IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 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 |
|---|---|---|---|---|---|---|---|
Q00534 | P42771 | 0 | binding | down-regulates | 0.871 | In addition, cytoplasmic p16 bound cyclin dependent kinase (cdk)4/6, potentially indicating that p16 could have a function in the cytoplasm. | SIGNOR-140412 |
P08559 | Q15120 | 0 | phosphorylation | down-regulates activity | 0.871 | Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes. | SIGNOR-109647 |
P32239 | P06307 | 0 | binding | up-regulates | 0.871 | Cck8 interacts with nanomolar affinities with two different receptors designated cck-a and cck-b | SIGNOR-66339 |
P04637 | P24941 | 0 | phosphorylation | up-regulates activity | 0.871 | The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A | SIGNOR-119379 |
P11802 | P42773 | 0 | binding | down-regulates | 0.871 | The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks,cdk4and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb. | SIGNOR-44598 |
Q8IZL2 | Q06330 | 0 | binding | up-regulates | 0.871 | When bound to the active intracellular domain of notch (nicd), rbpj recruits a coactivator complex, including a mastermind homologue (maml1-3 in mammals), and drives a complex transcriptional program with pervasive phenotypic effects | SIGNOR-176197 |
P04049 | P01111 | 0 | relocalization | up-regulates | 0.87 | The raf family of proteins (raf-1, a-raf, and b-raf) bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175231 |
Q12778 | P31749 | 0 | phosphorylation | down-regulates activity | 0.87 | Here we show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular growth factors induces phosphorylation, nuclear export, and transcriptional inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24 and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated nuclear export. | SIGNOR-236163 |
Q12933 | Q15628 | 0 | binding | up-regulates activity | 0.87 | The high affinity of the tradd-traf2 interaction is required for efficient suppression of apoptosis upon stimulation of the tumor necrosis factor receptor1 (tnfr1), tnf-receptor-associated death domain (tradd) provides a scaffold for the assembly of complex i at the plasma membrane by binding receptor interacting protein 1 (rip1), tnfreceptor- associated factor 2 ,traf2 these results provide evidence that tradd can serve as an adaptor protein and recruit traf1, traf2, or both to tnfrsf1a. The demonstration that tradd interacts with traf2 and fadd, and can recruit both to tnfrsf1a, suggested that traf2 and fadd may be involved in tnfrsf1a tradd-mediated signaling. That these interactions define two distinct signaling pathways emanating from tradd (figure 9) is supported by the ability of traf2 and fadd to activate nf-kb and induce apoptosis, respectively. | SIGNOR-179446 |
Q15561 | Q9GZV5 | 0 | binding | up-regulates | 0.869 | When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14. | SIGNOR-201459 |
O15055 | P48730 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.869 | 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-268000 |
P40189 | P05231 | 0 | binding | up-regulates activity | 0.869 | A crystal structure of the ligand-binding domains of gp130 in complex with human interleukin-6 (il-6) and its a-receptor (il-6ralpha) revealed a hexameric architecture in which the gp130 membrane-distal regions were approximately 100 a apart, in contrast to the close apposition seen between short cytokine receptor complexes. | SIGNOR-48041 |
P05198 | Q9UI10 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.869 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269127 |
P14784 | P60568 | 0 | binding | up-regulates | 0.869 | Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c). | SIGNOR-144540 |
P35568 | P08069 | 0 | phosphorylation | up-regulates | 0.868 | Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor. | SIGNOR-175665 |
Q13261 | P40933 | 0 | binding | up-regulates | 0.868 | Interleukin-15 specificity and high affinity binding are conferred by the IL-5-specific but nonsignaling IL-15R alpha subunit, which is structurally similar (but not homologous) to the alpha receptor subunit of IL-2 | SIGNOR-157415 |
P28347 | Q9GZV5 | 0 | binding | up-regulates | 0.868 | When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead1?_?_?4. | SIGNOR-192768 |
Q9NPH3 | P01584 | 0 | binding | up-regulates | 0.867 | The recently described il-1r accessory protein (il-1r acp) interacts with il-1beta and the il-1 type-ir (il-1ri). | SIGNOR-61744 |
Q9NRM7 | Q9H8S9 | 0 | binding | up-regulates | 0.867 | Lats1/2 are activated by association with the highly homologous scaffold proteins mps one binder kinase activator-like 1a (mobkl1a) and 1b (mobkl1b), which are collectively referred to as mob1 | SIGNOR-169755 |
P17181 | P01574 | 0 | binding | up-regulates | 0.867 | Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2. | SIGNOR-104663 |
Q8WU20 | P11362 | 0 | phosphorylation | up-regulates activity | 0.867 | As shown in xref , wild type FGFR1c phosphorylated FRS2\u03b1 on tyrosine 196 whereas the V429E mutant did not. | SIGNOR-280013 |
P60842 | P23588 | 0 | binding | up-regulates activity | 0.867 | Either eIF4B or eIF4H stimulated the initial rate and amplitude of eIF4A-dependent duplex unwinding, and the magnitude of stimulation is dependent on duplex stability | SIGNOR-261293 |
Q495A1 | P15151 | 0 | binding | up-regulates activity | 0.867 | Poliovirus receptor (PVR/CD155) is a ligand of the paired NK receptors, DNAM-1 (activating) and TIGIT (inhibiting). NK cells can kill cancer cells expressing PVR via the DNAM-1-mediated activating signaling (11,12). | SIGNOR-261425 |
P16499 | P18545 | 0 | 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 |
P42229 | O60674 | 0 | phosphorylation | up-regulates activity | 0.866 | Jak2 kinase induces tyrosine phosphorylation, dimerization, nuclear translocation, and dna binding of a concomitantly expressed stat5 protein | SIGNOR-249507 |
P31785 | P60568 | 0 | binding | up-regulates | 0.866 | Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c). | SIGNOR-144543 |
Q9NPB6 | P41743 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.866 | APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation. | SIGNOR-276432 |
P37173 | P10600 | 0 | binding | up-regulates | 0.866 | T?RII Is known to bind the isoforms tgf??1 And tgf??3. Binding of these ligands causes recruitment of the type i receptor (t?RI) into a signalling receptor complex followed by activation of t?RI Through transphosphorylation | SIGNOR-104798 |
Q15750 | Q9Y4K3 | 0 | binding | up-regulates activity | 0.865 | The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex. | SIGNOR-205455 |
P51692 | O60674 | 0 | phosphorylation | up-regulates | 0.865 | Jak2 kinase induces tyrosine phosphorylation, dimerization, nuclear translocation, and dna binding of a concomitantly expressed stat5 protein | SIGNOR-56894 |
P67775 | Q13362 | 0 | binding | up-regulates activity | 0.864 | We have identified by two-hybrid interaction a new human gene family encoding PP2A B subunits. This family, denoted B56, contains three distinct genes, one of which is differentially spliced. | SIGNOR-268155 |
Q9NYJ8 | Q13546 | 0 | binding | up-regulates activity | 0.864 | TNF_ induced the polyubiquitination of RIP and the association of polyubiquitinated RIP with TAB2. | SIGNOR-128406 |
P61586 | Q07960 | 0 | gtpase-activating protein | down-regulates activity | 0.864 | 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-260458 |
P0CG48 | P09936 | 0 | cleavage | up-regulates quantity | 0.864 | These data suggest that the physiological role of UCH is to hydrolyze small adducts of ubiquitin and to generate free monomeric ubiquitin from ubiquitin proproteins, but not to deubiquitinate ubiquitin-protein conjugates or disassemble polyubiquitin chains | SIGNOR-249693 |
P30793 | P30047 | 0 | binding | down-regulates activity | 0.864 | The enzyme activity of GTP cyclohydrolase I is controlled by a regulatory protein for this enzyme, GFRP, which is a pentamer of identical subunits. GFRP mediates feedback inhibition of GTP cyclohydrolase I activity by BH4, and the inhibition by BH4 is reversed by phenylalanine | SIGNOR-252203 |
P32241 | P01282 | 0 | binding | up-regulates | 0.864 | Pacap binds to a pacap-specific receptor (pac1) and to vpac receptors (vpac1 and vpac2), which share high affinity for vasoactive intestinal polypeptide (vip). | SIGNOR-116122 |
Q9HCK4 | O94813 | 0 | binding | up-regulates activity | 0.863 | This observation suggests that Slit2 may require the Robo2 and Robo3 receptors in this process . Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation. | SIGNOR-268380 |
Q9UQB8 | P60953 | 0 | binding | up-regulates activity | 0.863 | We conclude that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to the IRSp53 SH3 domain. This IRSp53:Mena complex initiates actin filament assembly into filopodia. | SIGNOR-268424 |
P22694 | P10644 | 0 | binding | down-regulates activity | 0.863 | 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 phosphorylate downstream targets | SIGNOR-258755 |
P09884 | Q7L590 | 0 | relocalization | up-regulates quantity by stabilization | 0.862 | Mcm10 is an essential eukaryotic protein required for the initiation and elongation phases of chromosomal replication. Specifically, Mcm10 is required for the association of several replication proteins, including DNA polymerase alpha (pol alpha), with chromatin. | SIGNOR-261271 |
P51681 | P13236 | 0 | binding | up-regulates activity | 0.862 | The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation. | SIGNOR-255116 |
Q13501 | P60520 | 0 | binding | up-regulates activity | 0.862 | P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha | SIGNOR-156307 |
Q04206 | Q9Y6K9 | 0 | phosphorylation | up-regulates activity | 0.862 | Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter. | SIGNOR-129947 |
P84077 | Q8N6T3 | 0 | gtpase-activating protein | up-regulates activity | 0.862 | The ARFGAP molecule binds to switch 2 and helix α3 to orient ARF1 residues for catalysis, but it supplies neither arginine nor other amino acid side chains to the GTPase active site. | SIGNOR-261915 |
O43603 | P22466 | 0 | binding | up-regulates | 0.862 | Galanin showed high affinity for the galr1 (ic(50) = 0.097 nm) and galr2 receptors (ic(50) = 0.48 nm). | SIGNOR-73125 |
O95166 | Q9Y4P1 | 0 | cleavage | up-regulates activity | 0.861 | In vivo and in vitro biochemical analyses have shown that human atg4b is an authentic cysteine protease essential for cleavage of the c terminus of each atg8 homolog to expose the c-terminal gly | SIGNOR-141929 |
Q14457 | Q9P2Y5 | 0 | binding | up-regulates activity | 0.861 | UVRAG interacts with Beclin 1, leading to activation of autophagy and thereof inhibition of tumorigenesis. | SIGNOR-150825 |
P84022 | O95405 | 0 | binding | up-regulates activity | 0.861 | We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex. | SIGNOR-62874 |
O43683 | P06493 | 0 | phosphorylation | up-regulates | 0.861 | The plk1-bub1 interaction requires the polo-box domain (pbd) of plk1 and is enhanced by cyclin-dependent kinase 1 (cdk1)-mediated phosphorylation of bub1 at t609 | SIGNOR-147065 |
Q02078 | Q09472 | 0 | binding | up-regulates | 0.861 | Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription. | SIGNOR-232165 |
Q5VWK5 | Q9NPF7 | 0 | binding | up-regulates | 0.861 | We identify a novel member of the hemopoietin receptor family as a subunit of the receptor for il-23, il-23r. | SIGNOR-87805 |
P08069 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.861 | Ptp-1b can regulate igf-ir kinase activity and function and that loss of ptp-1b can enhance igf-i-mediated cell survival, growth, and motility in transformed cells. | SIGNOR-115709 |
Q8IZL2 | Q99466 | 0 | binding | up-regulates | 0.86 | We show here identification of two new members of human mam family (human mastermind-2 (hmam-2) and human mastermind-3 (hmam-3)), which retain characteristics similar to human mastermind-1 (hmam-1) and drosophila mastermind. Both hmam-2 and hmam-3 stabilize and participate in the dna-binding complex rbp-j/cbf-1 protein and the notch intracellular domains that serve as intermediates of the signaling. Both hmam-2 and hmam-3 enhanced the activation of transcription from a target promoter by notch signaling. However, we also show evidence that the activation of the target promoter by notch3 and notch4 is more efficiently potentiated by hmam-2 than by hmam-1 or -3. | SIGNOR-94279 |
P35222 | P49841 | 0 | phosphorylation | down-regulates activity | 0.86 | Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC). | SIGNOR-116528 |
P25025 | P10145 | 0 | binding | up-regulates | 0.86 | Il-8 activates both the cxcr1 and the cxcr2 on microvascular endothelial cells, using different signal transduction cascades. | SIGNOR-107983 |
P10275 | Q13772 | 0 | binding | up-regulates | 0.86 | We demonstrated that ara70 and ar physically interact and that ara70 can function as an androgen-dependent coactivator for ar. | SIGNOR-67684 |
Q14974 | P52294 | 0 | 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 |
O96017 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.86 | Atm- and rad3-related also phosphorylates thr68 in addition to thr26 and ser50, which are not phosphorylated to a significant extent by atm in vitro.Substitution of thr68 with ala reduced the extent of phosphorylation and activation of chk2 in response to ir | SIGNOR-81442 |
P10912 | P01241 | 0 | binding | up-regulates | 0.859 | The hghr only binds primate gh. Arg43 in hghr interacts with asp171 of hgh. | SIGNOR-34129 |
Q07817 | P55957 | 0 | binding | down-regulates activity | 0.859 | Overexpression of antiapoptotic proteins including Bcl-XL and/or Bcl-2 contributes to tumor initiation, progression, and resistance to therapy by direct interactions with proapoptotic BH3 proteins. Release of BH3 proteins from antiapoptotic proteins kills some cancer cells and sensitizes others to chemotherapy. Binding of Bcl-XL and Bcl-2 to the BH3 proteins Bad, Bid, and the three major isoforms of Bim was measured for fluorescent protein fusions in live cells using fluorescence lifetime imaging microscopy and fluorescence resonance energy transfer. | SIGNOR-209675 |
P55210 | P98170 | 0 | binding | down-regulates quantity by destabilization | 0.859 | Our crystal structure of the complex between xiap (linker-bir2) and caspase-7 surprisingly revealed that the linker is the major determinant of binding and inhibition for the caspase. | SIGNOR-105732 |
P19174 | P09619 | 0 | phosphorylation | up-regulates | 0.859 | Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production. | SIGNOR-28179 |
O75943 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.858 | Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival. | SIGNOR-111248 |
O75051 | Q14563 | 0 | binding | up-regulates | 0.858 | Plexins form stable complexes with neuropilin-1 or -2. | SIGNOR-75168 |
P31785 | P05112 | 0 | binding | up-regulates | 0.858 | The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex | SIGNOR-108861 |
Q9UBF6 | Q13616 | 0 | binding | up-regulates activity | 0.857 | SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34. | SIGNOR-271444 |
Q00610 | O14976 | 0 | phosphorylation | up-regulates activity | 0.857 | Clathrin heavy chain (CHC) was phosphorylated at T606 by its association partner cyclin G-associated kinase (GAK). This phosphorylation was required for proper cell proliferation and tumor growth of cells implanted into nude mice. | SIGNOR-275448 |
P30411 | P01042 | 0 | binding | up-regulates activity | 0.857 | BK binds receptor B2 (B2R) and triggers inflammation, edema, and symptoms of anaphylaxis. | SIGNOR-263554 |
Q92956 | O43557 | 0 | binding | up-regulates | 0.857 | A member of the tumor necrosis factor (tnf) superfamily, human tnfsf14 (htnfsf14)/hvem-l (herpes virus entry mediator ligand) was isolated as a cellular ligand for hvem/tr2 and human lymphotoxin beta receptor (ltbetar). Tnfsf14 induces apoptosis and suppresses tumor formation | SIGNOR-79328 |
P15509 | P04141 | 0 | binding | up-regulates | 0.857 | We have determined the nmr structure of a ligand-binding domain of the granulocyte colony-stimulating factor (g-csf) receptor comparisons between the spectra of the 15n-labelled domain with and without g-csf indicate that the major ligand-recognition site is on the fg loop just upstream of the wsxws sequence. | SIGNOR-72458 |
P25929 | P01303 | 0 | binding | up-regulates | 0.857 | Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors. | SIGNOR-56522 |
P30304 | O14757 | 0 | phosphorylation | down-regulates | 0.857 | The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216). | SIGNOR-163134 |
Q9Y566 | O14490 | 0 | relocalization | up-regulates activity | 0.857 | 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-264586 |
Q06330 | Q9UM47 | 0 | binding | up-regulates | 0.857 | Both notch 1 and notch 3 ics displace the co-repressor smrt from the dna-binding protein rbp-j kappa on the hes promoter. The latter observation suggests that both notch 3 ic and notch 1 ic can access rbp-j kappa in vivo, and that the difference in activation capacity instead stems from structural differences in the two ics when positioned on rbp-j kappa. | SIGNOR-86128 |
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 |
P30307 | O96017 | 0 | phosphorylation | down-regulates activity | 0.856 | Activated chk2 in turn phosphorylates cdc25c at serine-216 contributing to the g2/m checkpoints. Cds1 phosphorylates and inactivates cdc25 in vitro|CDC25C is phosphorylated on Ser 216 throughout interphase, but not in mitosis. This creates a binding site for 14‐3‐3 proteins | It has been suggested that 14‐3‐3 protein binding is responsible for retaining Cdc25C in the cytoplasm during interphase, thereby contributing to the prevention of premature initiation of mitotic events | SIGNOR-102779 |
P17612 | P31321 | 0 | binding | down-regulates activity | 0.856 | 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 phosphorylate downstream targets | SIGNOR-258753 |
P24928 | Q9NP77 | 0 | dephosphorylation | up-regulates activity | 0.855 | Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.| Depletion of Ssu72 impairs transcription in vitro | SIGNOR-248815 |
P14635 | P30304 | 0 | dephosphorylation | up-regulates activity | 0.855 | Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] . | SIGNOR-277137 |
P46527 | Q00534 | 0 | phosphorylation | up-regulates | 0.855 | Phosphorylation on ser-10 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.p27(kip1) was phosphorylated by v-cyclin-cdk6 predominantly on ser10, which enhances its cytoplasmic localization. | SIGNOR-140401 |
Q9NT62 | Q9H492 | 0 | binding | up-regulates | 0.855 | Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe. | SIGNOR-191543 |
P08238 | P31948 | 0 | binding | down-regulates activity | 0.855 | Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine. | SIGNOR-261412 |
P42229 | P52333 | 0 | phosphorylation | up-regulates | 0.854 | For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated. | SIGNOR-182817 |
P15056 | P01111 | 0 | binding | up-regulates activity | 0.854 | The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175219 |
Q13404 | P61088 | 0 | binding | up-regulates activity | 0.854 | Ubc13, the partner of rnf8 and rnf168, usually cooperates with an e2-like protein, uev1 (also known as ube2v1) or mms2 (also known as ube2v2), for the synthesis of lys63-linked polyubiquitin chains. | SIGNOR-166177 |
P37173 | P01137 | 0 | binding | up-regulates activity | 0.853 | A cdna encoding the tgf-beta type ii receptor protein has been isolated by an expression cloning strategy. The cloned cdna, when transfected into cos cells, leads to overexpression of an approximately 80 kd protein that specifically binds radioiodinated tgf-beta 1. Excess tgf-beta 1 competes for binding of radioiodinated tgf-beta 1 in a dose-dependent manner and is more effective than tgf-beta 2. | SIGNOR-236080 |
P36897 | P62942 | 0 | binding | down-regulates activity | 0.853 | Blocking fkbp12/type i receptor interaction with fk506 nonfunctional derivatives enhances the ligand activity, indicating that fkbp12 binding is inhibitory to the signaling pathways of the tgf beta family ligands | SIGNOR-236142 |
P19838 | O14920 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.853 | Ikkbeta phosphorylates p105 resulting in its degradation, which releases tpl2 resulting in activation of the pro-proliferative map kinase- pathway. | SIGNOR-70473 |
P78552 | P35225 | 0 | binding | up-regulates | 0.853 | It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1. | SIGNOR-100750 |
P31785 | P40933 | 0 | binding | up-regulates | 0.853 | The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex. | SIGNOR-108815 |
P30556 | P01019 | 0 | binding | up-regulates activity | 0.852 | AT(1) receptor (AngII type-1 receptor), a G-protein-coupled receptor, mediates most of the physiological and pathophysiological actions of AngII, and this receptor is predominantly expressed in cardiovascular cells, such as VSMCs (vascular smooth muscle cells) | SIGNOR-252293 |
Q16512 | P61586 | 0 | binding | up-regulates activity | 0.852 | PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome. | SIGNOR-275465 |
P15735 | P46020 | 0 | binding | down-regulates activity | 0.852 | Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit. | SIGNOR-267407 |
P18075 | Q13253 | 0 | binding | down-regulates activity | 0.852 | We report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors. | SIGNOR-256484 |
P54132 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.852 | It is noteworthy that an active BLM seems to be unnecessary to the activation of BRCA1, either after gamma-rays or HU, even though BRCA1 and BLM helicase are activated by ATR in response to stalled replication, and despite the fact that they colocalize after replication arrest.|These results show that BLM phosphorylation by ATR after replication fork arrest is not important for its relocalization. | SIGNOR-278978 |
Q7L9L4 | Q13043 | 0 | phosphorylation | up-regulates | 0.851 | Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2mob1 interaction. | SIGNOR-175841 |
P13807 | Q9UQK1 | 0 | binding | up-regulates | 0.851 | In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2) | SIGNOR-271733 |
O14936 | Q02410 | 0 | binding | up-regulates activity | 0.851 | Interaction with Munc18 increases Mint1 binding to CASK. | SIGNOR-264041 |
P35222 | P22223 | 0 | binding | up-regulates activity | 0.851 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265865 |
P42338 | P27986 | 0 | binding | up-regulates activity | 0.851 | Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival | SIGNOR-242640 |
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