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 |
|---|---|---|---|---|---|---|---|
P03372 | Q9NRW4 | 0 | dephosphorylation | down-regulates activity | 0.261 | These results strongly suggest that DUSP22 acts as a negative regulator of the ERalpha-mediated signaling pathway|whereas E2-induced phosphorylation and activation of ERalpha was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. | SIGNOR-248827 |
Q12778 | P31751 | 0 | phosphorylation | down-regulates activity | 0.658 | Our results demonstrate that pkb/akt directly phosphorylates fkhr1, a member of the closely related fkhr subclass of the forkhead family of transcription factors, on at least two residues (threonine-24 and serine-253). These results indicate that phosphorylation by pkbyakt negatively regulates fkhr1 by promoting export from the nucleus. | SIGNOR-68652 |
P49137 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.769 | Here we show that in vitro rk phosphorylates human gst-mapkap kinase-2 at thr25 in the proline-rich n-terminal region thr222 and ser272 in the catalytic domain and thr334 in the c-terminal domain. Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation | SIGNOR-44351 |
Q7KZF4 | Q99685 | 2 | binding | down-regulates quantity by destabilization | 0.2 | Interaction of SND1 with MGLL resulted in ubiquitination and proteosomal degradation of MGLL. We demonstrate that interaction of SND1 with MGLL results in increased ubiquitination and subsequent proteosomal degradation of MGLL. This down-regulation of MGLL is required for SND1 to exert its pro-tumorigenic activity because forced overexpression of MGLL markedly abrogates cell proliferation. | SIGNOR-259138 |
O43791 | P52945 | 1 | ubiquitination | down-regulates quantity | 0.326 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. | SIGNOR-268859 |
P01106 | P84022 | 2 | binding | down-regulates activity | 0.685 | Through its direct interaction with smads, c-myc binds to the sp1-smad complex on the promoter of the p15(ink4b) gene, thereby inhibiting the tgf-beta-induced transcriptional activity of sp1 and smad/sp1-dependent transcription of the p15(ink4b) gene. These results suggest that oncogenic c-myc promotes cell growth and cancer development partly by inhibiting the growth inhibitory functions of smads. | SIGNOR-114284 |
Q9Y5H9 | Q9Y5G0 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265692 |
P29590 | P27361 | 0 | phosphorylation | up-regulates | 0.339 | Phosphorylation of pml by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. | SIGNOR-124317 |
P16104 | Q13315 | 0 | phosphorylation | up-regulates | 0.2 | H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk. | SIGNOR-160206 |
Q15717 | P49137 | 0 | phosphorylation | up-regulates | 0.303 | Mk2 and mk3 participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating the are-binding proteins ttp and hur, and by regulating eef2k | SIGNOR-166622 |
Q9H1Y0 | Q13153 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Here, we identified USP13 as an essential deubiquitinase that stabilizes ATG5 in a process that depends on the PAK1 serine/threonine-protein kinase and which enhances autophagy and promotes IM resistance in GIST cells. |As PAK1-mediated phosphorylation at residue T101 protects ATG5 from ubiquitination-dependent degradation | SIGNOR-275835 |
P28482 | P09917 | 1 | phosphorylation | up-regulates activity | 0.381 | Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells. | SIGNOR-264409 |
P49736 | P24941 | 0 | phosphorylation | up-regulates | 0.735 | In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2 | SIGNOR-144000 |
P84022 | P01106 | 2 | transcriptional regulation | down-regulates quantity by repression | 0.685 | Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter. | SIGNOR-251494 |
P23769 | P31749 | 0 | phosphorylation | down-regulates | 0.524 | We show that insulin induces gata2 phosphorylation on serine 401 in a pi-3k/akt-dependent manner. Insulin-dependent phosphorylation of serine 401 impairs gata2 translocation to the nucleus and its dna binding activity | SIGNOR-135614 |
Q8TD08 | P67775 | 0 | dephosphorylation | down-regulates | 0.289 | Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20% | SIGNOR-142977 |
O43318 | Q15750 | 2 | phosphorylation | up-regulates activity | 0.929 | We identified amino acids (aa) 452/453 and 456/457 of TAB1 as novel sites phosphorylated by TAK1 as well as by p38 MAPK in intact cells as well as in vitro. | SIGNOR-276365 |
P01116 | P52306 | 2 | binding | up-regulates | 0.416 | Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob | SIGNOR-171415 |
Q13972 | O96017 | 0 | phosphorylation | down-regulates | 0.405 | During interphase, cdc25 is inhibited by ser287 phosphorylation (xenopus cdc25;ser 216 in human cdc25c) and this inhibitory phosphorylation is maintained by dna-responsive checkpoints / s287 is targeted by many kinases, including chk1, chk2, ctak-1, pka, p38 and mapkap kinase-2 suggesting that phosphorylation of this site may integrate multiple signaling inputs. | SIGNOR-150843 |
Q96QT4 | O00418 | 1 | phosphorylation | up-regulates activity | 0.314 | TRPM7 interacts with, and phosphorylates mouse eEF2-k at serine site 77 | SIGNOR-277923 |
Q15418 | Q96RK0 | 1 | phosphorylation | down-regulates | 0.2 | Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3) | SIGNOR-169883 |
Q9UBI6 | P31751 | 2 | binding | up-regulates | 0.412 | We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3b from its complex with axin, thereby relieving the inhibitory phosphorylation of b-catenin and activating its signaling pathway. | SIGNOR-141792 |
P32927 | Q06124 | 0 | dephosphorylation | up-regulates | 0.511 | Shp2 is thought to act as a positive mediator of growth factor signals.. Hp2 could act as an adaptor between the activated c and grb2, thus leading to activation of the ras/mitogen-activated protein kinase pathway, known to be activated by il-3 | SIGNOR-48557 |
Q9Y4K3 | Q01638 | 2 | binding | up-regulates activity | 0.594 | As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation. | SIGNOR-277707 |
O14818 | P17861 | 2 | binding | down-regulates quantity by destabilization | 0.317 | We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination. | SIGNOR-239042 |
Q9UPT6 | P45983 | 2 | binding | up-regulates | 0.722 | The c-jun nh2-terminal kinase (jnk)-interacting protein (jip) group of scaffold proteins (jip1, jip2, and jip3) can interact with components of the jnk signaling pathway and potently activate jnk. | SIGNOR-134558 |
P06400 | P15172 | 2 | binding | up-regulates | 0.394 | Cycline/cdk2 blocks myod-induced gene expression through the phosphorylation of rb, preventing rb from binding and transactivating myod, and triggering s phase entry instead of differentiation. | SIGNOR-176563 |
P63096 | P30559 | 2 | binding | up-regulates activity | 0.449 | OT binds to its cognate G protein–coupled receptor (OTR) and exerts diverse effects, including stimulation (Gs) or inhibition (Gi/o) of adenylyl cyclase, stimulation of potassium channel currents (Gi), and activation of phospholipase C (Gq). | SIGNOR-270330 |
Q96GD4 | O14777 | 1 | phosphorylation | down-regulates | 0.848 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant). | SIGNOR-165558 |
O14965 | Q9Y657 | 1 | phosphorylation | up-regulates activity | 0.243 | The Ser84 and Ser99 amino acids within SPINDLIN1 were further identified as the key functional sites in WNT/TCF-4 signaling activation. Mutation of these two sites of SPINDLIN1 abolished its effects on promoting WNT/TCF-4 signaling and cancer cell proliferation. We further found that Aurora-A could interact with and phosphorylate SPINDLIN1 at its key functional sites, Ser84 and Ser99, suggesting that phosphorylation of SPINDLIN1 is involved in its oncogenic function. | SIGNOR-273550 |
Q9NP58 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated. | SIGNOR-279864 |
P17655 | P55085 | 1 | cleavage | down-regulates activity | 0.298 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3 | SIGNOR-263581 |
P19532 | P11802 | 0 | phosphorylation | up-regulates activity | 0.2 | CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .|We found that CDK4 and CDK6 interact with and phosphorylate nuclear TFEB and TFE3, thereby promoting their shuttling to the cytoplasm. | SIGNOR-279514 |
P15559 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.487 | In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs). | SIGNOR-256275 |
P0C6X7-PRO_0000037311 | Q86WV6 | 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 |
O95837 | Q9NQ66 | 2 | binding | up-regulates activity | 0.468 | This suggests that both Gal4 and Gal6 can activate PLC b1. | SIGNOR-278119 |
Q96SL8 | O43186 | 2 | binding | down-regulates activity | 0.455 | Interaction of Fiz1 and NRL-leucine zipper was validated by GST pulldown assays and co-immunoprecipitation from bovine retinal nuclear extracts. Fiz1 suppressed NRL- but not CRX-mediated transactivation of rhodopsin promoter activity in transiently transfected CV1 cells. | SIGNOR-223799 |
P25963 | P42574 | 0 | cleavage | up-regulates quantity by stabilization | 0.422 | The cell-death protease cpp32 (caspase-3) in vitro specifically cleaved chicken and human ikappab-alpha at a conserved asp-ser sequence.Therefore, cleavage of I_B-_ by a CPP32-like protease could create what is sometimes called a super-repressor form of I_B-_ (20). That is, cleavage by CPP32 would block the ability of I_B-_ to undergo signal-induced degradation by removing the sites of signal-induced ubiquitination and by likely disrupting the ability of I_B-_ to become phosphorylated at critical Ser residues. | SIGNOR-51936 |
O75807 | P19484 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We found that the main regulator of the starvation-induced transcriptional program, TFEB, counteracts protein synthesis inhibition by directly activating expression of GADD34, a component of the protein phosphatase 1 complex that dephosphorylates eIF2α. | SIGNOR-276789 |
P23443 | Q8TB45 | 1 | phosphorylation | down-regulates | 0.66 | Deptor is phosphorylated by s6k1 and rsk1 on the degron serine residues upon serum stimulation s6k1/rsk1 and _trcp are required for ubiquitination and degradation of endogenous deptor upon mitogen stimulation. | SIGNOR-176866 |
P16220 | P31751 | 0 | phosphorylation | up-regulates | 0.514 | Creb is a nuclear target for activation via the growth factor-dependent ser/thr kinase akt/pkb. When overexpressed in serum-stimulated cells, akt/pkb potently induced ser-133 phosphorylation of creb and promoted recruitment of cbp. | SIGNOR-62253 |
P17252 | P06127 | 1 | phosphorylation | up-regulates | 0.339 | Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation. | SIGNOR-85179 |
P24941 | P06748 | 1 | phosphorylation | down-regulates activity | 0.561 | Both subtypes of B23 proteins were phosphorylated during mitosis by cyclin B/cdc2. The RNA binding activity of B23.1 was repressed through cyclin B/cdc2-mediated phosphorylation at specific sites in B23. Thus, the RNA binding activity of B23.1 is stringently modulated by its phosphorylation and subtype association. | SIGNOR-89609 |
Q99801 | Q13547 | 2 | binding | down-regulates activity | 0.369 | NKX3.1 also binds HDAC1 and releases p53 from p53-MDM2-HDAC1 complex, promoting p53 acetylation and activity. | SIGNOR-251549 |
P31749 | Q9UBK2 | 1 | phosphorylation | down-regulates activity | 0.447 | Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1alpha At ser570 Is required for akt to inhibit recruitment of pgc-1alpha To chromatin. | SIGNOR-252502 |
Q9UPG8 | Q8WUI4 | 0 | deacetylation | down-regulates | 0.258 | Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7. | SIGNOR-140953 |
O95409 | Q86T96 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.374 | Rinescan directly interact with Zic2. the ubiquitination of endogenous Zic2 was enhanced by Myc-Rines in rat neural stem cellline MNS70 cells. Rines-induced degradation of Zic2 | SIGNOR-226303 |
P41240 | Q00987 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that activated c-Src kinase phosphorylates Y281 and Y302 of Mdm2, resulting in an increase in Mdm2 stability and its association with Ubc12, the E2 enzyme of the neddylating complex. | SIGNOR-279163 |
O00192 | Q9UDY2 | 0 | relocalization | down-regulates activity | 0.369 | We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. ZO-2, in contrast, relocated to the nucleus with ARVCF, and, given the interaction between the ZO-2 PDZ domains and ARVCF, raised the possibility that ZO-2 may play a role in nuclear localization of ARVCF. Such a role for ZO-2 is indeed supported by the ability of the ZO-2 PDZ domain to efficiently relocate ARVCF from the plasma membrane to the nucleus in a process that required the ability of the two proteins to interact and the presence of a functional NLS in the ZO-2 PDZ domains. Thus, ZO-2 could be involved in nuclear translocation and/or retention of ARVCF and play a role in regulating postulated functions of ARVCF in gene expression | SIGNOR-252122 |
Q14980 | P53350 | 0 | phosphorylation | down-regulates activity | 0.534 | Phosphorylation of NuMA by Plk1 at 1833/34 residue can impact its cortical localization.|These data strongly suggest that Plk1 negatively regulate cortical NuMA localization and that this impact of Plk1 on NuMA is presumably independent of LGN, at least in the anaphase cells. | SIGNOR-279345 |
Q9ULZ2 | P10721 | 2 | binding | up-regulates activity | 0.507 | STAP-1 was tyrosine-phosphorylated by activated c-kit. An in vitro binding assay suggested that the STAP-1 SH2 domain interacted with several tyrosine-phosphorylated proteins including c-kit and STAT5. These suggest that STAP-1 functions as an adaptor molecule downstream of c-kit in hematopoietic stem cells. | SIGNOR-261822 |
P78415 | P17302 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.278 | Irx3 directly represses Cx43 transcription | SIGNOR-266044 |
Q01094 | Q92466 | 2 | binding | up-regulates | 0.367 | We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription | SIGNOR-54102 |
P04637 | P53779 | 0 | phosphorylation | up-regulates | 0.628 | The targets of jnk include the transcription factors p53. P75ntr-mediated apoptosis was shown to be dependent of p53 | SIGNOR-120552 |
P24394 | P05112 | 2 | binding | up-regulates | 0.942 | IL-4R Is a 140-kd protein that binds il-4 with high affinity | SIGNOR-100762 |
P00533 | Q96JA1 | 2 | binding | down-regulates | 0.736 | Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation | SIGNOR-127304 |
P06493 | P49459 | 1 | phosphorylation | up-regulates | 0.37 | Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity. | SIGNOR-116504 |
P27361 | P42702 | 1 | phosphorylation | down-regulates | 0.299 | Thus, our results identify the human lifr as a substrate for mapk and suggest a mechanism of heterologous receptor regulation of lifr signaling occurring at ser-1044. | SIGNOR-32757 |
Q7L7X3 | Q7KZI7 | 1 | phosphorylation | up-regulates activity | 0.414 | MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase. | SIGNOR-276164 |
P04628 | Q9H461 | 2 | binding | up-regulates | 0.725 | Wnt signaling is mediated by the frizzled (fz) family of seven-pass transmembrane receptors that bind wnt via the conserved amino-terminal cysteine-rich domain (crd) | SIGNOR-109250 |
Q00535 | P78352 | 1 | phosphorylation | down-regulates activity | 0.655 | Cdk5 was shown to phosphorylate PSD-95 at three sites, Thr19, Ser25, and Ser35, in PSD fractions, which reduces the ability of PSD-95 to multimerize, resulting in decreased NMDAR clustering (Table 2). | SIGNOR-279152 |
Q9NPG1 | O14905 | 2 | binding | up-regulates | 0.623 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132111 |
P14921 | P24821 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Ets1 are potent transactivators of the TN-C promoter. | SIGNOR-261599 |
P11362 | P28482 | 0 | phosphorylation | down-regulates | 0.309 | Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling | SIGNOR-200880 |
O43603 | P50148 | 2 | binding | up-regulates activity | 0.4 | 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-257020 |
Q9Y283 | O14640 | 1 | ubiquitination | down-regulates | 0.641 | Inversin inhibits the canonical wnt pathway by targeting cytoplasmic dishevelled (dsh or dvl1) for degradation | SIGNOR-135766 |
Q00535 | O60260 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation by cdk5 decreased the auto-ubiquitylation of parkin both in vitro and in vivo. | SIGNOR-153445 |
P01106 | P38936 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.779 | C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a | SIGNOR-102740 |
P08754 | P29275 | 2 | binding | up-regulates activity | 0.279 | 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-257152 |
P07900 | Q9HC29 | 2 | binding | up-regulates quantity by stabilization | 0.348 | Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation. | SIGNOR-252414 |
P01116 | P42336 | 2 | binding | up-regulates | 0.91 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k phosphatidylinositol 3-kinase (pi3k) is one of the main effector pathways of ras, regulating cell growth, cell cycle entry, cell survival, cytoskeleton reorganization, and metabolism. | SIGNOR-175204 |
Q9Y3C5 | Q9HAU4 | 2 | binding | up-regulates activity | 0.54 | RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome. | SIGNOR-272952 |
P45983 | Q13043 | 1 | phosphorylation | up-regulates | 0.268 | C-jun n-terminal kinase enhances mst1-mediated pro-apoptotic signaling through phosphorylation at serine 82. | SIGNOR-162327 |
A8MUP2 | O75390 | 1 | methylation | down-regulates activity | 0.2 | A mitochondrial matrix-located methyltransferase, methyltransferase-like protein 12 (METTL12), has been reported to methylate CS on the lysine 368 (K368) [15] and K395 residues [16] which are near the active site of CS. The methylation on K395 inhibits CS activity, which can be antagonized by its substrate oxaloacetate. | SIGNOR-267638 |
P43405 | Q92835 | 0 | dephosphorylation | down-regulates activity | 0.418 | An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. | SIGNOR-268456 |
O15530 | P51812 | 1 | phosphorylation | up-regulates | 0.655 | We characterize two monoclonal antibodies raised against phosphorylated forms of the n- and c-terminal domain of rsk2 (p-s227 and p-t577, respectively). Using these two antibodies, we show that stress signals, such as uv light, induce phosphorylation and activation of the three rsks. | SIGNOR-70612 |
Q9ULL1 | P06241 | 0 | phosphorylation | up-regulates activity | 0.2 | We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1 .|We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1. | SIGNOR-279988 |
Q14114 | Q8WY64 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.444 | Here we demonstrate that Idol also targets two closely related LDLR family members, VLDLR and ApoE receptor 2 (ApoER2), proteins implicated in both neuronal development and lipid metabolism. Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails, leading to their degradation. | SIGNOR-271486 |
Q15418 | P50552 | 1 | phosphorylation | down-regulates | 0.45 | Rsk1 phosphorylated vasp on t278, a site regulating its binding to actin. | SIGNOR-172899 |
P06748 | P24941 | 0 | phosphorylation | down-regulates activity | 0.561 | Both subtypes of B23 proteins were phosphorylated during mitosis by cyclin B/cdc2. The RNA binding activity of B23.1 was repressed through cyclin B/cdc2-mediated phosphorylation at specific sites in B23. Thus, the RNA binding activity of B23.1 is stringently modulated by its phosphorylation and subtype association. | SIGNOR-89609 |
Q9NZQ3 | P27361 | 0 | phosphorylation | up-regulates | 0.422 | Spin90 was phosphorylated by erk1, which was, itself, activated by cell adhesion and platelet-derived growth factor. Such phosphorylation of spin90 likely promotes the interaction of the spin90.betapix.wasp complex and nck | SIGNOR-118747 |
P00519 | O60234 | 1 | phosphorylation | down-regulates activity | 0.2 | Acetylcholine stimulation also increased GMF-γ phosphorylation at Tyr-104. GMF-γ phosphorylation at this residue was mediated by c-Abl tyrosine kinase. The GMF-γ mutant Y104F (phenylalanine substitution at Tyr-104) had higher association with Arp2 in HASM cells upon contractile activation.Furthermore, expression of mutant Y104F GMF-γ attenuated actin polymerization and contraction in smooth muscle. | SIGNOR-273536 |
Q13546 | O00429 | 1 | phosphorylation | up-regulates activity | 0.51 | RIPK1 also activates DRP1 by phosphorylating DRP1 at Ser616 in a RIPK3-dependent fashion independent of MLKL. | SIGNOR-280104 |
P12644 | P12644 | 2 | binding | up-regulates | 0.2 | Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is anabsolute requirement for the biological action and interaction with receptors | SIGNOR-236169 |
Q96GD4 | O43683 | 1 | phosphorylation | up-regulates activity | 0.749 | Although our analysis identified only one of the 15 sites implicated in Bub1-Mad1 interaction, it suggests that following its rapamycin-induced dimerization, Ipl1 phosphorylates Bub1, and potentially Mad1, to drive eSAC signaling. | SIGNOR-279010 |
P55040 | P0DP24 | 2 | binding | up-regulates activity | 0.2 | Inhibition of voltage-gated calcium channels by Gem requires GTP and calmodulin binding, but not phosphorylation of serine 261 or 289. Calmodulin binding in the C-terminal extension of Gem is required for maximal inhibition of HVA Ca2+ channels by ectopically expressed Gem, as determined by measurement of electrical activity in primary neurons and by Ca2+-evoked secretion in PC12 cells. | SIGNOR-266325 |
Q8IVT5 | P04049 | 2 | binding | up-regulates activity | 0.654 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273880 |
Q99856 | P78347 | 2 | binding | up-regulates activity | 0.35 | In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels. | SIGNOR-268533 |
O15297 | P46527 | 1 | dephosphorylation | down-regulates activity | 0.259 | Increased expression of wildtype WIP1 reduces stability of p27 Kip1 while increased expression of similar amounts of phosphatase-dead WIP1 has no effect on p27 Kip1 protein stability.|We demonstrate that wildtype, but not phosphatase-dead WIP1, efficiently dephosphorylates p27 Kip1 Ser140 both in vitro and in cells and that this dephosphorylation is sensitive to the WIP1 specific inhibitor GSK 2830371. | SIGNOR-277109 |
P03372 | P68400 | 0 | phosphorylation | down-regulates | 0.246 | Additionally protein kinase ck2 was identified as a kinase that phosphorylated eralpha at s282 and s559 s282 and s559 represent the second and third sites of er_ regulation by ck2. Remarkably, mutation of s282 or s559 to alanine resulted in near opposite functional effects on er_ as compared to mutation of s167 to alanine. Er_ ligand independent transcriptional activity was markedly enhanced upon mutation of s282 and s559 to alanine | SIGNOR-162653 |
Q9H853 | Q5SQI0 | 0 | acetylation | up-regulates quantity by stabilization | 0.2 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272252 |
P50148 | Q96G91 | 2 | binding | up-regulates activity | 0.385 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257386 |
Q96QB1 | Q15139 | 0 | phosphorylation | down-regulates | 0.371 | The tumor suppressor protein dlc1 is regulated by pkd-mediated gap domain phosphorylation.Our results thus show that pkd-mediated phosphorylation of dlc1 on serine 807 negatively regulates dlc1 cellular function. | SIGNOR-169994 |
Q86Y07 | Q96EV8 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We show that VRK2 phosphorylates Ser 297 and Ser 299 of dysbindin using in vitro kinase assay. In addition, we found that VRK2-mediated phosphorylation of dysbindin enhanced ubiquitination of dysbindin and consequently resulted in the decrease in its protein stability through western blotting. | SIGNOR-277403 |
P19174 | P29317 | 0 | phosphorylation | up-regulates activity | 0.276 | EphA2 activates PLC\u03b31 in human lung cancer cells.|The result here showed that only wild-type EphA2, but not K646M\nor Y588F mutants, could phosphorylate PLC\u03b31, demonstrating that\nPLC\u03b31 phosphorylation is dependent on the kinase activity of EphA2. | SIGNOR-279708 |
P06213 | P0DP25 | 1 | phosphorylation | down-regulates | 0.375 | The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-266336 |
Q86UT6 | Q7Z434 | 2 | binding | down-regulates activity | 0.753 | Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-beta promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Co-immunoprecipitation studies demonstrate that HA–NLRX1 interacts with MAVS but not with other known mitochondrial outer membrane proteins (BCL2 and BCL2L1), indicating specificity of the NLRX1–MAVS interaction. Finally, endogenous NLRX1 associates strongly with endogenous MAVS after immunoprecipitation with two different MAVS antibodies | SIGNOR-260357 |
P63096 | P35462 | 2 | binding | up-regulates activity | 0.548 | 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-256702 |
P04150 | Q03135 | 2 | binding | up-regulates | 0.38 | He mGR appears to reside in caveolae and its association with caveolin-1 (Cav-1) was clearly detected in two of the four cell lines investigated using double recognition proximity ligation assay. | SIGNOR-251683 |
P04049 | P01112 | 2 | binding | up-regulates | 0.935 | We have examined whether the other two members of the Raf family, A-Raf and B-Raf, are regulated in a similar way to Raf-1. A-Raf behaves like Raf-1, being weakly activated by oncogenic Ras more strongly activated by oncogenic Src, and these signals synergize to give maximal activation. B-Raf by contrast is strongly activated by oncogenic Ras alone and is not activated by oncogenic Src. | SIGNOR-235786 |
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