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 |
|---|---|---|---|---|---|---|---|
P00533 | Q13191 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.76 | Here we describe that overexpression of cbl-b, a homologue of the c-cbl protooncogene, inhibits EGFR-induced apoptosis in MDA-MB-468 breast cancer cells. Overexpression of cbl-b results in a shortened duration of EGFR activation upon EGF stimulation. This is demonstrated by decreased amounts of phosphorylated EGFR as well as by inhibition of multiple downstream signaling pathways. The inhibition of signaling by cbl-b results from increased ubiquitination and degradation of the activated EGFR. | SIGNOR-272934 |
Q02548 | P28482 | 0 | phosphorylation | down-regulates activity | 0.351 | In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5. | SIGNOR-269087 |
P06493 | Q9Y6Q9 | 1 | phosphorylation | down-regulates | 0.368 | We demonstrate that aib1 is phosphorylated on ser728 and ser867 by cdk1/cyclin b at the onset of mitosis and remains phosphorylated until exit from m phase. | SIGNOR-195233 |
Q13118 | P29597 | 0 | phosphorylation | down-regulates activity | 0.438 | These data strongly supported that Tyk2 phosphorylates TIEG1.|Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited TIEG1 nuclear translocation. | SIGNOR-279575 |
P21675 | P52655 | 1 | phosphorylation | up-regulates activity | 0.678 | Taf(ii) 250 phosphorylates human transcription factor iia on serine residues important for tbp binding and transcription activity. | SIGNOR-105688 |
Q99459 | O00311 | 0 | phosphorylation | down-regulates activity | 0.344 | During SPOC, Dbf4 binds to Cdc5 and promotes Cdc7-mediated phosphorylation of Cdc5, which then presumably prevents Cdc5 from recognizing its substrates in the MEN pathway . | SIGNOR-280203 |
Q92777 | P17612 | 0 | phosphorylation | down-regulates activity | 0.326 | Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I | SIGNOR-250059 |
Q12837 | Q8N100 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.474 | Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins. | SIGNOR-261567 |
P98170 | P57078 | 1 | polyubiquitination | up-regulates activity | 0.333 | In this study, we report that in addition to RIP1 and RIP2, also RIP3 and RIP4 directly interact with XIAP, cIAP1 and cIAP2. When comparing the ability of these IAPs to directly conjugate RIP1–RIP4 with ubiquitin chains, we found that cIAP1 was the most effective E3 and was capable of ubiquitinating all four RIPs in the presence of the E2 component UbcH5a. On the contrary, XIAP was only capable of inducing weak ubiquitination of RIP4. | SIGNOR-272716 |
P35236 | Q15139 | 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-276046 |
P05129 | Q5JVS0 | 1 | phosphorylation | down-regulates activity | 0.293 | We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation | SIGNOR-249255 |
Q9NS71 | A6NJ46 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.371 | In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter. | SIGNOR-266096 |
Q14721 | P12931 | 0 | phosphorylation | up-regulates | 0.479 | In the present study we show that an n-terminal tyrosine of kv2.1 (y124), which is a known target of src kinase, is critical for the apoptotic current surge..Kv2.1-mediated k+ currents are also enhanced during non-injurious conditions through direct phosphorylation of intracellular n-terminal residue tyrosine 124 (y124) by src kinase | SIGNOR-187201 |
P48730 | Q02880 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.CK1 binds with and phosphorylates TOP2β at Ser1130 to promote its degradation by VM-26. | SIGNOR-277509 |
O14939 | Q05397 | 0 | phosphorylation | up-regulates activity | 0.32 | The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. | SIGNOR-279480 |
Q9Y566 | O14490 | 0 | relocalization | up-regulates activity | 0.857 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264586 |
Q05086 | Q13200 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.277 | 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-265133 |
P21333 | P17612 | 0 | phosphorylation | up-regulates | 0.2 | Site-directed mutagenesis analysis indicated that serine 2152 is the unique substrate in the c-terminal region of abp for endogenously activated pka. | SIGNOR-126659 |
Q9UKV5 | O95140 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.3 | Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2. | SIGNOR-272887 |
O14490 | Q9BYB0 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264588 |
P10275 | O00762 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.397 | The evolution of prostate cancer from an androgen-dependent state (ADPCa) to one that is androgen-independent (AIPCa) marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in AIPCa is poorly understood. We have defined the direct AR-dependent target genes in both AIPCa and ADPCa by generating AR-dependent gene expression profiles and AR cistromes. In contrast to ADPCa, AR selectively up-regulates M-phase cell cycle genes in AIPCa including UBE2C, a gene that inactivates the M-phase checkpoint. | SIGNOR-251543 |
Q05209 | O60674 | 1 | dephosphorylation | down-regulates activity | 0.377 | PTP-PEST-Containing Lysates from EGF-Treated HC11 Cells Dephosphorylate JAK2 More Efficiently than Lysates from Control Cells|phospho-JAK2-specific rabbit polyclonal antiserum (44-426, BioSource Technologies, Inc., Camarillo, CA) which recognizes Tyr1007/1008 in the activation site | SIGNOR-248657 |
Q12778 | P31749 | 0 | phosphorylation | down-regulates activity | 0.87 | Here we show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular growth factors induces phosphorylation, nuclear export, and transcriptional inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24 and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated nuclear export. | SIGNOR-236163 |
Q5VWQ8 | P01111 | 1 | gtpase-activating protein | down-regulates activity | 0.494 | The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP. | SIGNOR-254747 |
P23327 | Q8IXL6 | 0 | phosphorylation | up-regulates activity | 0.404 | Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts.The pSer96-HRC binds tighter to triadin than S96A-HRC, which cannot be phosphorylated. Conversely, S96A-HRC or unphosphorylated Ser96-HRC binds tighter to SERCA2a. This suggests that Ser96-HRC phosphorylation (P) regulates HRC’s interactions with the major SR Ca-cycling proteins. | SIGNOR-273639 |
Q8WYQ5 | O94782 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277308 |
P05412 | O14640 | 2 | binding | up-regulates | 0.458 | In this study, we discovered two novel interactions between dvl and c-jun and between dvl and beta-catenin in the nucleus that mediate the formation of a dvlc-junbeta-catenintcf functional complex. | SIGNOR-178038 |
O15550 | Q01543 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260034 |
Q6J9G0 | Q14457 | 1 | phosphorylation | up-regulates activity | 0.2 | We also demonstrated that STYK1 elevated the serine phosphorylation of BECN1, thereby decreasing the interaction between BECN1 and BCL2. |The results indicated that the level of BECN1 S90 phosphorylation significantly increased after STYK1 overexpression, but not STYK1K147R mutant.|STYK1 promotes autophagy through enhancing the assembly of autophagy-specific class III phosphatidylinositol 3-kinase complex I | SIGNOR-264568 |
P63092 | P50406 | 2 | binding | up-regulates activity | 0.502 | 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-256801 |
Q04206 | P08047 | 2 | binding | up-regulates | 0.63 | Rela (p65) nf-kappab subunit interacts with the zinc finger dna-binding domain of sp1. | SIGNOR-75004 |
P52945 | P78426 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.503 | In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1. | SIGNOR-255542 |
P21917 | P08754 | 2 | binding | up-regulates activity | 0.448 | 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-256846 |
P30542 | P19086 | 2 | binding | up-regulates activity | 0.335 | 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-257092 |
Q13467 | Q92997 | 2 | binding | up-regulates activity | 0.641 | Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. | SIGNOR-258963 |
Q8NEL9 | P67775 | 0 | dephosphorylation | up-regulates activity | 0.2 | Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo.Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730. The results of two independent experiments with each type of assay indicated that the incubation caused a 50% loss of phospholipase activity (TableV). These results differed from those of corresponding incubation experiments with PA-PLA1α plus ERK2 and MgATP (see “Experimental Procedures”), which provided no evidence for complex formation or phosphorylation-dependent loss of phospholipase activity | SIGNOR-262975 |
P30405 | P48047 | 2 | binding | up-regulates activity | 0.2 | We here hypothesized that CypD phosphorylation on its residue S191 induces its translocation and binding to the OSCP to favor mPTP opening. | SIGNOR-264881 |
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 |
O00253 | P33032 | 2 | binding | down-regulates activity | 0.55 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268714 |
Q9NRS4 | P0DTC2 | 1 | cleavage | up-regulates activity | 0.2 | TMPRSS2 and TMPRSS4 serine proteases mediate this process by inducing cleavage of the S protein and enhancing membrane fusion. | SIGNOR-262306 |
P17676 | P37231 | 1 | transcriptional regulation | up-regulates quantity | 0.729 | Induction of C/EBP beta DNA-binding activity in NIH-3T3 beta 2 cells exposed to dexamethasone in the presence of insulin and fetal bovine serum activates the expression of an adipocyte-specific nuclear hormone receptor, PPAR gamma, that stimulates the conversion of these fibroblasts into committed preadipocytes | SIGNOR-255730 |
O95997 | P27361 | 0 | phosphorylation | up-regulates | 0.304 | Pttg is phosphorylated in vitro on ser(162) by map kinase and this phosphorylation site plays an essential role in pttg transactivation function. | SIGNOR-79519 |
P08254 | P16112 | 1 | cleavage | down-regulates quantity by destabilization | 0.738 | Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE374 | SIGNOR-266986 |
Q92963 | P15056 | 2 | binding | up-regulates activity | 0.55 | It is possible that RIT1 interacts with RAF1 and that gain-of-function mutations in RIT1 and RAF1 exert similar effects in heart development. | SIGNOR-251650 |
Q9BPV8 | 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-257027 |
Q92914 | P35499 | 2 | binding | down-regulates activity | 0.2 | 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-253434 |
Q8N3U4 | P53350 | 0 | dephosphorylation | down-regulates activity | 0.737 | Two phosphorylation sites in Scc1 (Thr144 and Thr312) match the consensus proposed by Nakajima et al. [24]. These two sites, in addition to one in Scc1 (Ser454) and three in SA2 (Thr1109, Ser1137, and Ser1224) conform with the consensus proposed by Barr et al. [25]. These findings are consistent with the possibility that at least some of the sites in Scc1 and SA2 are directly phosphorylated by Plk1.|Phosphorylation of SA2 Is Essential for the Dissociation of Cohesin from Chromosomes during Prophase and Prometaphase | SIGNOR-275534 |
P63092 | P43119 | 2 | binding | up-regulates activity | 0.53 | 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-256806 |
P06493 | P67870 | 1 | phosphorylation | up-regulates | 0.459 | In cells, the casein kinase ii beta-subunit is phosphorylated at an autophosphorylation site and at a site (ser-209) that is maximally phosphorylated in mitotic cells. These studies provide strong biochemical evidence that p34cdc2 is the enzyme that phosphorylates ser-209 on the beta-subunit of ckii in mitotic cells. | SIGNOR-29462 |
P45983 | O43561 | 1 | phosphorylation | down-regulates | 0.308 | Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.Mutational analysis revealed that t155 but not t94 or t140 is the site of jnk-mediated phosphorylation (figure 2b). Erk also phosphorylated lat at t155 (figure 2c), whereas p38, which was able to phosphorylate atf2, failed to induce threonine phosphorylation of lat (figure 2d). These results indicate that lat is directly phosphorylated by erk and jnk at the same site, t155. | SIGNOR-125774 |
O75122 | P46940 | 2 | binding | up-regulates activity | 0.416 | IQGAP1 is a novel CLASP2-interacting protein| nonphosphorylated CLASP2 on microtubules is allowed to associate with IQGAP1 for the coupling of microtubules to actin filaments at the front of migrating cells. | SIGNOR-264828 |
Q00534 | P30304 | 0 | dephosphorylation | up-regulates activity | 0.704 | Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs. | SIGNOR-267569 |
Q96P31 | P43405 | 2 | binding | up-regulates activity | 0.353 | 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-274011 |
P32248 | O00585 | 2 | binding | up-regulates | 0.786 | The regulated expression of the chemokine secondary lymphoid tissue chemokine (slc/ccl21) and its corresponding receptor, ccr7. | SIGNOR-117566 |
P28069 | Q92793 | 2 | binding | up-regulates activity | 0.381 | We and others have recently shown that CBP can constitutively bind to Pit-1 and synergistically activate transcription of promoters containing Pit-1 DNA-binding sites. | SIGNOR-267204 |
O95398 | P62834 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.71 | Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well. | SIGNOR-263956 |
P28482 | Q53EZ4 | 1 | phosphorylation | down-regulates | 0.367 | Upon mitotic entry, centrosome dissociation of cep55 is triggered by erk2/cdk1-dependent phosphorylation at s425 and s428. S425/428 phosphorylation is required for interaction with plk1, enabling phosphorylation of cep55 at s436. enabling it to relocate to the midbody to function in mitotic exit and cytokinesis. | SIGNOR-140890 |
P53396 | Q9H0H3 | 2 | binding | down-regulates quantity by destabilization | 0.344 | Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. | SIGNOR-272333 |
P51148 | Q15075 | 2 | binding | up-regulates activity | 0.829 | The Rab5 effector early endosome antigen 1 (EEA1) is a parallel coiled coil homodimer with an N-terminal C(2)H(2) Zn(2+) finger and a C-terminal FYVE domain. Rab5 binds to independent sites at the N and C terminus of EEA1.|The results demonstrate that the C(2)H(2) Zn(2+) finger is both essential and sufficient for the N-terminal interaction with Rab5. | SIGNOR-261266 |
P09874 | Q13535 | 0 | phosphorylation | down-regulates | 0.357 | Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity. | SIGNOR-278506 |
O00268 | P17544 | 2 | binding | down-regulates activity | 0.397 | These results not only demonstrate an interaction between ATF7 and TAF4 but also indicate, as in the case of TAF12 (see Figure 3e), that no additional cellular component is required for this binding. They also suggest that TAF4 may interfere with the formation of ATF7TAF12 subcomplexes, thereby inhibiting ATF7-induced transactivation. | SIGNOR-225300 |
P38405 | P46663 | 2 | binding | up-regulates activity | 0.25 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- 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-256907 |
P41002 | O43303 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.539 | Using a mode of substrate binding distinct from other F-box protein-substrate pairs, CP110 and Cyclin F physically associate on the centrioles during the G2 phase of the cell cycle, and CP110 is ubiquitylated by the SCF(Cyclin F) ubiquitin ligase complex, leading to its degradation. | SIGNOR-266364 |
P16520 | Q99835 | 2 | binding | up-regulates | 0.2 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling as pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp | SIGNOR-199180 |
Q9HBX9 | P04090 | 2 | binding | up-regulates | 0.76 | Lgr7 and lgr8, are capable of mediating the action of relaxin through an adenosine 3',5'-monophosphate (camp)-dependent pathway | SIGNOR-114549 |
Q9NY65 | Q8NG68 | 0 | tyrosination | down-regulates | 0.31 | 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-176930 |
P05549 | P68400 | 0 | phosphorylation | up-regulates | 0.307 | Ck2 phosphorylates ap-2_ and increases its transcriptional activity | SIGNOR-175130 |
P23443 | P67775 | 0 | dephosphorylation | down-regulates | 0.72 | Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells | SIGNOR-23575 |
P19174 | Q06187 | 0 | phosphorylation | up-regulates activity | 0.581 | Then, BTK and ITK are activated by Src kinases and proceed to phosphorylate the lipase PLCgamma2 / PLCgamma1, which cleaves PIP2 in the plasma membrane and generates the secondary messengers IP3 and DAG. | SIGNOR-279444 |
Q05209 | P42768 | 1 | dephosphorylation | down-regulates | 0.444 | Furthermore, we demonstrate that pstpip serves as a scaffold protein between ptp-pest and wasp and allows ptp-pest to dephosphorylate wasp. This finding suggests a possible mechanism for ptp-pest to directly modulate actin remodeling through the pstpip-wasp interaction. | SIGNOR-121136 |
Q14694 | Q14457 | 2 | deubiquitination | up-regulates quantity by stabilization | 0.509 | Similarly, the overexpression of USP13 reduced the levels of ubiquitinated Beclin1 which was inhibited by spautin-1 (Figure 4E) | SIGNOR-260299 |
P12931 | Q8IXJ6 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.291 | In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104. | SIGNOR-263104 |
O75197 | P56704 | 2 | binding | up-regulates activity | 0.699 | Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.All the frizzled genes studied have | SIGNOR-169657 |
P35568 | Q6ZMU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.477 | Here, we demonstrate that MG53 induces IRS-1 ubiquitination with the help of the E2 enzyme UBE2H during skeletal myogenesis by examining MG53 disrupted skeletal muscle cells and tissues.|The IRS-1 protein level was decreased by MG53 in a concentration dependent manner and was restored by the addition of MG132, a proteasome inhibitor (XREF_FIG; XREF_SUPPLEMENTARY). | SIGNOR-278520 |
P28335 | P09471 | 2 | binding | up-regulates activity | 0.296 | 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-257013 |
P04049 | Q14738 | 2 | binding | up-regulates activity | 0.449 | ... the PP2A holoenzymes ABC and ABC act downstream of Ras and upstream of MEK1 to promote activation of this MAPK signaling cascade. Furthermore both PP2A holoenzymes were found to associate with Raf1 and catalyze dephosphorylation of inhibitory phospho-Ser-259. | SIGNOR-243420 |
Q13526 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | Pka and pkc readily phosphorylated pin1 and its ww domain in summary, we have demonstrated that phosphorylation of the pin1 ww domain on ser16 regulates its ability to function as a pser/thr-binding module. |To examine the importance of Ser16 of Pin1, it was mutated to Glu to mimic pSer, and the mutant Pin1S16E failed to bind mitotic phosphoproteins | SIGNOR-112164 |
P50148 | Q06187 | 2 | binding | up-regulates activity | 0.35 | AlF− 4-activated Gaq-GDP increased Btk activity as expected, whereas AlF− 4 alone had no stimulatory effect (Table 1), so we conclude that Gaq directly stimulates Btk kinase activity | SIGNOR-278083 |
Q96I25 | P21127 | 0 | phosphorylation | up-regulates activity | 0.207 | However, Clk1 enhanced SPF45 protein expression, but not mRNA expression, whereas inhibition of Clk1 increased SPF45 degradation through a proteasome dependent pathway.|In the present work, we show that Clk1 phosphorylates SPF45 in vitro on eight serine residues, all of which are N-terminal to the RRM domain required for splicing. | SIGNOR-279510 |
P60953 | Q5JSP0 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.648 | 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-260553 |
P10644 | P17612 | 2 | binding | down-regulates activity | 0.886 | Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets | SIGNOR-258751 |
Q969P5 | P15172 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.56 | Here we present evidence that mafbx targets myod for degradation in several models of skeletal muscle atrophy. | SIGNOR-184861 |
P23443 | Q53EL6 | 1 | phosphorylation | down-regulates | 0.614 | Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation. | SIGNOR-150144 |
P14373 | Q9UJ55 | 2 | binding | up-regulates activity | 0.52 | MAGE proteins are a family of proteins that contain a conserved domain known as the MAGE homology domain. Recently, we showed that MAGE proteins function biochemically to bind to and enhance the activity of E3 RING ubiquitin ligases. The E3 RING ubiquitin ligase TRIM27 was identified as a major binding partner of MAGE-L2. | SIGNOR-253513 |
O95644 | P17252 | 0 | phosphorylation | down-regulates activity | 0.384 | Protein kinase A negatively modulates the nuclear accumulation of NF-ATc1. | Here we show that overexpression of PKA causes phosphorylation and cytoplasmic accumulation of NF-ATc1 in direct opposition to calcineurin by phosphorylating Ser-245, Ser-269, and Ser-294 in the conserved serine-proline repeat domain, and that mutation of these serines blocks the effect of PKA. Activation of endogenous PKA is similarly able to promote phosphorylation of these sites on NF-ATc1 in two lymphoid cell lines. | SIGNOR-249175 |
Q00535 | P00519 | 0 | phosphorylation | up-regulates activity | 0.585 | Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity. | SIGNOR-245288 |
P15172 | Q92793 | 0 | acetylation | up-regulates | 0.616 | Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo. | SIGNOR-81050 |
Q53ET0 | P16220 | 2 | binding | up-regulates activity | 0.912 | The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting | SIGNOR-256102 |
O96017 | P62380 | 1 | phosphorylation | down-regulates activity | 0.291 | In vitro, TRF2 was phosphorylated by recombinant Chk2 ( Figure\u00a04 C) on residues located in the first 350 aa ( Figure\u00a0S11 ).|To evaluate whether Chk2 activity affected the binding of TRF2 for telomeric TTAGGG repeats in duplex DNA, electrophoretic mobility shift assays (EMSA) were performed in the presence of ATP to allow phosphorylation and found that in contrast to Chk2 KD, Chk2 WT decreased the binding of TRF2 to DNA. | SIGNOR-280227 |
P68400 | P49321 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. | SIGNOR-273627 |
P43034 | Q9GZM8 | 2 | binding | up-regulates activity | 0.843 | We demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL. LIS1 is required for the proper distribution of NUDEL and cellular components regulated by CDHC function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex | SIGNOR-252157 |
Q16611 | Q07820 | 2 | binding | down-regulates | 0.625 | Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax | SIGNOR-149774 |
P62873 | Q9NPG1 | 2 | binding | up-regulates | 0.385 | In the non-canonical wnt signalling pathway, frizzled uses galphaq or galphai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat. | SIGNOR-152600 |
Q9NYA1 | Q14192 | 2 | binding | down-regulates activity | 0.424 | FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1. | SIGNOR-237775 |
P46527 | Q00536 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.333 | In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells.|Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target. | SIGNOR-273016 |
P40763 | P08631 | 0 | phosphorylation | up-regulates activity | 0.618 | Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain. Direct Phosphorylation of STAT3 on Tyr-705 by Src Family Kinases | SIGNOR-251267 |
Q9Y252 | P53667 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.432 | Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. | SIGNOR-271481 |
Q8NFZ3 | P58401 | 2 | binding | up-regulates activity | 0.2 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264158 |
Q9NRC8 | Q96LA8 | 0 | methylation | down-regulates activity | 0.259 | Protein arginine methyltransferase 6 (PRMT6) directly interacts with and methylates SIRT7 at R388 in vitro and in vivo R388 methylation suppresses the H3K18 deacetylase activity of SIRT7 without modulating its subcellular localization. | SIGNOR-275888 |
P49336 | Q01094 | 1 | phosphorylation | down-regulates | 0.483 | E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1. | SIGNOR-181078 |
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