IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P61925 | P00533 | 0 | phosphorylation | up-regulates | 0.307 | The difference in inhibitory potency between pki_ and pki_ has been attributed to the absence of a tyrosine residue (tyr7) in pki_ that is present in the nh2-terminal region of pki_. This suggests that the absence of a single amino acid residue can result in variations in how the catalytic subunit of camp-dependent protein kinase interacts with pki which ultimately can result in alterations in pki inhibitory potency. | SIGNOR-22455 |
P55036 | Q969Q1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.403 | S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10). | SIGNOR-272741 |
P43405 | P22681 | 0 | ubiquitination | down-regulates quantity | 0.816 | Thus, c-Cbl specifically downregulates Syk levels in the presence of LMP2A.|c-Cbl promoted LMP2A degradation through ubiquitination, specifically degraded the Syk protein tyrosine kinase in the presence of LMP2A, and inhibited LMP2A induction of the EBV lytic cycle | SIGNOR-278689 |
P68400 | Q14761 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | We demonstrated for the first time that LPAP is a substrate for protein kinase CK2 that phosphorylates it at Ser153, presumably ensuring LPAP resistance to degradation. | SIGNOR-273629 |
Q16658 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.324 | Phosphorylation of human fascin inhibits its actin binding and bundling activities. | SIGNOR-248944 |
Q9UHD2 | Q9Y2E6 | 0 | ubiquitination | down-regulates | 0.584 | Nlrp4 negatively regulates type i interferon signaling by targeting the kinase tbk1 for degradation via the ubiquitin ligase dtx4 | SIGNOR-71565 |
P16112 | P08254 | 0 | cleavage | down-regulates quantity by destabilization | 0.738 | Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE374 | SIGNOR-266986 |
P35612 | Q05513 | 0 | phosphorylation | down-regulates | 0.275 | We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta. | SIGNOR-139914 |
Q15858 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.334 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253458 |
P62330 | P35125 | 0 | relocalization | up-regulates | 0.66 | Here we show that tre17 (also called tre-2 and usp6), a founding member of the tbc family, targets the arf family gtpase arf6, which regulates plasma membrane-endosome trafficking. Surprisingly, tre17 does not function as a gap for arf6 but rather promotes its activation in vivo. Forced expression of tre17 promotes the localization of arf6 to the plasma membrane, leading to arf6 activation, presumably due to facilitated access to membrane-associated guanine nucleotide exchange factors (gefs). | SIGNOR-130019 |
P17612 | Q6PIY7 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259402 |
Q6VVB1 | Q86XI6 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.398 | Here, we show that the laforin-malin complex downregulates PTG-induced glycogen synthesis in FTO2B hepatoma cells through a mechanism involving ubiquitination and degradation of PTG. We show here that laforin and malin play a crucial role in the regulation of glycogen biosynthesis in FTO2B hepatoma cells. In these cells, the laforin–malin complex counteracts the glycogenic effect of PTG because it promotes its ubiquitination and degradation. | SIGNOR-271728 |
Q99250 | P67870 | 0 | phosphorylation | up-regulates activity | 0.2 | We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. | SIGNOR-275752 |
Q9NR48 | Q16620 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Depletion of ASH1L decreases neurite outgrowth and decreases expression of the gene encoding the neurotrophin receptor TrkB whose signaling pathway is linked to neuronal morphogenesis. | SIGNOR-269058 |
P46531 | Q4G148 | 0 | glycosylation | up-regulates | 0.383 | Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. | SIGNOR-177691 |
P42224 | P10721 | 0 | phosphorylation | up-regulates activity | 0.725 | KIT is responsible for the permanent phosphorylation of all three STAT proteins. STAT1, -3, and -5 were phosphorylated on their activation-specific Tyr701, Tyr704, and Tyr694, respectively, following KIT stimulation. | SIGNOR-251365 |
Q02363 | Q9Y574 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.341 | Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion. | SIGNOR-272053 |
Q13882 | P56945 | 1 | phosphorylation | up-regulates | 0.599 | Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 crk-associated substrate. Tyrosine residues 165 and 664 of p130cas were both phosphorylated by ptk6 in vitro | SIGNOR-177242 |
Q86X55 | Q92922 | 1 | methylation | up-regulates activity | 0.537 | CARM1-mediated BAF155 methylation affects gene expression by directing methylated BAF155 to unique chromatin regions (e.g., c-Myc pathway genes). Collectively, our studies uncover a mechanism by which BAF155 acquires tumorigenic functions via arginine methylation. | SIGNOR-251708 |
P35222 | Q9UPN9 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.457 | TRIM33 ubiquitylates nuclear beta-catenin.|Tumour suppressor TRIM33 targets nuclear beta-catenin degradation. | SIGNOR-278578 |
Q09472 | P50750 | 0 | phosphorylation | up-regulates activity | 0.376 | As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity , the effects of CUR and PyrC on the kinase activity of Cdk9 were examined .|As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity, the effects of CUR and PyrC on the kinase activity of Cdk9 were examined. | SIGNOR-279690 |
Q5T7B8 | P51955 | 0 | phosphorylation | up-regulates activity | 0.695 | Nek2 binds and phosphorylates Kif24.|We also provide evidence that Nek2 dependent phosphorylation induces a conformational change in Kif24 that promotes its activity. | SIGNOR-278413 |
P15173 | Q92833 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells|Addition of Differentiation Media (DM) to human myoblasts was associated with the induction of MYOG, MYOD and MYL1 and a decrease in JARID2 RNA expression|Furthermore, we that showed JARID2 binds to and alters the methylation status of histone H3 lysine 27 in the promoter regions of MYOG and MYL1 and that the interaction of JARID2 at these promoters is dependent upon EED, a core component of the Polycomb Repressive Complex 2 (PRC2). Therefore JARID2 is a downstream effector of PAX3-FOXO1 that maintains an undifferentiated myogenic phenotype that is characteristic of RMS | SIGNOR-249599 |
Q00535 | P56817 | 1 | phosphorylation | up-regulates activity | 0.44 | BACE1 is phosphorylated by p25 and Cdk5 at Thr252.|Our finding that p25/Cdk5 stimulates BACE1 activity supports that p25/Cdk5 may represent a promising target for the development of drugs to treat Alzheimer's disease. | SIGNOR-278249 |
P24941 | Q99741 | 1 | phosphorylation | down-regulates activity | 0.942 | Hscdc6 is an excellent substrate for cdk2 in vitro and is phosphorylated in vivo at three sites (ser-54, ser-74, and ser-106)|An HsCdc6A1A2A3 mutant, which mimics unphosphorylated HsCdc6, is exclusively nuclear, and its expression inhibits initiation of DNA replication. An HsCdc6E1E2E3 mutant, which mimics phosphorylated HsCdc6, is exclusively cytoplasmic and is not associated with the chromatin/nuclear matrix fraction. | SIGNOR-67544 |
P16104 | Q86Y13 | 0 | 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-271752 |
Q19QW5 | Q14974 | 1 | relocalization | down-regulates activity | 0.2 | ORF6 also retained KPNB1 at the ER/Golgi membrane in complex with KPNA2. Deletion of the N terminus of KPNA2, which binds KPNB1, no longer retained KPNB1 at the ER/Golgi membrane in the presence of ORF6 and did not antagonize STAT1 nuclear import in response to IFN-beta | SIGNOR-260275 |
P00740 | P38435 | 0 | carboxylation | up-regulates activity | 0.683 | The direct gamma-carboxyglutamic acid analysis and the N-terminal sequence analysis of the myotube-synthesized F.IX demonstrate efficient carboxylation at 11 of 12 γ-carboxyglutamic acid residues. |In previous work54 we have demonstrated that the γ-glutamyl carboxylase is present in skeletal muscle, but at a level only 5% to 10% of that found in the liver. This level of enzyme appears to be sufficient to provide full carboxylation of F.IX synthesized in myotubes|Glu 7, 8, 15, 17, 20, 21, 26, 27, 30, 33, and 36 are each less than 10% of the yield at the previous and subsequent cycles. Only a single γ-carboxylated residue, Gla 40, was not assessed by N-terminal sequencing. | SIGNOR-263687 |
P17481 | P62736 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261641 |
P49841 | Q05513 | 0 | phosphorylation | down-regulates | 0.597 | Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent. | SIGNOR-119889 |
P49137 | Q14457 | 1 | phosphorylation | up-regulates activity | 0.432 | Beclin 1 S90 is phosphorylated by MAPKAPK2 (MK2) and MAPKAPK3 (MK3). | SIGNOR-278342 |
Q9H2X6 | P15923 | 1 | phosphorylation | down-regulates activity | 0.2 | This result provides a mechanistic explanation for the context-dependent function of HIPK2 in Wnt signaling | SIGNOR-279193 |
P51955 | P35222 | 1 | phosphorylation | down-regulates quantity | 0.469 | NEK2 silencing reduced the phosphorylation of beta-catenin at Ser33 and Ser37, but did not decrease the level of total beta-catenin.|NEK2 slightly decreased the level of total beta-catenin (XREF_FIG). | SIGNOR-278173 |
O43318 | Q9UBE8 | 1 | phosphorylation | up-regulates | 0.651 | The tak1-nlk-mapk-related pathway antagonizes signalling between beta-catenin and transcription factor tcf. | SIGNOR-96425 |
Q14493 | Q93079 | 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-265391 |
Q9H4B4 | P05412 | 1 | phosphorylation | up-regulates | 0.369 | Stress-induced c-jun activation mediated by polo-like kinase 3 in corneal epithelial cells. Hypoxia/reoxygenation activated plk3 in hce cells to directly phosphorylate c-jun proteins at phosphorylation sites ser-63 and ser-73, and to increase dna binding activity of c-jun. | SIGNOR-157721 |
P61586 | Q92974 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.806 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260529 |
P49674 | O15534 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.842 | We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. | SIGNOR-267997 |
Q07866 | P28482 | 0 | phosphorylation | down-regulates | 0.271 | Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro. | SIGNOR-172638 |
P38398 | Q13363 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.603 | Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells. | SIGNOR-259196 |
Q12948 | P09238 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Therefore, FOXC1 is strongly suggested as a pro-metastatic gene in CRC by transcriptionally activating MMP10, SOX4 and SOX13|MMP10 was demonstrated as the direct target and mediator of FOXC1. | SIGNOR-275915 |
P35548 | P05771 | 0 | phosphorylation | up-regulates quantity | 0.322 | PKCbeta increased the level of overexpressed Msx2, but PKC alpha, delta and zeta did not have any significant effects.|Thr135 and Thr141 in Msx2 can be phosphorylated by PKC\u03b2, and Thr135 is important for regulating the protein stability of Msx2 by PKCs. | SIGNOR-278982 |
O95786 | P53355 | 0 | phosphorylation | down-regulates activity | 0.33 | DAPK1 also phosphorylates the N-terminal serine at position 8 (S8) of RIG-I, which is also reported to undergo phosphorylation by PKC-\u03b1/\u03b2 to suppress TRIM25-mediated RIG-I ubiquitination, thereby negatively regulating RIG-I activity (84). | SIGNOR-279519 |
Q6ZNA4 | Q15796 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.685 | Arkadia represses the expression of myoblast differentiation markers through degradation of ski and the ski-bound smad complex in c2c12 myoblastsarkadia bound smad2/3 via ski to induce the ubiquitination of smad2/3. These results suggest that arkadia targets ski-bound, inactive phospho-smad2/3 to regulate positively myostatin/tgf-beta signaling. | SIGNOR-236873 |
P31749 | Q6PKG0 | 1 | phosphorylation | down-regulates activity | 0.288 | LARP1 is a direct substrate of Akt/S6K1 and mTORC1. Akt is a physiologically relevant primary kinase for S770/S979 phosphorylation of LARP1|Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5’UTRs and relieves its inhibitory activity on RP mRNA translation. | SIGNOR-260992 |
Q68CZ2 | P12931 | 0 | phosphorylation | up-regulates | 0.408 | Tyrosines in the sh2 domain contribute to the biological activity of tensin-3, and phosphorylation of these tyrosines can regulate ligand binding. tensin-3 is a src substrate | SIGNOR-187843 |
Q9UHD2 | O95865 | 1 | phosphorylation | down-regulates activity | 0.2 | TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. |The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o | SIGNOR-275648 |
Q15119 | Q9H300 | 1 | phosphorylation | up-regulates activity | 0.2 | As expected, knocking down PDK2 in HEK293 cells that overexpress PARL resulted in a significant increase in beta cleavage in comparison to the control cells.|Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates \u03b2 cleavage. | SIGNOR-280018 |
Q15042 | P20336 | 1 | gtpase-activating protein | down-regulates activity | 0.439 | Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP). | SIGNOR-265580 |
P68400 | P30260 | 1 | phosphorylation | up-regulates | 0.378 | We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling. | SIGNOR-170872 |
P04637 | Q9UEE5 | 0 | phosphorylation | up-regulates | 0.286 | Genetic and biochemical studies have shown that ser20 phosphorylation in the transactivation domain of p53 mediates p300-catalyzed dna-dependent p53 acetylation and b-cell tumor suppression. a cell-free ser20 phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser20 kinases. | SIGNOR-153532 |
Q9UBU7 | Q13315 | 0 | phosphorylation | down-regulates | 0.375 | Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication. | SIGNOR-177793 |
Q96QT4 | P04083 | 1 | phosphorylation | up-regulates | 0.544 | Trpm7 was responsible for phosphorylation of the serine 5 (ser5) residue [29]. In 2009, the study focused on an association between anxa1 and trpm7 confirmed the presence of a trpm7/annexin a1/mg2_+ complex, suggesting a novel pathway in bradykinin signaling, dependent on pkc and c-src [30]. Even though that pathway is not fully characterized, the same team that discovered the ser5 phosphorylation of anxa1 also reported crucial relevance of this modification for anxa1 membrane binding and especially for the interaction between annexin a1 and its known partner, the calcium binding protein s100a11 | SIGNOR-202804 |
Q13153 | Q92934 | 1 | phosphorylation | down-regulates | 0.335 | Pak phosphorylates bad in vitro and in vivo on ser112 and ser136, resulting in a markedly reduced interaction between bad and bcl-2 or bcl-x(l) and the increased association of bad with 14-3-3tau. | SIGNOR-73533 |
Q05655 | Q14896 | 1 | phosphorylation | up-regulates | 0.2 | The triple aspartic acid mutation shows greater distance between the two thick myosin filaments (affects the steric arrangement of the filament distances) in heart tissue. Mutation is cardioprotective during stress (ischemia-reprofusion injury) against apoptosis similar to isoproterenol treatment. | SIGNOR-150355 |
P48730 | O15534 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.807 | Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIdelta and hCKIepsilon phosphorylated and caused protein instability of human period 2 protein (hPER2). | SIGNOR-268001 |
Q2V2M9 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.275 | In addition we were able to throw light on the mechanism of activation of FHOD3 by ROCK1 and could demonstrate the effects of constitutively active FHOD3 on actin filament synthesis in cardiomyocytes.|ROCK1 can directly phosphorylate FHOD3 and FHOD3 seems to be the downstream mediator of the exaggerated actin filament formation phenotype that is induced in cardiomyocytes upon the overexpression of constitutively active ROCK1. | SIGNOR-278903 |
Q16143 | Q9H4B4 | 0 | phosphorylation | down-regulates activity | 0.38 | 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-189057 |
O75582 | Q7L7L0 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that MSK1 phosphorylated histone H2A on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by MSK1. Furthermore, we found that acetylation of histone H3 by the p300 and CREB-binding protein associated factor, PCAF, suppressed the kinase-dependent inhibition of transcription. These results suggest that acetylation of histones may stimulate transcription by suppressing an inhibitory phosphorylation by a kinase as MSK1. | SIGNOR-262942 |
P17252 | P41180 | 1 | phosphorylation | down-regulates | 0.351 | Casr(t888) is a protein kinase c (pkc) phosphorylation site in the receptor's intracellular domain that has previously been identified as a critical negative regulator of casr downstream signaling in vitro, thus, casr(t888) represents a functionally important, inhibitory phosphorylation site that contributes to the control of pth secretion. | SIGNOR-170334 |
Q9Y566 | O95886 | 0 | relocalization | up-regulates activity | 0.8 | 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-264592 |
P04049 | P27361 | 0 | phosphorylation | down-regulates activity | 0.637 | Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 | SIGNOR-143688 |
Q96PV0 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.383 | CDK5 increases recombinant SYNGAP1 activity on Ras-GAP by 98% and its Rap-GAP activity by 20%.|Interestingly, phosphorylation of SYNGAP1 by CDK5 and CaMKII increases overall SYNGAP1 activity, but also alters the ratio of its GAP activity towards Ras- and Rap-GTPases. | SIGNOR-279157 |
Q96AP0 | O76064 | 0 | polyubiquitination | up-regulates quantity by stabilization | 0.2 | The Rnf8 RING-finger domain is essential for Tpp1 stability and retention at telomeres. Rnf8 physically interacts with Tpp1 to generate Ubc13-dependent Lys63 polyubiquitin chains that stabilize Tpp1 at telomeres. The conserved Tpp1 residue Lys233 is important for Rnf8-mediated Tpp1 ubiquitylation and localization to telomeres. | SIGNOR-272722 |
P78536 | P46531 | 1 | cleavage | up-regulates activity | 0.739 | ... here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to tace (tnfalpha-converting enzyme), a member of the adam (a disintegrin and metalloprotease domain) family of metalloproteases. | SIGNOR-78903 |
P12931 | Q13936 | 1 | phosphorylation | up-regulates activity | 0.443 | Cotransfection of human embryonic kidney (HEK)-293 cells with hCa(v)1.2b and c-Src resulted in tyrosine phosphorylation of the calcium channel, which was prevented by nitration of tyrosine residues by peroxynitrite. Whole cell calcium currents were reduced by 58 + 5% by the Src kinase inhibitor PP2 and 64 + 6% by peroxynitrite. | SIGNOR-276081 |
P07948 | P42768 | 1 | phosphorylation | up-regulates activity | 0.378 | We demonstrated that WASP is phosphorylated on tyrosine 291 in macrophages, and the WASP phosphorylation is important for the phagocytic cup formation. In addition, we showed that WASP and WASP-interacting protein (WIP) form a complex at the phagocytic cup and that the WASP.WIP complex plays a critical role in the phagocytic cup formation. | SIGNOR-273959 |
Q7KZI7 | Q8WUI4 | 1 | phosphorylation | down-regulates | 0.344 | We further show that emk and c-tak1 phosphorylate class iia hdacs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function | SIGNOR-149583 |
Q86Y13 | Q99878 | 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-271762 |
P17655 | P27361 | 0 | phosphorylation | up-regulates | 0.565 | Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo. | SIGNOR-123083 |
Q96J02 | P41240 | 0 | phosphorylation | down-regulates activity | 0.2 | CISK strongly interacts and colocalizes with the E3 ubiquitin ligase AIP4, which is important for the ubiquitin-dependent lysosomal degradation of CXCR4. Moreover, the observed inhibition is both dependent on the interaction between CISK and AIP4 and on the activation status of CISK. Consistent with this, an activated form of CISK but not of the related kinase SGK1 phosphorylates specific sites of AIP4 in vitro. | SIGNOR-245327 |
Q13530 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | The two serines within the PSAC of Serinc3 are phosphorylated by casein kinase II and mediate interaction with the μ subunits in vitro. | SIGNOR-273631 |
P15923 | Q02779 | 0 | phosphorylation | down-regulates | 0.2 | Mlk2 inhibits e47 transactivation activity on the trkb promote | SIGNOR-161544 |
P10398 | Q15796 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.37 | Araf promotes Smad2 linker phosphorylation through S253.|In this study, we demonstrate that Araf can directly bind to and phosphorylate the linker of Smad2, leading to degradation of activated Smad2. | SIGNOR-279391 |
Q00535 | Q16665 | 1 | phosphorylation | up-regulates activity | 0.259 | In conclusion, we obtained compelling evidence that CDK5 directly stabilizes the transcription factor hypoxia inducible factor-1\u03b1 by phosphorylation, and thus promotes the formation of blood vessels.|Mass spectrometry and site directed mutagenesis revealed a stabilizing phosphorylation of HIF-1\u03b1 at Ser687 by CDK5. | SIGNOR-279020 |
Q9UQM7 | Q7Z6G8 | 1 | phosphorylation | down-regulates activity | 0.257 | CaMKII-mediated displacement of AIDA-1 out of the postsynaptic density core. The present study indicates that CaMKII activation is necessary for the NMDA-induced movement of AIDA-1 out of the PSD core. | SIGNOR-264231 |
O60825 | P31749 | 0 | phosphorylation | up-regulates activity | 0.654 | These findings suggest that PKB-dependent binding of 14-3-3s to phospho-Ser483 of cardiac PFK-2 mediates the stimulation of glycolysis by growth factor. | SIGNOR-252555 |
P07948 | Q01344 | 1 | phosphorylation | up-regulates activity | 0.475 | Lyn activate and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex, provoking eosinophils proliferation and exaggerated activation manifested as CEL.|We further delineated that Lyn can induce IL-5RA tyrosine phosphorylation and physically associate with IL-5RA in F/P expressing cells. | SIGNOR-279059 |
Q12913 | P07949 | 1 | dephosphorylation | down-regulates activity | 0.277 | The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.|PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels | SIGNOR-248701 |
P11831 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.369 | Skeletal muscle CaMKII enriches in nuclei and phosphorylates myogenic factor SRF at multiple sites. | Microsequencing of these phosphorylated peptides identified that both Ser-103 and a novel residue, Thr-160 in the MADS box of SRF, were sites of phosphorylation. | The location of Thr-160 in the 3-D structure of SRF suggests that its phosphorylation by nuclear CaMKII may directly influence DNA binding of SRF and other MADS box factors. | SIGNOR-250639 |
P35558 | Q12778 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.428 | Phosphorylated foxo1 is inactive and retained in the cytosol. Mkp-3 mediated dephosphorylation activates foxo1 and subsequentially promotes its nuclear translocation and binding to the promoters of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (pepck) and glucose-6-phosphatase (g6pase). | SIGNOR-197200 |
Q13224 | P06241 | 0 | phosphorylation | up-regulates activity | 0.768 | We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases | SIGNOR-247176 |
P23470 | Q13224 | 1 | dephosphorylation | up-regulates activity | 0.277 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254702 |
P35612 | P17612 | 0 | phosphorylation | down-regulates activity | 0.283 | Ser-726 and Ser-713 in the C-terminal MARCKS-related domains of - and -adducin, respectively, were identified as the major phosphorylation sites common for PKA and PKC. Phosphorylation by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin. | SIGNOR-250332 |
Q13131 | Q96EB6 | 1 | phosphorylation | down-regulates activity | 0.395 | Previous studies have reported that AMP-activated protein kinase phosphorylates and inactivates SIRT1, resulting in increased p53 acetylation in liver cancer [ xref , xref ]. | SIGNOR-280076 |
P14618 | Q92519 | 0 | phosphorylation | up-regulates activity | 0.2 | This study demonstrated that TRIB2, not a "pseudokinase", has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. | SIGNOR-275431 |
Q92945 | P38936 | 1 | post transcriptional regulation | down-regulates quantity by destabilization | 0.252 | Importantly, KSRP knockdown in C2C12 GM cells (Figure 2D) stabilized endogenous my- ogenin and p21 transcripts (Figure 2E). Furthermore, stable knockdown of KSRP, using shRNA, induced the accumulation of p21 mRNA in C2C12 GM while it did not affect the expression of late myogenic markers (MHC and muscle-creatine kinase [MCK]) | SIGNOR-235859 |
P56524 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.264 | We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions | SIGNOR-198646 |
P18031 | P17252 | 0 | phosphorylation | up-regulates activity | 0.249 | PKC\u03b1 then phosphorylates and activates endothelial cell protein tyrosine phosphatase 1B (PTP1B) , . | SIGNOR-279257 |
P11387 | O00327 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.342 | We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition. | SIGNOR-277354 |
Q14493 | Q96A08 | 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-265393 |
Q14344 | Q08881 | 0 | phosphorylation | up-regulates activity | 0.2 | This ability of Itk to phosphorylate Galpha13 was abolished in Itk mutants R29C (no longer able to interact with the membrane, and thus unable to interact with Galpha13) and K391M (no kinase activity) (XREF_FIG).|To determine whether Itk is a downstream mediator of Galpha13, we examined whether Galpha13 could interact with Itk when locked in the GDP bound or GTP bound state. | SIGNOR-279623 |
Q13315 | Q9H7Z6 | 1 | phosphorylation | up-regulates activity | 0.469 | In this study we present evidence that MOF is phosphorylated at the threonine 392 residue (pT392-MOF) by ATM subsequent to IR induced DNA damage.|Interestingly, ATM dependent-MOF phosphorylation increases MOF retention on DNA post-irradiation in S/G2-phase cells. | SIGNOR-278350 |
P68431 | Q15652 | 0 | demethylation | down-regulates activity | 0.2 | We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state. | SIGNOR-265171 |
Q9NY28 | P00533 | 1 | glycosylation | down-regulates activity | 0.2 | Interestingly, the O-GalNAcylation of EGFR, which is the key factor related to the metastasis cascade, was impacted by GALNT8. Furthermore, our results suggested that the GALNT8-mediated O-GalNAcylation led to the suppression of the EGFR signaling pathway and metastatic potential in breast cancer cells. | SIGNOR-269679 |
Q14814 | Q13164 | 0 | phosphorylation | up-regulates | 0.705 | Here, we demonstrate that, in addition to mef2c, bmk1 phosphorylates and activates mef2a and mef2d but not mef2b. the sites phosphorylated by activated bmk1 were mapped to ser-355, thr-312, and thr-319 of mef2a and ser-179 of mef2d both in vitro and in vivo. | SIGNOR-236041 |
Q9Y2T1 | Q9NTX7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.671 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263336 |
P14618 | Q99708 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we uncover an unexpected mechanism through which pyruvate kinase M2 (PKM2), the highly expressed PK isoform in cancer cells and a master regulator of cancer metabolic reprogramming, integrates with the DDR to directly promote DNA double-strand break (DSB) repair. In response to ionizing radiation and oxidative stress, ATM phosphorylates PKM2 at T328 resulting in its nuclear accumulation. | SIGNOR-277413 |
P14416 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.383 | These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling. | SIGNOR-259401 |
P06493 | O15297 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.348 | Phosphorylation of multiple residues in the catalytic domain of PPM1D during mitosis, including Ser40 by Cyclin-dependent kinase 1 (CDK1), leads to ubiquitination of PPM1D and subsequent proteasomal degradation by Adenomatous polyposis coli (APC) and cell-division cycle protein 20 (CDC20) | SIGNOR-275489 |
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