IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P49593 | Q9UQM7 | 1 | dephosphorylation | down-regulates | 0.331 | Ppm1f specifically dephosphorylates the phospho-thr-286 in autophosphorylated camkii substrate and thus deactivates the camkii in vitro. | SIGNOR-124309 |
O00141 | Q96PU5 | 1 | phosphorylation | down-regulates activity | 0.787 | Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1. | SIGNOR-263076 |
P30305 | Q15418 | 0 | phosphorylation | up-regulates | 0.253 | Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b. | SIGNOR-202125 |
P12931 | O15162 | 1 | phosphorylation | up-regulates activity | 0.476 | Plscr1 is phosphorylated by c-src, within the tandem repeat sequence 68vynqpvynqp77.|The EGF-mediated Interaction between PLSCR1 and Shc Requires Phosphorylation of Tyr69 and Tyr74 in PLSCR1 | SIGNOR-103773 |
P84243 | O75582 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun. | SIGNOR-119233 |
Q8WYL5 | P53667 | 1 | dephosphorylation | down-regulates activity | 0.597 | In addition to its cofilin\u2013phosphatase activity, SSH1 can also dephosphorylate LIMK1 and LIMK2, although LIMK1 is a better substrate than LIMK2 [63] .|SSH1 suppresses the kinase activity of LIMK1 toward cofilin by dephosphorylation at Thr 508 in the kinase catalytic domain and other autophosphorylated residues [63]. | SIGNOR-277096 |
P03951 | P00748 | 0 | cleavage | up-regulates activity | 0.494 | Activation of factor XI in plasma is dependent on factor XII | Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided. | SIGNOR-263519 |
P14649 | Q15746 | 0 | phosphorylation | up-regulates | 0.72 | Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin ii that are regulated by myosin light chain kinase (mlck)-mediated phosphorylation of the regulatory myosin light chain (mlc). | SIGNOR-65865 |
P24928 | P50750 | 0 | phosphorylation | up-regulates | 0.777 | Cyclin-dependent kinase 9 (cdk9) promotes elongation by rna polymerase ii (rnapii), mrna processing, and co-transcriptional histone modification. Cdk9 phosphorylates multiple targets, including the conserved rnapii elongation factor spt5 and rnapii itself | SIGNOR-203528 |
P05198 | P36873 | 0 | dephosphorylation | up-regulates activity | 0.412 | Dephosphorylation of eIF2α is central to ISR signal termination to restore protein synthesis and normal cell functioning. It is mediated by protein phosphatase 1 (PP1) complex that recruits a PP1 catalytic subunit (PP1c) and one of the two regulatory subunits. In mammals, phosphatase activity is regulated by either PPP1R15A (also known as growth arrest and DNA damageâ€inducible protein, GADD34), which is induced as part of the ISR. the GADD34–PP1 complex acts as an important negative feedback loop to restore protein synthesis once the ER stress has been resolved, and as such aids in cell survival | SIGNOR-254119 |
P49327 | B0YJ81 | 0 | chemical activation | up-regulates activity | 0.2 | Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, | SIGNOR-267760 |
Q16236 | P04040 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.426 | BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2 | SIGNOR-254651 |
Q8IU85 | Q8N5S9 | 0 | phosphorylation | up-regulates activity | 0.416 | CaM-KIdelta exhibits Ca(2+)/CaM-dependent activity that is enhanced (approximately 30-fold) in vitro by phosphorylation of its Thr180 by CaM-K kinase (CaM-KK)alpha, consistent with detection of CaM-KIdelta-activating activity in HeLa cells. | This sustained activation of CaM-KIdelta was completely abolished by Thr180Ala mutation and inhibited by CaM-KK inhibitor, STO-609, indicating a functional CaM-KK/CaM-KIdelta cascade in HeLa cells. | SIGNOR-250715 |
Q09472 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.404 | In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigenesis. In vitro and in vivo experiments aimed showed that cyclin-dependent kinase 1 (CDK1) and ERK1/2 phosphorylated p300 on Ser1038 and Ser2039. Mutations of Ser1038 and Ser2039 increased p300 protein stability and levels. | SIGNOR-276457 |
P49841 | P53805 | 1 | phosphorylation | up-regulates activity | 0.484 | Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin. | SIGNOR-249359 |
P19525 | P28482 | 0 | phosphorylation | up-regulates | 0.2 | Our results provide strong evidence that dsrna binding is required for dimerization of full-length pkr molecules in vivo, leading to autophosphorylation in the activation loop and stimulation of the eif2alpha kinase function of pkr. | SIGNOR-56337 |
P31749 | Q05195 | 1 | phosphorylation | down-regulates | 0.363 | Here, we present evidence that akt inhibits mad1-mediated transcription repression by physical interaction with and phosphorylation of mad1. | SIGNOR-252525 |
P35240 | P17252 | 0 | phosphorylation | down-regulates activity | 0.328 | PKC\u03b1\nnormally phosphorylates and inactivates NF2.|PKCalpha normally phosphorylates and inactivates NF2. | SIGNOR-280081 |
P52948 | Q9HC98 | 0 | phosphorylation | down-regulates activity | 0.315 | To elucidate which of the identified sites can be targeted by CDK1/cyclin B1 and Nek6 in vitro (Figure S1D), we performed phosphorylation reactions using recombinant kinases and unlabeled ATP followed by phosphopeptide mapping (Table S1). MS analysis confirmed phosphorylation of S591 and S822 by Nek6 as well as phosphorylation of T529, T536, S595, S606, and T653 by CDK1. Phosphomimetic Mutants of Nup98 Show Defects in NPC Localization | SIGNOR-273893 |
P11831 | P05231 | 1 | null | up-regulates | 0.281 | Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy. | SIGNOR-255966 |
P05067 | Q5JRX3 | 0 | cleavage | down-regulates activity | 0.373 | In the present study we have identified and characterized the human PreP homologue, hPreP, in brain mitochondria, and we show its capacity to degrade the amyloid beta-protein (Abeta). PreP belongs to the pitrilysin oligopeptidase family M16C containing an inverted zinc-binding motif. We show that hPreP is localized to the mitochondrial matrix. In situ immuno-inactivation studies in human brain mitochondria using anti-hPreP antibodies showed complete inhibition of proteolytic activity against Abeta. | SIGNOR-260661 |
Q08209 | Q92934 | 1 | dephosphorylation | up-regulates activity | 0.471 | Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis. | SIGNOR-248694 |
Q9UBF6 | Q13794 | 1 | ubiquitination | down-regulates activity | 0.39 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271446 |
P22415 | P78527 | 0 | phosphorylation | up-regulates | 0.293 | Feeding induces the recruitment of dna-pk to usf-1 and its phosphorylation, which then allows recruitment of p/caf, resulting in usf-1 acetylation and fas promoter activation. | SIGNOR-184849 |
Q9UNE7 | Q13485 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.396 | We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process. | SIGNOR-272947 |
P61073 | P11309 | 0 | phosphorylation | up-regulates quantity | 0.365 | Pim-1 and Pim-3 enhance phosphorylation and cell surface expression of CXCR4.|When the in vitro phosphorylated fragments were detected with the anti-phospho (Ser339)-CXCR4 antibody, it became evident that both Pim-1 and Pim-3, but not Pim-2 can phosphorylate CXCR4 on Ser339 (XREF_FIG). | SIGNOR-278450 |
P17252 | P61587 | 1 | phosphorylation | down-regulates activity | 0.2 | PKCalpha dependent Rnd3 phosphorylation downregulates Rnd3 inhibitory activity and leads to increased signaling through the Rho-ROCK pathway.|We further show that PKC\u03b1 directly phosphorylates Rnd3 in an in vitro kinase assay. | SIGNOR-279557 |
P54762 | Q03135 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | EphB1-dependent Y-14 phosphorylation of Cav-1 regulates caveolae endocytosis and endothelial permeability. | SIGNOR-280008 |
P05129 | O94768 | 1 | phosphorylation | down-regulates activity | 0.2 | These results suggest that phosphorylation of Ser350 plays an essential role in regulating translocation of DRAK2 to the nucleus from the cytoplasm, possibly by affecting the activity of the NLS. Ectopic expression of PKC-gamma induced cytoplasmic localization of DRAK2 and PKC-gamma phosphorylated Ser350 flanking the NLS. | SIGNOR-263178 |
Q9UPY5 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.424 | 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 directly binds to the promoter region of SLC7A11, leading to increased expression of this transporter, which in turn contributes to the resistance to ferroptosis and to radiotherapy | SIGNOR-279867 |
A2RUS2 | Q6IQ22 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.624 | ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.|active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy. | SIGNOR-264734 |
O00311 | P06493 | 0 | phosphorylation | up-regulates | 0.535 | Hucdc7 and ask proteins can also be phosphorylated by cdks in vitro. Among four possible cdk phosphorylation sites of hucdc7, replacement of thr-376, corresponding to the activating threonine of cdk, with alanine (t376a mutant) dramatically reduces kinase activity, indicative of kinase activation by phosphorylation of this residue. | SIGNOR-78311 |
P09619 | P24666 | 0 | dephosphorylation | down-regulates activity | 0.308 | Insight into the role of low molecular weight phosphotyrosine phosphatase (LMW-PTP) on platelet-derived growth factor receptor (PDGF-r) signaling. LMW-PTP controls PDGF-r kinase activity through TYR-857 dephosphorylation|On the basis of these results, we propose a key role for LMW-PTP in PDGF-r down-regulation through the dephosphorylation of the activation loop Tyr-857, thus determining a general negative regulation of all downstream signals, with the exception of those elicited by internalized receptors. | SIGNOR-248452 |
Q96NX9 | P15173 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.367 | We confirmed Dach2 is a Mgn transcriptional repressor that mediates HDAC-dependent regulation by (i) overexpressing Dach2 in myotubes harboring the 133-bp Mgn promoter and (ii) rescuing TSA-mediated Mgn repression by Dach2 knockdown. | SIGNOR-261579 |
P02452 | P03956 | 0 | cleavage | down-regulates quantity by destabilization | 0.378 | In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4. | SIGNOR-272336 |
Q12834 | P06493 | 0 | phosphorylation | down-regulates activity | 0.935 | Cdk1 phosphorylates Cdc20 to negatively regulate its ability to bind and activate the APC/C. | SIGNOR-279321 |
P10636 | P28482 | 0 | phosphorylation | down-regulates activity | 0.566 | Using nanoelectrospray mass spectrometry, we have undertaken an extensive comparison of phosphorylation in vitro by several candidate tau kinases, namely, JNK, p38, ERK2, and glycogen synthase kinase 3beta (GSK3beta). Between 10 and 15 sites were identified for each kinase. The three MAP kinases phosphorylated Ser202 and Thr205 but not detectably Ser199, whereas conversely GSK3beta phosphorylated Ser199 but not detectably Ser202 or Thr205. Phosphorylated Ser404 was found with all of these kinases except JNK. The MAP kinases may not be strictly proline specific: p38 phosphorylated the nonproline sites Ser185, Thr245, Ser305, and Ser356, whereas ERK2 was the most strict. All of the sites detected except Thr245 and Ser305 are known or suspected phosphorylation sites in paired helical filament-tau extracted from Alzheimer brains. Thus, the three MAP kinases and GSK3beta are importantly all strong candidates as tau kinases that may be involved in the pathogenic hyperphosphorylation of tau in Alzheimer's disease. | SIGNOR-249416 |
P42345 | O75143 | 1 | phosphorylation | down-regulates | 0.651 | Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2. | SIGNOR-183965 |
P00519 | P19484 | 1 | phosphorylation | down-regulates activity | 0.2 | Our data show that c-Abl promotes TFEB tyrosine phosphorylation and that its inhibition induces TFEB activity.|c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder Summary The transcription factor EB ( TFEB ) has emerged as a master regulator of lysosomal biogenesis , exocytosis , and autophagy , promoting the clearance of substrates stored in cells . | SIGNOR-279583 |
P03956 | P08123 | 1 | cleavage | down-regulates quantity by destabilization | 0.401 | In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4. | SIGNOR-272337 |
P17706 | Q02790 | 1 | dephosphorylation | down-regulates | 0.399 | We have documented that a cellular protein that binds the immunosuppressant drug fk506, termed the fk506-binding protein (fkbp52), interacts with the single-stranded d sequence within the aav inverted terminal repeats, inhibits viral second-strand dna synthesis, and consequently limits high-efficiency transgene expression. Deliberate overexpression of the murine wild-type (wt) tc-ptp gene, but not that of a cysteine-to-serine (c-s) mutant, caused tyrosine dephosphorylation of fkbp52, leading to efficient viral second-strand dna synthesis and resulting in a significant increase in aav-mediated transduction efficiency in hela cells in vitro. | SIGNOR-97794 |
P31749 | Q96QF0 | 1 | phosphorylation | up-regulates activity | 0.2 | Rabin8 is phosphorylated and activated by Akt in cells grown on stiff ECM. | SIGNOR-277802 |
P68400 | P42575 | 1 | phosphorylation | down-regulates | 0.309 | Here we show that protein kinase (pk) ck2 phosphorylates procaspase-2 directly at serine-157. When intracellular pkck2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a piddosome-independent manner. | SIGNOR-140836 |
O15350 | Q9P2P5 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.37 | P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability. | SIGNOR-269457 |
Q16659 | O60729 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.571 | Reciprocally, we found that the phosphatases Cdc14A and Cdc14B (Cdc is cell-division cycle) bind to ERK3 and reverse its C-terminal phosphorylation in mitosis. Importantly, alanine substitution of the four C-terminal phosphorylation sites markedly decreased the half-life of ERK3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.|In vitro phosphorylation of a series of ERK3-deletion mutants by mitotic cell extracts revealed that phosphorylation is confined to the unique C-terminal extension of the protein. Using MS analysis, we identified four novel phosphorylation sites, Ser684, Ser688, Thr698 and Ser705, located at the extreme C-terminus of ERK3. | SIGNOR-248336 |
P00747 | P25116 | 1 | cleavage | down-regulates activity | 0.624 | Plasmin mediates the lysis of fibrin clots and could in different studies activate platelets or inhibit the responses induced by thrombin (41-43). Our study favors a net inactivating effect on PAR1 despite minor cleavage at Arg41, on the basis of preferential cleavage at positions Arg70 and Lys76, COOH-terminal to the Arg41-Ser42 activation site. | SIGNOR-263572 |
P52333 | P29350 | 0 | dephosphorylation | up-regulates | 0.688 | The expression of shp-1 protein was associated with dephosphorylation of the jak3 kinase. | SIGNOR-82764 |
Q13191 | P00533 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.76 | Here we describe that overexpression of cbl-b, a homologue of the c-cbl protooncogene, inhibits EGFR-induced apoptosis in MDA-MB-468 breast cancer cells. Overexpression of cbl-b results in a shortened duration of EGFR activation upon EGF stimulation. This is demonstrated by decreased amounts of phosphorylated EGFR as well as by inhibition of multiple downstream signaling pathways. The inhibition of signaling by cbl-b results from increased ubiquitination and degradation of the activated EGFR. | SIGNOR-272934 |
O43293 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.316 | ZIP kinase phosphorylates p21(WAF1) at Thr145 and alanine-substituted mutations in the p21(WAF1) phosphorylation site alter its ability to be phosphorylated by ZIP kinase. | Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1) | SIGNOR-251085 |
P01106 | P50750 | 0 | phosphorylation | down-regulates activity | 0.54 | CDK9 promotes phosphorylation of MYC on Ser 62 . | SIGNOR-279024 |
P68431 | Q8TF76 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we show that phosphorylation of histone H3 threonine 3 (H3T3ph) by Haspin is necessary for CPC accumulation at centromeres and that the CPC subunit Survivin binds directly to H3T3ph. | SIGNOR-275428 |
P31749 | P62714 | 0 | dephosphorylation | down-regulates | 0.508 | These results confirm that the activity changes observed are achieved by a reversible phosphorylation mechanism, and also argue that pp2a may negatively regulate rac-pk activity in vivo. Dephosphorylation of the activated rac-pk in itro by pp2ac resulted in an 87% reduction of kinase activity | SIGNOR-252636 |
Q9BXM7 | Q8IXI1 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.719 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C). | SIGNOR-272727 |
P45984 | P49768 | 1 | phosphorylation | up-regulates | 0.376 | This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity. | SIGNOR-179676 |
Q13642 | O75925 | 0 | sumoylation | down-regulates | 0.256 | Pias1 (the protein inhibitor of activated stat1) interacts with kyot2 directly and attenuates kyot2-mediated transcriptional repression. We demonstrate that kyot2 is modified by sumoylation at two lysine residues, k144 and k171. Sumoylation of the transfected kyot2 is enhanced by pias1 | SIGNOR-154801 |
P41143 | P01189 | 0 | chemical activation | up-regulates activity | 0.65 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258409 |
P06493 | Q9UGL1 | 1 | phosphorylation | down-regulates activity | 0.258 | Phosphorylation of the histone demethylase KDM5B and regulation of the phenotype of triple negative breast cancer|Here, we demonstrate that KDM5B is phosphorylated at Ser1456 by the cyclin-dependent kinase 1 (CDK1). Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes. | SIGNOR-273435 |
P78527 | Q9UBK2 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. | SIGNOR-277911 |
Q00535 | P00352 | 1 | phosphorylation | up-regulates quantity | 0.2 | Cdk5 Phosphorylates ALDH1A1 at S75 and S274.|These results demonstrate that Cdk5 increases ALDH1A1 levels in neurotoxin exposed neuronal cells both at transcriptional level and by direct phosphorylation at S75 and S274 sites. | SIGNOR-279399 |
Q16555 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.655 | Cdk5 and DYRK2 phosphorylate CRMP2 and CRMP4, respectively, priming these proteins at S522 before their subsequent phosphorylation by GSK-3b at T509, T516 and S518|e CRMP2 phosphorylation by GSK-3b disrupts its interaction with tubulin (Yamashita & Goshima, 2012), leading to growth inhibition | SIGNOR-264838 |
P22413 | P0DMV8 | 0 | post transcriptional regulation | up-regulates quantity | 0.2 | We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. | SIGNOR-252197 |
O60341 | P68431 | 1 | demethylation | up-regulates activity | 0.2 | Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. | SIGNOR-264507 |
P06493 | P39880 | 1 | phosphorylation | down-regulates | 0.357 | Phosphorylation of serines 1237 and 1270 caused inhibition of dna binding in vitro. In cotransfection studies, cyclin a-cdk1 inhibited cdp/cux stable dna binding and prevented repression of the p21(waf1) reporter. | SIGNOR-110912 |
P24941 | P06400 | 1 | phosphorylation | down-regulates | 0.884 | We demonstrate that phosphorylation by either cdk2-cyclin a, which phosphorylates t821, or cdk4-cyclin d1, which phosphorylates threonine 826, can disable prb for subsequent binding of an lxcxe protein. | SIGNOR-47895 |
P08047 | Q9BSI4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression. | SIGNOR-271698 |
P28482 | P37802 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.269 | ERK2 interacted with 29-31 amino acids of transgelin-2 and subsequently phosphorylated the S145 residue of transgelin-2. S145 phosphorylation of transgelin-2 played important roles in cell proliferation and tumorigenesis of PDAC.| We found that the protein stability of transgelin-2 was regulated by KRAS. ERK-mediated phosphorylation resulted in accumulation of transgelin-2 protein. | SIGNOR-265221 |
Q9NX47 | Q13794 | 1 | ubiquitination | down-regulates quantity | 0.2 | MARCH5 promotes ubiquitination of MCL1 and NOXA.|Of note, MARCH5 depletion led to the accumulation of MCL1 and NOXA in asynchronous as well as G2 cells, suggesting that MARCH5 controls NOXA/MCL1 levels throughout the cell cycle. | SIGNOR-278758 |
O43521 | P45983 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.759 | Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination. | SIGNOR-250132 |
Q8ND25 | P00533 | 0 | phosphorylation | up-regulates activity | 0.27 | Together, these results demonstrate that EGFR-dependent phosphorylation of ZNRF1 at Y103 promotes degradation of AKT and resultant activation of GSK3\u03b2, which mediates oxidative stress\u2013induced neuronal apoptosis ( xref ). | SIGNOR-279522 |
P49840 | O75030 | 1 | phosphorylation | up-regulates | 0.294 | Glycogen synthase kinase 3 (gsk3) was found to phosphorylate ser298 in vitro, thereby enhancing the binding of mitf to the tyrosinase promoter | SIGNOR-72878 |
P51959 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.791 | Individual promoter and intron p53-binding motifs from the rat Cyclin G1 promoter region support transcriptional activation by p53 but do not show co-operative activation. | SIGNOR-268961 |
Q7Z6M1 | P20645 | 1 | relocalization | up-regulates activity | 0.385 | P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking. | SIGNOR-253091 |
Q9P0J1 | Q15797 | 1 | dephosphorylation | down-regulates | 0.243 | We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1. | SIGNOR-144876 |
Q93008 | P62987 | 1 | cleavage | up-regulates quantity | 0.611 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270825 |
Q06124 | O95297 | 1 | dephosphorylation | down-regulates | 0.522 | In vitro, tyrosine-phosphorylated pzr was efficiently dephosphorylated by the full-length form of shp-2 but not by its sh2 domain-truncated form. The coexisting binding and dephosphorylation of pzr by shp-2 may function to terminate signal transduction initiated by pzr and shp-2 and to set a threshold for the signal transduction to be initiated. | SIGNOR-75220 |
Q9UGL1 | P48431 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.309 | Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes. | SIGNOR-273450 |
P49841 | Q68CJ9 | 1 | phosphorylation | down-regulates activity | 0.549 | It is possible that phosphorylation of CREBH by GSK3beta leads to altered CREBH conformation with a resulting decreased affinity toward the COPII coated transport complex.|Similarly, expression of dominant negative GSK3beta can rescue the decreased CREBH cleavage activity in the Bmal1 knockdown hepatocytes under the circadian clock (XREF_FIG), thus confirming that BMAL1 controls circadian regulated CREBH cleavage and activation through AKT and GSK3beta signaling in hepatocytes. | SIGNOR-279785 |
Q96AV8 | O14757 | 0 | phosphorylation | down-regulates activity | 0.387 | Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage. | SIGNOR-279692 |
P24844 | O75116 | 0 | phosphorylation | up-regulates activity | 0.647 | Here we found that Rho-kinase stoichiometrically phosphorylated myosin light chain (MLC). Peptide mapping and phosphoamino acid analyses revealed that the primary phosphorylation site of MLC by Rho-kinase was Ser-19, which is the site phosphorylated by MLC kinase. Rho-kinase phosphorylated recombinant MLC, whereas it failed to phosphorylate recombinant MLC, which contained Ala substituted for both Thr-18 and Ser-19. We also found that the phosphorylation of MLC by Rho-kinase resulted in the facilitation of the actin activation of myosin ATPase. | SIGNOR-261709 |
Q05682 | P17252 | 0 | phosphorylation | down-regulates | 0.357 | Phosphorylation of both intact caldesmon and of its c-terminal fragment (658c), containing residues 658-756, significantly decreased their ability to inhibit acto-heavy meromyosin atpase. | SIGNOR-36792 |
Q05209 | P17252 | 0 | phosphorylation | down-regulates | 0.322 | Ptp-pest is phosphorylated in vitro by both cyclic amp-dependent protein kinase (pka) and protein kinase c (pkc) at two major sites, which we have identified as ser39 and ser435 / phosphorylation of ser39 in vitro decreases the activity of ptp-pest by reducing its affinity for substrate. | SIGNOR-27300 |
Q99873 | Q92804 | 1 | methylation | up-regulates | 0.431 | The methylation of taf15 by prmt1 is required for the ability of taf15 to positively regulate the expression of the studied endogenous taf15-target genes. | SIGNOR-183137 |
P17612 | P09917 | 1 | phosphorylation | down-regulates activity | 0.335 | These results indicate that PKA phosphorylates 5-LO on Ser-523, which inhibits the catalytic activity of 5-LO and reduces cellular LT generation. | SIGNOR-264410 |
P31751 | P35226 | 1 | phosphorylation | up-regulates activity | 0.292 | the polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate | SIGNOR-249582 |
P28482 | P43354 | 1 | phosphorylation | up-regulates | 0.395 | We have shown that erk2 is a kinase to phosphorylate nurr1 on multiple sites. S126 and t132, which are located near af1 core of nurr1, are dominant sites phosphorylated by erk2. reporter gene assays show that nurr1delta124-133/t185a, an erk2 phospho-site mutant form, could not further increase its transcriptional activity on th promoter, suggesting that nurr1 phosphorylation by erk2 may regulate its transcriptional activity on th promoter. | SIGNOR-157167 |
P03209 | Q14653 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs. | SIGNOR-266644 |
Q13315 | Q9NUW8 | 1 | phosphorylation | up-regulates | 0.542 | Optimal function of the dna repair enzyme tdp1 requires its phosphorylation by atm and/or dna-pk. Here we show that top1-associated dna double-stranded breaks (dsbs) induce the phosphorylation of tdp1 at s81. This phosphorylation is mediated by the protein kinases: ataxia-telangiectasia-mutated (atm) and dna-dependent protein kinase (dna-pk) | SIGNOR-188772 |
Q7KZI7 | Q15831 | 0 | phosphorylation | up-regulates activity | 0.588 | MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase. | SIGNOR-276165 |
Q16236 | P48637 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.31 | 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.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy | SIGNOR-279870 |
Q13671 | P00519 | 0 | phosphorylation | up-regulates | 0.751 | We also report that the amino-terminal domain of rin1 contains sequences that can mediate interactions with the abl tyrosine kinase and that rin1 is itself tyrosine phosphorylated by c-abl. | SIGNOR-48142 |
P00519 | Q05086 | 1 | phosphorylation | down-regulates activity | 0.273 | Our results suggest that c-Abl protects p53 from HPV-E6-E6AP complex-mediated degradation by phosphorylating E6AP and impairing its E3 ligase activity | SIGNOR-260930 |
P29323 | P00519 | 0 | phosphorylation | down-regulates | 0.515 | Two-hybrid screens identified regions of abl and arg that bind to the ephb2 and epha4 receptors, suggesting a novel signaling connection involving the two kinase families.The connection between EphB2 and Abl/Arg appears to be reciprocal. Activated EphB2 causes tyrosine phosphorylation of Abl and Arg, and vice versa. Interestingly, treatment of COS cells and B35 neuronal-like cells with ephrin-B1 to activate endogenous EphB2 decreased the kinase activity of endogenous Abl. | SIGNOR-109668 |
P68400 | Q96G74 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. Treatment with CK2 could activate DUBA purified from E. coli, and this activity was associated with a species monophosphorylated at Ser177 (Fig. 1d). | SIGNOR-265872 |
Q13557 | P13688 | 1 | phosphorylation | up-regulates | 0.2 | Camkiid specifically phosphorylates thr-457 on ceacam1-sf, which in turn regulates the process of lumen formation via apoptosis of the central acinar cells. | SIGNOR-203402 |
P25490 | Q9HAU4 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.364 | In addition, Smurf2 decreased the protein half-life and transcriptional activity of YY1.|Wild type Smurf2, but not the E3 ubiquitin ligase defective mutant, increased the poly-ubiquitination of YY1. | SIGNOR-278544 |
O14807 | P49354 | 0 | null | up-regulates activity | 0.2 | 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-242553 |
P24941 | Q08999 | 1 | phosphorylation | down-regulates | 0.849 | When expressed in u2os cells, the phosphorylation-deficient mutant p130(delta)(cdk4), in which the cdk4 specific sites were mutated to alanine residues, imposed a more sustained g1 arrest than a constitutively active prb(delta)(cdk), known to repress all cellular e2f activity | SIGNOR-87492 |
Q96R06 | Q96SN8 | 1 | relocalization | up-regulates activity | 0.465 | By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically. | SIGNOR-271719 |
O15169 | Q5JTC6 | 0 | relocalization | up-regulates activity | 0.789 | Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6. | SIGNOR-171886 |
Q14449 | P49840 | 0 | phosphorylation | down-regulates activity | 0.264 | Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3. | SIGNOR-264871 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.