IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
O14920 | P31946 | 1 | phosphorylation | down-regulates | 0.37 | We provide a mechanism for these observations through the phosphorylation of 14-3-3beta by ikkbeta and pkcdelta on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm. | SIGNOR-138608 |
P04626 | P06493 | 1 | phosphorylation | down-regulates | 0.274 | Phosphorylation on tyrosine-15 of p34(cdc2) by erbb2 inhibits p34(cdc2) activation and is involved in resistance to taxol-induced apoptosis | SIGNOR-88671 |
Q13469 | P45983 | 0 | 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 |
P60891 | Q13131 | 0 | phosphorylation | down-regulates activity | 0.2 | We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. | SIGNOR-265729 |
Q13153 | Q9UQ80 | 1 | phosphorylation | up-regulates | 0.2 | We found that pak1 phosphorylated ebp1 in vitro and mapped the phosphorylation site to threonine 261. these studies demonstrate for the first time that ebp1 is a substrate of pak1 and the importance of the pak1 phosphorylation site for the functional activity of ebp1 in breast cancer cells. | SIGNOR-160963 |
Q9NX47 | O00429 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1.Pulse–chase experiment also indicated that MITOL overexpression promoted Drp1 turnover. | SIGNOR-271894 |
P42224 | Q14164 | 0 | phosphorylation | up-regulates | 0.4 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154775 |
O00141 | O15530 | 0 | phosphorylation | up-regulates activity | 0.65 | PDK1 activates SGK in vitro by phosphorylating Thr256. | SIGNOR-250275 |
O75116 | P24844 | 1 | 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 |
A0AVK6 | O14757 | 0 | phosphorylation | down-regulates activity | 0.315 | 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-279693 |
P00533 | Q13315 | 1 | phosphorylation | up-regulates activity | 0.399 | Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks. | SIGNOR-276872 |
P52565 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.246 | Hence, it may be reasonable to deduce that N-formyl-methionyl-leucyl-phenylalanine binds its receptors to activate protein kinase C\u03b6 to generate superoxide, which in turn stimulates the motility in an autocrine manner via the protein kinase C\u03b6-RhoGDI-1-RhoGTPase pathway.|In these cells, protein kinase C zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation. | SIGNOR-280089 |
Q14980 | P11171 | 0 | relocalization | up-regulates activity | 0.533 | These results indicate that 4.1 proteins recruit NuMA and dynein to the anaphase cell cortex through their conserved CTD (Figure 2I). | SIGNOR-266012 |
P11274 | P18031 | 0 | dephosphorylation | down-regulates | 0.33 | These results illustrate selectivity in the effects of ptps in a cellular context and suggest that ptp1b may function as a specific, negative regulator of p210 bcr-abl signalling in vivo. | SIGNOR-56818 |
Q06187 | P42229 | 1 | phosphorylation | up-regulates activity | 0.467 | Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo. BTK-mediated tyrosine phosphorylation of ectopically expressed wild type (but not Tyr(694) mutant) STAT5A enhanced its DNA binding activity. | SIGNOR-250603 |
O75582 | P84243 | 1 | 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 |
P15923 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.372 | Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. |Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)|anti_phospho_M2 peptide (SSPSpTPVGSPQG) | SIGNOR-249117 |
P30989 | P25098 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively. | SIGNOR-278280 |
Q13042 | P06493 | 0 | phosphorylation | up-regulates | 0.638 | Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation | SIGNOR-119762 |
P20908 | P13497 | 0 | cleavage | up-regulates activity | 0.623 | BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro.NH2-terminal sequencing of an ∼35-kDa band in the BMP-1-treated material (N-α1(V), Fig. 3 B,lanes 2 and 3) showed it to correspond to the NH2-terminal portion of the pro-α1(V) N-propeptide previously shown to be cleaved in pro-α1(V)3 homotrimers by BMP-1 (39), whereas NH2-terminal sequencing of an ∼38-kDa band (C-α1(V)BMP-1, Fig. 3 B,lanes 2 and 3) showed it to correspond to pro-α1(V) C-propeptides cleaved between Asp-1594 and Asp-1595. | SIGNOR-256344 |
P06401 | P28482 | 0 | phosphorylation | down-regulates | 0.605 | Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome | SIGNOR-74712 |
P19784 | Q13541 | 1 | phosphorylation | down-regulates activity | 0.333 | The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex. | SIGNOR-249334 |
P14618 | P00533 | 0 | phosphorylation | down-regulates activity | 0.449 | EGFR binds to and phosphorylates PKM2 to inhibit its activity. | SIGNOR-277197 |
P35222 | P67775 | 0 | dephosphorylation | up-regulates | 0.462 | In the absence of the wt apc protein, phosphorylated beta-catenin is rapidly dephosphorylated by serine/threonine protein phosphatase 2a (pp2a). phosphorylated beta-catenin associated with the wild-type apc protein is recruited to the scf(beta-trcp) complex, ubiquitin conjugated, and degraded. | SIGNOR-182637 |
Q9UMX1 | Q9BZE0 | 1 | relocalization | down-regulates | 0.266 | Negative regulation of gli1 and gli2 activator function by suppressor of fused through multiple mechanisms.Together, these observations reveal that su(fu) regulates the activity of gli1 and gli2 through distinct cytoplasmic and nuclear mechanisms. | SIGNOR-142608 |
Q13467 | Q9ULT6 | 0 | ubiquitination | down-regulates quantity | 0.515 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260118 |
P01574 | Q13526 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | To investigate the temporal regulation of IRF3-dependent transcription by Pin1, we used a rapid-response luciferase reporter gene. Real-time reporter gene assays showed that suppression of endogenous Pin1 expression substantially prolonged both IRF3-dependent transcription and IFN-beta promoter activation after poly(I)dotpoly(C) stimulation (Fig. 4c,d). Consistent with the inhibitory effects of Pin1 on the IFN-beta promoter | SIGNOR-252289 |
Q13501 | P46934 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.277 | Depletion of NEDD4 dramatically reduced the LC3 protein level and elevated the SQSTM1 protein level.|Furthermore, SQSTM1 is ubiquitinated by NEDD4 while LC3 functions as an activator of NEDD4 ligase activity. | SIGNOR-278637 |
Q9NQ66 | Q92997 | 0 | null | up-regulates activity | 0.347 | Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin | SIGNOR-258980 |
Q9UNF0 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | PKCα phosphorylates PACSIN2 at serine 313 in the linker region and decreases its membrane binding and tubulation activities. Phosphorylation of PACSIN2 at S313 negatively regulated protein interaction between NS5A and core, which affected viral assembly | SIGNOR-273799 |
Q9UQM7 | Q9NSC5 | 1 | phosphorylation | down-regulates activity | 0.2 | Homer3 is phosphorylated at Ser120, Ser159, and Ser176 by CaMKII in vitro. Homer3 phosphorylation reduces its affinity for target molecules and modulates the Ca2+ signaling patterns induced by mGluR1α activation | SIGNOR-262685 |
P38398 | Q15424 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.2 | These results suggest that the BRCA1 and BARD1 heterodimer ubiquitinates SAFB and increases SAFB protein levels. | SIGNOR-278624 |
P36888 | Q12913 | 0 | dephosphorylation | down-regulates activity | 0.49 | Moreover, activated FLT3 could be dephosphorylated by recombinant DEP-1 in vitro.|The data indicate that DEP-1 is negatively regulating FLT3 signaling activity and that its loss may contribute to but is not sufficient for leukemogenic cell transformation. | SIGNOR-277092 |
O14757 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.496 | Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo. | SIGNOR-248615 |
O75925 | P15927 | 1 | sumoylation | up-regulates | 0.2 | Pias1 and pias4 promote brca1 accumulation and sumoylation, rpa phosphorylation, and dsb repair | SIGNOR-162153 |
P31749 | Q8N6T7 | 1 | phosphorylation | down-regulates activity | 0.532 | AKT1 interacts with and phosphorylates SIRT6 on Ser 338.|Because AKT1 suppresses SIRT6 protein abundance by decreasing its stability, we investigated whether MDM2 is involved in this process. | SIGNOR-278465 |
P31749 | P54198 | 1 | phosphorylation | up-regulates activity | 0.2 | Consistently, HIRA phosphorylation was effectively decreased by Akt1 knockdown and was completely eliminated by the depletion of both Akt1 and Akt2, suggesting that HIRA is phosphorylated primarily by Akt1 and that Akt2 seemed to contribute to HIRA phosphorylation as a supplementary kinase in myoblasts (XREF_FIG).|In this study, HIRA was more efficiently targeted by Akt1 in myoblasts. | SIGNOR-279584 |
Q09472 | P84243 | 1 | acetylation | down-regulates activity | 0.2 | These results highlight the substrate and site specificities of hats in cells, demonstrate the distinct roles of gcn5/pcaf- and cbp/p300-mediated histone acetylations in gene activation, and suggest an important role of cbp/p300-mediated h3k18/27ac in nr-dependent transcription. | SIGNOR-170266 |
P06744 | Q14258 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.25 | Gp78 is a ubiquitin ligase that plays a vital role in endoplasmic reticulum (ER)-associated degradation (ERAD). Here we report that autocrine motility factor (AMF), also known as phosphoglucose isomerase (PGI), is a novel substrate of gp78. We show that polyubiquitylation of AMF requires cooperative interaction between gp78 and the ubiquitin ligase TRIM25 (tripartite motif-containing protein 25). While TRIM25 mediates the initial round of ubiquitylation, gp78 catalyzes polyubiquitylation of AMF. | SIGNOR-272178 |
P05771 | Q16236 | 1 | phosphorylation | up-regulates | 0.418 | Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress | SIGNOR-91830 |
P04406 | O14867 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. | SIGNOR-259339 |
P54274 | Q8TDX7 | 0 | phosphorylation | up-regulates activity | 0.342 | Using KR-TRF2 to induce telomeric DNA damage, we found that TRF1 degradation was also exacerbated when ATM was inhibited after damage induction (55.2% of mock treated cells) (XREF_FIG), indicating that the ATM signal pathway is required for Nek7 mediated TRF1 stabilization.|We show that Nek7 phosphorylates TRF1 at Ser114 and in turn maintains stability of the shelterin complex at telomeres. | SIGNOR-278447 |
Q13315 | Q9Y297 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.299 | ATM phosphorylates and stabilizes β-TrCP1 upon DNA damage. | SIGNOR-277549 |
Q07912 | P09619 | 0 | phosphorylation | up-regulates activity | 0.359 | Mutational analysis suggested that Y635 of ACK1 is a PDGFR-β phosphorylation site and that the ACK1 Y635F mutant abrogated the sequential activation of AKT. | SIGNOR-276854 |
Q13224 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.7 | By peptide mapping, automated sequencing, and mass spectrometry, we identified the major site of phosphorylation on the fusion protein as Ser-383, corresponding to Ser-1303 of full-length NR2B. The Km for phosphorylation of this site in the fusion protein was approximately 50 nM, much lower than that of other known substrates for CaM kinase II, suggesting that the receptor is a high affinity substrate. We show that serine 1303 in the full-length NR2B and/or the cognate site in NR2A is a major site of phosphorylation of the receptor both in the postsynaptic density fraction and in living hippocampal neurons. | SIGNOR-250630 |
P48431 | Q9NQU5 | 0 | phosphorylation | up-regulates quantity | 0.2 | PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.|The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo. | SIGNOR-280060 |
Q16828 | P41162 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation. | SIGNOR-262780 |
P68431 | P29375 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264299 |
Q13332 | P00533 | 1 | dephosphorylation | down-regulates activity | 0.43 | Similarly, Pestana et al. (89) have reported that overexpression of RPTPsigma in human A431 carcinoma cells partially inhibits EGFR activation, whereas antisense mediated suppression of RPTPsigma expression enhances EGFR activation, substrate phosphorylation, and signalling.|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types. | SIGNOR-277145 |
Q15911 | Q14258 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.451 | In the present study we show that EFP (oestrogen-responsive finger protein) is an E3 ubiquitin ligase mediating oestrogen-induced ATBF1 protein degradation. Knockdown of EFP increases ATBF1 protein levels, whereas overexpression of EFP decreases ATBF1 protein levels. | SIGNOR-272048 |
P00533 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.368 | These data indicate that activation of protein kinase C and subsequent phosphorylation of the EGF receptor at T654 lead to rapid physiological attenuation of EGF receptor signaling. | SIGNOR-248858 |
Q16665 | Q96KS0 | 0 | hydroxylation | down-regulates quantity by destabilization | 0.856 | There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization | SIGNOR-261999 |
Q9BRZ2 | Q86WV6 | 1 | ubiquitination | up-regulates activity | 0.2 | In contrast, we found that TRIM56 preferentially promoted K63 linked ubiquitination of the same lysine residue of STING that was important for the dimer formation and TBK1 activation.|Specifically, TRIM56 induces STING dimerization during dsDNA triggered signaling to potentiate antiviral responses while RNF5 may induce degradation of mitochondrial STING to suppress RLR induced antiviral responses.The findings that TRIM56 failed to interact with dsDNA and that there was no colocalization between TRIM56 and dsDNA within cells suggest that TRIM56 is unlikely to be a dsDNA sensor, and instead facilitates the STING function by ubiquitination. | SIGNOR-278621 |
P60880 | P17252 | 0 | phosphorylation | up-regulates | 0.353 | Phosphorylation of snap-25 at ser187 mediates enhancement of exocytosis by a phorbol ester in ins-1 cells. | SIGNOR-160313 |
Q05195 | P17480 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.36 | MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter. | SIGNOR-269646 |
Q15466 | O15516 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.388 | CLOCK knockdown activated MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK upregulated SHP by binding to its E box. | SIGNOR-253698 |
O75367 | Q8IWR1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Nuclear TRIM59 induces ubiquitination and degradation of the tumor suppressive histone variant macroH2A1, leading to enhanced STAT3 signaling activation and tumorigenicity. | SIGNOR-272931 |
P00533 | Q96J02 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.48 | In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination. | SIGNOR-272604 |
P05067 | O75116 | 0 | phosphorylation | up-regulates quantity | 0.386 | Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms. | SIGNOR-280109 |
P17612 | P46019 | 1 | phosphorylation | down-regulates activity | 0.325 | Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme. | SIGNOR-267410 |
O14828 | P00533 | 0 | phosphorylation | up-regulates activity | 0.399 | In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation | SIGNOR-262858 |
O00187 | P0C0L4 | 1 | cleavage | up-regulates activity | 0.798 | MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a). | SIGNOR-263431 |
Q9BYG3 | P49840 | 0 | phosphorylation | up-regulates activity | 0.2 | The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1. | SIGNOR-262697 |
P15036 | P10451 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.251 | We demonstrated that Ets2 is capable of binding to and transactivating the OPN promoter using gel shift and transient transfection assays | SIGNOR-259872 |
P49841 | P46527 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.389 | GSK-3\u03b2 phosphorylates p27 Kip1 at S160 and S161, resulting in increased p27 Kip1 stability [ xref ]. | SIGNOR-278938 |
P14598 | Q05655 | 0 | phosphorylation | up-regulates | 0.447 | Pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation. The use of p47phox mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc?, ???, And ?. | SIGNOR-89229 |
Q9NYY3 | Q16143 | 1 | phosphorylation | down-regulates activity | 0.248 | Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. | SIGNOR-189049 |
Q00535 | P04637 | 1 | phosphorylation | up-regulates | 0.732 | We show that cdk5 phosphorylates p53 on ser15, ser33 and ser46 cdk5-stabilized p53 protein is transcriptionally active | SIGNOR-156422 |
P24723 | P49841 | 1 | phosphorylation | down-regulates | 0.2 | Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka). | SIGNOR-188585 |
P48730 | O43312 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.327 | Mechanistically, we defined that Casein Kinase Iδ (CKIδ) phosphorylates Ser322 to trigger MTSS1's interaction with β-TRCP for subsequent ubiquitination and degradation. | SIGNOR-276611 |
P55286 | Q14653 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | CHD8 binds to histone H3 di- and trimethylated on lysine 4. It resides on the human U6 promoter as well as the mRNA IRF3 promoter in vivo and contributes to efficient transcription from both these promoters | SIGNOR-266898 |
Q96EP1 | Q14807 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.399 | Chfr ubiquitinates Kif22 and promotes its degradation. | SIGNOR-271469 |
P10275 | P31749 | 0 | phosphorylation | down-regulates activity | 0.586 | Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Here, we demonstrate that akt phosphorylates the androgen receptor (ar) at ser-210 and ser-790 | SIGNOR-108508 |
P20273 | P07948 | 0 | phosphorylation | down-regulates activity | 0.743 | LYN is a BCR-associated SRC kinase involved in the positive regulation of BCR, but it also functions as a negative regulator by phosphorylating the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of CD22. | SIGNOR-268443 |
Q9H7P9 | P12931 | 0 | phosphorylation | up-regulates activity | 0.2 | Through deletion and base substitution mutagenesis we have identified Tyr489 of PLEKHG2 as the site phosphorylated by cSrc.The interaction between PLEKHG2 and the full-length of PIK3R3, but not ABL1, occurs in a tyrosine-phosphorylation-dependent manner. | SIGNOR-273808 |
P17612 | P27987 | 1 | phosphorylation | down-regulates activity | 0.351 | Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328 | SIGNOR-249995 |
P43403 | Q13094 | 1 | phosphorylation | up-regulates | 0.804 | Zap-70 phosphorylates slp-76 at specific sites that allow vav sh2 domain bindingwe also show by in vitro and in vivo analysis that two slp-76 pyesp motifs (y113 and y128) mediate binding, the first being more efficient. | SIGNOR-46859 |
P35637 | Q08211 | 1 | relocalization | down-regulates activity | 0.482 | We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons | SIGNOR-262810 |
P06241 | P42681 | 1 | phosphorylation | up-regulates activity | 0.347 | We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association. | SIGNOR-249341 |
P51608 | Q7Z2K8 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.298 | 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-264679 |
A5D8V6 | Q9UHD2 | 0 | phosphorylation | down-regulates activity | 0.366 | We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling. | SIGNOR-279768 |
Q05513 | P14598 | 1 | phosphorylation | up-regulates | 0.394 | Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation. | SIGNOR-89280 |
P27361 | P42229 | 1 | phosphorylation | up-regulates | 0.706 | Serine 780 is the only substrate in full-length stat5a for active erk | SIGNOR-66247 |
O14966 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.581 | In an attempt to mimic phosphorylation of Rab29 by LRRK2, we mutated the phosphorylation sites to Glu and observed that the Rab29[T71E,S72E] mutant failed to activate LRRK2 (Fig\u00a0 xref B).|To test whether phosphorylation of Rab29 at Thr71 and Ser72 by LRRK2 was required for activation of LRRK2, we mutated these sites both to Ala. | SIGNOR-279474 |
Q13309 | P38936 | 1 | ubiquitination | down-regulates | 0.772 | Up-regulation of skp2 by notch signaling enhances proteasome-mediated degradation of the ckis, p27 kip1 and p21 cip1, and causes premature entry into s phase. | SIGNOR-138490 |
O95714 | Q9Y2K6 | 1 | ubiquitination | down-regulates quantity | 0.372 | HERC2 promotes USP20 degradation.|Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase. | SIGNOR-278692 |
P00519 | Q05655 | 1 | phosphorylation | up-regulates activity | 0.384 | Specifically, we have shown that nuclear targeting of PKCdelta is necessary and sufficient for epithelial cell apoptosis, and that nuclear translocation requires phosphorylation of PKCdelta at Y155 and Y64 by c-Abl and c-Src, respectively. | SIGNOR-279436 |
P14210 | P03952 | 0 | cleavage | up-regulates activity | 0.323 | the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain. | SIGNOR-256513 |
Q08050 | O96017 | 0 | phosphorylation | up-regulates | 0.721 | Chk2 mediates stabilization of the foxm1 transcription factor to stimulate expression of dna repair genesthis phosphorylation of foxm1 on serine residue 361 caused increased stability of the foxm1 protein | SIGNOR-150746 |
Q15418 | P49815 | 1 | phosphorylation | down-regulates | 0.768 | The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1 | SIGNOR-128634 |
Q96EP1 | Q14527 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.482 | CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer. | SIGNOR-271460 |
P48730 | Q00535 | 1 | phosphorylation | up-regulates activity | 0.555 | We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro. | SIGNOR-250798 |
Q15327 | Q7Z570 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269461 |
P28482 | P41212 | 1 | phosphorylation | down-regulates | 0.317 | Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation. | SIGNOR-260086 |
Q86Y13 | Q93077 | 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-271759 |
Q96EB6 | O43781 | 0 | phosphorylation | up-regulates activity | 0.502 | DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr (522), promoting deacetylation of p53.|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. | SIGNOR-279705 |
P00533 | Q9UQM7 | 0 | phosphorylation | down-regulates activity | 0.371 | We show that serines 1046/1047 are sites for CaM kinase II phosphorylation, although there is a preference for serine 1047, which resides within the consensus -R-X-X-S-. In addition, we have identified major phosphorylation sites at serine 1142 and serine 1057, which lie within a novel -S-X-D- consensus. Mutation of serines 1046/1047 in full-length EGFR enhanced both fibroblast transformation and tyrosine autokinase activity that was significantly potentiated by additional mutation of serines 1057 and 1142. A single CaM kinase II site was also identified at serine 744 within sub-kinase domain III, and autokinase activity was significantly affected by mutation of this serine to an aspartic acid making this site appear constitutively phosphorylated. We have addressed the mechanism by which CaM kinase II phosphorylation of the EGFR might regulate receptor autokinase activity and show that this modification can hinder association of the cytoplasmic tail with the kinase domain to prevent an enzyme-substrate interaction. | SIGNOR-250621 |
Q9UM73 | P23467 | 0 | dephosphorylation | down-regulates | 0.334 | Rptpbeta/zeta dephosphorylates alk at the site(s) in alk that is undergoing autophosphorylation through autoactivation. | SIGNOR-157175 |
Q92915 | P68400 | 0 | phosphorylation | up-regulates activity | 0.269 | Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents. | SIGNOR-275738 |
Q13200 | Q9HC98 | 0 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273894 |
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