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 |
|---|---|---|---|---|---|---|---|
Q86UF1 | O14672 | 2 | binding | up-regulates activity | 0.483 | Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. | SIGNOR-261251 |
P50148 | Q9UBY5 | 2 | binding | up-regulates activity | 0.483 | 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-257297 |
P52803 | P29320 | 2 | binding | up-regulates | 0.943 | Highly promiscuous for ephrin-a ligands it binds preferentially efna5 and became active. | SIGNOR-52470 |
Q15154 | O00444 | 0 | phosphorylation | up-regulates activity | 0.573 | Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372. | SIGNOR-279556 |
Q01974 | Q9ULK5 | 1 | phosphorylation | down-regulates activity | 0.59 | In support of this, ror2 mutants abolish Vangl2 activity gradient and localization, and ror2; vangl2 double mutants phenocopy the wnt5a limb phenotype (Gao et al., 2011).4.6.|This process is mediated by its receptor Ror2, which in turn phosphorylates Vangl2 and induces asymmetric localization of Vangl2, propagating an activity gradient of Vangl2 in the proximal direction (Gao et al., 2011). | SIGNOR-280111 |
P42680 | P42680 | 2 | phosphorylation | up-regulates | 0.2 | Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated | SIGNOR-98098 |
Q9Y6X9 | Q9H0A0 | 2 | binding | up-regulates activity | 0.2 | MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1. | SIGNOR-273716 |
O43524 | P46527 | 1 | transcriptional regulation | up-regulates quantity | 0.747 | AFX transcriptionally activates p27kip1, resulting in increased protein levels. | SIGNOR-238610 |
P60484 | P10636 | 1 | dephosphorylation | up-regulates activity | 0.382 | Reduced phosphorylation of PTEN can dramatically increase tau phosphorylation and impair the ability of tau to bind to microtubules . | SIGNOR-277079 |
P63096 | P30939 | 2 | binding | up-regulates activity | 0.45 | 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-256673 |
P51812 | P06241 | 0 | phosphorylation | up-regulates | 0.326 | Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529. | SIGNOR-160048 |
P68400 | O43395 | 1 | phosphorylation | up-regulates | 0.2 | Our findings provide new insights into the biology of hprp3p and suggest that the loss of hprp3p phosphorylation at thr494 is a key step for initiating thr494met aberrant interactions within u4/u6 snrnp complex and that these are likely linked to the rp18 phenotype. | SIGNOR-158319 |
P15336 | Q8WYK2 | 2 | binding | down-regulates activity | 0.557 | JDP2 dimerizes with other AP-1 proteins such as activating transcription factor-2 (ATF2) and Jun to repress transcription from promoters that contain a cyclic AMP-responsive element (CRE). | SIGNOR-226395 |
P68400 | P49959 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1. The MRE11-PIH1D1 interaction is dependent on casein kinase 2 (CK2) phosphorylation of two acidic sequences within the MRE11 C terminus containing serines 558/561 and 688/689. | SIGNOR-265893 |
Q14012 | Q9UQL6 | 1 | phosphorylation | down-regulates | 0.419 | Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation. | SIGNOR-85022 |
P53350 | P11388 | 1 | phosphorylation | up-regulates | 0.481 | Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin | SIGNOR-182844 |
Q13501 | Q9BY78 | 0 | ubiquitination | up-regulates activity | 0.358 | SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors. | SIGNOR-269830 |
P08913 | P63096 | 2 | binding | up-regulates activity | 0.556 | 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-256698 |
P12931 | O14757 | 0 | phosphorylation | up-regulates activity | 0.338 | In this study, we show that Chk1 phosphorylates human Src at the newly identified site serine 51 to fully induce Src kinase activity. | SIGNOR-278332 |
P16403 | P78527 | 0 | phosphorylation | down-regulates activity | 0.2 | Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation. | SIGNOR-273834 |
O60675 | P35452 | 2 | binding | down-regulates activity | 0.377 | Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf. | SIGNOR-221929 |
Q9H3M7 | Q9NX09 | 2 | binding | up-regulates quantity by stabilization | 0.508 | In the present study, we identify TXNIP that inhibits mTOR activity by binding to and stabilizing Redd1 protein. | SIGNOR-277470 |
Q8IUD6 | O95786 | 1 | ubiquitination | up-regulates activity | 0.764 | Our data suggest that Riplet/RNF135 is a novel factor of the RIG-I pathway that is involved in the evoking of human innate immunity against RNA virus infection, and activates RIG-I through ubiquitination of its C-terminal region. | SIGNOR-265569 |
Q9UBR4 | Q92793 | 2 | binding | up-regulates activity | 0.2 | Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing hormone (TRH). P-Lim and CBP Act Synergistically in TRH Stimulation of the Human α-GSU Promoter. | SIGNOR-267206 |
P22891 | P38435 | 0 | carboxylation | up-regulates activity | 0.507 | Gamma-carboxylation is essential in the activation and proper functioning of multiple VK-dependent proteins (VKDP), the most well-known of which are involved in blood clotting, including coagulation factors (FII, FVII, FIX and FX) and natural anti-clotting agents (protein C, protein S (ProS; OMIM*176880) and protein Z | SIGNOR-265926 |
Q9NP31 | P06239 | 0 | phosphorylation | up-regulates activity | 0.578 | Here we mapped Lck phosphorylation and interaction sites on TSAd and evaluated their functional importance. The three C-terminal TSAd tyrosines Tyr(280), Tyr(290), and Tyr(305) were phosphorylated by Lck and functioned as docking sites for the Lck Src homology 2 (SH2) domain. Lck binds to TSAd prolines and phosphorylates and interacts with the three C-terminal TSAd tyrosines. We propose that through multivalent interactions with Lck, TSAd diverts Lck from phosphorylating other substrates, thus modulating its functional activity through substrate competition. | SIGNOR-262888 |
P42681 | P16410 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.498 | We demonstrate that rlk (resting lymphocyte kinase) is capable of phosphorylating ctla-4 at the yvkm motif. Consistent with this finding, rlk is capable of providing conditions for the binding of the sh2 domains of pi 3-kinase to the receptor. Ctla-4 is therefore the first known substrate for rlk suggesting the possibility that this kinase may participate in ctla-4 function | SIGNOR-61624 |
P54764 | P54764 | 2 | phosphorylation | up-regulates activity | 0.2 | Two dimensional phosphopeptide mapping and site-directed mutagenesis defined juxtamembrane residue Y602 as a major site of in vitro autophosphorylation in Sek, whilst Y596 was phosphorylated to a lower stoichiometry. | SIGNOR-251118 |
P01100 | Q15418 | 0 | phosphorylation | up-regulates activity | 0.529 | We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kda ribosomal s6 kinase (rsk) and mitogen-activated protein kinase (map kinase), contribute to the serum-induced phosphorylation of c-fos. The major phosphopeptides derived from biosynthetically labeled c-fos correspond to phosphopeptides generated after phosphorylation of c-fos in vitro with both rsk and map kinase. The phosphorylation sites identified for rsk (ser-362) and map kinase (ser-374) are in the transrepression domain. Cooperative phosphorylation at these sites by both enzymes was observed in vitro and reflected in vivo by the predominance of the peptide phosphorylated on both sites, as opposed to singly phosphorylated peptides. This study suggests a role for nuclear rsk and map kinase in modulating newly synthesized c-fos phosphorylation and downstream signaling. | SIGNOR-37154 |
Q01105 | Q9UBY8 | 2 | binding | down-regulates activity | 0.2 | CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8. | SIGNOR-265584 |
O60675 | O14867 | 2 | binding | up-regulates activity | 0.474 | Bach1 forms a heterodimer with the small Maf oncoproteins and binds to the Maf-recognition element (MARE) to inhibit target genes | SIGNOR-226409 |
Q9UL54 | Q13188 | 1 | phosphorylation | up-regulates | 0.274 | In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2. | SIGNOR-201327 |
Q14134 | P49137 | 0 | phosphorylation | up-regulates activity | 0.307 | ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC. | SIGNOR-273675 |
Q13043 | Q15208 | 1 | phosphorylation | up-regulates activity | 0.332 | Although MST1, MST2, and MST3 potently activated NDR1 in vitro, MST4 had only a minor effect.|Indeed, NDR1 phosphorylated at Thr444 by MST1 displayed greatly (7-fold) enhanced protein kinase activity. | SIGNOR-279641 |
P25105 | P50148 | 2 | binding | up-regulates activity | 0.437 | 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-257387 |
Q13535 | Q8WXE1 | 1 | phosphorylation | up-regulates | 0.878 | When dna is damaged, the atr-atrip complex is recruited to chromatin and is activated to transduce the checkpoint signal, but the precise kinase activation mechanism remains unknown. Here, we show that atrip is phosphorylated in an atr-dependent manner after genotoxic stimuli. The serine 68 and 72 residues are important for the phosphorylation in vivo and are required exclusively for direct modification by atr in vitro. | SIGNOR-129473 |
P20823 | P05019 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.301 | Growth hormone induces insulin-like growth factor-I gene transcription by a synergistic action of STAT5 and HNF-1α | SIGNOR-251720 |
P42772 | P11802 | 2 | binding | down-regulates | 0.879 | We present evidence that the different subcellular location of p15 and p27 ensures the prior access of p15 to cdk4. In the cell, p15 is localized mostly in the cytoplasm, whereas p27 is nuclear. p15 prevails over p27 or a p27 construct consisting of the cdk inhibitory domain tagged with a nuclear localization signal. However, when p15 and p27 are forced to reside in the same subcellular location, either the cytoplasm or the nucleus, p15 no longer prevents p27 from binding to cdk4. These properties allow p15 and p27 to coordinately inhibit cdk4 and cdk2. | SIGNOR-46758 |
Q9NRF2 | P43405 | 1 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK. | SIGNOR-268445 |
Q86WV6 | P0C6X7-PRO_0000037311 | 2 | binding | down-regulates activity | 0.2 | Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING | SIGNOR-260247 |
P53350 | Q96EP1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.468 | Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A. | SIGNOR-271464 |
P35222 | O96013 | 0 | phosphorylation | up-regulates | 0.286 | Pak4 interacts with and phosphorylates _-catenin on ser675, which promotes the tcf/lef transcriptional activity and stabilizes _-catenin through inhibition of its degradation. | SIGNOR-191557 |
Q8N4N8 | Q9Y448 | 0 | relocalization | down-regulates activity | 0.407 | The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation. | SIGNOR-252053 |
P28702 | P10826 | 2 | binding | up-regulates | 0.666 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins. | SIGNOR-16677 |
Q13233 | Q15796 | 1 | phosphorylation | up-regulates activity | 0.474 | As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity . | SIGNOR-279064 |
Q13315 | P16220 | 1 | phosphorylation | down-regulates | 0.522 | Individual ala substitutions at thr-100, ser-111, or ser-121 inhibited atm-catalyzed phosphate incorporationatm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp) | SIGNOR-124051 |
P20339 | Q15276 | 2 | binding | up-regulates | 0.928 | We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5. | SIGNOR-109352 |
Q15389 | Q03112 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266059 |
P49959 | Q9NRR5 | 2 | binding | up-regulates activity | 0.2 | These data suggest that MRE11 is one of probably many UBQLN4 interaction partners. >Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease | SIGNOR-265077 |
Q86YT6 | P54132 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.281 | BLM is Ubiquitinated by E3 Ligase MIB1.|Moreover, MIB1 mediated BLM degradation in G1 phase appears to be important for DNA double-strand break repair. | SIGNOR-278548 |
O75569 | P19525 | 0 | phosphorylation | up-regulates activity | 0.796 | In stressed cells, this activation occurs when PACT, a PKR-binding protein, is phosphorylated and activates PKR. | SIGNOR-280003 |
P55072 | Q92890 | 2 | binding | up-regulates activity | 0.2 | These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. VCP is thus likely to provide the energy required for extraction of CD4 from membranes. | SIGNOR-252424 |
Q96J02 | Q16621 | 1 | ubiquitination | down-regulates activity | 0.413 | Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination| Interestingly, Itch suppressed the transactivation activity of p45/NF-E2 by adding a Lys63-linked polyubiquitin chain. Confocal microscopy revealed that ubiquitinated p45/NF-E2 became localized in the cytoplasm when Itch was over-expressed. Thus, Itch-mediated ubiquitination of p45/NF-E2 does not target the protein for proteasomal degradation, but instead retains p45/NF-E2 in the cytoplasm, where it cannot function as a transactivator. | SIGNOR-275553 |
Q96CG3 | Q96QP1 | 0 | phosphorylation | up-regulates activity | 0.247 | The authors proposed that binding of ADP-Hep caused a conformational change exposing the catalytic cleft and allowing for ALPK1 to phosphorylate and activate TIFA leading to downstream NF-kB activation. | SIGNOR-279789 |
P28329 | P17252 | 0 | phosphorylation | up-regulates | 0.383 | We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation. | SIGNOR-129264 |
P06493 | Q9UNZ2 | 1 | phosphorylation | down-regulates activity | 0.325 | Now, we have found that p47, which mainly localizes to the nucleus during interphase, is phosphorylated on serine-140 by cdc2 at mitosis. The phosphorylated p47 does not bind to golgi membranes. | SIGNOR-102350 |
P62913 | O15350 | 2 | binding | up-regulates | 0.359 | We report that rpl5 and rpl11 can also enhance the transcriptional activity of a p53 homolog tap73 | SIGNOR-205514 |
P42336 | O95819 | 0 | phosphorylation | down-regulates activity | 0.2 | MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061 | SIGNOR-277921 |
Q13153 | P16949 | 1 | phosphorylation | down-regulates | 0.374 | The hgf-induced wave2 transport, lamellipodia formation, stathmin/op18 phosphorylation at ser38 and binding to kinesin-wave2 complex, but not stathmin/op18 phosphorylation at ser25 and microtubule growth, were abrogated by pak1 inhibitor ipa-3 | SIGNOR-183503 |
O60353 | O96014 | 2 | binding | up-regulates activity | 0.672 | Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors. | SIGNOR-141431 |
P68400 | O75379 | 1 | phosphorylation | up-regulates | 0.446 | The r-snare vamp4, which contains a dileucine motif, binds to the ap-1 or the ggas. Serine 20 and leucines 25,26 are essential for this binding. Ap-1 association with vamp4 is enhanced when serine 30 is phosphorylated by casein kinase 2. This phosphorylation-dependent modulation of ap-1 binding is mediated by pacs-1 (phosphofurin acidic cluster sorting protein). Ablation of both the dileucine motif and serine 30 results in a dramatic mislocalization of vamp4 in the regulated secretory pathway. | SIGNOR-119090 |
Q16539 | Q14765 | 1 | phosphorylation | up-regulates | 0.599 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154787 |
Q70Z35 | Q13153 | 0 | phosphorylation | down-regulates activity | 0.367 | P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. | SIGNOR-277181 |
Q9NP31 | O60469 | 2 | binding | up-regulates activity | 0.2 | Our findings now further suggest that STAT3 and the adaptor protein SH2D2A interact with tyrosine‐containing motifs within the DSCAM/L1 ICDs. The SH2 domains of both STAT3 and SH2D2A are known to bind to phosphorylated tyrosine residues in the context of such motifs. Thus, the interactions between DSCAMs and SH2‐domain containing proteins seem to play a central and conserved role in Dscam signaling in the context of dynamic changes of tyrosine‐phosphorylation levels. | SIGNOR-264279 |
Q9Y4K3 | P04637 | 1 | ubiquitination | up-regulates activity | 0.61 | Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK.|We mutated every conserved lysine (K) residue on p53 and found that TRAF6 preferentially ubiquitinates p53 at K24 in the in vivo ubiquitination assay (XREF_FIG, XREF_SUPPLEMENTARY, XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY). | SIGNOR-278728 |
P19367 | P12931 | 0 | phosphorylation | down-regulates activity | 0.492 | Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its K m and increases its V max by disrupting its dimer formation.|Mechanistically, c-Src-mediated Y732 phosphorylation disrupts HK1 dimer formation, alters its enzyme kinetics and eventually enhances enzymatic activity ( ). | SIGNOR-278209 |
Q9Y463 | Q96S59 | 2 | binding | down-regulates activity | 0.418 | Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M. | SIGNOR-238008 |
P10415 | P04637 | 2 | binding | down-regulates activity | 0.749 | Mechanistic insights into the mitochondrial function of wtp53 came when it was realized that mitochondrially translocated p53 interacts directly with members of the Bcl-2 family, which are central in governing the induction of mitochondrial outer membrane permeabilization. In response to stress, wtp53 interacts with and neutralizes the anti-apoptotic members Bcl-xL and Bcl-2. This interaction stimulates MOMP and subsequent apoptosis | SIGNOR-99712 |
O15169 | O14641 | 2 | binding | up-regulates activity | 0.669 | Dishevelled (dvl) transduces the wnt signal by interacting with the cytoplasmic axin complex. | SIGNOR-155221 |
Q6PIY7 | P22612 | 0 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259404 |
P68400 | Q15672 | 1 | phosphorylation | up-regulates | 0.2 | Further investigation revealed that il-6 stabilizes twist in scchn cell lines through casein kinase 2 (ck2) phosphorylation of twist residues s18 and s20, and that this phosphorylation inhibits degradation of twist. | SIGNOR-173668 |
Q5H8A4 | Q07326 | 2 | binding | up-regulates quantity by stabilization | 0.645 | We show that the human homolog of Gpi7p, termed hGPI7, binds to and is stabilized by PIG-F and that hGPI7 competes with PIG-O for binding to PIG-F. PIG-F Binds to and Stabilizes hGPI7 and PIG-O Independently. These results are consistent with the hypothesis that overexpression of hGPI7 decreases the biosynthetic activity of PIG-O by decreasing the available PIG-F, thereby destabilizing PIG-O. | SIGNOR-261358 |
Q96BY6 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.522 | 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-260549 |
P10721 | P27986 | 2 | binding | up-regulates activity | 0.727 | Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells | SIGNOR-255948 |
Q9BYV8 | Q16665 | 2 | binding | up-regulates activity | 0.2 | We performed these assays in HEK 293T cells and observed CEP41 binds HIF1α under both normoxic and hypoxic conditions. Of note, we found hypoxia induces more expression of HIF1α and increases its binding to CEP41 (Fig 8B and C). Hence, these results suggest CEP41 modulates the activation of HIF1α via a physical interaction | SIGNOR-269662 |
P29353 | P09619 | 0 | phosphorylation | up-regulates | 0.659 | In this study, we have characterized the interaction between the pdgf beta-receptor and shc. multiple autophosphorylation sites in the pdgf beta-receptor are responsible for the binding of shc. | SIGNOR-36906 |
P41236 | P19784 | 0 | phosphorylation | up-regulates activity | 0.307 | Recombinant wild-type I-2 and the Ala-120/121 mutant were phosphorylated synergistically by GSK-3 and casein kinase II. The Thr-72 and Ser-86 mutants, however, did not undergo this synergistic phosphorylation. Our studies indicate that Thr-72 is the only GSK-3 site and that Ser-86 is the casein kinase II site required for the potentiation of GSK-3 action. | SIGNOR-251021 |
P51608 | Q13224 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.35 | The interaction of MeCP2 with the 2BI3 and 2BI5 sites was strikingly reduced in neurons maintained in the presence of TTX (Fig. 2C). This result is consistent with the classical view of MeCP2 as a general transcriptional repressor, in that the reduced association leads to increased expression of NR2B. | SIGNOR-264685 |
O15530 | Q9BXL7 | 1 | phosphorylation | up-regulates | 0.55 | We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts. | SIGNOR-134866 |
P07948 | Q12972 | 1 | phosphorylation | down-regulates activity | 0.312 | Tyrosine phosphorylation of NIPP1 by Lyn was abolished by the Tyr-264 to Asp mutation. | SIGNOR-251405 |
O14640 | Q9Y283 | 0 | ubiquitination | down-regulates | 0.641 | Inversin inhibits the canonical wnt pathway by targeting cytoplasmic dishevelled (dsh or dvl1) for degradation | SIGNOR-135766 |
P38936 | P15172 | 0 | transcriptional regulation | up-regulates | 0.4 | P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells | SIGNOR-251574 |
Q5S007 | P53805 | 1 | phosphorylation | up-regulates activity | 0.371 | LRRK2 Directly Phosphorylates RCAN1. | SIGNOR-278340 |
P0DP25 | P16298 | 2 | binding | up-regulates | 0.576 | Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain. | SIGNOR-266338 |
P06241 | Q9H204 | 1 | phosphorylation | up-regulates | 0.446 | To unravel the cellular functions of magicin, we used a yeast two-hybrid system and identified fyn tyrosine kinase as a specific binding partner for magicin. Fyn phosphorylates magicin in vitro. | SIGNOR-148700 |
O43663 | Q02241 | 2 | binding | up-regulates activity | 0.572 | These data indicate that PRC1 binds to KIF4, MKLP1 and CENP-E during late mitosis; however, it apparently does not interact simultaneously with more than one of these motor proteins. | SIGNOR-265989 |
P46531 | P78536 | 0 | cleavage | up-regulates activity | 0.739 | ... here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to tace (tnfalpha-converting enzyme), a member of the adam (a disintegrin and metalloprotease domain) family of metalloproteases. | SIGNOR-78903 |
O60674 | Q9UGK3 | 1 | phosphorylation | up-regulates activity | 0.343 | To examine this possibility, STAP-2 was co-transfected with constitutively active tyrosine kinases in HEK-293 cells. STAP-2 was strongly phosphorylated by various tyrosine kinases, including v-Src (Fig.2 A-a), a JAK2 tyrosine kinase |On the other hand, the phosphorylation levels of Y22F, Y310F, and Y322F by GST-JH1 were reduced to 8060% of the levels of wild-type STAP-2, which suggests that these three are potential phosphorylation sites by activated JAK2. | SIGNOR-249372 |
A0PJZ3 | Q04721 | 2 | binding | up-regulates | 0.322 | We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum. | SIGNOR-177717 |
P06493 | Q13415 | 1 | phosphorylation | up-regulates | 0.637 | Horc1p contains three (s/t)px(k/r) consensus sites for cdk phosphorylation (ser258, ser273, and thr375). These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability. | SIGNOR-116329 |
Q13043 | P10275 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we showed that MST1 is an androgen receptor kinase and phosphorylates androgen receptor at Ser-650 ( ).|Mst1 plays a critical role in the regulation of programmed cell death and it has been implicated in PCa development. Interestingly, MST1 has been detected in AR-chromatin complexes, and forced expression of MST1 reduces AR binding to androgen-responsive elements along the PSA promoter. | SIGNOR-280143 |
Q9HCK8 | P35222 | 2 | binding | down-regulates | 0.644 | Duplin (axis duplication inhibitor) interacts with beta-catenin and prevents its binding to tcf, thereby inhibiting downstream wnt signaling | SIGNOR-128976 |
Q9NYV4 | P50613 | 0 | phosphorylation | up-regulates activity | 0.51 | Although Cdk12/CycK kinase complex lacking T-loop phosphorylation showed some basal activity towards a CTD substrate prephosphorylated at position Ser7, its activity was significantly increased upon coexpression with the CAK from S. cerevisiae (Supplementary Fig. 9a). Mutation of T893 to E to mimic phosphorylation showed no effect on basal kinase activity. Quantitative phosphorylation of a single residue occurred upon coexpression with Cak1, as determined by ESI mass spectrometry (Supplementary Fig. 9b). | SIGNOR-275509 |
P04637 | O43819 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.64 | P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway. | SIGNOR-267463 |
Q6SZW1 | P45983 | 0 | phosphorylation | down-regulates activity | 0.423 | C-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD+ cleavage activity to inhibit mitochondrial respiration|Here, we report that NAD+ cleavage activity of SARM1 is regulated by its own phosphorylation at serine 548. The phosphorylation of SARM1 was mediated by c-jun N-terminal kinase (JNK) under oxidative stress conditions, resulting in inhibition of mitochondrial respiration concomitant with enhanced activity of NAD+ cleavage. Nonphosphorylatable mutation of Ser-548 or treatment with a JNK inhibitor decreased SARM1 activity. | SIGNOR-275554 |
Q99527 | P00533 | 2 | binding | up-regulates | 0.389 | Gpcr-mediated transactivation of egfrs by estrogen provides a previously unappreciated mechanism of cross-talk between estrogen and serum growth factors, and explains prior data reporting the egf-like effects of estrogen | SIGNOR-115988 |
O14827 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.553 | 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-260573 |
Q86YT6 | Q16637 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.324 | The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein | SIGNOR-253112 |
Q86YF9 | P49841 | 0 | phosphorylation | up-regulates activity | 0.39 | Phosphorylation of Dzip1 by GSK3\u03b2 Promotes the Release of Rab8 GDP from GDI2. | SIGNOR-278251 |
P11441 | Q92995 | 0 | 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 |
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