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 |
|---|---|---|---|---|---|---|---|
Q92949 | Q9UIF3 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.324 | FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1). | SIGNOR-266937 |
O00505 | P46531 | 1 | relocalization | up-regulates | 0.324 | Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. | SIGNOR-165280 |
Q00765 | P25024 | 1 | binding | up-regulates activity | 0.324 | In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. | SIGNOR-261366 |
Q9Y6E2 | Q14152 | 1 | binding | up-regulates activity | 0.324 | BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro | SIGNOR-261221 |
P12931 | Q08050 | 1 | phosphorylation | up-regulates activity | 0.324 | Hence, c-Src-dependent phosphorylation of MPP2 could be part of a negative feedback loop within the circuitry that modulates c-Src activity by MPP2. | SIGNOR-279117 |
Q9UBF6 | P05412 | 1 | ubiquitination | down-regulates activity | 0.324 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271452 |
P17612 | Q86UR1 | 1 | phosphorylation | down-regulates | 0.324 | We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I | SIGNOR-163663 |
Q15418 | Q9UBP6 | 1 | phosphorylation | down-regulates | 0.324 | Pkb and ribosomal s6 kinase (rsk) both phosphorylated mettl1 at ser27 in vitro. | SIGNOR-135948 |
P68400 | O60936 | 1 | phosphorylation | up-regulates activity | 0.324 | Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm. | SIGNOR-262837 |
P63092 | Q9NQ66 | 1 | binding | up-regulates activity | 0.324 | The beta- but not the gamma- and delta-type isozymes of inositol phospholipid-specific phospholipase c (plc) are activated by g protein alpha q and beta gamma subunits. | SIGNOR-265066 |
Q15139 | O43597 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.324 | PKD negatively affects the stability of Spry2 WT but not of mutant Spry2 S112A.|Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. | SIGNOR-280091 |
P08047 | O43186 | 1 | binding | up-regulates activity | 0.324 | Zinc finger DNA-binding domains of both Sp1 and Sp3 interact with Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains. | SIGNOR-225336 |
P53350 | Q8N137 | 1 | phosphorylation | up-regulates activity | 0.324 | However, unlike NEK2, PLK1 phosphorylation enhances the microtubule stabilizing activity of centrobin [22].|PLK1 phosphorylation of centrobin is critical for bipolar spindle formation. | SIGNOR-279551 |
P49841 | Q14449 | 1 | phosphorylation | down-regulates activity | 0.323 | Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3. | SIGNOR-264867 |
P45984 | P41970 | 1 | phosphorylation | down-regulates activity | 0.323 | JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export. | SIGNOR-250138 |
P50750 | O96019 | 1 | phosphorylation | up-regulates activity | 0.323 | Collectively, these results suggest that the cdk9 and Cyclin T complex more efficiently phosphorylates Baf53 in vitro. | SIGNOR-279689 |
P28482 | P08151 | 1 | phosphorylation | up-regulates activity | 0.323 | We conclude that multisite phosphorylation of GLI1 by ERK2 or other MAP kinases weakens GLI1-SUFU binding, thereby facilitating GLI1 activation and contributing to both physiological and pathological crosstalk. | SIGNOR-277601 |
P07949 | P31749 | 1 | phosphorylation | up-regulates | 0.323 | The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity | SIGNOR-252619 |
P27361 | Q15366 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.323 | We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B). | SIGNOR-262916 |
P67775 | P24071 | 1 | dephosphorylation | up-regulates activity | 0.323 | Furthermore, FcalphaRI activation is induced by protein phosphatase 2A (PP2A) after it dephosphorylates a single serine residue (S263) in the FcalphaRI intracellular tail | SIGNOR-264858 |
P43657 | Q5JWF2 | 1 | binding | up-regulates activity | 0.323 | LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa. | SIGNOR-278872 |
Q15788 | P51692 | 1 | binding | up-regulates | 0.323 | Ncoa-1/src-1 is an essential coactivator of stat5 that binds to the fdl motif in the alpha-helical region of the stat5 transactivation domain. | SIGNOR-100261 |
Q7Z3K3 | Q96GD4 | 1 | binding | up-regulates activity | 0.323 | POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis. | SIGNOR-264497 |
Q12913 | O60674 | 1 | dephosphorylation | down-regulates activity | 0.323 | These results support PTPRJ preferentially dephosphorylating Y813 and Y868 in JAK2.|We revealed that PTPRJ negatively regulates leptin signaling by dephosphorylating specific tyrosine residues (Y813 and Y868) in JAK2, the simultaneous phosphorylation of which plays a pivotal role in JAK2 activation. | SIGNOR-277094 |
P09238 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.323 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256332 |
P06493 | Q9Y6I3 | 1 | phosphorylation | down-regulates activity | 0.323 | Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin. | SIGNOR-262723 |
P03952 | P14210 | 1 | cleavage | up-regulates activity | 0.323 | the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain. | SIGNOR-256513 |
P68400 | P08473 | 1 | phosphorylation | down-regulates | 0.323 | The cytoplasmic n-terminal domain of nep interacts with the phosphatase and tensin homologue deleted on chromosome 10 (pten) thereby regulating intracellular signaling via akt. Ser 6 is efficiently phosphorylated by protein kinase ck2. The phosphorylation of the cytoplasmic domain of nep inhibits its interaction with pten. | SIGNOR-168673 |
O15111 | Q15717 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.323 | Furthermore, mutational analysis indicates that IKKα-dependent phosphorylation at Ser-304 is crucial to the binding of HuR to β-TrCP1. Mechanistically, this HuR degradation pathway differs from that reported for heat shock and hypoxia, which underlies the complexity in the regulation of HuR turnover under different stress stimuli. | SIGNOR-276422 |
Q96RI0 | P63092 | 1 | binding | up-regulates activity | 0.323 | 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- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256772 |
P51608 | P42262 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.323 | Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A. | SIGNOR-264684 |
O15550 | P31269 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.323 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260025 |
P45983 | P41970 | 1 | phosphorylation | down-regulates activity | 0.323 | JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export. | SIGNOR-250139 |
P43657 | P63092 | 1 | binding | up-regulates activity | 0.323 | LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa. | SIGNOR-278873 |
P27361 | Q12929 | 1 | phosphorylation | down-regulates activity | 0.323 | We further show that the actin barbed-end capping activity of Eps8 is inhibited by brain-derived neurotrophic factor (BDNF) treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation. | SIGNOR-263058 |
P47900 | P63092 | 1 | binding | up-regulates activity | 0.323 | 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- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256800 |
Q9ULL1 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.323 | 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-260563 |
Q15173 | P10415 | 1 | dephosphorylation | down-regulates | 0.323 | Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site. | SIGNOR-181559 |
Q12955 | P12830 | 1 | binding | up-regulates activity | 0.323 | Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. Ankyrin-G also recruits beta-2-spectrin to E-cadherin-beta-catenin complexes, thus providing a direct connection between E-cadherin and the spectrin/actin skeleton. | SIGNOR-266710 |
Q16236 | P22830 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.322 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated. | SIGNOR-279865 |
P62136 | Q13263 | 1 | dephosphorylation | up-regulates activity | 0.322 | PP1\u03b1 dephosphorylates KAP1 at Ser 824 . | SIGNOR-277075 |
P31749 | O43464 | 1 | phosphorylation | down-regulates | 0.322 | Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212 | SIGNOR-252500 |
P49760 | P18031 | 1 | phosphorylation | up-regulates activity | 0.322 | The clk family kinases, clk1 and clk2, phosphorylate and activate the tyrosine phosphatase, ptp-1b.|Phosphorylation of PTP-1B at Ser(50) by CLK1 or CLK2 is responsible for its enzymatic activation. | SIGNOR-70603 |
P06493 | Q02952 | 1 | phosphorylation | up-regulates activity | 0.322 | Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis. | SIGNOR-271839 |
P05771 | P35548 | 1 | phosphorylation | up-regulates quantity | 0.322 | PKCbeta increased the level of overexpressed Msx2, but PKC alpha, delta and zeta did not have any significant effects.|Thr135 and Thr141 in Msx2 can be phosphorylated by PKC\u03b2, and Thr135 is important for regulating the protein stability of Msx2 by PKCs. | SIGNOR-278982 |
P16591 | P16284 | 1 | phosphorylation | up-regulates activity | 0.322 | PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1. | SIGNOR-262866 |
P45983 | Q9NRA8 | 1 | phosphorylation | up-regulates | 0.322 | Identification of 4e-t phosphorylation sites regulated by jnk. identification of these residues as phosphorylation sites (ser301, ser374, ser513, ser587, ser693, and ser752) was obtained by ms/ms sequencing, these results demonstrate that jnk activity is required to stimulate the assembly of pbs in response to oxidative stress. | SIGNOR-199004 |
P09237 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.322 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256329 |
P17252 | P22681 | 1 | phosphorylation | down-regulates quantity | 0.322 | However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway. | SIGNOR-249056 |
A0PJZ3 | Q04721 | 1 | binding | up-regulates | 0.322 | We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum. | SIGNOR-177717 |
P49840 | Q14596 | 1 | phosphorylation | down-regulates activity | 0.322 | The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation. | SIGNOR-261794 |
P17612 | Q93034 | 1 | phosphorylation | up-regulates activity | 0.322 | Elimination of the S730 but not the T325 PKA phosphorylation site of VACM-1 resulted in a complete inhibition of the VACM-1 activity, thus suggesting a direct effect of PKA on the VACM-1 receptor. | SIGNOR-250352 |
P23443 | Q15633 | 1 | phosphorylation | up-regulates activity | 0.322 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274068 |
Q9H0K1 | P27986 | 1 | phosphorylation | up-regulates activity | 0.322 | The Regulatory Subunit of PI3K Is a Direct Catalytic Target of SIK2. These data confirm that p85α is a direct catalytic substrate of SIK2 and that SIK2 S154 phosphorylation significantly increases the activity of the PI3K/AKT pathway in ovarian cancer cells. | SIGNOR-277269 |
Q05655 | P05787 | 1 | phosphorylation | up-regulates | 0.322 | The present study showed that shear stress, but not stretch, activates PKC delta and phosphorylates K8 Ser-73, which then mediates the disassembly/reorganization of keratin IF in AEC. | SIGNOR-260887 |
P12931 | P19404 | 1 | phosphorylation | up-regulates activity | 0.322 | Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants. | SIGNOR-276419 |
Q14814 | P35580 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.322 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238766 |
Q9UNE7 | Q8IXT1 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.322 | HSP70 recruits DDIAS to the CHIP E3 ligase, whereas CHIP promotes the ubiquitination of DDIAS.|However, the findings clearly demonstrated that HSP70 was solely involved in CHIP mediated proteasomal degradation of DDIAS. | SIGNOR-278784 |
P00519 | Q14498 | 1 | phosphorylation | up-regulates activity | 0.322 | In this paper, we report that RBM39 interacts with the nonreceptor tyrosine kinase c-Abl. Both the Src homology (SH) 2 and SH3 domains of c-Abl interact with RBM39. The major tyrosine phosphorylation sites on RBM39 that are phosphorylated by c-Abl are Y95 and Y99, as demonstrated by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and mutational analysis. c-Abl was shown boost the transcriptional coactivation activity of RBM39 for ERα and PRβ in a tyrosine kinase-dependent manner. | SIGNOR-262609 |
P49674 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.322 | CKIepsilon phosphorylates and activates DARPP-32, a key molecule in various complex signaling pathways, including dopamine and glutamine signaling, which have both been demonstrated to be main pathways in substance dependence. | SIGNOR-279701 |
P17252 | Q05209 | 1 | phosphorylation | down-regulates | 0.322 | Ptp-pest is phosphorylated in vitro by both cyclic amp-dependent protein kinase (pka) and protein kinase c (pkc) at two major sites, which we have identified as ser39 and ser435 / phosphorylation of ser39 in vitro decreases the activity of ptp-pest by reducing its affinity for substrate. | SIGNOR-27300 |
Q92597 | P20338 | 1 | binding | up-regulates | 0.322 | In this report evidence is provided that ndrg1 is a rab4a effector protein that localizes to perinuclear recycling/sorting vesicles in the trans golgi network by binding to phophatidylinositol 4-phosphate and is involved in recycling of e-cadherin. This is the first demonstration providing evidence that ndrg1 is a rab4a effector recruiting to recycling/sorting endosomes. | SIGNOR-157697 |
O96017 | Q13362 | 1 | phosphorylation | up-regulates | 0.322 | Found that chk2 associated with the b' regulatory subunit of protein phosphatase pp2a. In vitro kinase assays showed that b'gamma3 was a potent chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of pp2a. | SIGNOR-129255 |
P28482 | Q9UQ13 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.322 | Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation. | SIGNOR-277442 |
P42684 | P07203 | 1 | phosphorylation | up-regulates activity | 0.322 | GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress. | SIGNOR-104328 |
P20962 | Q09472 | 1 | binding | up-regulates activity | 0.322 | Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells. | SIGNOR-268461 |
P01009 | Q07954 | 1 | binding | up-regulates | 0.322 | In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp | SIGNOR-41180 |
O00311 | Q8TEA8 | 1 | phosphorylation | up-regulates activity | 0.321 | Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D). | SIGNOR-273967 |
P49336 | P46937 | 1 | phosphorylation | up-regulates activity | 0.321 | CDK8 phosphorylates YAP and promotes its activation. Of interest, mutating four amino acid positions (T119, S128, S289, and S367) to alanines (YAP-4A) completely blocked phosphorylation (Fig. 6J), suggesting that CDK8 phosphorylates these sites in YAP in vitro. | SIGNOR-277651 |
P05129 | P28329 | 1 | phosphorylation | up-regulates | 0.321 | We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation. | SIGNOR-129320 |
Q02156 | Q99259 | 1 | phosphorylation | down-regulates activity | 0.321 | We have identified one specific phosphorylation site, threonine 91 (T91), in hGAD67 that can be phosphorylated by PKA using MALDI-TOF. Site-directed mutation of T91 to alanine abolished PKA-mediated phosphorylation and inhibition of GAD activity. | SIGNOR-249264 |
Q9H0K1 | Q9BV73 | 1 | phosphorylation | down-regulates | 0.321 | Here, we show that the salt inducible kinase 2 (sik2) localizes at the centrosome, plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, c-nap1, through s2392 phosphorylation | SIGNOR-167488 |
Q9BXM7 | P04637 | 1 | phosphorylation | up-regulates activity | 0.321 | Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria. | SIGNOR-278418 |
P24723 | P49840 | 1 | phosphorylation | down-regulates | 0.321 | Furthermore, several pkc isotypes phosphorylate gsk-3 in vitro and in vivo. in the presence of atp, several isoforms (?, ___, _, ?, And of pkc phosphorylated both gsk-3? At ser 21 and gsk-3_ at ser 9 | SIGNOR-115730 |
Q05513 | Q15831 | 1 | phosphorylation | up-regulates | 0.321 | Here, we have identified s307 as a novel phosphorylation site in lkb1 and provide evidence that, in multiple cell types, phosphorylation of this site by protein kinase c ? (pkc-?) Induces nucleocytoplasmic transport of lkb1. | SIGNOR-185640 |
Q16539 | Q92993 | 1 | phosphorylation | up-regulates activity | 0.321 | We found that phosphorylation of Tip60-T158 was increased by p38\u03b1 isolated from Dox- or \u03b3-radiation-treated cells over that from untreated cells (Figure xref ), indicating that DNA damage induces the protein kinase activity of p38\u03b1 towards Tip60-T158. | SIGNOR-278958 |
P04150 | Q13886 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.321 | We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα | SIGNOR-256119 |
P08238 | Q9HC29 | 1 | binding | up-regulates quantity by stabilization | 0.321 | Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation. | SIGNOR-252415 |
Q13233 | Q6UUV9 | 1 | phosphorylation | up-regulates | 0.321 | We report on the activation oftorc1through mekk1-mediated phosphorylation. | SIGNOR-180816 |
P34947 | Q16143 | 1 | phosphorylation | down-regulates activity | 0.321 | GRK5 prefers alpha-synuclein as a substrate. GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser118 practically abolishes β-synuclein phosphorylation by both GRK2 and GRK5 | SIGNOR-251203 |
Q15569 | Q9Y281 | 1 | phosphorylation | down-regulates activity | 0.321 | Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin | SIGNOR-246719 |
Q96S53 | Q9Y281 | 1 | phosphorylation | down-regulates activity | 0.321 | Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin | SIGNOR-246711 |
P24666 | P31749 | 1 | dephosphorylation | down-regulates activity | 0.321 | Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3 | SIGNOR-248455 |
P42574 | Q13635 | 1 | cleavage | down-regulates | 0.321 | Like other dependence receptors, ptc1 contains a dependence-as-associated receptor c-terminal motif that is cleaved by caspases at a conserved aspartic acid (asp 1392) in the absence of shh, to expose a proapoptotic domain. | SIGNOR-199111 |
Q9NP60 | P62166 | 1 | binding | up-regulates activity | 0.321 | IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis. our data show that IL1RAPL interacts only with NCS-1 through its specific C-terminal domain. The functional relevance of IL1RAPL activity was further supported by the inhibitory effect on exocytosis in PC12 cells overexpressing IL1RAPL. Taken together, our data suggest that IL1RAPL may regulate calcium-dependent exocytosis and provide insight into the understanding of physiopathological mechanisms underlying cognitive impairment resulting from IL1RAPL dysfunction. | SIGNOR-264476 |
P68400 | Q16666 | 1 | phosphorylation | up-regulates activity | 0.321 | Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). | Specific phosphorylation of IFI 16 Ser132 in HeLa cell extracts and by purified CK2 in vitro | SIGNOR-250902 |
P09603 | Q99062 | 1 | binding | up-regulates | 0.321 | A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (gcsf) and a ligand binding region of gcsf receptor (gcsf-r), has been determined to 2.8 a resolution | SIGNOR-144737 |
Q92730 | P45983 | 1 | binding | up-regulates | 0.321 | In the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor | SIGNOR-152811 |
P12931 | O95319 | 1 | phosphorylation | up-regulates activity | 0.321 | Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA. | SIGNOR-263195 |
P29466 | P49810 | 1 | cleavage | up-regulates activity | 0.32 | In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329. | SIGNOR-261748 |
P51668 | Q8NEG5 | 1 | binding | up-regulates activity | 0.32 | MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expression of MEX promoted apoptosis that was induced through Fas, DR (death receptor) 3 and DR4 signalling, but not that mediated by the BH3 (Bcl-2 homology 3)-only protein BimEL or the chemotherapeutic drug adriamycin. | SIGNOR-271554 |
Q92499 | Q9NR30 | 1 | binding | up-regulates activity | 0.32 | We demonstrated here that DDX1-DDX21-DHX36 represents a dsRNA sensor that uses the adaptor molecule TRIF to activate the NF-κB pathway and type I IFN responses in dendritic cells. Our study suggests that the DDX1-DDX21-DHX36 complex represents this missing poly I:C sensor, which uses DDX1 to bind poly I:C and uses DDX21 and DXH36 to bind TRIF. Poly I:C is a synthetic form of RNA that mimics double-stranded viral RNA. | SIGNOR-260191 |
P41743 | Q92934 | 1 | phosphorylation | down-regulates | 0.32 | In-vitro kinase activity assay showed that pkc-_ directly phosphorylated bad at phospho specific residues, ser-112, ser-136 and ser-155 which in turn induced inactivation of bad and disruption of bad/bcl-xl dimer | SIGNOR-172894 |
Q9NXK8 | P51648 | 1 | binding | down-regulates quantity by destabilization | 0.32 | We now show that SCFFBXL12 is an authentic E3 for the ALDH3 family of enzymes. We now show that the ubiquitin-dependent degradation of ALDH3 mediated by FBXL12 (F box and leucine-rich repeat protein 12) is essential for execution of the differentiation program of trophoblast stem cells (TSCs). FBXL12 is present only in eutherian mammals, and its expression is largely restricted to the placenta during mouse embryogenesis. FBXL12 was found to interact specifically with members of the ALDH3 family and to mediate their polyubiquitylation. Finally, coimmunoprecipitation analysis revealed that FBXL12 interacted efficiently only with members of the ALDH3 family (ALDH3A1, ALDH3A2, and ALDH3B1), showing little if any association with those of the ALDH1 family (ALDH1A1, ALDH1A2, and ALDH1A3) (Fig. 2H). Collectively, these results suggested that SCFFBXL12 is an authentic E3 specific for ALDH3 family members. | SIGNOR-272814 |
P52954 | O95863 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.32 | Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively | SIGNOR-266053 |
P17612 | Q16613 | 1 | phosphorylation | up-regulates activity | 0.32 | AANAT1–207 was phosphorylated in vitro at both PKA sites, Thr-31 and Ser-205. regulation is achieved by binding to 14-3-3, which structurally modulates the substrate binding sites, leading to measurable effects on the affinity of AANAT for its substrates with an accompanying increase in activity at low substrate concentrations. | SIGNOR-250324 |
P06493 | Q15468 | 1 | phosphorylation | down-regulates activity | 0.32 | Importantly, we show that CDK1 and CyclinB phosphorylates the N-terminal domain of STIL, but not the region encompassing the CC or STAN motifs. | SIGNOR-279145 |
P68400 | P51636 | 1 | phosphorylation | up-regulates activity | 0.32 | We show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells. Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae | SIGNOR-101110 |
Q86TM6 | P10909 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.32 | We also report that the ER-associated ubiquitin ligase Hrd1/synoviolin can interact with, and ubiquitinate clusterin. The fact that cleaved endogenous clusterin appears, under certain conditions, to be subject to polyubiquitination (Figure 2C) and proteasomal degradation (1, 2) strongly suggests that it passed through the secretory pathway before reaching the cytosol. | SIGNOR-272629 |
P05129 | Q7Z2E3 | 1 | phosphorylation | up-regulates | 0.32 | We show the novel molecular consequences of increased kinase activities of mutants: aprataxin (aptx), a dna repair protein causative for autosomal recessive ataxia, was found to be a preferential substrate of mutant pkc gamma, and phosphorylation inhibited its nuclear entry. ollectively, phosphorylation occurred at thr111, reducing nuclear aptx. | SIGNOR-186409 |
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