IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40
values | effect stringclasses 10
values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q13043 | Q96EB6 | 1 | phosphorylation | down-regulates activity | 0.344 | We found that MST1 increases p53 acetylation and transactivation by inhibiting the deacetylation of Sirtuin 1 (Sirt1) and its interaction with p53 and that Sirt1 can be phosphorylated by MST1 leading to the inhibition of Sirt1 activity. | SIGNOR-279574 |
Q9UHD2 | O75688 | 0 | dephosphorylation | down-regulates activity | 0.352 | PPM1B dephosphorylates TBK1 in vivo and in vitro.|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172. | SIGNOR-276985 |
P29372 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.265 | ATM phosphorylates MPG at serine 172 (XREF_FIG).|In summary, our results show that ATM and MPG are directly associated in vitro and in vivo, phosphorylation of MPG at serine 172 is dependent on ATM and that of loss of phospho ATM reduces MPG glycosylase activity. | SIGNOR-279004 |
P35813 | Q04206 | 1 | dephosphorylation | down-regulates activity | 0.353 | 23 Here we show that PPM1A directly dephosphorylated RelA at S536 and S276, with resultant inhibition of NF-kappaB transactivation and decreased expression of target genes, notably including MCP-1 and CCL2.|Taken together, these data suggest that dephosphorylation of S276 by PPM1A may contribute to inhibit RelA transcr... | SIGNOR-276963 |
P51812 | P35916 | 0 | phosphorylation | down-regulates | 0.2 | Upon truncation of this c-terminal stretch, or mutation of the tyr-707 residue alone, autoinhibition is attenuated, and the kinase becomes constitutively active. Based on these findings we propose that phosphorylation of the tyr-707 represents a novel alternative regulatory mechanism for p90rsk activation. | SIGNOR-98708 |
O43583 | Q9ULC4 | 2 | binding | up-regulates activity | 0.746 | The MCT-1 protein modifies mRNA translational profiles through its interaction with DENR/DRP, a protein containing an SUI1 domain involved in recognition of the translation initiation codon. | SIGNOR-269674 |
O60674 | Q5VWK5 | 2 | binding | up-regulates | 0.701 | Il-23 activates the same jak-stat signaling molecules as il-12: jak2, tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different dna-binding stat complexes form in response to il-23 compared with il-12. | SIGNOR-87808 |
O95613 | Q76N32 | 0 | relocalization | up-regulates activity | 0.34 | We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Cep68 stabilization increases the amount of PCNT at metaphase centrosomes, but does not affect its removal at the end of mitos... | SIGNOR-275623 |
Q15139 | P53367 | 1 | phosphorylation | up-regulates | 0.385 | We report that arfaptins contain an amphipathic helix (ah) preceding the bar domain, which is essential for their binding to phosphatidylinositol 4-phosphate (pi(4)p)-containing liposomes and the tgn of mammalian cells. The binding of arfaptin1, but not arfaptin2, to pi(4)p is regulated by protein kinase d (pkd) mediat... | SIGNOR-202101 |
Q92858 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity | 0.304 | Huwe1 ubiquitinates and degrades Atoh1, and robustly affects development of GNPs that express this transcription factor [ xref ].|This provides further evidence that phosphorylation of Atoh1 affects Huwe1-mediated degradation, and demonstrates that Huwe1 inhibits Atoh1 to affect cellular differentiation in multiple cel... | SIGNOR-278693 |
P11912 | P07948 | 0 | phosphorylation | up-regulates activity | 0.738 | Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing nec... | SIGNOR-251397 |
Q03112 | O15123 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266060 |
Q16566 | P46531 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.36 | In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ). | SIGNOR-279596 |
P51787 | Q9Y6H6 | 2 | binding | up-regulates activity | 0.66 | Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K⁺ channels|The KCNQ1 potassium channel associates with various KCNE ancillary subunits that drastically affect channel gating and pharmacology. Co-assembly with KCNE3 produces a current with nearly instantaneous... | SIGNOR-275923 |
Q9H461 | P56704 | 2 | binding | up-regulates | 0.797 | Structural basis of wnt recognition by frizzled. | SIGNOR-197638 |
P52294 | Q14974 | 2 | binding | up-regulates activity | 0.86 | Although ORF6 causes a relocalization of KPNA2 from the cytosol to the ER/Golgi membrane, KPNA2 is not directly involved in the translocation of the STAT1:STAT2:IRF9 (ISGF3) complex into the nucleus; rather, KPNA1 interacts with KPNB1 to initiate ISGF3's nuclear localization. | SIGNOR-260273 |
P01579 | Q9UL17 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.475 | T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells | SIGNOR-266234 |
P51610 | Q06547 | 2 | binding | down-regulates activity | 0.328 | The C1 factor interacts with the GABP_ transactivation domain.The domain of the C1 factor required for C1GABP interaction can inhibit GABP_dependent transcriptional activation | SIGNOR-221377 |
Q02556 | P10914 | 2 | binding | up-regulates activity | 0.396 | We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP. | SIGNOR-222841 |
P52789 | P31749 | 0 | phosphorylation | up-regulates activity | 0.445 | K63-linked ubiquitination enhances the interaction between Akt and HK2 and eventually increases HK2 phosphorylation on Thr473 and mitochondrial localization | SIGNOR-259984 |
P06239 | P08575 | 0 | dephosphorylation | up-regulates activity | 0.797 | CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56(lck) tyrosine kinase phosphorylation sites. We propose that high wild-type CD45 expression is necessary to dephosphorylate p56(lck) pTyr-394, suppressing CD4 T+ cell lineage commitment and hyperactivity. | SIGNOR-259933 |
P11678 | P12724 | 1 | post translational modification | up-regulates activity | 0.477 | Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr ni... | SIGNOR-261705 |
P36507 | O15530 | 0 | phosphorylation | up-regulates | 0.256 | The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation. | SIGNOR-125176 |
Q92913 | Q9Y5Y9 | 2 | binding | down-regulates activity | 0.2 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253439 |
P16499 | P18545 | 2 | binding | down-regulates activity | 0.866 | Both PDE6C-A and PDE6C-B were potently and similarly inhibited by both Pγ subunits, with Ki values ranging from 33 to 46 pm (Fig. 5). The inhibition analysis revealed no significant differences between PDE6C-A and PDE6C-B | SIGNOR-260010 |
Q13546 | O43318 | 2 | binding | up-regulates activity | 0.553 | RIP-1 recruitment of MEKK-3 and transforming growth factor-beta (TGFbeta)-activated kinase (TAK1) subsequently activates the IKK (inhibitor of κB kinase) complex | SIGNOR-256022 |
Q9UL54 | P46734 | 2 | binding | up-regulates activity | 0.67 | Cotransfection experiments suggested that tao2 selectively activates mek3 and mek6 but not meks 1, 4, or 7. | SIGNOR-70947 |
P23769 | P17947 | 2 | binding | down-regulates activity | 0.577 | Here we demonstrate that a region of the PU.1 Ets domain (the winged helix–turn–helix wing) interacts with the conserved carboxyl-terminal zinc finger of GATA-1 and GATA-2 and that GATA proteins inhibit PU.1 transactivation of critical myeloid target genes. | SIGNOR-256071 |
O95837 | P43657 | 2 | binding | up-regulates activity | 0.422 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-257212 |
Q9Y4K3 | Q9BVN2 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.32 | We demonstrated that NESCA and NEMO interact by their N-terminal region. Beside to NEMO, we revealed that NESCA directly associates to the E3 ubiquitin ligase TRAF6, which in turn catalyzes NESCA polyubiquitination. Finally, we demonstrated that NESCA overexpression strongly inhibits TRAF6-mediated polyubiquitination ... | SIGNOR-272774 |
P19022 | P35222 | 2 | binding | up-regulates activity | 0.818 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265864 |
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... | SIGNOR-119762 |
Q13309 | P24385 | 2 | binding | down-regulates quantity by destabilization | 0.594 | We show that SK-UT-1B cells express a novel splice variant of Skp2 that localizes to the cytoplasm and that cyclin D1 ubiquitination takes place in the nucleus. We propose that the translocation of Skp2 into the nucleus is required for the ubiquitination of cyclin D1 and that the absence of the SCF(Skp2) complex in the... | SIGNOR-272575 |
Q2M1P5 | Q99835 | 0 | relocalization | up-regulates activity | 0.632 | Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factorsIn response to activation of Smo Kif7 at the cilia tip may antagonize Sufu to promote activation of Gli protei... | SIGNOR-209605 |
P17252 | P17812 | 1 | phosphorylation | down-regulates | 0.2 | These data indicated that protein kinase c phosphorylation at ser(462) stimulates human ctp synthetase 1 activity, whereas phosphorylation at thr(455) inhibits activity. | SIGNOR-154621 |
P21860 | P62993 | 2 | binding | up-regulates | 0.839 | All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor. In this study, we identify grb2 as a specific binding partner to tyrosines y1199 and y1268 of erbb3. | SIGNOR-121971 |
P68400 | Q9NYV6 | 1 | phosphorylation | down-regulates | 0.206 | Here we show that ck2 phosphorylates the transcription initiation factor tif-ia at serines 170 and 172 (ser170/172), and this phosphorylation triggers the release of tif-ia from pol i after transcription initiation. | SIGNOR-178943 |
P27361 | P04150 | 1 | phosphorylation | down-regulates | 0.542 | Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple... | SIGNOR-154409 |
P14778 | P18510 | 2 | binding | down-regulates activity | 0.897 | Homozygous truncating mutations result in lack of secreted interleukin-1–receptor antagonist protein, which inhibits the proinflammatory cytokines interleukin-1α and interleukin-1β | SIGNOR-262302 |
Q92823 | P16157 | 1 | relocalization | up-regulates quantity | 0.544 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with... | SIGNOR-266721 |
P78527 | P04637 | 1 | phosphorylation | up-regulates | 0.793 | We demonstrate that phosphorylation of p53 at serines 15 and 37 impairs the ability of mdm2 to inhibit p53-dependent transactivation. We present evidence that these effects are most likely due to a conformational change induced upon phosphorylation of p53. Our studies provide a plausible mechanism by which the inductio... | SIGNOR-53030 |
P10275 | Q15466 | 2 | binding | down-regulates | 0.415 | We demonstrated that shp inhibited both ar-lbd and ntd-dependent transactivation, which evidenced for the first time a protein capable of inhibiting a steroid receptor amino-terminal-dependent transactivation. We further characterized the shp mechanism of action by showing that shp reversed ar coactivator-mediated acti... | SIGNOR-112589 |
P63000 | O75044 | 0 | gtpase-activating protein | down-regulates activity | 0.588 | 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... | SIGNOR-260516 |
Q9NYY3 | P05067 | 1 | phosphorylation | up-regulates activity | 0.348 | Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in\u00a0vitro and associates with APP in\u00a0vivo.|Plk2 was necessary and sufficient to induce BACE-1-mediated APP amyloidogenic processing follo... | SIGNOR-279424 |
P17252 | P09758 | 1 | phosphorylation | down-regulates activity | 0.2 | Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosph... | SIGNOR-273821 |
Q9BYB0 | Q15398 | 0 | relocalization | up-regulates activity | 0.2 | 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 prot... | SIGNOR-264600 |
Q9Y490 | P05107 | 2 | binding | up-regulates activity | 0.719 | Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y mo... | SIGNOR-257618 |
P20265 | O75030 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.437 | We further demonstrate that BRN2 induces MITF transcription through a binding site located at 50/36 of the MITF promoter | SIGNOR-249616 |
P02511 | P07315 | 2 | binding | up-regulates activity | 0.531 | Human gamma-crystallins are long-lived, unusually stable proteins of the eye lens exhibiting duplicated, double Greek key domains. The lens also contains high concentrations of the small heat shock chaperone alpha-crystallin, which suppresses aggregation of model substrates in vitro. Mature-onset cataract is believed t... | SIGNOR-253622 |
O15273 | Q8WZ42 | 2 | binding | up-regulates activity | 0.908 | TCAP, a core sarcomeric component capping the titin proteins, was identified as a positive hit (Figure 1A). TCAP is a small (19 kDa), highly abundant cytoplasmic protein expressed exclusively in skeletal muscle and the heart (Valle et al., 1997). TCAP interacts with titin through its N-terminal beta sheet to anchor tit... | SIGNOR-264854 |
Q9HAU4 | Q9Y3C5 | 2 | binding | up-regulates activity | 0.54 | RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-... | SIGNOR-272952 |
Q9UNE7 | P11142 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.728 | BAG-1 stimulates CHIP-induced degradation of the glucocorticoid hormone receptor (GR). A model for the cooperation of CHIP and BAG-1 in coupling Hsc/Hsp70 to the ubiquitin/proteasome system. CHIP associates with Hsc/Hsp70 via its TPR chaperone adaptor (TPR) and, at the same time, recruits E2 ubiquitin-conjugating enzym... | SIGNOR-272588 |
Q16820 | Q05655 | 0 | phosphorylation | down-regulates quantity | 0.307 | These findings suggest that activation of a protein kinase, presumably PKC, mediates PMA-induced hmeprinβ shedding. By labeling COS-1 cells transfected with mutant constructs lacking the potential phosphorylation sites, we identified Ser687 as the main 32P-acceptor. These data provide evidence that the cytoplasmic doma... | SIGNOR-263171 |
P41221 | Q01973 | 2 | binding | up-regulates | 0.747 | Ror1 and ror2 bind wnt5a. | SIGNOR-196133 |
Q92997 | Q9NQ66 | 1 | 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 |
O76064 | P16104 | 1 | ubiquitination | up-regulates | 0.2 | Rnf8 can ubiquitylate histone h2a and h2ax, | SIGNOR-159309 |
P04637 | P51955 | 0 | phosphorylation | down-regulates | 0.318 | NEK2 Phosphorylates p53 at Ser315 and Reduces Its Stability.|These results are consistent with NEK2 inhibiting p53 transcriptional activation functions. | SIGNOR-278488 |
P61586 | Q9NPG1 | 2 | binding | up-regulates activity | 0.344 | Upon ligand binding, non-canonical wnt signaling controls tissue polarity and cell movement through the activation of rhoa, c-jun n-terminal kinase (jnk), and nemo-like kinase (nlk) signaling cascades. | SIGNOR-167865 |
Q99996 | P20701 | 2 | binding | up-regulates activity | 0.2 | However, association of CG-NAP/AKAP450 was signifi-cantly enhanced at 37°C in LFA-1-activated cells triggered toundergo motility. Taken together, our findings provide the first definitiveevidence that the protein CG-NAP/AKAP450 is a key scaffoldingcomponent of the multimolecular complex assembled in T cellsupon LFA cro... | SIGNOR-260304 |
O95863 | Q13131 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases r... | SIGNOR-161779 |
Q96PY6 | Q13535 | 2 | binding | up-regulates activity | 0.2 | It was reported that NEK1 associates with ATR/ATRIP and primes it for activation in response to a variety of genotoxic agents | SIGNOR-275841 |
Q9Y3F4 | O15105 | 2 | binding | up-regulates | 0.61 | Strap recruits smad7 to the activated type i receptor and forms a complex | SIGNOR-76771 |
Q05655 | P52757 | 1 | phosphorylation | down-regulates | 0.269 | A novel cross-talk in diacylglycerol signaling: the rac-gap beta2-chimaerin is negatively regulated by protein kinase cdelta-mediated phosphorylation. phosphorylation of beta2-chimaerin on ser(169) located in the sh2-c1 domain linker region via protein kinase cdelta, which retained beta2-chimaerin in the cytosol and pr... | SIGNOR-164687 |
Q5S007 | P62841 | 1 | phosphorylation | up-regulates activity | 0.485 | Taken together, these results suggest that phosphorylation of s15 on T136 by LRRK2 mediates enhanced cap-dependent and cap-independent reporter translation and that a stimulatory effect of LRRK2 on mRNA translation contributes to LRRK2 toxicity. | SIGNOR-279058 |
P25100 | P38405 | 2 | binding | up-regulates activity | 0.278 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-256951 |
Q8TAB3 | P47869 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited ep... | SIGNOR-267218 |
O95271 | O15169 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.774 | Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. | SIGNOR-187972 |
P35222 | P55290 | 2 | binding | up-regulates activity | 0.534 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265853 |
Q13627 | P01106 | 1 | phosphorylation | down-regulates quantity | 0.374 | We also found that DYRK1A phosphorylated c-Myc on Ser62, priming phosphorylation on Thr58 by GSK3\u03b2 and subsequent degradation.|c-Myc expression is down-regulated by DYRK1A. | SIGNOR-279609 |
P24385 | Q13547 | 2 | binding | up-regulates | 0.697 | Cyclin d1 bound hdac in vivo and preferentially physically associated with hdac1, hdac2, hdac3, and hdac5. | SIGNOR-134059 |
P35226 | P42771 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.455 | In HEK293A cells transfected with luciferase reporter constructs, necdin relieves Bmi1-dependent repression of p16 promoter activity, | SIGNOR-253385 |
P06899 | Q14493 | 0 | 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 cy... | SIGNOR-265381 |
P08237 | Q8IYT8 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanc... | SIGNOR-274044 |
P61586 | Q8IW93 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.636 | 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... | SIGNOR-260543 |
Q15365 | P31751 | 0 | phosphorylation | down-regulates activity | 0.429 | We show that heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) binds a structural, 33-nucleotide TGF-beta-activated translation (BAT) element in the 3' untranslated region of disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI) transcripts, and represses their translation.TGF-beta activation leads to phosphory... | SIGNOR-262625 |
P29320 | P20827 | 2 | binding | up-regulates | 0.817 | Transmembrane ligands for eph receptors also exhibit properties of signal transducing molecules, suggesting that bidirectional signaling occurs when receptor-expressing cells contact ligand-expressing cells. | SIGNOR-52005 |
Q92831 | P0DPK2 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269614 |
P49815 | Q92574 | 2 | binding | up-regulates activity | 0.934 | Furthermore, tsc2 is directly phosphorylated by akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. Tsc2 is inactivated by akt-dependent phosphorylation, which destabilizes tsc2 and disrupts its interaction with tsc1. | SIGNOR-77400 |
P13861 | P17612 | 2 | binding | down-regulates activity | 0.876 | Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to ph... | SIGNOR-258752 |
Q16620 | P19174 | 1 | phosphorylation | up-regulates activity | 0.647 | Both Shc and PLCgamma1 are phosphorylated by TrkB, thereby initiating Shc/Ras/MAP kinase and PLCgamma1 signaling respectively.|We conclude that activation of pY783 PLCgamma1 is due mainly to TrkB activation in these models and that TrkB induced PLCgamma1 signaling promotes limbic epileptogenesis. | SIGNOR-279241 |
Q12965 | Q05397 | 2 | binding | up-regulates activity | 0.2 | Myosin-1E (MYO1E), an actin-dependent molecular motor protein, directly interacts with FAK to induce Y397 autophosphorylation, which, in turn, causes changes in gene expression commonly observed in aggressive cancer. | SIGNOR-265427 |
Q9NQC7 | Q14164 | 0 | phosphorylation | down-regulates activity | 0.441 | CYLD is phosphorylated by IKK\u03b5 at Ser418.|Together, these observations demonstrate that I\u03baB kinase\u03b5-mediated phosphorylation of CYLD at Ser418 inhibits CYLD deubiquitinase activity. | SIGNOR-278311 |
Q8IUC6 | Q86XR7 | 2 | binding | up-regulates activity | 0.586 | Tram binds trif directly and recruits it to tlr4 | SIGNOR-118367 |
P35398 | P48539 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally express... | SIGNOR-266848 |
Q9HCK8 | O43602 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and... | SIGNOR-268915 |
P49841 | P30291 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.329 | Serine 211 phosphorylation occurred under control conditions in the absence of CK1δ and in the presence of GSK3-β (Fig. 5, D and E). | SIGNOR-276632 |
P62873 | P59768 | 2 | binding | up-regulates activity | 0.94 | GNB1 dissociates from the receptor, bound with GNG2 as stable dimer | SIGNOR-251105 |
P27361 | P49841 | 1 | phosphorylation | down-regulates activity | 0.294 | We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels | SIGNOR-262523 |
P45984 | Q9NYV6 | 1 | phosphorylation | down-regulates | 0.472 | Inactivation is due to phosphorylation of tif-ia by c-jun n-terminal kinase (jnk) at a single threonine residue (thr 200). Phosphorylation at thr 200 impairs the interaction of tif-ia with pol i and the tbp-containing factor tif-ib/sl1, thereby abrogating initiation complex formation. | SIGNOR-134878 |
P01909 | Q86YJ5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino aci... | SIGNOR-271538 |
P56178 | P28360 | 2 | binding | down-regulates activity | 0.389 | We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperati... | SIGNOR-240921 |
Q149N8 | P12004 | 1 | ubiquitination | up-regulates | 0.553 | We provide evidence that similar to rad5, shprh physically interacts with the human rad6rad18 and mms2ubc13 protein complexes, and importantly, we show that it exhibits an ubiquitin ligase activity and mediates mms2ubc13-dependent polyubiquitylation of pcna. Thus, shprh is a functional homolog of rad5. | SIGNOR-187757 |
Q99675 | P00533 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | CGRRF1 ubiquitinates EGFR through K48-linked ubiquitination, which leads to proteasome degradation. | SIGNOR-272220 |
Q8TDX7 | P52732 | 1 | phosphorylation | up-regulates activity | 0.407 | NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites. | SIGNOR-273890 |
Q9UQM7 | P16615 | 1 | phosphorylation | up-regulates activity | 0.397 | SERCA2 and SERCA2 mutants S38A, S167A, and S531A were expressed in HEK-293 cells and tested for phosphorylation with CaM kinase. Mutant S38A was not phosphorylated, while mutants S167A and S531A were phosphorylated, suggesting that Ser38 is the site of CaM kinase phosphorylation in SERCA2. This conclusion was supported... | SIGNOR-250616 |
P26441 | P40189 | 2 | binding | up-regulates | 0.682 | Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. The dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. Some of these biological activities of il-6 are also often exerte... | SIGNOR-47991 |
P12931 | P18031 | 0 | dephosphorylation | up-regulates activity | 0.781 | Incubation of the inactivated c-Src with PTP1B results in a dose-dependent reactivation of c-Src tyrosine kinase activity. Incubation of c-Src with 2 or 10 g of PTP1B results in partial or full restoration of c-Src kinase activity, respectively. The activation is accompanied by dephosphorylation of c-Src, both of Tyr-4... | SIGNOR-245299 |
P38405 | P21918 | 2 | binding | up-regulates activity | 0.509 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali... | SIGNOR-256914 |
P60484 | Q9BXM7 | 0 | phosphorylation | down-regulates activity | 0.47 | PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import. | SIGNOR-277915 |
P56524 | Q13131 | 0 | phosphorylation | down-regulates | 0.272 | We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases. | SIGNOR-173689 |
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