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 |
|---|---|---|---|---|---|---|---|
P23759 | Q86X55 | 0 | methylation | up-regulates | 0.421 | Carm1 specifically methylates Pax7 at multiple arginine residues in the N terminus of Pax7 | SIGNOR-255898 |
P42345 | P42345 | 2 | phosphorylation | up-regulates activity | 0.2 | We have found that in HEK293 cells and 3T3-L1 adipocytes, insulin promotes both raptor- and rictor-associated mTOR Ser(P)-2481 in a wortmannin-sensitive manner. Thus, insulin signals via PI3K to promote both mTORC1- and mTORC2-associated mTOR Ser-2481 autophosphorylation. | SIGNOR-235427 |
P48775 | P04150 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.337 | Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development. | SIGNOR-268995 |
Q15465 | P35398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.251 | 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-266846 |
P01112 | Q13671 | 2 | binding | up-regulates | 0.636 | We demonstrate that the ras effector protein rin1 binds to activated ras with an affinity (k(d), 22 nm) similar to that observed for raf1. | SIGNOR-113967 |
Q07955 | P78362 | 0 | phosphorylation | up-regulates activity | 0.616 | In contrast, SRPK1 or SRPK2 overexpression upregulated the phosphorylation and nucleus accumulation of SRSF1.|Therefore, SRPK1 and SRPK2 may directly phosphorylate SRSF1 and promote it nucleus translocation, subsequently modulate MKNK2 alternative splicing. | SIGNOR-279660 |
Q9H211 | Q13309 | 2 | binding | down-regulates quantity by destabilization | 0.659 | Biochemical studies showed that Skp2 interacts specifically with cyclin E and thereby promotes its ubiquitylation and degradation both in vivo and in vitro. These results suggest that specific degradation of cyclin E and p27(Kip1) is mediated by the SCF(Skp2) ubiquitin ligase complex, and that Skp2 may control chromos... | SIGNOR-272565 |
P09884 | P09874 | 2 | binding | up-regulates activity | 0.342 | We provide evidence that in proliferating cells: (i) PARP is physically associated with the catalytic subunit of the DNA polymerase α–primase tetramer, an association confirmed by confocal microscopy, demonstrating that both enzymes are co-localized at the nuclear periphery of HeLa cells.|(iii) PARP-deficient cells der... | SIGNOR-261270 |
P09619 | P19174 | 1 | 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 |
Q9Y5Y9 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.32 | 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 ... | SIGNOR-253463 |
P24941 | P46527 | 2 | phosphorylation | down-regulates | 0.95 | Ubiquitination and subsequent degradation play a critical role in regulating the levels of p27 during cell cycle progression. Here we provide evidence suggesting that both cdk2/e and phosphorylation of thr(187) on p27 are essential for the recognition of p27 by the scf(skp2/cks1) complex, the ubiquitin-protein isopepti... | SIGNOR-154188 |
P06241 | Q99490 | 1 | phosphorylation | up-regulates | 0.467 | We demonstrate that fyn is essential for phosphorylating pike-a and protects it from apoptotic cleavage. Active but not kinase-dead fyn interacts with pike-a and phosphorylates it on both y682 and y774 residues. Tyrosine phosphorylation in pike-a is required for its association with active fyn but not for akt. Mutation... | SIGNOR-147936 |
Q9Y6D9 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.2 | ATM mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint.|Together, these findings reveal an important role of ATM-mediated Mad1 Serine 214 phosphorylation in mitosis. | SIGNOR-278467 |
P31749 | Q9BPZ7 | 1 | phosphorylation | up-regulates activity | 0.703 | Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt. | SIGNOR-276932 |
Q9NRW1 | O43896 | 0 | relocalization | up-regulates quantity | 0.2 | Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentr... | SIGNOR-266878 |
P02749 | P00742 | 0 | cleavage | down-regulates activity | 0.386 | In the previous study, we found that factor Xa can produce the nicked form by cleaving Lys 317-Thr 318, using recombinant human domain V (r-Domain V). |The cleavage was completely inhibited by plasmin inhibitor (alpha2PI). The nicked form was demonstrated to show reduced affinity for CL with a dissociation constant of ... | SIGNOR-266997 |
P43403 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.26 | 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 V... | SIGNOR-254733 |
Q13153 | P30291 | 1 | phosphorylation | down-regulates | 0.299 | Kinases targeted sequentially to the neck, cla4/pak and cdc5/polo, are responsible for stepwise phosphorylation and down-regulation of swe1. | SIGNOR-123528 |
Q13490 | Q6GPH4 | 2 | binding | down-regulates | 0.415 | Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3. | SIGNOR-156843 |
O43151 | O15294 | 2 | binding | up-regulates | 0.443 | Tet2 and tet3 associate with the o_glcnac transferase ogt / tet2 and tet3 promote ogt_mediated glcnacylation | SIGNOR-200729 |
O75928 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.316 | The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as t... | SIGNOR-262949 |
O43524 | Q96KS0 | 0 | hydroxylation | down-regulates activity | 0.287 | Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.|Here we report that EglN2 can hydroxylate FOXO3a on two specific prolyl residues in vitro and in vivo. Hydroxylation of these sites prevents the binding of USP9x deubiquitinase, thereby promoting the proteasomal... | SIGNOR-261998 |
P06850 | P34998 | 2 | binding | up-regulates | 0.958 | Crf and ucn bind and activate crf-r1 with similarly high affinities. | SIGNOR-108713 |
Q9UQB8 | P60953 | 2 | 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 |
P28482 | Q99956 | 2 | binding | down-regulates | 0.699 | Here we demonstrate that inactivation of both erk1/2 and p38_ by dusp9/mkp-4 is mediated by a conserved arginine-rich kinase interaction motif located within the amino-terminal non-catalytic domain of the protein. | SIGNOR-176583 |
Q13263 | Q05655 | 0 | phosphorylation | down-regulates | 0.2 | This work demonstrates that tif1beta is phosphorylated on ser473, the alteration of which is dynamically associated with cell cycle progression and functionally linked to transcriptional regulation. Phosphorylation of tif1beta/ser473 is mediated by the pkcdelta pathway and is closely linked to cell proliferation. Phosp... | SIGNOR-179250 |
P08151 | P41743 | 0 | phosphorylation | up-regulates activity | 0.402 | Although functioning downstream of SMO, aPKC-\u03b9/\u03bb phosphorylates and activates GLI1, resulting in maximal DNA binding and transcriptional activation [ xref ]. | SIGNOR-279262 |
P11388 | Q9H4B4 | 0 | phosphorylation | up-regulates | 0.268 | The direct phosphorylation of thr(1342) of topoisomerase iialpha by plk3 was demonstrated with an in vitro kinase assay, and overexpression of plk3 induced the phosphorylation of thr(1342) in cellular topoisomerase iialpha. it is possible that plk3 regulates the activity of topoisomerase iia by phosphorylation in a ce... | SIGNOR-159596 |
Q03113 | O15085 | 2 | binding | up-regulates activity | 0.631 | This RGS-like (RGL) domain provides a structural motif by which heterotrimeric G protein alpha subunits of the Galpha(12) family can bind and regulate the activity of RhoGEFs. Hence, these newly discovered RGL domain-containing RhoGEFs provide a direct link from Galpha(12) and Galpha(13) to Rho | SIGNOR-256516 |
P27361 | P27708 | 1 | phosphorylation | up-regulates | 0.2 | Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible fo... | SIGNOR-137179 |
P17612 | P05549 | 1 | phosphorylation | up-regulates | 0.2 | Recombinant ap-2 was phosphorylated in vitro by protein kinase a (pka) at ser239. Mutation of ser239 to ala abolished in vitro phosphorylation of ap-2 by pka, but not the dna binding activity of ap-2. Cotransfection studies showed that pka stimulated the effect of ap-2 on the apoe promoter, but not that of the s239a mu... | SIGNOR-64955 |
Q14164 | Q04864 | 1 | phosphorylation | up-regulates | 0.354 | The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel. | SIGNOR-148620 |
P27361 | Q14005 | 1 | phosphorylation | up-regulates | 0.266 | The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 in antigen receptor-, sdf1alpha- and il-2-activated t cells. Genetic and pharmacological-inhibitor experiments showed that the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by m... | SIGNOR-121856 |
Q8N5S9 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | In vitro, CaMKK is phosphorylated by PKA and this is associated with inhibition of enzyme activity. The major site of phosphorylation is threonine 108, although additional sites are phosphorylated with lower efficiency. | SIGNOR-256115 |
P28482 | P05023 | 1 | phosphorylation | down-regulates activity | 0.519 | Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phos... | SIGNOR-262940 |
P14653 | P55347 | 2 | binding | up-regulates activity | 0.613 | we observe the formation of a ternary Prep1-Pbx1-HOXB1 complex on a HOXB1-responsive target in vitro. Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target. | SIGNOR-241215 |
P49760 | Q07955 | 1 | phosphorylation | up-regulates activity | 0.298 | In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates... | SIGNOR-273858 |
P02686 | Q8TAS1 | 0 | phosphorylation | down-regulates | 0.2 | Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic re... | SIGNOR-143485 |
P42701 | P29459 | 2 | binding | up-regulates | 0.572 | Like il-12, il-23 binds to the il-12r subunit il-12rbeta1. | SIGNOR-87677 |
P61586 | P45983 | 2 | binding | up-regulates activity | 0.827 | We found that in the human kidney epithelial cell line, 293T, Cdc42 and all Rho proteins, RhoA, RhoB, and RhoC, but not Rac or Ras can induce activation of JNK. | SIGNOR-258974 |
O14965 | P25963 | 1 | phosphorylation | down-regulates activity | 0.541 | The results of the in vitro kinase assay, using purified human recombinant AURKA and IkappaBalpha proteins, confirmed that AURKA can directly phosphorylate IkappaBalpha (Ser32) at a concentration as low as 2.5 ng/mul (XREF_FIG).|While an earlier study suggested that AURKA down-regulates IkappaBalpha indirectly through ... | SIGNOR-278912 |
P35568 | P60484 | 0 | dephosphorylation | down-regulates activity | 0.576 | In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser 307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon HCV infection occurred in a PTEN dependent manner.|In contrast, IRS-1 level were signi... | SIGNOR-277078 |
P17302 | P48730 | 0 | phosphorylation | up-regulates activity | 0.6 | We have examined the role of casein kinase 1 (CK1) in connexin-43 (Cx43) gap junction assembly. Cellular co-immunoprecipitation experiments and in vitro CK1 phosphorylation reactions indicate that CK1 interacted with and phosphorylated Cx43, initially on serine(s) 325, 328, or 330.| To examine CK1 function, normal rat ... | SIGNOR-249331 |
P43405 | P51452 | 1 | phosphorylation | up-regulates activity | 0.363 | ZAP-70 and Syk also tyrosine-phosphorylated VHR in COS-1 cells (Fig. 2d), whereas other kinases (Csk, Lck, Fyn, Jak2, Bcr-Abl and Itk) had little effect. Finally, recombinant ZAP-70 readily phosphorylated VHR in vitro (Fig. 2f). | SIGNOR-275999 |
Q99623 | Q02078 | 2 | binding | down-regulates | 0.31 | Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation. | SIGNOR-235840 |
C9JLW8 | P28482 | 0 | phosphorylation | down-regulates activity | 0.2 | When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.| While substitution of S4 or S18 with Ala did not affect the phosphorylation of MCRIP1 ... | SIGNOR-264774 |
P06400 | P06493 | 0 | phosphorylation | down-regulates | 0.688 | The retinoblastoma gene product (prb) is a nuclear phosphoprotein that is thought to play a key role in the negative regulation of cellular proliferation. The active form of prb is underphosphorylated. Using synthetic peptides corresponding to potential cdc2 phosphorylation sites, we have developed a strategy which has... | SIGNOR-21564 |
P25092 | Q02747 | 2 | binding | up-regulates | 0.771 | Guanylins activate two receptors, gc-c and ok-gc, which are expressed in intestine and/or kidney | SIGNOR-78096 |
O94953 | Q16665 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.261 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C... | SIGNOR-271569 |
Q99608 | P01106 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.265 | Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cy... | SIGNOR-253381 |
Q13315 | O15360 | 1 | phosphorylation | up-regulates | 0.407 | The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a c... | SIGNOR-182949 |
Q99250 | Q92915 | 2 | binding | down-regulates activity | 0.375 | 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-253429 |
Q16549 | Q92945 | 1 | phosphorylation | down-regulates | 0.2 | Ksrp phosphorylated by p38 displays compromised binding to are-containing transcripts and fails to promote their rapid decay,although it retains the ability to interact with the mrna degradation machinery. | SIGNOR-143167 |
Q96QT6 | Q9H808 | 2 | binding | up-regulates activity | 0.2 | We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family m... | SIGNOR-266991 |
Q9Y490 | P26012 | 2 | binding | up-regulates activity | 0.469 | 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-257636 |
Q8N5S9 | Q14012 | 1 | phosphorylation | up-regulates activity | 0.414 | Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase. | SIGNOR-250717 |
Q05469 | P27361 | 0 | phosphorylation | up-regulates activity | 0.415 | Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL. | SIGNOR-249470 |
Q96N96 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.718 | 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-260576 |
O00763 | Q9NPA3 | 2 | binding | up-regulates activity | 0.28 | Recently, we reported the discovery that MIG12, a 183 amino acid protein, binds to ACC1 and ACC2, which induces polymerization and subsequently increases the enzymatic activity of the protein | SIGNOR-267112 |
Q96LB2 | P09471 | 2 | binding | up-regulates activity | 0.2 | 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-257259 |
P20702 | P05362 | 2 | binding | up-regulates | 0.679 | Using assays to quantify cd11c-mediated cell adhesion, we demonstrate that cd11c recognizes icam-2 and vcam-1. The cd11c-binding site on vcam-1 appears to be different from that used by the integrin alpha4. | SIGNOR-31388 |
Q9NS23 | Q8WWW0 | 2 | binding | up-regulates activity | 0.543 | NORE1A can heterodimerize with RASSF1A and, thus, mediate K-Ras regulation of RASSF1A | SIGNOR-249587 |
P51812 | Q99990 | 1 | phosphorylation | down-regulates activity | 0.2 | Site-directed mutagenesis and immunoprecipitation experiments revealed that RSK2 phosphorylated VGLL1 at S84 in the presence of TGF-β. Mutation of VGLL1 at S84 suppressed VGLL1-TEAD4 binding and the subsequent transcriptional activation of matrix metalloprotease 9 (MMP9). | SIGNOR-273842 |
Q06187 | P12931 | 0 | phosphorylation | up-regulates activity | 0.529 | This interaction of BTK with SRC kinases transphosphorylated BTK on tyrosine at residue 551, which led to BTK activation. | SIGNOR-251100 |
P14921 | Q99102 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level. | SIGNOR-254098 |
Q52LW3 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.552 | 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-260484 |
Q9UM73 | P23467 | 0 | dephosphorylation | down-regulates | 0.334 | Rptpbeta/zeta dephosphorylates alk at the site(s) in alk that is undergoing autophosphorylation through autoactivation. | SIGNOR-157175 |
Q06124 | P35568 | 1 | dephosphorylation | down-regulates | 0.897 | The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1b (ptp1b), sh2 domain-containing ptpase-2 (shp-2), leukocyte common antigen-related (lar), and leukocyte antigen-related phosphatase) (lrp) toward irs-1 dephosphorylation was studied using recombinant proteins in vitro.... | SIGNOR-74856 |
Q15796 | Q92830 | 2 | binding | up-regulates | 0.337 | Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 an... | SIGNOR-123315 |
P08047 | P49585 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 function as transcriptional activators of the Ctpct promoter | SIGNOR-266231 |
Q96MM3 | Q9NVW2 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.337 | RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. | SIGNOR-269002 |
Q13315 | Q9NZM5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PICT-1 S233 and T289 were identified as the key phosphorylation sites in this pathway, as mutating both to alanine abolished UVB-induced increase of PICT-1 phosporylation. Inhibition of PIKKs or ATM (with wortmannin and KU55933, respectively) prevented the agglomeration and degradation of PICT-1, suggesting that ATM is... | SIGNOR-273506 |
Q16288 | P29353 | 2 | binding | up-regulates | 0.732 | We demonstrate that the phosphotyrosine binding domain of frs-2 directly binds the trk receptors at the same phosphotyrosine residue that binds the signaling adapter shc, suggesting a model in which competitive binding between frs-2 and shc regulates differentiation versus proliferation. | SIGNOR-65958 |
Q09472 | Q13315 | 0 | phosphorylation | up-regulates | 0.4 | Atm mediates phosphorylation of p300 in response to dna damageexpression of nonphosphorylatable serine to alanine form of p300 (s106a) destabilized both p300 and nbs1 proteins, after dna damage | SIGNOR-165567 |
O00712 | P41161 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles f... | SIGNOR-268880 |
P56645 | P48730 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.719 | 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-267998 |
Q9H2K2 | Q9NTX7 | 0 | ubiquitination | down-regulates quantity | 0.614 | We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. | SIGNOR-260005 |
Q15375 | P20827 | 2 | binding | up-regulates | 0.812 | The best known function is their role in the guidance of migration of axons and cells in the nervous system through repulsive interactions | SIGNOR-56965 |
Q8TDN4 | P31749 | 0 | phosphorylation | down-regulates activity | 0.34 | Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3-dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly ... | SIGNOR-276756 |
P30990 | O95665 | 2 | binding | down-regulates | 0.898 | Neurotensin binding to recombinant neurotensin nt2 receptor expressed in cho cells does not elicit a biological response as determined by second messenger measurements. | SIGNOR-62519 |
Q9Y6E0 | P61006 | 1 | phosphorylation | up-regulates activity | 0.275 | In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting intera... | SIGNOR-260265 |
Q05655 | P40763 | 1 | phosphorylation | up-regulates | 0.596 | Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation. | SIGNOR-143828 |
Q13547 | P04150 | 2 | binding | up-regulates | 0.445 | The GR directly interferes with Hes1 promoter activity, triggering the recruitment of histone deacetylase (HDAC) activities to the Hes1 gene | SIGNOR-253057 |
O94991 | Q15465 | 2 | binding | down-regulates activity | 0.2 | SLITRK5 interacts with SHH and PTCH1. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative reg... | SIGNOR-268437 |
O43561 | Q12913 | 0 | dephosphorylation | down-regulates activity | 0.353 | Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation | SIGNOR-248696 |
O15524 | P51451 | 0 | phosphorylation | down-regulates activity | 0.2 | These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors. | SIGNOR-277889 |
P63096 | Q5NUL3 | 2 | binding | up-regulates activity | 0.25 | 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-257045 |
Q96BF3 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | We observed that IGPR-1 is activated by shear stress and tensile force and that flow shear stress-mediated IGPR-1 activation modulates remodeling of endothelial cells. Mechanistically, shear stress stimulated activation of AKT Ser/Thr kinase 1 (AKT1), leading to phosphorylation of IGPR-1 at Ser-220. | SIGNOR-273481 |
P78362 | Q9UKV3 | 1 | phosphorylation | up-regulates | 0.476 | Here, we show that srpk2 binds and phosphorylates acinus, an sr protein essential for rna splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin a1 but not a2 up-regulation. Acinus s422d, an srpk2 phosphorylation mimetic, enhances cyclin a1 transcription, whereas acinus s422a, ... | SIGNOR-179006 |
Q92570 | P10415 | 2 | binding | down-regulates activity | 0.2 | NR4A3 physically interacted with an anti-apoptotic Bcl-2 protein hence sequestering it from blunting apoptosis. | SIGNOR-259399 |
Q96FI4 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Mule and TRIM26 ubiquitylate NEIL1 in vitro within C-terminal lysine residues. | SIGNOR-278695 |
Q8WXE1 | Q13535 | 0 | phosphorylation | up-regulates | 0.878 | When dna is damaged, the atr-atrip complex is recruited to chromatin and is activated to transduce the checkpoint signal, but the precise kinase activation mechanism remains unknown. Here, we show that atrip is phosphorylated in an atr-dependent manner after genotoxic stimuli. The serine 68 and 72 residues are importan... | SIGNOR-129473 |
P09769 | P41240 | 0 | phosphorylation | down-regulates activity | 0.537 | CSK catalyzed phosphorylation affects Tyr-511 of c-Fgr, homologous to Tyr-527 of c-Src and it prevents the autophosphorylation normally occurring at c-Fgr Tyr-400, homologous to c-Src Tyr-416. | Once phosphorylated at Tyr-511 and down-regulated by CSK, c-Fgr is no more susceptible to polylysine stimulation. | SIGNOR-250779 |
P10589 | P28702 | 2 | binding | up-regulates | 0.274 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site | SIGNOR-79449 |
P23470 | P29353 | 1 | dephosphorylation | down-regulates activity | 0.2 | 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 V... | SIGNOR-254724 |
P53602 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation. | SIGNOR-265891 |
P49841 | Q9UM73 | 0 | phosphorylation | up-regulates activity | 0.248 | It has been reported that Alk phosphorylates and activates Gsk3beta in mouse neural crest explants and neuroblastoma cell lines.|Therefore, we tested whether Alk indeed phosphorylates Y279-GSK3\u03b2 in stomach epithelial cells. | SIGNOR-280180 |
O43541 | O43318 | 2 | binding | down-regulates activity | 0.57 | Smad6 interacts with tak1 and tab1, and smad7 with tab1. The interaction of i-smads with tak1 and/or tab1 implies that several mechanisms exist underlying the repression of the tak1-p38 kinase pathway by i-smads. | SIGNOR-235571 |
P37173 | P01137 | 2 | 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 radioiodinat... | SIGNOR-236080 |
Q9HC98 | Q9HC35 | 1 | phosphorylation | up-regulates activity | 0.253 | The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stabil... | SIGNOR-273883 |
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