosis. Phosphorylation of nusap inhibits its microtubule-binding activity in vitro and in vivo. | SIGNOR-177549 |
Q9Y618 | Q96EB6 | 0 | null | up-regulates | 0.494 | In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription. | SIGNOR-253506 |
P68400 | P11473 | 1 | phosphorylation | up-regulates | 0.336 | Casein kinase ii (ckii) phosphorylates vdr both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of vdr to bind dna, but increases its ability to transactivate target promoters | SIGNOR-153711 |
Q9UI10 | P41091 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.698 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269137 |
Q9NQR1 | P06493 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | We found that PR-Set7 is phosphorylated at Ser 29 (S29) specifically by the cyclin-dependent kinase 1 (cdk1)/cyclinB complex, primarily from prophase through early anaphase, subsequent to global accumulation of H4K20me1. While S29 phosphorylation did not affect PR-Set7 methyltransferase activity, this event resulted in the removal of PR-Set7 from mitotic chromosomes. S29 phosphorylation also functions to stabilize PR-Set7 by directly inhibiting its interaction with the anaphase-promoting complex (APC), an E3 ubiquitin ligase. | SIGNOR-259832 |
P78368 | Q9Y5P4 | 1 | phosphorylation | down-regulates | 0.2 | These results indicate that ckigamma2 hyperphosphorylates the serine-repeat motif of cert, thereby inactivating cert and down-regulating the synthesis of sphingomyelin. | SIGNOR-182160 |
P56178 | P01106 | 1 | transcriptional regulation | up-regulates quantity | 0.274 | Here we demonstrate by luciferase assay that the MYC promoter is specifically activated by overexpression of DLX5 and that two DLX5 binding sites in the MYC promoter are important for transcriptional activation of MYC. We also show that DLX5 binds to the MYC promoter both in vitro and in vivo and that transfection of a DLX5 expression plasmid promotes the expression of MYC in a dose-dependent manner in mammalian cells | SIGNOR-241914 |
P28482 | Q9UPP1 | 1 | phosphorylation | down-regulates activity | 0.2 | Upon IFNgamma treatment, PHF8 is phosphorylated by ERK2 and evicted from the promoters, which correlates with an increase in H4K20me1 and H3K4me3 levels. | SIGNOR-279745 |
Q05209 | Q9Y6E0 | 0 | phosphorylation | down-regulates activity | 0.272 | In addition, MST3 can phosphorylate PTP-PEST and inhibit the tyrosine phosphatase activity of PTP-PEST.|MST3 directly phosphorylates and inactivates protein tyrosine phosphatase PTP-PEST, which enhances cell migration by enhancing the tyrosine phosphorylation of paxillin Y31 and Y118 [ ]. | SIGNOR-279127 |
O15393 | P10275 | 0 | 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 |
P31751 | Q6ZWJ1 | 1 | phosphorylation | down-regulates activity | 0.42 | Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.Thus, our data demonstrate that insulin-stimulated Akt2-dependent phosphorylation of Synip on serine residue 99 results in reduced binding interactions between Synip and Syntaxin4. | SIGNOR-262635 |
P60953 | Q9NR80 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.739 | 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-260532 |
P00533 | P24752 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 ( xref ).|We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 (XREF_FIG). | SIGNOR-279996 |
P55957 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.519 | Bid is a p53 primary-response gene. | SIGNOR-140248 |
P36896 | O95551 | 1 | phosphorylation | up-regulates activity | 0.28 | ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function. | SIGNOR-262612 |
Q13555 | Q9UQD0 | 1 | phosphorylation | up-regulates activity | 0.271 | CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel. | SIGNOR-275794 |
P28482 | P49418 | 1 | phosphorylation | down-regulates activity | 0.265 | Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2. | SIGNOR-126859 |
P00533 | Q13480 | 1 | phosphorylation | up-regulates | 0.76 | Gab-1 is a multisubstrate docking protein downstream in the signaling pathways of different receptor tyrosine kinases, including the epidermal growth factor receptor (egfr)the entire protein was phosphorylated by regfr at eight tyrosine residues (y285, y373, y406, y447, y472, y619, y657, and y689). | SIGNOR-236400 |
P22681 | P16333 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.644 | Taken together, these results show that lysine 178 in Nck1 is the acceptor site for ubiquitin transferred by c-Cbl, and that the ubiquitination of Nck1 by c-Cbl is blocked in the presence of synaptopodin. | SIGNOR-278606 |
P04049 | P17612 | 0 | phosphorylation | down-regulates activity | 0.5 | Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). | SIGNOR-250041 |
P68431 | Q9H3R0 | 0 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263864 |
Q9H1Y0 | Q13153 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Here, we identified USP13 as an essential deubiquitinase that stabilizes ATG5 in a process that depends on the PAK1 serine/threonine-protein kinase and which enhances autophagy and promotes IM resistance in GIST cells. |As PAK1-mediated phosphorylation at residue T101 protects ATG5 from ubiquitination-dependent degradation | SIGNOR-275835 |
Q6PHR2 | Q96CF2 | 1 | phosphorylation | down-regulates activity | 0.286 | CHMP4C was phosphorylated by recombinant ULK3 in these experiments, whereas CHMP4A and CHMP4B were not (Figure 7\u2014figure supplement 1A). | SIGNOR-279771 |
Q15915 | P08151 | 1 | relocalization | up-regulates | 0.377 | Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels | SIGNOR-105491 |
P53350 | O00139 | 1 | phosphorylation | up-regulates activity | 0.684 | Taken together, KIF2A is phosphorylated at T554 by PLK1 in the subdistal appendages of the mother centriole, which enhances MT depolymerization to disassemble primary cilia in a growth-signal-dependent manner.|Thus, PLK1 and APC/C mediated dual regulation connect the MT depolymerizing activity of KIF2A to a physiological primary cilia disassembly during the proliferative phase. | SIGNOR-278380 |
P01106 | P20839 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.243 | Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The mRNA levels of IMPDH1 and IMPDH2, the rate-limiting enzyme in purine de novo synthesis, increased with MYC induction both in vitro and in vivo. | SIGNOR-267378 |
P49585 | P28482 | 0 | phosphorylation | down-regulates | 0.45 | Oxysterols inhibit phosphatidylcholine synthesis via erk docking and phosphorylation of ctp:phosphocholine cytidylyltransferase. Mutagenesis of ser315 within cctalpha was both required and sufficient to confer significant resistance to 22-hc/9-cis-ra inhibition of ptdcho synthesis. | SIGNOR-134837 |
P04792 | P49137 | 0 | phosphorylation | down-regulates | 0.809 | Notably mk2 is well known to play an important role in actin filament remodellng by phosphorylating hsp27. | SIGNOR-94021 |
Q86UR1 | P17252 | 0 | phosphorylation | down-regulates | 0.29 | Phosphorylation of nadph oxidase activator 1 (noxa1) on serine 282 by map kinases and on serine 172 by protein kinase c and protein kinase a prevents nox1 hyperactivation. | SIGNOR-163667 |
P06493 | Q9H8V3 | 1 | phosphorylation | down-regulates | 0.577 | We show that phosphorylation of ect2 at threonine-341 (t341) affects the autoregulatory mechanism of ect2. In g2/m phase, ect2 was phosphorylated at t341 most likely by cyclin b/cyclin-dependent kinase 1 (cdk1) ect2 is biologically active even when it is not phosphorylated at t341 | SIGNOR-140549 |
Q9Y572 | Q13489 | 0 | polyubiquitination | up-regulates activity | 0.647 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272714 |
P10619 | Q9NR19 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276550 |
P06400 | P04049 | 0 | phosphorylation | down-regulates activity | 0.578 | Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently.|Raf-1 can inactivate Rb function and can reverse Rb mediated repression of E2F1 transcription and cell proliferation efficiently. | SIGNOR-279481 |
Q86UR1 | Q8NFA2 | 0 | relocalization | up-regulates activity | 0.777 | Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation | SIGNOR-264709 |
P31749 | Q99497 | 1 | phosphorylation | up-regulates activity | 0.465 | Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. |Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation. | SIGNOR-275582 |
Q7L7X3 | Q9Y6E0 | 0 | phosphorylation | up-regulates activity | 0.2 | Thus, MST3 phosphorylates TAO1 and TAO2, enabling their association with Myosin Va. | SIGNOR-280140 |
P18031 | Q8TD08 | 1 | dephosphorylation | down-regulates | 0.326 | Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20% | SIGNOR-142981 |
Q16690 | Q16539 | 1 | dephosphorylation | down-regulates | 0.537 | The activity of mapks can be also regulated by a family of dusps, which dephosphorylates bot phosphotyrosine and phopsphothreonine residues. | SIGNOR-166574 |
O60602 | Q15139 | 0 | phosphorylation | up-regulates | 0.353 | Pkd phosphorylated the tlr5-derived target peptide in vitro, and phosphorylation of the putative target serine 805 in hek 293t cell-derived tlr5 was identified by mass spectrometry. These results demonstrate that both pkd1 and pkd2 are required for inflammatory responses following tlr2, tlr4, or tlr5 activation, although pkd1 is more strongly involved | SIGNOR-154473 |
Q13224 | P51608 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.35 | The interaction of MeCP2 with the 2BI3 and 2BI5 sites was strikingly reduced in neurons maintained in the presence of TTX (Fig. 2C). This result is consistent with the classical view of MeCP2 as a general transcriptional repressor, in that the reduced association leads to increased expression of NR2B. | SIGNOR-264685 |
Q5FBB7 | O14965 | 0 | phosphorylation | up-regulates activity | 0.2 | Loss of INCENP/Aurora B in Mitosis Correlates with Delocalization of MEI-S332|MEI-S332 Is Phosphorylated by Aurora B In Vitro|Of these, MEI-S332S124,125,126A was a poor substrate for Aurora B kinase in vitro | SIGNOR-252046 |
P31749 | P78563 | 1 | 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 |
Q9NX47 | Q8IWA4 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH5, a mitochondrial E3 ubiquitin ligase, has been identified as a molecule that binds mitochondrial fission 1 protein (hFis1), dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2), key proteins in the control of mitochondrial fission and fusion.|Notably, a significant increase in Mfn1 level, but not Mfn2, Drp1 or hFis1 levels, was observed in MARCH5-depleted cells, indicating that Mfn1 is a major ubiquitylation substrate. | SIGNOR-274133 |
P14136 | P17252 | 0 | phosphorylation | down-regulates activity | 0.366 | Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7. | SIGNOR-248862 |
Q05513 | P29474 | 1 | phosphorylation | down-regulates activity | 0.371 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251637 |
P28482 | Q9BYT3 | 0 | phosphorylation | up-regulates activity | 0.273 | In vitro kinase assay results indicated that STK33 can phosphorylate ERK2.|STK33 phosphorylated ERK2 and increased the activity of ERK2 and promote the tumorigenesis of colorectal cancer HCT15 cells. | SIGNOR-279351 |
P53779 | Q93045 | 1 | phosphorylation | down-regulates | 0.444 | We demonstrate that purified scg10 can be phosphorylated by two subclasses of mitogen-activated protein (map) kinases, c-jun n-terminal/stress-activated protein kinase (jnk/sapk) and p38 map kinase;jnk3/sapkbeta phosphorylation occurs at ser-62 and ser-73, residues that result in reduced microtubule-destabilizing activity for scg10. | SIGNOR-112114 |
O94953 | P68431 | 1 | demethylation | down-regulates activity | 0.2 | The KDM4 family of Jumonj domain histone demethylases specifically target di- and tri-methylated lysine 9 on histone H3 (H3K9me3), removing a modification central to defining heterochromatin and gene repression. The majority of studies regarding its function describe it as an activator that removes repressive H3K9me3 and H3K9me2 at or near regulated promoters in order to facilitate expression of the indicated pathways. | SIGNOR-263734 |
P23470 | Q05397 | 1 | dephosphorylation | up-regulates activity | 0.243 | 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-254719 |
P06493 | Q16665 | 1 | phosphorylation | up-regulates activity | 0.274 | In vitro kinase assays reveal that CDK1 directly phosphorylates HIF-1\u03b1 at a previously unidentified regulatory site, Ser668.|Overexpression of CDK1 and/or cyclin B1 is sufficient to stabilize HIF-1alpha under normoxic conditions, whereas inhibition of CDK1 enhances the proteasomal degradation of HIF-1alpha, reducing its half-life and steady-state levels. | SIGNOR-279599 |
P41236 | P49841 | 0 | phosphorylation | up-regulates activity | 0.412 | Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol. In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg. This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen synthase kinase 3 (GSK3). | SIGNOR-251257 |
P61077 | O95071 | 1 | ubiquitination | up-regulates activity | 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-272669 |
P62805 | Q86Y97 | 0 | methylation | down-regulates activity | 0.2 | SUV420H1 and SUV420H2 are two highly homologous enzymes that methylate lysine 20 of histone H4 (H4K20), a mark that has been implicated in transcriptional regulation. | SIGNOR-266650 |
P27708 | P62136 | 0 | dephosphorylation | down-regulates activity | 0.332 | Cyclic AMP-dependent protein kinase phosphorylates two serine residues on the protein termed sites 1 and 2| Site 1: Arg-Leu-Ser(P)-Ser-Phe-Val-Thr-Lys Site 2: Ile-His-Arg-Ala-Ser(P)-Asp-Pro-Gly-Leu-Pro-Ala-Glu-Glu-Pro-Lys | Both phosphorylation and activation can be reversed using purified preparations of the catalytic subunits of protein phosphatases 1- and -2A, and inactivation also correlates better with dephosphorylation of site 1 rather than site 2. | SIGNOR-263741 |
O00170 | P04155 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | We show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells. | SIGNOR-259911 |
P24941 | Q9UM11 | 1 | phosphorylation | down-regulates activity | 0.745 | A nuclear localization signal conserved in various species was identified in CDH1, and it sufficiently targets green fluorescent protein to the nucleus. Interestingly, a CDH1-4D mutant mimicking the hyperphosphorylated form was constitutively found in the cytoplasm. In further support of the notion that phosphorylation inhibits nuclear import, the nuclear localization signal of CDH1 with two phospho-accepting serine/threonine residues changed into aspartates was unable to drive heterologous protein into the nucleus. | SIGNOR-250732 |
Q9Y2H1 | O75385 | 1 | phosphorylation | down-regulates quantity | 0.2 | STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination | SIGNOR-270348 |
Q13131 | P05771 | 0 | phosphorylation | down-regulates activity | 0.2 | Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle. | SIGNOR-276460 |
O14757 | Q96GD4 | 1 | phosphorylation | up-regulates | 0.36 | Chk1 phosphorylates aurora-b and enhances its catalytic activity in vitro. | SIGNOR-152926 |
Q8N1B4 | Q9H4P4 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.433 | RNF41 ubiquitinates and relocates VPS52 away from VPS53, another shared subunit of the GARP and EARP complexes, towards RNF41-positive structures. | SIGNOR-278597 |
Q92819 | Q14541 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.337 | Transcription was activated by HNF4G in reporter assays using the promoter/enhancer region of the HAS2 gene. The endogenous expression of the HAS2 gene was suppressed by knockdown of HNF4G. | SIGNOR-261626 |
P51636 | P68400 | 0 | phosphorylation | up-regulates activity | 0.32 | We show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells. Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae | SIGNOR-101110 |
P52333 | P08575 | 0 | dephosphorylation | down-regulates activity | 0.456 | CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling | SIGNOR-248359 |
Q5S007 | P31749 | 1 | phosphorylation | up-regulates | 0.379 | Expression of wild-type LRRK2 promoted neuronal survival against apoptosis through activation of the downstream effector, Akt by phosphorylation of Ser473. Phosphorylated Akt in turn inhibited FOXO 1 signaling | SIGNOR-252598 |
Q99497 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Together, these results demonstrate that parkin selectively recognizes and ubiquitinates misfolded DJ-1 in vivo. | SIGNOR-278526 |
P62745 | O14757 | 0 | phosphorylation | up-regulates activity | 0.328 | We identified that Thr173 and Thr175 of RhoB was phosphorylated by Chk1 using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) (Supplementary Fig.\u00a06f). | SIGNOR-279727 |
P55075 | P10071 | 0 | transcriptional regulation | down-regulates quantity | 0.445 | Whereas Fgf8 expression was almost absent in Shh-/- mutants, it was up-regulated in Gli3-/-;Shh-/- double mutants, suggesting that SHH is not required for Fgf8 induction, and that GLI3 normally represses Fgf8 independently of SHH | SIGNOR-268949 |
O14522 | P49023 | 1 | dephosphorylation | down-regulates activity | 0.462 | To this end, using a phospho-proteomics approach, we identified and validated paxillin and STAT3 as the substrates of PTPRT [15, 16]|the PTPRT target site on paxillin is a previously uncharacterized tyrosine-88 residue (paxillin Y88)|In this study, we also show how pY88 paxillin transduces a signal to activate Akt | SIGNOR-263978 |
P00533 | Q99675 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | CGRRF1 ubiquitinates EGFR through K48-linked ubiquitination, which leads to proteasome degradation. | SIGNOR-272220 |
Q96KG9 | Q9BV73 | 1 | relocalization | down-regulates activity | 0.2 | Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting. | SIGNOR-265497 |
Q99873 | P62633 | 1 | methylation | down-regulates | 0.368 | Cnbp interacts with protein arginine methyltransferase prmt1 / r25 or r27 appear to be the major methylation sites in cnbp /arginine methylation of cnbp impedes rna binding | SIGNOR-204958 |
P11908 | Q9NRM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness. | SIGNOR-276507 |
Q06187 | Q13422 | 1 | phosphorylation | up-regulates activity | 0.432 | We demonstrate that BTK phosphorylates Ikaros at unique phosphorylation sites S214 and S215 in the close vicinity of its zinc finger 4 (ZF4) within the DNA binding domain, thereby augmenting its nuclear localization and sequence-specific DNA binding activity. | SIGNOR-279442 |
P04150 | P24941 | 0 | phosphorylation | up-regulates activity | 0.291 | Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action. | SIGNOR-249427 |
Q8N8S7 | Q13976 | 0 | phosphorylation | down-regulates activity | 0.302 | Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts. PKG may preferentially phosphorylate sites of Ena/VASP proteins that reduce or inactivate these proteins. Inactivated Ena/VASP proteins dissociate from actin filaments, allowing capping proteins to bind and block monomer addition to plus ends, resulting in filament retraction. | SIGNOR-268288 |
Q86Y13 | P0C0S8 | 1 | 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-271749 |
Q96S44 | P31749 | 0 | phosphorylation | up-regulates | 0.297 | Here we show that such an activation of prpk is mediated by another kinase, akt/pkb, which phosphorylates prpk at ser250. | SIGNOR-252503 |
P46937 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.668 | In the present study, we demonstrate that PP1A (catalytic subunit of protein phosphatase-1) interacts with and dephosphorylates YAP2 in vitro and in vivo, and PP1A-mediated dephosphorylation induces the nuclear accumulation and transcriptional activation of YAP2.|PP1A dephosphorylates endogenous YAP2 at serine 127. | SIGNOR-276999 |
P61981 | Q9NRM7 | 0 | 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 |
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