IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P06493 | Q15910 | 1 | phosphorylation | down-regulates | 0.575 | Cdk1, which phosphorylates ezh2 at threonines 345 and 487.Phosphorylation of thr-345 and thr-487 promotes ezh2 ubiquitination and subsequent degradation by the proteasome | SIGNOR-174058 |
O75461 | O14757 | 0 | phosphorylation | down-regulates activity | 0.574 | the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters. | SIGNOR-266371 |
P42574 | P38398 | 1 | cleavage | down-regulates quantity by destabilization | 0.473 | We demonstrate the cleavage and the consequential downregulation of full-length BRCA1 by caspase-3 during UV-induced apoptosis. Finally, mutation of a caspase-3 specific cleavage site (D/A1154) rendered BRCA1 non-cleavable. | SIGNOR-256326 |
Q99541 | P35790 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In addition, as a protein kinase, CHKalpha2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth | SIGNOR-267649 |
Q969H0 | P23771 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.403 | Fbw7 promotes degradation of GATA3 in a Thr-156-dependent manner. | SIGNOR-276635 |
O14490 | Q9UPX8 | 1 | relocalization | up-regulates activity | 0.827 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264587 |
Q9P2R6 | Q07812 | 1 | relocalization | up-regulates activity | 0.2 | We detected RERE protein mainly in the nucleus, where it colocalizes with the promyelocytic leukemia protein in promyelocytic leukemia oncogenic domains (PODs). Overexpression of RERE recruits a fraction of the proapoptotic protein BAX to PODS: This observation correlates with RERE-induced apoptosis, which occurs in a caspase-dependent manner. | SIGNOR-264485 |
Q9BUB5 | P47712 | 1 | phosphorylation | up-regulates activity | 0.577 | The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727. | SIGNOR-226633 |
Q16875 | P53778 | 0 | phosphorylation | up-regulates quantity | 0.2 | KRAS transformation and overexpression of p38gamma increased expression of PFKFB3 and glucose transporter GLUT2 | SIGNOR-279539 |
P51955 | P04637 | 1 | phosphorylation | down-regulates | 0.318 | NEK2 Phosphorylates p53 at Ser315 and Reduces Its Stability.|These results are consistent with NEK2 inhibiting p53 transcriptional activation functions. | SIGNOR-278488 |
P22681 | P27986 | 1 | ubiquitination | down-regulates | 0.694 | Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner. | SIGNOR-110060 |
P00751 | P00746 | 0 | cleavage | up-regulates activity | 0.804 | The resulting proconvertase C3bB is subsequently cleaved by factor D (FD), generating the AP C3 convertase C3bBb | SIGNOR-263488 |
Q96PM5 | O14579 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.471 | PIRH2 promotes the ubiquitylation of epsilon-COP in vitro and in vivo and consequently promotes the degradation of epsilon-COP. | SIGNOR-272630 |
O60664 | P51151 | 0 | null | up-regulates activity | 0.591 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253089 |
Q14493 | Q5TEC6 | 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-265415 |
P78536 | P05067 | 1 | cleavage | up-regulates activity | 0.539 | By the use of gene disruption (knockout), we now demonstrate that TACE (tumor necrosis factor alpha converting enzyme), a member of the ADAM family (a disintegrin and metalloprotease-family) of proteases, plays a central role in regulated alpha-cleavage of APP. Our data suggest that TACE may be the alpha-secretase responsible for the majority of regulated alpha-cleavage in cultured cells. | SIGNOR-262829 |
P27361 | Q9BR01 | 1 | phosphorylation | down-regulates | 0.2 | The phosphorylation of sult4a1 allows interaction with pin1, which then promotes degradation of the sulfotransferase. | SIGNOR-168248 |
P98177 | Q13627 | 0 | phosphorylation | down-regulates | 0.315 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity | SIGNOR-183677 |
O75531 | Q86Y07 | 0 | phosphorylation | down-regulates | 0.502 | We demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. Coexpression of vrk1 and gfp-baf greatly diminishes the association of baf with the nuclear chromatin/matrix and leads to its dispersal throughout the cell | SIGNOR-143368 |
O60346 | P17252 | 1 | dephosphorylation | down-regulates quantity | 0.25 | In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha | SIGNOR-237043 |
P15311 | P43405 | 0 | phosphorylation | up-regulates activity | 0.447 | Phospho-SYK has also been shown to specifically activate ezrin upon CD81 engagement.|We found that the activated SYK led to a time dependent phosphorylation of ezrin (pY354 and pThr567) and radixin (pThr564) (XREF_FIG). | SIGNOR-279129 |
Q13501 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Once activated, parkin interacts with and subsequently ubiquitinates p62 at the K13 residue, resulting in the degradation of p62 via the proteasomal dependent pathway. | SIGNOR-278524 |
O75151 | P68431 | 1 | demethylation | down-regulates activity | 0.2 | PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. | SIGNOR-264521 |
Q5T197 | P52630 | 1 | ubiquitination | down-regulates activity | 0.448 | DCST1 promotes ubiquitination of STAT2.|The ability of DCST1 to degrade STAT2 levels was visible both in the presence and absence of IFNbetastimulation.|In our study, DCST1 was found to interact with and promote ubiquitination of STAT2, leading to reduced STAT2 expression and attenuated activation of the ISG induction pathway. | SIGNOR-278747 |
P04637 | P25445 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.605 | In an attempt to understand how CD95 expression is regulated by p53, we identified a p53-responsive element within the first intron of the CD95 gene, as well as three putative elements within the promoter. The intronic element conferred transcriptional activation by p53 and cooperated with p53-responsive elements in the promoter of the CD95 gene. wt p53 bound to and transactivated the CD95 gene, | SIGNOR-62376 |
P62834 | O95398 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.71 | Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well. | SIGNOR-263956 |
O14965 | O75496 | 1 | phosphorylation | up-regulates activity | 0.51 | Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis.|Thr25 of geminin is phosphorylated by Aurora-A. | SIGNOR-278509 |
P68400 | Q9HA82 | 1 | phosphorylation | up-regulates activity | 0.2 | Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue. | SIGNOR-273984 |
O15294 | P11413 | 1 | glycosylation | up-regulates activity | 0.264 | O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth|O-GlcNAcylation of G6PD activates enzyme activity|G6PD is dynamically modified by O-GlcNAc at serine 84|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267582 |
P00533 | Q38SD2 | 1 | phosphorylation | down-regulates activity | 0.343 | In this study, we demonstrate that EGFR regulates the kinase activity of LRRK1 via tyrosine phosphorylation and that this is required for proper endosomal trafficking of EGFR. Phosphorylation of LRRK1 at Tyr-944 results in reduced LRRK1 kinase activity. | SIGNOR-262856 |
P25098 | P08069 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation | SIGNOR-276413 |
Q01974 | P49841 | 0 | phosphorylation | down-regulates activity | 0.312 | We identify ror2 ser 864 as a critical residue phosphorylated by gsk3 and required for noncanonical receptor activation by wnt5a, analogous to the priming phosphorylation of low-density receptor-related protein 6 (lrp6) in response to wnt3a. | SIGNOR-169642 |
Q13224 | P54829 | 0 | dephosphorylation | down-regulates activity | 0.547 | These previous results, together with the present findings, indicate that STEP61 dephosphorylates the NR2B subunit at its regulatory tyr1472 site, and dephosphorylation of this site leads to internalization of the NMDAR complex from neuronal surface membranes. | SIGNOR-265744 |
Q00987 | Q16665 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.643 | We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. | SIGNOR-271385 |
Q08493 | P28482 | 0 | phosphorylation | down-regulates | 0.256 | The short-form pde4b2 isoenzyme was activated by erk2 phosphorylation. sub-family selective actions in the ability of erk2 map kinase to phosphorylate and regulate the activity of pde4 cyclic amp-specific phosphodiesterases | SIGNOR-83187 |
P52564 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.613 | A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. | SIGNOR-45353 |
Q96NT3 | P46934 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.419 | The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1. | SIGNOR-272846 |
Q9Y243 | O15111 | 1 | phosphorylation | up-regulates | 0.414 | Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta | SIGNOR-187062 |
P00533 | P09211 | 1 | phosphorylation | up-regulates | 0.437 | Taken together, these results and those of the ms/ms analyses confirmed tyr-3, tyr-7, and tyr-198 to be primary residues phosphorylated by egfr in the gstp1 protein. The phosphorylation increased gstp1 enzymatic activity significantly, | SIGNOR-184387 |
P78344 | P68400 | 0 | phosphorylation | up-regulates activity | 0.226 | DAP5(S902) is phosphorylated by CK2α. Phosphorylation of DAP5(S902) by CK2α is required for eIF2β binding. | SIGNOR-266384 |
P17612 | P05114 | 1 | phosphorylation | down-regulates activity | 0.307 | PKA preferentially phosphorylates serine 6 in human HMGN1. specific phosphorylation of the NBD of HMGN proteins serves to prevent the interaction of these proteins with their chromatin targets during mitosis. | SIGNOR-249993 |
P55072 | P31749 | 0 | phosphorylation | up-regulates | 0.509 | Site-directed mutagenesis identified ser-351, ser-745, and ser-747 as akt phosphorylation sites on vcp. however, our study also suggests that other known biological activities of vcp, such as those related to intracellular trafficking, ubiquitin-mediated proteolysis, and activation of transcription (28), might be regulated by akt through the activation of vcp. I | SIGNOR-252491 |
Q06413 | P51608 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.346 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264680 |
P09543 | P02686 | 1 | null | down-regulates activity | 0.455 | We provide evidence that CNP directly associates with and organizes the actin cytoskeleton, thereby providing an intracellular strut that counteracts membrane compaction by myelin basic protein (MBP). | SIGNOR-269269 |
Q15717 | Q05655 | 0 | phosphorylation | up-regulates | 0.637 | Tandem phosphorylation of serines 221 and 318 by protein kinase cdelta coordinates mrna binding and nucleocytoplasmic shuttling of hurstabilization of mrna by the ubiquitous rna binding protein human antigen r (hur), a member of the embryonic lethal abnormal vision (elav) protein family, requires canonical binding to au-rich element (are)-bearing target mrna and export of nuclear hur-mrna complexes to the cytoplasm. In human mesangial cells (hmc) both processes are induced by angiotensin ii (angii) via protein kinase cdelta (pkcdelta)-triggered serine phosphorylation of hur. | SIGNOR-163524 |
O15392 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.795 | Phosphorylation by aurora-b negatively regulates survivin function . hat survivin is phosphorylated at t117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphaseduring mitosis | SIGNOR-154569 |
P35241 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.68 | A peak of the phosphopeptide, in which only T573 was phosphorylated, was not detected. Quantitative analyses revealed that _100% of T564, but at most _40% of T573, was phosphorylated when C-rad was incubated with Rho-Kc for 1 h. Then we concluded that the major and primary phosphorylation site of radixin by Rho-kinase was T564 and referred to the Rho-Kcphosphorylated C-rad as T564-phosphorylated C-rad. | In this study, we found that the T564 phosphorylation of radixin markedly suppressed its head-to-tail association. This suggests that the T564-phosphorylation of radixin (and probably also the phosphorylation of ezrin T567 and moesin T558) keeps them open and active. | SIGNOR-248994 |
O75116 | Q16555 | 1 | phosphorylation | up-regulates | 0.383 | Rho-kinase phosphorylated crmp-2 at thr-555 in vitro.we demonstrated that crmp-2 is phosphorylated by rho-kinase in drg neurons during lpa-induced growth cone collapse. | SIGNOR-77543 |
Q9HC98 | P52732 | 1 | phosphorylation | up-regulates activity | 0.444 | Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles. | SIGNOR-273886 |
P51149 | Q8NEB9 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.484 | The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7 | SIGNOR-261302 |
Q92529 | P62993 | 1 | relocalization | up-regulates | 0.819 | In addition to direct binding of grb2 to phosphotyrosine residues of receptor kinases, grb2 can also be recruited to the receptor by binding to shc when shc is tyrosine phosphorylated as a result of receptor stimulation. | SIGNOR-146897 |
P40763 | P14618 | 0 | phosphorylation | up-regulates activity | 0.443 | PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor | SIGNOR-267716 |
P40763 | P53350 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.306 | Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3. | SIGNOR-271690 |
Q8TDC3 | P20810 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that an AZ cytomatrix protein CAST and an AZ-associated protein kinase SAD-B coordinately regulate STD by controlling reloading of the AZ with release-ready synaptic vesicles. SAD-B phosphorylates the N-terminal serine (S45) of CAST, and S45 phosphorylation increases with higher firing rate. | SIGNOR-263051 |
Q07817 | Q9H4B4 | 0 | phosphorylation | up-regulates | 0.391 | Polo kinase 3 (plk3) was implicated in bcl-xl(ser49) phosphorylation. These data indicate that, during g2 checkpoint, phospho-bcl-xl(ser49) is another downstream target of plk3, acting to stabilize g2 arrest. | SIGNOR-172230 |
P25963 | Q9UN86 | 0 | relocalization | down-regulates activity | 0.342 | IkappaBalpha interacts with G3BP2 both in vivo and in vitrothrough the IkappaBalpha CRS. Overexpression of G3BP2 directly promotes retention of IkappaBalpha in the cytoplasm. | SIGNOR-260985 |
Q9UGI9 | O75385 | 0 | phosphorylation | down-regulates | 0.406 | Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity phosphorylation of ampk by ulk1 represents a negative feedback circuit. | SIGNOR-173053 |
Q8TAE6 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.546 | Pka predominantly phosphorylated a site distinct from the inhibitory t73 in kepi. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c | SIGNOR-101835 |
P17252 | P48048 | 1 | phosphorylation | down-regulates activity | 0.2 | The giant patch clamp together with site direct mutagenesis revealed that Thr-193 is the phosphorylation site on PKC that regulates the pH(i) sensitivity of ROMK1 channels. Mutation of PKC-induced phosphorylation sites (T193A) decreases the pH(i) sensitivity and increases the interaction of channel-PIP(2). | SIGNOR-276389 |
Q13554 | Q9UQD0 | 1 | phosphorylation | up-regulates activity | 0.272 | 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-275788 |
Q14493 | P23527 | 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-265379 |
Q9Y243 | Q13043 | 1 | phosphorylation | down-regulates | 0.261 | Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt. | SIGNOR-201129 |
Q9BZS1 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.285 | Our previous study showed, by mass spectrometry analysis, that GSK-3β phosphorylates Foxp3 at Ser270 and Ser275 | SIGNOR-277245 |
P35222 | Q9NW38 | 0 | ubiquitination | up-regulates activity | 0.2 | Here we provide evidence that FANCL increases the activity and expression of beta-catenin, a key pluripotency factor in hematopoietic stem cells.|We show that FANCL ubiquitinates \u03b2-catenin with atypical ubiquitin chain extension known to have nonproteolytic functions. | SIGNOR-278651 |
Q9C0C7 | P42345 | 0 | phosphorylation | down-regulates activity | 0.471 | We show that under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated. In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. As ULK1 has been shown to activate AMBRA1 by phosphorylation, the proposed pathway may act as a positive regulation loop, which may be targeted in human disorders linked to impaired autophagy.|mTOR phosphorylates AMBRA1 at Ser 52, inhibiting its role in ULK1 modification | SIGNOR-272986 |
Q08050 | P06493 | 0 | phosphorylation | up-regulates | 0.762 | A conserved phosphorylation site within the forkhead domain of foxm1b is required for its activation by cyclin-cdk1further analysis reveals that the leu-641 residue within an lxl motif is required for the recruitment of the cyclin-cdk complex, and the thr-596 residue is a critical cdk1 phosphorylation site within the activation domain of foxm1b. Cdk-dependent phosphorylation stimulates the foxm1b transcriptional activity | SIGNOR-187880 |
Q01543 | O15550 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260034 |
Q04912 | P31749 | 0 | phosphorylation | up-regulates | 0.559 | Akt/pkb phosphorylates ron ser-1394, thus providing a docking site for 14-3-3based on these results, we propose a mechanism based on msp-ron-dependent phosphorylation and 14-3-3 association, whereby the function of alpha6beta4 switches from a mechanical adhesive device into a signaling component, and might be critically involved in human epidermal wound healing | SIGNOR-252471 |
O14757 | Q9BXW9 | 1 | phosphorylation | up-regulates activity | 0.585 | In vitro and in vivo experiments show that phosphorylation of s331 is mediated by chk1, the s-phase checkpoint kinase implicated in the fanconi anemia dna repair pathway. phosphorylation at this site is dependent on chk1, signifying the importance of the s-phase checkpoint in the activation of fanconi anemia pathway. | SIGNOR-107042 |
P40763 | P15692 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.786 | Stat3 directly regulated the promoter of the VEGF gene. Blockade of activated Stat3 by ectopic expression of dominant-negative Stat3 significantly inhibited VEGF expression, and the growth and metastasis of human pancreatic cancer cells. | SIGNOR-259456 |
Q8IWJ2 | P11717 | 1 | relocalization | up-regulates activity | 0.529 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253085 |
P06748 | P51452 | 0 | dephosphorylation | down-regulates activity | 0.2 | In the absence of DUSP3, these three residues remain phosphorylated and favor the dissociation equilibrium of NPM homo-oligomerization and/or its association with ARF, therefore promoting an early nuc|Therefore, here we focused on the molecular mechanisms used by DUSP3-NPM interaction to affect the abovementioned cellular responses and found out that DUSP3 dephosphorylates three tyrosine residues (Y29, Y67, and Y271) of NPM. | SIGNOR-277005 |
P45983 | Q13469 | 1 | phosphorylation | down-regulates | 0.752 | Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin jnk directly regulated nuclear factor of activated t-cell (nfat) activation in culture and in transgenic mice containing an nfat-dependent luciferase reporter. | SIGNOR-118217 |
P40818 | P08581 | 1 | destabilization | down-regulates quantity | 0.456 | Degradation of acutely stimulated receptor tyrosine kinases, epidermal growth factor receptor and Met, is strongly inhibited in UBPY knockdown cells suggesting that UBPY function is essential for growth factor receptor down-regulation. | SIGNOR-266903 |
Q8NB16 | P30530 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6). | SIGNOR-274119 |
P05771 | Q16625 | 1 | phosphorylation | up-regulates activity | 0.455 | Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X. | SIGNOR-249106 |
Q92570 | Q9BXH1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax. | SIGNOR-259396 |
P28482 | Q14686 | 1 | phosphorylation | up-regulates activity | 0.2 | In vitro phosphorylation studies with His-tagged TRBP (795–931) suggested that S884 can be phosphorylated by MAPK (ERK2) in vitro (Fig. 10A).Analysis of in vitro and in vivo receptor interactions with TRBP suggested that S884 allowed selective interactions for ERβ, TR, and RXR vs. ERα. | SIGNOR-265882 |
Q13555 | Q9Y618 | 1 | phosphorylation | down-regulates | 0.2 | The kinase activity of camkii was essential for the activation of notch signaling. We also determined that camkii could enhance the association between notch1-ic and rbp-jk. Furthermore, the physical association between rbp-jk and smrt was substantially suppressed by camkii. We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation. | SIGNOR-191777 |
Q16620 | P12931 | 0 | phosphorylation | up-regulates activity | 0.46 | Indeed, activated Src can directly phosphorylate recombinant TrkB protein in a cell-free system.|We found that both exogenous H 2 O 2 and endogenous ROS activate TrkB signaling by a Src family kinase dependent but brain derived neurotrophic factor independent mechanism in cultured rat cortical neurons. | SIGNOR-280130 |
Q9HBY8 | O43524 | 1 | phosphorylation | down-regulates activity | 0.521 | Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)|However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis. | SIGNOR-249130 |
P24941 | O60934 | 1 | phosphorylation | up-regulates activity | 0.507 | Nbs1 is phosphorylated by Cdk2 on Ser432 in human whole-cell extracts. | SIGNOR-279500 |
Q01860 | P26358 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.437 | Oct4 and Nanog upregulate Dnmt1 through direct binding to its promoter, thereby leading to the repressed expression of p16 and p21 and genes associated with development and lineage differentiation | SIGNOR-253158 |
P42574 | Q9BQQ3 | 1 | cleavage | up-regulates activity | 0.396 | In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein | SIGNOR-260613 |
Q96RR4 | Q13131 | 1 | phosphorylation | up-regulates | 0.604 | Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli. | SIGNOR-176602 |
Q00613 | P27361 | 0 | phosphorylation | down-regulates | 0.631 | Sequential phosphorylation of hsf1 by mitogen-activated protein kinase and glycogen synthase kinase 3 at ser-303 and ser-307 represses transcriptional activation by heat shock factor-1. | SIGNOR-44999 |
O43521 | P53779 | 0 | phosphorylation | up-regulates activity | 0.689 | JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity. | SIGNOR-250130 |
P17252 | P13726 | 1 | phosphorylation | up-regulates | 0.2 | We previously showed that the phosphorylation of ser253 within the cytoplasmic domain of human tissue factor (tf) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of ser258 terminates this process. The phosphorylation of ser253 is known to be mediated by protein kinase c_ | SIGNOR-199872 |
P14679 | P05771 | 0 | phosphorylation | up-regulates | 0.441 | We conclude that pkc-beta activates tyrosinase directly by phosphorylating serine residues at positions 505 and 509 in the cytoplasmic domain of this melanosome-associated protein. our results strongly suggest that direct phosphorylation of tyrosinase by pkc-_ leads to its activation. | SIGNOR-67870 |
Q9BUB5 | O00141 | 0 | phosphorylation | down-regulates activity | 0.2 | We show that SGK1 phosphorylates MNK1 at a conserved site, which represses its activity. | SIGNOR-277357 |
O75385 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.361 | NEDD4L ubiquitylates ULK1 at lysine 925 and lysine 933.|Next, we found that down-regulation of the ULK1 protein by NEDD4L is blocked by proteasome inhibitors (MG132 and lactacystin), but not by lysosomal inhibitors (leupeptin and Clq; XREF_FIG and S2 C), indicating that NEDD4L triggers ULK1 degradation exclusively through the proteasome pathway. | SIGNOR-278523 |
P24941 | P98177 | 1 | phosphorylation | down-regulates | 0.518 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity | SIGNOR-183655 |
P25098 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | PKA directly phosphorylates GRK2 on serine 685. This modification increases G subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. | SIGNOR-250334 |
P20823 | P05019 | 1 | 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 |
Q13315 | O95863 | 1 | phosphorylation | up-regulates activity | 0.482 | ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity. | SIGNOR-279587 |
P18031 | P19235 | 1 | dephosphorylation | down-regulates activity | 0.459 | In vivo interaction between EPO-R and PTP1B suggested that PTP1B dephosphorylates the EPO-R intracellularly.|Protein tyrosine phosphatase 1B participates in the down-regulation of erythropoietin receptor signalling. | SIGNOR-276994 |
O96017 | P53350 | 0 | phosphorylation | up-regulates | 0.492 | Plk1 overexpression enhances phosphorylation of chk2 at thr-68. | SIGNOR-96637 |
Q13950 | Q09472 | 0 | acetylation | up-regulates quantity | 0.453 | Bmp-induced non-smad erk signaling pathway cooperatively regulates osteoblast differentiation, in part, through increasing the stability and transcriptional activity of runx2 or increasing runx2 acetylation by p300. | SIGNOR-195579 |
Q92538 | P84077 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.719 | GBF1 Stimulates Production of Arf-GTP In Vivo | SIGNOR-277400 |
P01116 | P49356 | 0 | null | up-regulates activity | 0.419 | Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials. | SIGNOR-242556 |
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