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 |
|---|---|---|---|---|---|---|---|
Q03052 | P17096 | 2 | binding | up-regulates activity | 0.307 | Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibited an increased affinity for this AT-rich element. | SIGNOR-240155 |
P04637 | O14965 | 0 | phosphorylation | up-regulates activity | 0.778 | The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A | SIGNOR-120836 |
O60260 | P42345 | 0 | phosphorylation | down-regulates activity | 0.2 | MTOR phosphorylates PARK2 at Ser127 Through biochemical, mutational, and genetic studies, we identified PARK2 as a mTORC1 substrate. mTORC1 phosphorylates PARK2 at Ser127, which blocks its cellular ubiquitination activity, thereby hindering its tumor suppressor effect on eIF4B's stability. | SIGNOR-277586 |
P61244 | Q8IWI9 | 2 | binding | up-regulates activity | 0.57 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240261 |
P61088 | P16104 | 1 | ubiquitination | up-regulates | 0.2 | In an h2ax- and mdc1-dependent manner , rnf8/ubc13 complexes go to sites of dna damage through their fha domain and initiate the synthesis of k63 polyubiquitin chains on chromatin that recruit the brca1 a complex through the uim domains of rap80. | SIGNOR-159880 |
P49841 | P04150 | 1 | phosphorylation | down-regulates activity | 0.54 | We found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta [ ]Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB | SIGNOR-181541 |
Q6FI13 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265396 |
P21453 | P19086 | 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-257108 |
P10636 | Q13131 | 0 | phosphorylation | down-regulates activity | 0.2 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275439 |
Q96LB1 | O95837 | 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-257434 |
O60216 | Q6P1N0 | 2 | binding | up-regulates activity | 0.2 | Akt kinase-interacting protein 1 (Aki1)/Freud-1/CC2D1A is localized in the cytosol, nucleus, and centrosome. Aki1 plays distinct roles depending on its localization. | In the centrosome, it regulates spindle pole localization of the cohesin subunit Scc1, thereby mediating centriole cohesion during mitosis. | SIGNOR-268294 |
O75688 | O14920 | 1 | dephosphorylation | down-regulates activity | 0.404 | PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation|Overexpression of PPM1A or PPM1B results in dephosphorylation of IKKbeta at Ser177 and Ser181 and termination of IKKbeta-induced NF-kappaB activation. | SIGNOR-248343 |
O15327 | P31749 | 1 | dephosphorylation | down-regulates activity | 0.374 | Further, we show that INPP4B but not PTEN is able to reduce tyrosine phosphorylation of Akt1 and both the lipid and PTP activity of INPP4B likely contribute to the reduction of Akt1 phosphorylation.|Further, we show that INPP4B but not PTEN is able to reduce tyrosine phosphorylation of Akt1 and both the lipid and protein tyrosine phosphatase activity of INPP4B likely contribute to the reduction of Akt1 phosphorylation. | SIGNOR-277106 |
Q13330 | Q8NHY2 | 2 | binding | down-regulates quantity by destabilization | 0.2 | MTA1 destabilizes COP1 by promoting its autoubiquitination. in addition to polyubiquitination of its substrates, COP1 also catalyzes its autoubiquitination for degradation as a part of an autoregulatory mechanism | SIGNOR-271892 |
P28482 | Q13485 | 1 | phosphorylation | up-regulates | 0.511 | Phosphorylation of thr276 is shown to be important for tgf-?-Induced nuclear accumulation and, as a consequence, transcriptional activity of smad4. these results suggest that smad4 can be phosphorylated by erk2 at thr276. | SIGNOR-101660 |
P28335 | P19086 | 2 | binding | up-regulates activity | 0.253 | 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-257129 |
Q03405 | O95644 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Inducible podocyte-specific expression of constitutively active NFATc1 increased podocyte uPAR expression by binding to the Plaur gene promoter (encoding uPAR) in chromatin immunoprecipitation assays. | SIGNOR-253336 |
P10636 | P49841 | 0 | phosphorylation | down-regulates activity | 0.739 | We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235. | SIGNOR-249346 |
P20749 | Q6UUV7 | 2 | binding | up-regulates | 0.36 | The ankyrin repeat domain of bcl3 interacted with torc3 / we determined that bcl3 inhibited transcription from the htlv-1 ltr in a manner dependent on torc3 | SIGNOR-156950 |
Q6ZMI3 | Q12955 | 1 | relocalization | up-regulates quantity | 0.41 | Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin. | SIGNOR-266725 |
P49682 | O14625 | 2 | binding | up-regulates activity | 0.777 | The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells. | SIGNOR-260971 |
O60674 | Q6N021 | 1 | phosphorylation | up-regulates activity | 0.418 | Specifically, cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines 1939 and 1964. Phosphorylated TET2 interacts with the erythroid transcription factor KLF1, and this interaction with TET2 is increased upon exposure to erythropoietin. | SIGNOR-277289 |
P08754 | Q96G91 | 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-257173 |
P08581 | Q14289 | 1 | phosphorylation | up-regulates activity | 0.28 | In this study, using a protein array approach, we found that c-Met phosphorylates FAK and Pyk2 in medulloblastoma cells.|Our study shows for the first time that c-Met activates FAK and Pyk2 and that FAK and Pyk2 mediate the effects of c-Met in medulloblastoma. | SIGNOR-280040 |
P68104 | P15056 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.262 | Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. | SIGNOR-276404 |
P09471 | 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-257251 |
Q9NPH3 | Q01638 | 2 | binding | up-regulates activity | 0.504 | The initial step in IL-33 signal transduction is ligand-induced conformational changes in IL-33R, which facilitate recruitment of interleukin-1 receptor accessory protein (IL-1RAP). | SIGNOR-277715 |
P31749 | Q9P0U3 | 0 | desumoylation | down-regulates quantity by destabilization | 0.28 | Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity. | SIGNOR-252736 |
Q96EB6 | Q13131 | 0 | phosphorylation | down-regulates activity | 0.395 | Previous studies have reported that AMP-activated protein kinase phosphorylates and inactivates SIRT1, resulting in increased p53 acetylation in liver cancer [ xref , xref ]. | SIGNOR-280076 |
Q16695 | Q92831 | 0 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269621 |
O14757 | P24941 | 0 | phosphorylation | up-regulates | 0.554 | Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency | SIGNOR-175083 |
Q9Y2U5 | Q15208 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.402 | Our data suggest that Ser91 phosphorylation of STK38 by MEKK2 possibly blocks the interaction of calpain with STK38 or disrupts proper conformation for cleaving, thereby protecting STK38 from calpain-dependent degradation. | SIGNOR-279066 |
O95476 | P36894 | 2 | binding | up-regulates | 0.291 | We show that dullard promotes the ubiquitin-mediated proteosomal degradation of bmp receptors (bmprs). Dullard preferentially complexes with the bmp type ii receptor (bmprii) and partially colocalizes with the caveolin-1-positive compartment, suggesting that dullard promotes bmpr degradation via the lipid raft-caveolar pathway | SIGNOR-150998 |
Q13546 | Q9Y4K3 | 2 | binding | up-regulates activity | 0.66 | Collectively, TRIF forms a multiprotein signaling complex along with TRAF6, TRADD, Pellino-1 and RIP1 for the activation of TAK1, which in turn activates the NF-_B and MAPK pathways. | SIGNOR-216325 |
Q9BZS1 | P84022 | 0 | null | up-regulates | 0.523 | The TCR, IL-2R, and TbetaR must all be stimulated to induce Foxp3 + Tregs. Failure to engage any one of these receptors prevents the generation of Foxp3 + Tregs | SIGNOR-254363 |
P0DMV9 | P22413 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. | SIGNOR-252198 |
Q9UHW9 | Q9H4A3 | 0 | phosphorylation | down-regulates | 0.453 | We have attempted to identify kinases and phosphatases involved in the modulation of phosphorylation at kcc3 t991 and t1048. the wnk kinases and spak/osr1 are strong candidates for kcc3 regulatory kinases. | SIGNOR-187564 |
Q9P286 | P17844 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PAK5 promotes RNA helicase DDX5 sumoylation and miRNA-10b processing in a kinase-dependent manner in breast cancer|The increased expression levels of PAK5 and phospho-DDX5 threonine 69 are associated with metastasis and poor clinical outcomes of patients. PAK5 facilitates the phosphorylation-dependent sumoylation of DDX5 to stabilize DDX5. Both the phosphorylation and sumoylation of DDX5 enhance the formation of a DDX5/Drosha/DGCR8 complex, thus promoting microRNA-10b processing. | SIGNOR-275658 |
P51170 | O95180 | 2 | binding | up-regulates activity | 0.2 | This study describes the functional interaction between Cav3.2 calcium channels and the Epithelial Sodium Channel (ENaC). β- and γ-ENaC subunits could be co-immunoprecipitated with Cav3.2 calcium channels from brain lysates, dorsal horn and lumbar dorsal root ganglia. Αβγ-ENaC channels enhanced Cav3.2 calcium channel trafficking to the plasma membrane in tsA-201 cells. This effect was reciprocal such that Cav3.2 channel expression also enhanced β-ENaC trafficking to the cell surface. these findings reveal ENaC as an interactor and potential regulator of Cav3.2 calcium channels expressed in neuronal tissues. | SIGNOR-269274 |
Q96QU1 | Q8TDI7 | 2 | binding | up-regulates activity | 0.436 | Although several studies show that the tip links, composed of PCDH15 and CDH23, are required for normal mechanotransduction, it is unclear how they are coupled to the transduction machinery. Likewise, it has been demonstrated that the transmembrane channel-like proteins TMC1 and TMC2 are required for mechanosensitive responses in hair cells, but how they interact with other components of the mechanotransduction complex is not known. Here, we show that TMC1 and TMC2 can interact with PCDH15, thereby establishing a critical connection between the tip link and these putative components of the mechanotransduction channel in hair cells. | SIGNOR-262583 |
P53350 | O15392 | 1 | phosphorylation | up-regulates | 0.583 | Thus, we conclude that plk1-mediated phosphorylation of sur at ser20 is critical for accurate chromosome segregation|SUR (survivin) | SIGNOR-170460 |
Q99250 | P61328 | 2 | binding | down-regulates activity | 0.309 | 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-253428 |
Q8WYH8 | P24941 | 0 | phosphorylation | up-regulates quantity | 0.401 | We report that ING5 is phosphorylated in a cell cycle dependent manner by CDK2 at T152 (Figs 1 and 3). | SIGNOR-279447 |
P00519 | P42224 | 1 | phosphorylation | up-regulates activity | 0.343 | Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production. | SIGNOR-279491 |
P57078 | Q13490 | 0 | polyubiquitination | up-regulates activity | 0.355 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation. | SIGNOR-272708 |
P51812 | Q8IX03 | 1 | phosphorylation | up-regulates | 0.2 | Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2. | SIGNOR-203302 |
P38405 | P47900 | 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-256943 |
P19525 | P35568 | 1 | phosphorylation | down-regulates activity | 0.339 | First, PKR induces phosphorylation of IRS1 at Ser312 and suppresses tyrosine phosphorylation of IRS1, mediated by the insulin receptor substrates kinases, JNK and I\u03baB kinase.|These results suggest that PKR induces the inhibitory phosphorylation of IRS1 at Ser312 in HepG2 cells, thereby suppressing the phosphorylation at Tyr941. | SIGNOR-278310 |
Q8WVD3 | O75771 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.39 | RNF138 dependent ubiquitination of RAD51D and proteasome mediated degradation. | SIGNOR-278775 |
P43405 | P17252 | 1 | phosphorylation | up-regulates activity | 0.391 | We present evidence that Tyr-662 and Tyr-658 of PKCbetaI and PKCalpha, respectively, are phosphorylated by Syk in the membrane compartment of FcepsilonRI-stimulated mast cells. These phosphorylations require prior PKC autophosphorylation of the adjacent serine residues (Ser-661 and Ser-657, respectively) and generate a binding site for the SH2 domain of the adaptor protein Grb-2. | SIGNOR-246581 |
Q9P0V3 | P02786 | 2 | binding | down-regulates | 0.353 | Here, we report that ttp (sh3bp4), a sh3-containing protein, specifically regulates the internalization of the transferrin receptor (tfr). / overexpression of ttp specifically inhibits tfr internalization | SIGNOR-142840 |
Q8N531 | P29401 | 1 | ubiquitination | up-regulates activity | 0.2 | Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. | SIGNOR-277843 |
Q92793 | P16220 | 2 | binding | up-regulates | 0.941 | When overexpressed in serum-stimulated cells, akt/pkb potently induced ser-133 phosphorylation of creb and promoted recruitment of cbp. | SIGNOR-62260 |
Q9BX84 | Q96QT4 | 1 | phosphorylation | down-regulates quantity | 0.498 | We found TRPM6 and TRPM7 both autophosphorylate threonine residues, but only TRPM6 crossphosphorylates TRPM7, and not the reverse . | SIGNOR-279770 |
P21554 | P08754 | 2 | binding | up-regulates activity | 0.541 | 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-256867 |
P14316 | Q7Z5L9 | 2 | binding | up-regulates activity | 0.631 | We have identified two novel proteins that interact specifically with the C-terminal repression domain of Interferon Regulatory Factor-2 (IRF-2). These proteins, which we term IRF-2 binding proteins 1 and 2 (IRF-2BP1 and IRF-2BP2, the latter having two splicing isoforms, A and B), are nuclear proteins, and have the properties of IRF-2-dependent transcriptional co-repressors that can inhibit both enhancer-activated and basal transcription in a manner that is not dependent upon histone deacetylation. | SIGNOR-224073 |
P16144 | P17252 | 0 | phosphorylation | down-regulates | 0.531 | Egf stimulates a pkc-?-Dependent pathway that results in the phosphorylation of the ?4 Integrin subunit on serine residues and its redistribution to actin-rich structures together, these results highlight the importance of serine phosphorylation in regulating type ii hemidesmosome disassembly, implicate a cluster of serine residues within the connecting segment of ?4, and argue for a key role for pkc-? In regulating these structures | SIGNOR-124494 |
P22455 | P08620 | 2 | binding | up-regulates | 0.672 | Our results establish an fgf binding profile for fgfr-4 with afgf having the highest affinity, followed by k-fgf/hst-1 and bfgf. In addition, fgf-6 was found to bind to fgfr-4 in ligand competition experiments. Ligands binding to fgfr-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides. | SIGNOR-18567 |
Q14493 | P23527 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265379 |
Q05397 | Q9H9S0 | 1 | phosphorylation | up-regulates activity | 0.274 | In addition, FAK directly phosphorylates Nanog in a dose-dependent manner by in vitro kinase assay and in cancer cells in vivo. The site-directed mutagenesis of Nanog tyrosines, Y35F and Y174F, blocked phosphorylation and binding by FAK. | SIGNOR-276410 |
P98177 | P31751 | 0 | phosphorylation | down-regulates activity | 0.606 | FOXO4 transcription factor, also referred to AFX, contains three putative phosphorylation motif sites for protein kinase B (PKB), Thr32, Ser197, and Ser262, and it is proposed that phosphorylated FOXO4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression.[...]These results indicate that phosphorylation at Thr32 and Ser197 is indispensable, whereas that at Ser262 is not critical, for regulation of the nuclear localization and transcriptional activity of FOXO4 | SIGNOR-248055 |
Q8TF76 | P68431 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that phosphorylation of histone H3 threonine 3 (H3T3ph) by Haspin is necessary for CPC accumulation at centromeres and that the CPC subunit Survivin binds directly to H3T3ph. | SIGNOR-275428 |
Q13094 | P43403 | 0 | phosphorylation | up-regulates | 0.804 | Zap-70 phosphorylates slp-76 at specific sites that allow vav sh2 domain bindingwe also show by in vitro and in vivo analysis that two slp-76 pyesp motifs (y113 and y128) mediate binding, the first being more efficient. | SIGNOR-46859 |
Q9NRM7 | Q8NHZ8 | 1 | phosphorylation | up-regulates activity | 0.46 | LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C|Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C | SIGNOR-275474 |
P54274 | Q8TDX7 | 0 | phosphorylation | up-regulates activity | 0.342 | Using KR-TRF2 to induce telomeric DNA damage, we found that TRF1 degradation was also exacerbated when ATM was inhibited after damage induction (55.2% of mock treated cells) (XREF_FIG), indicating that the ATM signal pathway is required for Nek7 mediated TRF1 stabilization.|We show that Nek7 phosphorylates TRF1 at Ser114 and in turn maintains stability of the shelterin complex at telomeres. | SIGNOR-278447 |
Q96BR1 | Q14524 | 1 | phosphorylation | up-regulates activity | 0.275 | Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5 | SIGNOR-275767 |
Q92529 | Q15303 | 0 | relocalization | up-regulates | 0.497 | Like erbb1, erbb4 recruits grb2, shc and stat5. | SIGNOR-147850 |
P50461 | P23409 | 2 | binding | up-regulates activity | 0.446 | we found that nuclear MLP functions through a physical interaction with the muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin. we propose that it serves as a cofactor for the myogenic bHLH proteins by increasing their interaction with specific DNA regulatory elements. | SIGNOR-241096 |
P19388 | P13984 | 2 | binding | up-regulates activity | 0.921 | Direct Interaction Between the Subunit RAP30 of Transcription Factor IIF (TFIIF) and RNA Polymerase Subunit 5, Which Contributes to the Association Between TFIIF and RNA Polymerase II. we showed that RPB5 binds RAP30 but not RAP74 and associates to TFIIF through the binding to RAP30. | SIGNOR-261179 |
P10827 | P13631 | 2 | binding | up-regulates | 0.419 | We report that the retinoic acid receptors (rars), a distinct class of nuclear receptors, are also efficient heterodimer partners for trs. | SIGNOR-133246 |
Q13043 | P00519 | 2 | phosphorylation | down-regulates | 0.343 | Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3 | SIGNOR-181060 |
Q14004 | P24928 | 1 | phosphorylation | up-regulates activity | 0.541 | Together, these studies demonstrate the important, yet largely redundant, role for CDK12 and CDK13 for the regulation of POLII CTD phosphorylation at multiple residues, as well as the global role for both of these kinases in regulating POLII occupancy across the genome.|CDK12 and CDK13 are thus evolutionarily related and structurally similar kinases, and biochemical assays have demonstrated that both have POLII C-terminal domain (CTD) kinase activity and the ability to phosphorylate the Ser2 residue of the repetitive CTD heptad sequence | SIGNOR-273054 |
Q9Y4P1 | Q99942 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.405 | These results substantiate the notion that RNF5 negatively regulates ATG4B availability with concomitant effect on LC3 processing and autophagy under normal growth conditions.|These results suggest that RNF5 directly induces ATG4B ubiquitination. | SIGNOR-278664 |
P40763 | O60674 | 0 | phosphorylation | up-regulates activity | 0.818 | Activation of wild type stat3: il-6 treatment causes stat3 recruitment to receptor tyrosine phosphopeptides (gp130) where it is phosphorylated on tyrosine 705 (y) by jak kinase | SIGNOR-236463 |
P36897 | P61812 | 2 | binding | up-regulates | 0.745 | Tgf-? Signaling mediates a wide range of biological activities in development and disease. Tgf-? Ligands signal through heterodimeric type i and type ii receptors (tgf-? Receptor type i [t?RI, also known as alk5 and tgfbr1] and t?RII) that are members of the serine/threonine kinase family. | SIGNOR-196025 |
P49715 | P23771 | 2 | binding | down-regulates | 0.361 | Whereas others, such as GATA2/3 and SMAD3, physically interact with C/EBPα to inhibit its transcriptional activity on the Pparg2 promoter. | SIGNOR-250569 |
O75914 | Q9UM54 | 1 | phosphorylation | up-regulates activity | 0.336 | P21-activated kinase 3 phosphorylated myosin VI, and the site was identified as Thr(406). The phosphorylation of myosin VI significantly facilitated the actin-translocating activity of myosin VI. | SIGNOR-250244 |
P30679 | Q9UNW8 | 2 | binding | up-regulates activity | 0.402 | 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-257444 |
Q9UDY6 | P60484 | 1 | ubiquitination | down-regulates quantity | 0.2 | Collectively, these results indicate that TRIM10 may lead to ubiquitination and degradation of PTEN, which could be an underlying reason for AKT signalling inhibition in cardiac hypertrophy processes (Figure\u00a05D).4\n\nDISCUSSION.|In addition, we found that the effect regulated by TRIM10 was mediated by interactions with phosphatase and tensin homolog (PTEN); specifically, TRIM10 promoted PTEN ubiquitination, thus leading to AKT signalling activation.|The results showed that TRIM10 overexpression decreased PTEN expression, and MG132 reversed the reduction in PTEN (Figure\u00a05C). | SIGNOR-278729 |
Q01196 | Q13951 | 2 | binding | up-regulates quantity by stabilization | 0.848 | The RUNX genes encode the α subunit of the transcription factor PEBP2/CBF. The β subunit consists of the non-RUNX protein PEBP2β. We found that RUNX1/AML1, which is essential for hematopoiesis, is continuously subjected to proteolytic degradation mediated by the ubiquitin–proteasome pathway. When PEBP2β is present, however, the ubiquitylation of RUNX1 is abrogated and this causes a dramatic inhibition of RUNX1 proteolysis. | SIGNOR-255742 |
Q9Y5J3 | Q06330 | 2 | binding | down-regulates | 0.657 | These findings suggest a novel mechanism for negative feedback on notch signaling that requires rbp-jkappa to interact physically with hrt and hes. | SIGNOR-146687 |
O60542 | Q9GZZ7 | 2 | binding | up-regulates | 0.747 | Glial cell line-derived neurotrophic factor (gdnf) family ligands signal through receptor complex consisting of a glycosylphosphatidylinositol-linked gdnf family receptor (gfr) alpha subunit and the transmembrane receptor tyrosine kinase ret. | SIGNOR-85162 |
Q05655 | Q14896 | 1 | phosphorylation | up-regulates | 0.2 | The triple aspartic acid mutation shows greater distance between the two thick myosin filaments (affects the steric arrangement of the filament distances) in heart tissue. Mutation is cardioprotective during stress (ischemia-reprofusion injury) against apoptosis similar to isoproterenol treatment. | SIGNOR-150355 |
Q9GZV1 | P31751 | 0 | phosphorylation | up-regulates | 0.414 | In vitro and in vivo studies confirmed that akt phosphorylates ankrd2 at ser-99. moreover, the forced expression of a phosphorylation-defective mutant form of ankrd2 in c2c12 myoblasts promoted a faster differentiation program, implicating akt-dependent phosphorylation at ser-99 in the negative regulation of myogenesis in response to stress conditions. | SIGNOR-236978 |
O43148 | P06493 | 0 | phosphorylation | up-regulates activity | 0.255 | We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. | SIGNOR-265501 |
O00585 | Q9NPB9 | 2 | binding | up-regulates activity | 0.666 | In the present study, however, we demonstrate for the first time the concentration-dependent recruitment of β-arrestins to the atypical chemokine receptor CCX-CKR upon stimulation with CCL19, CCL21, or CCL25 using three different methodologies in various transfected cell lines. | SIGNOR-268417 |
Q9UI47 | P12830 | 1 | relocalization | up-regulates quantity | 0.567 | Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14 | SIGNOR-265492 |
P45452 | P02671 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain | SIGNOR-263613 |
P46531 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.32 | An in vitro kinase reaction demonstrated that T2132, S2136, and S2141 were CDK5\u2010phosphorylated sites in the Notch1 peptide (Figure\u00a02B, C, and D).|In conclusion, CDK5 positively regulates Notch1 function via phosphorylation, which in turn promotes cell proliferation and migration. | SIGNOR-279401 |
P45985 | Q16539 | 1 | phosphorylation | up-regulates activity | 0.591 | Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. | SIGNOR-34121 |
Q9NX09 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In conclusion, our work in cellular and animal models and in human samples strongly indicates that RTP801 is a substrate of parkin and that RTP801 elevation due to parkin loss of function in both AR-JP and sporadic Parkinson's disease may contribute to neurodegeneration.|We showed that parkin poly-ubiquitinates RTP801, both in vitro and in vivo. | SIGNOR-278560 |
O15264 | Q15139 | 1 | phosphorylation | down-regulates | 0.2 | P38delta catalyzes an inhibitory phosphorylation of pkd1, thereby attenuating stimulated insulin secretion. | SIGNOR-183280 |
P51956 | P51956 | 2 | phosphorylation | down-regulates activity | 0.2 | Autophosphorylation at Thr-165 is required for NEK3 kinase activity in vitro. | SIGNOR-260919 |
P14416 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.383 | These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling. | SIGNOR-259401 |
P46937 | P31749 | 0 | phosphorylation | down-regulates | 0.593 | One protein that associates with 14-3-3 in an akt-dependent manner is shown here to be the yes-associated protein (yap), which is phosphorylated by akt at serine 127, leading to binding to 14-3-3. Akt promotes yap localization to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73. | SIGNOR-252593 |
P00533 | P18031 | 2 | phosphorylation | up-regulates | 0.76 | After binding to egfr, ptp1b becomes tyrosine-phosphorylated at tyr-66 phosphorylation of ptp1b by egfr enhances its catalytic activity | SIGNOR-52950 |
P46937 | O00506 | 0 | phosphorylation | up-regulates activity | 0.265 | Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results. | SIGNOR-278993 |
P61244 | Q9BW11 | 2 | binding | up-regulates activity | 0.467 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240393 |
P48729 | P55957 | 1 | phosphorylation | up-regulates activity | 0.286 | Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid. | SIGNOR-250785 |
P41240 | P16284 | 1 | phosphorylation | up-regulates activity | 0.55 | We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances. | SIGNOR-262741 |
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