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 |
|---|---|---|---|---|---|---|---|
P15336 | Q9H6S0 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.275 | Collectively, these data show that YTHDC2 plays an important role in tumor cells growth and activation/recruitment of c-Jun and ATF-2 to the YTHDC2 promoter is necessary for the transcription of YTHDC2, and that HDAC activity is required for the efficient expression of YTHDC2 in both of hepatocyte and HCC cells. | SIGNOR-269001 |
Q12981 | Q13501 | 2 | binding | up-regulates activity | 0.334 | RNF185 functions as a ubiquitin E3 ligase, enabling BNIP1-p62 interaction. BNIP1 is polyubiquitinated by RNF185 and associates with autophagy receptor p62. In addition, we checked the endogenous localization of BNIP1 and p62 in HeLa cells (Fig. 7F). Alexa Fluor 488 conjugated endogenous BNIP1 and TRITIC conjugated endogenous p62 overlapped well in the cytoplasm, further providing the locational evidence for the recruitment of p62 by BNIP1. | SIGNOR-271932 |
P06493 | Q6PGN9 | 1 | phosphorylation | down-regulates activity | 0.236 | MT-polymerizing activity was decreased from samples with DDA3 phosphorylated by Cdk1 ( xref , lanes 4 vs 6) and Aurora A ( xref , lanes 14 vs 16).|Taken together, the mitotic Cdk1 and Aurora A kinases inhibit MT polymerization activities and MT bundling activities of DDA3. | SIGNOR-279601 |
Q03113 | Q9BPV8 | 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- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257231 |
Q9UKV5 | Q14258 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.364 | We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78. | SIGNOR-272176 |
P01106 | Q13526 | 2 | binding | up-regulates | 0.573 | Pin1 prolyl isomerase enhances recruitment of serine 62-phosphorylated myc and its coactivators to select promoters during gene activation. | SIGNOR-202134 |
P28562 | Q09472 | 0 | acetylation | up-regulates | 0.309 | A recent report shows that mkp1 may also be regulated by acetylation. When raw macrophages are stimulated with lps, mkp1 becomes acetylated on lys57 by p300 | SIGNOR-166581 |
O75197 | Q9H461 | 2 | binding | up-regulates activity | 0.728 | Ligands such as Wnt1, Wnt3a, and Wnt8 couple the seven-transmembrane domain receptor Frizzled (Fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (LRP5/6) to activate WntBeta-catenin signaling. | SIGNOR-169635 |
Q5MJ70 | P24941 | 1 | relocalization | up-regulates activity | 0.791 | Speedy/RINGO A, a noncanonical activator of CDK2, was recently identified as a key regulator for CDK2 recruitment to meiotic telomeres | SIGNOR-263310 |
P17612 | P20810 | 1 | phosphorylation | up-regulates activity | 0.2 | The results showed that PKA promoted the phosphorylation of calpastatin, and a high phosphorylation level was maintained during incubation. Phosphorylation at serine 133 of calpastatin enhanced its inhibition on calpain activity by maintaining its structural stability, thus inhibiting the tenderization of meat. | SIGNOR-277839 |
P78527 | P49917 | 1 | phosphorylation | down-regulates | 0.808 | Using tandem mass spectrometry, we identified a dna-pk phosphorylation site at thr-650 in human lig4 and a potential second phosphorylation site at ser-668 or ser-672. Phosphorylation of lig4 per se was not required for lig4 dna end joining activity. Substitution of these amino acids with alanine, individually or in combination, led to changes in lig4 protein stability of mouse lig4. The phosphomimetic mutation s650d returned lig4 stability to that of the wild-type protein. Furthermore dna-pk was found to negatively regulate lig4 protein stability. | SIGNOR-125877 |
O14936 | Q16650 | 2 | binding | up-regulates | 0.458 | Here we report that, through its guanylate kinase domain, CASK interacts with Tbr-1, a T-box transcription factor that is involved in forebrain development. CASK enters the nucleus and binds to a specific DNA sequence (the T-element) in a complex with Tbr-1. CASK acts as a coactivator of Tbr-1 to induce transcription of T-element containing genes, including reelin, a gene that is essential for cerebrocortical development. | SIGNOR-266835 |
Q13304 | P25098 | 0 | phosphorylation | down-regulates activity | 0.2 | As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17. | SIGNOR-279999 |
P28482 | Q16690 | 0 | dephosphorylation | down-regulates | 0.781 | Here we demonstrate that dusp5, an inducible nuclear phosphatase, interacts specifically with erk2 via a kinase interaction motif (kim) within its amino-terminal noncatalytic domain. This binding determines the substrate specificity of dusp5 in vivo, as it inactivates erk2 but not jun n-terminal protein kinase or p38 map kinase. | SIGNOR-134049 |
P53396 | P42345 | 0 | phosphorylation | up-regulates activity | 0.332 | Biochemical studies indicated that mTOR directly and specifically phosphorylated ACL on Ser 455 in vitro. | SIGNOR-278962 |
P63096 | P08172 | 2 | binding | up-regulates activity | 0.511 | 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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256685 |
Q9H6S0 | P15336 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.275 | Collectively, these data show that YTHDC2 plays an important role in tumor cells growth and activation/recruitment of c-Jun and ATF-2 to the YTHDC2 promoter is necessary for the transcription of YTHDC2, and that HDAC activity is required for the efficient expression of YTHDC2 in both of hepatocyte and HCC cells. | SIGNOR-269001 |
O60729 | Q9NQR1 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.2 | The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis. | SIGNOR-248339 |
Q9ULT6 | Q13467 | 1 | ubiquitination | down-regulates quantity | 0.515 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260118 |
P43403 | Q96P31 | 2 | binding | up-regulates activity | 0.364 | Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2. | SIGNOR-274012 |
P50221 | P15863 | 2 | binding | up-regulates activity | 0.512 | We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family. | SIGNOR-222193 |
P28482 | P08047 | 1 | phosphorylation | up-regulates | 0.644 | Here we show that p42/p44 mapk directly phosphorylates sp1 on threonines 453 and 739 both in vitro and in vivo. Mutation of these sites to alanines decreases by half the mapk-dependent transcriptional activity of sp1. Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate sp1 on serine 59 and regulate cellular senescence via transcription of p21sdi1/cip1/waf1. | SIGNOR-116158 |
P17612 | Q9NRD9 | 1 | phosphorylation | up-regulates | 0.2 | We analyzed the duox1 phosphorylation state with an anti-rxx(ps/pt) antibody that could potentially recognize phosphorylation on ser955 and ser1217 but not on thr1007. duox1 but not duox2 activity is stimulated by forskolin (ec50 = 0.1 _m) via protein kinase a-mediated duox1 phosphorylation on serine 955. duox1 is positively regulated by the camp-dependent protein kinase a (pka)6 cascade | SIGNOR-183449 |
P68400 | P25490 | 1 | phosphorylation | up-regulates | 0.286 | More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis | SIGNOR-200083 |
O43921 | P29322 | 2 | binding | up-regulates | 0.75 | The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion. Therefore, eph receptors mediate signals that can override cell adhesion. | SIGNOR-52269 |
O95235 | P53350 | 0 | phosphorylation | up-regulates activity | 0.761 | MKlp2 treated with Plk1 did not form the regular microtubule bundles seen with MKlp2 only; many single microtubules were seen instead, and the bundles that were formed were loose parallel arrays rather than the dense bundles seen with untreated MKlp2.|We propose that phosphorylation of MKlp2 by Plk1 is necessary for the spatial restriction of Plk1 to the central spindle during anaphase and telophase, and the complex of these two proteins is required for cytokinesis. | SIGNOR-278201 |
P63096 | P61073 | 2 | binding | up-regulates activity | 0.561 | Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner | SIGNOR-278102 |
Q6UVJ0 | Q969U6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.536 | We identify the centriolar protein HsSAS-6 (refs 4,5) as a critical substrate of the SCF-FBXW5 complex. FBXW5 binds HsSAS-6 and promotes its ubiquitylation in vivo. |expression of the wild-type form of FBXW5 accelerated the degradation of HsSAS-6 to a half-life of less than two hours | SIGNOR-275478 |
O14965 | Q49MG5 | 1 | phosphorylation | up-regulates | 0.326 | Asap is a novel substrate of the oncogenic mitotic kinase aurora-a: phosphorylation on ser625 is essential to spindle formation and mitosis. | SIGNOR-158210 |
Q96PH1 | P00519 | 0 | phosphorylation | up-regulates activity | 0.303 | As shown in Fig. xref and c, c-Abl-phosphorylated NOX5 was mostly inhibited when c-Abl plasmid co-transfected with NOX5 Y476/Y478F mutant, then the NOX5 Y487F mutant, but not with NOX5 Y519F mutant.|Collectively, these results indicate that Pyk2 may act as a scaffolding protein for c-Abl stimulation of NOX5 activity in Pyk2 and NOX5 complex, and c-Abl-enhanced NOX5 activity is mainly dependent on phosphorylation of NOX5 Tyr 476/478 sites. | SIGNOR-280170 |
Q6VAB6 | P10398 | 2 | binding | up-regulates activity | 0.553 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273875 |
Q9NPG1 | Q9UBE8 | 2 | binding | up-regulates | 0.352 | Upon ligand binding, non-canonical wnt signaling controls tissue polarity and cell movement through the activation of rhoa, c-jun n-terminal kinase (jnk), and nemo-like kinase (nlk) signaling cascades. | SIGNOR-167862 |
Q9BXF3 | Q9UJQ4 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | SALL4 activates Cecr2 by directly binging to its promotor region and CECR2 in turn promotes reprogramming through forming a SMARCA1-contained chromatin remodeling complex with its DTT domain. | SIGNOR-263893 |
P04626 | Q92529 | 1 | relocalization | up-regulates | 0.549 | Erbb3 is characterized by a large number of binding sites for phosphatidylinositol-3-kinase (pi3k), while erbb2 has only few interaction partners with shc as the most frequent one. | SIGNOR-146855 |
P38398 | P24941 | 0 | phosphorylation | up-regulates | 0.677 | However, shrna-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated s phase cell-cycle arrest and the phosphorylation of a subset of atr/atm targets after dna damage. Loss of dna damage-induced checkpoint control was caused by a reduction in formation of brca1-containing foci. Mutation of brca1 at s1497 and s1189/s1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of brca1-containing foci. | SIGNOR-187607 |
Q06187 | O43516 | 1 | phosphorylation | up-regulates activity | 0.542 | Based on previous reports and the present data we suggest that Btk can induce WASP activation and also facilitates its subsequent inactivation through WIP phosphorylation.|We confirmed that Btk can indeed phosphorylate Y468 of baculovirus-generated human His-tagged WIP ( xref ), but that this is more difficult to show in cell extracts where WIP would be purified along with cellular WASP (). | SIGNOR-279801 |
P61586 | Q13459 | 0 | gtpase-activating protein | down-regulates activity | 0.774 | 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-260509 |
P35236 | P24723 | 0 | phosphorylation | up-regulates activity | 0.2 | HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient. | SIGNOR-276049 |
Q14680 | Q15910 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.329 | We observed a MELK-mediated increase of EZH2 S220 phosphorylation along with a concomitant loss of EZH2 K222 ubiquitination, suggesting a phosphorylation-dependent regulation of EZH2 ubiquitination. | SIGNOR-277480 |
P24394 | P35225 | 2 | binding | up-regulates activity | 0.896 | IL-4 and IL-13 have overlapping but distinct effects on MFs, dependent on a common IL-4R, with profound changes in the expression of a range of cellular proteins and functions broadly implicated in the regulation of inflammation and repair. | SIGNOR-249528 |
Q16539 | Q92945 | 1 | phosphorylation | down-regulates activity | 0.572 | KSRP, an important factor for AU-rich element (ARE)-directed mRNA decay, undergoes p38-dependent phosphorylation during muscle differentiation. 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-235856 |
P27361 | C9JLW8 | 1 | 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 by ERK, substitution of either S21 or T30 significantly reduced MCRIP1 phosphorylation | SIGNOR-264772 |
P32249 | P08754 | 2 | binding | up-regulates activity | 0.431 | 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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256858 |
Q96P68 | P50148 | 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- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257368 |
Q86YJ5 | P01880 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271542 |
P04626 | O60674 | 0 | phosphorylation | up-regulates activity | 0.623 | Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation. | SIGNOR-279197 |
P11387 | P00519 | 0 | phosphorylation | up-regulates activity | 0.399 | This study demonstrates that ABL1-dependent phosphorylation up-regulates topo I activity. The ABL1 SH3 domain bound directly to the N-terminal region of topo I. The results demonstrate that ABL1 phosphorylated topo I at Tyr268 in core subdomain II. | SIGNOR-260775 |
P61006 | Q9BXM7 | 0 | phosphorylation | down-regulates activity | 0.271 | For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8. | SIGNOR-260268 |
P48729 | P78362 | 1 | phosphorylation | up-regulates activity | 0.25 | Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. | SIGNOR-275460 |
Q12834 | Q9UBZ9 | 2 | binding | down-regulates quantity by destabilization | 0.273 | Here, we show that human REV1 undergoes proteosomal degradation mediated by the E3 ubiquitin ligase known as anaphase-promoting complex (APC). REV1 associates with APC. Overexpression of APC coactivator CDH1 or CDC20 promotes polyubiquitination and proteosomal degradation of REV1. | SIGNOR-272892 |
Q86TM6 | P05198 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | HRD1 overexpression also decreased the expression of eIF2alpha and p-eIF2alpha in HKC-8 cells.|HRD1 promoted eIF2alpha ubiquitylation and degradation, thereby providing a protective mechanism that suppressed tubular epithelial cell apoptosis. | SIGNOR-278671 |
O43524 | O15111 | 0 | phosphorylation | down-regulates | 0.572 | Ikappab kinase promotes tumorigenesis through inhibition of forkhead foxo3a. The tnf treatment of ht-29 cells increased ikk-dependent foxo3 ser644 phosphorylation. | SIGNOR-124203 |
O95837 | Q96G91 | 2 | binding | up-regulates activity | 0.385 | 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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257435 |
P46663 | P63096 | 2 | binding | up-regulates activity | 0.435 | 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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257036 |
O14929 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.2 | Together, these results indicate that AMPK phosphorylated DNMT1-Ser730, RBBP7-Ser314, and HAT1-Ser190|AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314 | SIGNOR-264782 |
P68400 | P10242 | 1 | phosphorylation | down-regulates activity | 0.34 | For c-Myb mutational analysis of the CKII phosphorylation sites showed altered steady state DNA binding. Replacing Ser-11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation constants. | SIGNOR-250918 |
Q9H4E7 | P61224 | 2 | binding | up-regulates activity | 0.2 | Mechanistic studies revealed that SLAT interacts, through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B). This interaction has been further shown to facilitate the interdependent recruitment of Rap1 and SLAT to the T cell immunological synapse upon TCR engagement. Furthermore, a SLAT mutant lacking its PH domain drastically inhibited LFA-1 activation and CD4(+) T cell adhesion. | SIGNOR-253366 |
P19086 | P08913 | 2 | binding | up-regulates activity | 0.503 | 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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257093 |
P40763 | P51813 | 0 | phosphorylation | up-regulates activity | 0.6 | BMX activates STAT3 in glioblastoma stem cells.|BMX has previously been identified as an activator of STAT3, and BMX can phosphorylate STAT3 in vitro. | SIGNOR-279497 |
P14598 | Q9NWZ3 | 0 | phosphorylation | up-regulates | 0.38 | Phosphorylation of the cytosolic factor p47phox is essential for activation of the nadph oxidase.We found that thr133, ser288 and thr356, targets for irak-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after lps stimulation. We conclude that irak-4 phosphorylates p47phox and regulates nadph oxidase activation after lps stimulation. | SIGNOR-152027 |
Q8NG68 | Q71U36 | 1 | tyrosination | down-regulates | 0.533 | Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization | SIGNOR-176912 |
P68400 | Q13541 | 1 | phosphorylation | down-regulates | 0.341 | Phosphorylation at s112 directly affects binding of 4e-bp1 to eif4e without influencing phosphorylation of other sites. | SIGNOR-98280 |
P63096 | P35367 | 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- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257050 |
P27694 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.2 | In this article, we found that Ser-135 and Thr-180 of RPA1 are directly phosphorylated by PAK1 in a DOCK7-Rac1/Cdc42-dependent manner.|We further explored the biological role of PAK1 in replication stress and found that depletion of PAK1 resulted in decreased RPA1 and RPA2 chromatin loading and RPA2 foci formation ( Figure 4I-K ) . | SIGNOR-279378 |
P01008 | P00734 | 1 | cleavage | down-regulates activity | 0.948 | Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1 | SIGNOR-264136 |
P48357 | Q06124 | 2 | binding | up-regulates activity | 0.471 | Because the long leptin receptor lacking tyrosine 985 exhibits a significantly reduced ability to activate ERK phosphorylation, this residue is at least in part mediating stimulation of the ERK pathway by ObRb. This residue binds SHP-2 and is required for tyrosine phosphorylation of SHP-2 | SIGNOR-263506 |
Q12986 | Q13310 | 2 | binding | up-regulates activity | 0.246 | We identifiednew protein partners of NFX1-123, including several cytoplasmic poly(A) binding proteins (PABPCs) thatinteracted with NFX1-123 through its N-terminal PAM2 motif. Central to our findings were our observations that PABPCs copurify with NFX1-123, that a PAM2 motif is present in NFX1, and this motif and the PABPCs are important in the enhancement of hTERT activity by NFX1-123. | SIGNOR-261051 |
O95150 | O95407 | 2 | binding | down-regulates | 0.709 | Tl1a, is a ligand for dr3 and decoy receptor tr6/dcr3. Tr6-fc protein antagonizes nf-kappab activation and apoptosis induced by tl1a | SIGNOR-116256 |
P49841 | P38936 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.4 | Glycogen synthase kinase 3beta phosphorylates p21waf1/cip1 for proteasomal degradation after uv irradiationhere, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (gsk-3beta) is required for its degradation in response to uv irradiation | SIGNOR-152941 |
Q05193 | P08247 | 2 | binding | up-regulates activity | 0.333 | The GTPase dynamin I is required for synaptic vesicle (SV) endocytosis. Our observation that dynamin binds to the SV protein synaptophysin in a Ca2+-dependent fashion suggested the possibility that a dynamin/synaptophysin complex functions in SV recycling. | SIGNOR-264119 |
P06493 | Q92574 | 1 | phosphorylation | down-regulates | 0.489 | Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin b.Cyclin-dependent kinase 1 phosphorylates hamartin at three sites, one of which (thr417) is in the hamartin-tuberin interaction domain. Tuberin interacts with phosphohamartin, and tuberin expression attenuates the phosphorylation of exogenous hamartin. Hamartin with alanine mutations in the three cyclin-dependent kinase 1 phosphorylation sites increased the inhibition of p70s6 kinase by the hamartin-tuberin complex | SIGNOR-118584 |
P55957 | P45983 | 0 | phosphorylation | up-regulates activity | 0.594 | (b) Phosphorylation of Bid at Thr59 by JNK1 and JNK2 (in vitro kinase assay). | SIGNOR-279076 |
Q14676 | P68400 | 0 | phosphorylation | up-regulates | 0.346 | The mdc1-nbs1 interaction occurs through a specific region (residues 200-420) of mdc1, which contains multiple consensus casein kinase 2 (ck2) phosphorylation sites. | SIGNOR-179887 |
P28702 | Q07869 | 2 | binding | up-regulates | 0.564 | Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology | SIGNOR-105448 |
O76064 | O95999 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.328 | Phosphorylated and ubiquitinated BCL10 is stabilized on the damage sites through binding to and presenting UBC13 to RNF168.|We thus concluded that BCL10 is ubiquitinated mainly with K63-linked ubiquitination by RNF8. | SIGNOR-278778 |
P35998 | Q05086 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.385 | Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits. | SIGNOR-265132 |
P49841 | P49716 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.384 | Phosphorylation of C/EBPdelta by GSK-3beta is required for its degradation by FBXW7alpha. | SIGNOR-279180 |
Q03113 | P21554 | 2 | binding | up-regulates activity | 0.358 | 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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257285 |
P01178 | P16519 | 0 | cleavage | down-regulates quantity | 0.265 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270328 |
Q9UN86 | Q13283 | 2 | binding | up-regulates activity | 0.459 | Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer. In this study, we examined the role of G3BP2, a close relative of G3BP1, in SG formation. Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. G3BP2 formed a homo-multimer and a hetero-multimer with G3BP1. Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli. | SIGNOR-260863 |
P50613 | Q01094 | 1 | phosphorylation | down-regulates | 0.493 | These results suggest that tfiih-mediated phosphorylation of e2f-1 plays a role in triggering e2f-1 degradation during s phase. here we show that the e2f-1 activation domain interacts with a kinase activity which phosphorylates two sites, ser403 and thr433, within the activation domain. | SIGNOR-69776 |
P28482 | Q07889 | 1 | phosphorylation | down-regulates activity | 0.714 | In this report, we describe the identification of five map kinase sites (s-1137, s-1167, s-1178, s-1193, and s-1197) on hsos1Replacing the MAP kinase phosphorylation sites with alanine residues results in an increase in the binding affinity of Grb2 to hSos1 | SIGNOR-235929 |
P41180 | P17252 | 0 | phosphorylation | down-regulates | 0.351 | Casr(t888) is a protein kinase c (pkc) phosphorylation site in the receptor's intracellular domain that has previously been identified as a critical negative regulator of casr downstream signaling in vitro, thus, casr(t888) represents a functionally important, inhibitory phosphorylation site that contributes to the control of pth secretion. | SIGNOR-170334 |
P01903 | Q5T0T0 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271411 |
P60953 | Q92502 | 0 | gtpase-activating protein | down-regulates activity | 0.511 | 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-260520 |
Q13153 | Q96IF1 | 1 | phosphorylation | up-regulates activity | 0.256 | The Rac effector PAK1 was also transiently activated upon cell-cell adhesion and directly phosphorylated Ajuba (Thr172). | SIGNOR-278449 |
Q5RD31 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.487 | 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.NFE2L2-mediated upregulation of NQO1 is implicated in promoting resistance to ferroptosis inducers, such as erastin and sorafenib, in HCC cells | SIGNOR-279860 |
Q14790 | Q9UKL3 | 2 | binding | up-regulates | 0.448 | The caspase-8-binding protein flice-associated huge protein (flash) would form a molecular complex with caspase-8, thereby presumably activating the mitochondrial apoptosis pathway by regulating caspase-8 activity. | SIGNOR-152473 |
Q9ULV1 | O75581 | 2 | binding | up-regulates activity | 0.649 | Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. | SIGNOR-258964 |
P49757 | Q8TBB1 | 0 | ubiquitination | down-regulates | 0.74 | Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation. | SIGNOR-112201 |
P18433 | P06241 | 1 | dephosphorylation | up-regulates | 0.658 | Ptpalpha is a more widely expressed transmembrane ptp that has been shown to regulate the src family kinases, src and fyn, and is also present in t cells. | SIGNOR-154796 |
P68400 | Q04724 | 1 | phosphorylation | up-regulates | 0.32 | These results suggest that ck2 phosphorylation of serine 239 of gro/tle1 is important for its function during neuronal differentiation. | SIGNOR-129026 |
P42684 | P46108 | 1 | phosphorylation | down-regulates | 0.695 | Abl2 kinase activity toward crk leads to increased phosphorylation of crk, inhibiting this cytoskeletal regulator by promoting intramolecular over intermolecular associations. | SIGNOR-136958 |
O15534 | Q9UKB1 | 0 | ubiquitination | down-regulates | 0.493 | We have found that per1 interacts with both _-trcp1 and _-trcp2 in a manner that depends on casein kinase 1 activity, and depletion of both _-trcp1 and _-trcp2 by rnai leads to dramatic stabilization of per1 | SIGNOR-137758 |
P67870 | Q9UGP8 | 1 | phosphorylation | up-regulates activity | 0.2 | Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62. | SIGNOR-265270 |
P29459 | P42701 | 2 | binding | up-regulates | 0.572 | Like il-12, il-23 binds to the il-12r subunit il-12rbeta1. | SIGNOR-87677 |
Q9BPU6 | P49841 | 0 | phosphorylation | up-regulates activity | 0.431 | The T516 phosphorylation was achieved by the glycogen synthase kinase-3beta (GSK-3beta), which can phosphorylate the wildtype protein but not the non-phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin-binding property of CRMP5. Therefore, CRMP5-induced growth inhibition is dependent on T516 phosphorylation through the GSK-3beta pathway. | SIGNOR-264835 |
Q92995 | P11441 | 1 | deubiquitination | up-regulates activity | 0.61 | USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding. | SIGNOR-272857 |
Q12913 | P07949 | 1 | dephosphorylation | down-regulates activity | 0.277 | The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.|PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels | SIGNOR-248701 |
O75840 | Q6PIJ6 | 2 | binding | up-regulates activity | 0.576 | Interaction between MoKA and KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and by coimmunoprecipitation of the proteins overexpressed in mammalian cells. Functional assays documented that MoKA is a KLF7 coactivator | SIGNOR-224621 |
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