IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 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 |
|---|---|---|---|---|---|---|---|
P51608 | Q13451 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.306 | These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress. | SIGNOR-264542 |
P12931 | Q9Y613 | 1 | phosphorylation | up-regulates activity | 0.306 | Our results show that only Src can efficiently phosphorylate FHOD1 at Y99 to enable the downstream activation by ROCK. | SIGNOR-276612 |
P40763 | P53350 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.306 | Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3. | SIGNOR-271690 |
Q13535 | Q9Y2K6 | 1 | phosphorylation | down-regulates activity | 0.306 | On the other hand, USP20 is phosphorylated by ATR, which disrupts the interaction between USP20 and HERC2, resulting in USP20 stabilization.|USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation. | SIGNOR-278393 |
P49683 | P09471 | 1 | binding | up-regulates activity | 0.306 | 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-256973 |
Q8NFU7 | P31269 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.306 | Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9. | SIGNOR-259094 |
P54821 | Q9Y5Q3 | 1 | binding | down-regulates activity | 0.306 | 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-221899 |
P12931 | Q9Y446 | 1 | phosphorylation | up-regulates activity | 0.306 | We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS. | SIGNOR-273807 |
P43026 | Q9UHF7 | 1 | relocalization | up-regulates activity | 0.306 | Treatment of cells with Gdf5 enhanced Trps1 protein levels and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner. Nuclear translocation of Trps1 was also induced by Gdf5. These effects were blocked by a dominant negative form of activin-linked kinase 6 (dn-Alk6) and by SB203580, an inhibitor of the p38 MAPK pathway. Conversely, Gdf5 expression was suppressed by the over-expression of Trps1. | SIGNOR-251867 |
P43250 | P08069 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.306 | GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation | SIGNOR-276412 |
P49841 | P20929 | 1 | phosphorylation | down-regulates | 0.306 | Gsk3b is able to phosphorylate nebulin at two ser sites in the c-terminal region of nebulin localized to the z-disk, thus preventing the interaction of nebulin with neuronal wiscott-aldrich syndrome protein (nwasp), a ubiquitously expressed member of the wasp family, which is involved in actin assembly. | SIGNOR-175659 |
Q13464 | O43293 | 1 | phosphorylation | up-regulates activity | 0.306 | ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes. | SIGNOR-279102 |
P50553 | O94907 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.306 | We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. | SIGNOR-245885 |
Q15118 | P05106 | 1 | phosphorylation | down-regulates activity | 0.306 | PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3. | SIGNOR-250264 |
Q13882 | P35222 | 1 | phosphorylation | down-regulates quantity | 0.305 | PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo. | SIGNOR-278289 |
Q13627 | A8MYZ6 | 1 | phosphorylation | down-regulates | 0.305 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity | SIGNOR-183680 |
P68400 | Q13428 | 1 | phosphorylation | up-regulates activity | 0.305 | Phosphorylated Thr 210 in Treacle is the major interaction site for NBS1|A purified GST fragment of this region was efficiently phosphorylated by CK2 in vitro (Supplementary Fig. 4; T-2) and this fragment pulled down the MRN complex from Hela nuclear extracts only when previously phosphorylated by CK2 | SIGNOR-265086 |
P05121 | P00748 | 1 | binding | down-regulates activity | 0.305 | C1INH is a serine protease inhibitor (serpin) that acts on both the complement pathway and the contact system and is the main inhibitor of the contact system by targeting both FXIIa and PK 9. Additionally, FXIIa can be inhibited by α1‐antitrypsin and plasminogen activator inhibitor‐1 (PAI‐1). | SIGNOR-263516 |
P28482 | Q02447 | 1 | phosphorylation | up-regulates | 0.305 | Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. in the inducible cell lines, expression of wild-type form of sp3 increases vegf production whereas the s73a form has a reduced potential reflecting its lower transcriptional activity. | SIGNOR-157272 |
Q15831 | P46937 | 1 | phosphorylation | down-regulates activity | 0.305 | LKB1 induces phosphorylation of Yap, leading to Yap nuclear exclusion and ultimately its degradation.|These data indicated that LKB1 expression inhibits Yes-associated protein transcriptional function. | SIGNOR-280139 |
P15036 | P09486 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.305 | Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin | SIGNOR-259874 |
Q14012 | P46527 | 1 | phosphorylation | up-regulates activity | 0.305 | We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia. | SIGNOR-261194 |
P07900 | Q8NFG4 | 1 | binding | up-regulates quantity by stabilization | 0.305 | Here we show that the stability of the tumour suppressor folliculin (FLCN) depends on the chaperone function of Hsp90. | SIGNOR-256505 |
Q8NFP9 | P46531 | 1 | binding | down-regulates activity | 0.305 | Yeast two-hybrid identified the Notch1 intracellular domain as a physical interactor of the PBW domain and a role for NBEA as a negative regulator in Notch-mediated transcription was demonstrated.|Defining novel interaction partners of conserved NBEA domain modules identified a role for NBEA as transcriptional regulator in the nucleus. The physical interaction of NBEA with NOTCH1 is most relevant for ASD pathogenesis because NOTCH signaling is essential for neural development. | SIGNOR-266010 |
P10275 | P06850 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.305 | A direct androgenic involvement in the expression of human corticotropin-releasing hormone|A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. | SIGNOR-268723 |
P00519 | Q96MU7 | 1 | phosphorylation | down-regulates | 0.305 | We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites. | SIGNOR-125167 |
P51149 | Q96Q42 | 1 | binding | down-regulates activity | 0.305 | The absence of active Rab7 prolongs ALS2presence and Rab5 activation on macropinosomes, indicating that activeRab7 is necessary for Rab5 inactivation through ALS2 dissociation and playskey roles in the Rab switch on macropinosomes. Taken together, active Rab7is necessary for Rab5 down-regulation through ALS2dissociation, thereby acting as a central component inthe Rab5-to-Rab7 switch in macropinocytosis | SIGNOR-277778 |
P17612 | O00418 | 1 | phosphorylation | up-regulates activity | 0.305 | EEF-2K can be phosphorylated in vitro by cAMP-dependent protein kinase (PKA) and that this induces significant Ca(2+)/calmodulin (CaM)-independent eEF-2K activity. sites of phosphorylation were Ser-365 and Ser-499 | SIGNOR-250354 |
Q13464 | P48436 | 1 | phosphorylation | up-regulates | 0.305 | Rho kinase-dependent activation of sox9 in chondrocytes. In vitro, rock directly phosphorylated sox9 at ser(181), and the overexpression of rock or the activation of the rhoa pathway in sw1353 chondrosarcoma cells increased sox9(ser181) phosphorylation | SIGNOR-162643 |
Q9UQ88 | P21127 | 1 | phosphorylation | up-regulates | 0.305 | Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58) | SIGNOR-169628 |
Q00535 | Q05397 | 1 | phosphorylation | up-regulates | 0.305 | Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo. | SIGNOR-86223 |
O00141 | P19634 | 1 | phosphorylation | up-regulates activity | 0.304 | Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment. | SIGNOR-280123 |
Q16584 | Q13153 | 1 | phosphorylation | up-regulates activity | 0.304 | Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3.|MLK3 was able to directly phosphorylate PAK1 on two Serine residues of which Ser204 is critical for MLK3-induced PAK1 activation and downstream functions. | SIGNOR-279418 |
O95819 | Q16584 | 1 | phosphorylation | up-regulates activity | 0.304 | The MAP4K4 and MLK3 associates with each other, and MAP4K4 phosphorylates MLK3 on Thr738 and increases MLK3 kinase activity and downstream signaling. | SIGNOR-277571 |
Q12913 | P06213 | 1 | dephosphorylation | down-regulates | 0.304 | Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta. | SIGNOR-21295 |
P43378 | P04626 | 1 | dephosphorylation | down-regulates activity | 0.304 | Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells. | SIGNOR-277170 |
O43353 | Q13568 | 1 | phosphorylation | up-regulates | 0.304 | Activation of interferon regulatory factor 5 by site specific phosphorylation. Phosphorylation of carboxyl serines 451 and 462 appear the primary trigger of irf5 function in nuclear accumulation, transcription, and apoptosis. Rip2 activation of the irf5 aspartic acid substitutions showed a similar positive effect of s451d and s462d function in this assay | SIGNOR-196524 |
P07947 | Q969T9 | 1 | phosphorylation | up-regulates activity | 0.304 | Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα. | SIGNOR-273582 |
O15119 | P38936 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.304 | TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS | SIGNOR-249602 |
Q13627 | O43597 | 1 | phosphorylation | down-regulates | 0.304 | We identify dyrk1a as one of the protein kinases of sprouty2. We show that dyrk1a interacts with and regulates the phosphorylation status of sprouty2. Moreover, we identify thr75 on sprouty2 as a dyrk1a phosphorylation site in vitro and in vivo. | SIGNOR-179828 |
Q14CS0 | O14965 | 1 | binding | down-regulates activity | 0.304 | The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts | SIGNOR-265042 |
P28482 | Q15672 | 1 | phosphorylation | up-regulates | 0.304 | We identified the serine 68 (s68) as a major phosphorylation site of twist1 by mass spectrometry and with specific antibodies. This s68 is phosphorylated by p38, jnk and erk1/2 in vitro, and its phosphorylation levels positively correlate with twist1 protein levels in hek293 and breast cancer cells. | SIGNOR-173401 |
Q96PU5 | P43004 | 1 | ubiquitination | down-regulates quantity | 0.304 | Our results confirm that Nedd4-2 knockdown in MPTP treated mice increased GLT-1 expression at the membrane protein level (XREF_FIG; P < 0.01).|These results suggest that Nedd4-2 mediates the ubiquitination of both GLT-1 and GLAST in the midbrain in MPTP treated mice, and Nedd4-2 maybe a potential target in regulating glutamate transporters in PD. | SIGNOR-278706 |
P23759 | O14686 | 1 | binding | up-regulates | 0.304 | Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5. | SIGNOR-198629 |
P23443 | Q05195 | 1 | phosphorylation | down-regulates | 0.304 | Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway, which in turn promotes the transcriptional activity of myc. | SIGNOR-178590 |
Q16539 | Q16584 | 1 | phosphorylation | down-regulates | 0.304 | Jnk and p38 mapk activation have antagonistic effects in many cases. From a mechanicistic point of view, the p38 mapk pathway can negatively regulate jnk activity at the level of map3ks, either by phosphorylating mlk3 or the tak1 regulatory subunit tab2 | SIGNOR-166605 |
P27361 | O95997 | 1 | 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 |
Q7Z6Z7 | Q92858 | 1 | ubiquitination | down-regulates quantity | 0.304 | Huwe1 ubiquitinates and degrades Atoh1, and robustly affects development of GNPs that express this transcription factor [ xref ].|This provides further evidence that phosphorylation of Atoh1 affects Huwe1-mediated degradation, and demonstrates that Huwe1 inhibits Atoh1 to affect cellular differentiation in multiple cell types. | SIGNOR-278693 |
P27361 | O43561 | 1 | phosphorylation | down-regulates | 0.304 | 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. | SIGNOR-125770 |
Q08999 | Q92878 | 1 | binding | up-regulates activity | 0.304 | We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells. | SIGNOR-265029 |
Q8IYT8 | P54646 | 1 | phosphorylation | down-regulates | 0.304 | We could prove that ulk1-mediated phosphorylation of ampk reduced its level of phosphorylation at t172 of the _-subunit and hence interferes with its catalytic activity. I | SIGNOR-173089 |
O96017 | Q99459 | 1 | phosphorylation | down-regulates activity | 0.304 | Remarkably, however, the activation of the DDC triggers a Rad53-dependent phosphorylation of Cdc5 that inhibits the polo-like kinase, thus favoring Cdh1 activity and subsequently also restraining spindle elongation and anaphase progression [34,54] (Figure 1). | SIGNOR-279694 |
Q676U5 | P53675 | 1 | binding | up-regulates | 0.304 | Clathrin heavy-chain interacts with atg16l1, and is involved in the formation of atg16l1-positive early autophagosome precursors | SIGNOR-166705 |
P28066 | P17861 | 1 | binding | down-regulates quantity by destabilization | 0.304 | 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-239213 |
P09619 | P42684 | 2 | phosphorylation | up-regulates activity | 0.303 | PDGFRβ directly phosphorylates multiple novel sites on the N-terminal half of Abl2, including Y116, Y139, and Y161 within the Src homology 3 domain, and Y299, Y303, and Y310 on the kinase domain.We also found that PDGFRβ-mediated phosphorylation of Abl2 in vitro activates Abl2 kinase activity, but mutation of these four tyrosines (Y116, Y161, Y272, and Y310) to phenylalanine abrogated PDGFRβ-mediated activation of Abl2. | SIGNOR-277303 |
P31749 | P29375 | 1 | phosphorylation | up-regulates activity | 0.303 | We immunoprecipitated ectopically expressed wild-type KDM5A or KDM5Amut5A and performed an in vitro kinase assay using recombinant AKT1 in the presence or absence of AKT inhibition.Wild-type KDM5A is phosphorylated by AKT1 and this modification is sensitive to AKT inhibition, whereas KDM5Amut5A is not phosphorylated in the presence of AKT1 (Figure 3C).These results suggest that AKT-mediated KDM5A phosphorylation enhances KDM5A promoter recruitment. | SIGNOR-274062 |
Q8WY54 | Q13153 | 1 | dephosphorylation | down-regulates activity | 0.303 | The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family|POPX Can Dephosphorylate and Downregulate PAK| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX. | SIGNOR-248761 |
P67775 | Q9H0H5 | 1 | dephosphorylation | down-regulates | 0.303 | We report here that (i) mgcracgap is phosphorylated by aurora b and cdk1, (ii) pp2a dephosphorylates aurora b and cdk1 phosphorylated sites and (iii) inhibition of pp2a abrogates mgcracgap/ect2 interaction. Therefore, pp2a may regulate cytokinesis by dephosphorylating mgcracgap and its interacting partners. | SIGNOR-160398 |
Q04759 | Q5JVS0 | 1 | phosphorylation | down-regulates activity | 0.303 | 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-249256 |
Q9UNE7 | Q01860 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.303 | CHIP overexpression decreased OCT4 stability through proteasomal degradation.|CHIP E3 ligase ubiquitinates OCT4 at lysine 284.|These data suggest that CHIP induces OCT4 ubiquitination and degradation. | SIGNOR-278562 |
Q13490 | Q86VP3 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.303 | Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. | SIGNOR-272851 |
P62633 | P01106 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.303 | These data verified that the binding of CNBP with c-myc promoter G-quadruplex can indeed down-regulate its associated gene expression for a certain period of time. This result with human CNBP is somehow consistent with previous reports that c-myc G-quadruplex serves as a silencer of c-myc transcription [7] and CNBP promotes the formation of c-myc G-quadruplex. | SIGNOR-261571 |
Q13315 | O15355 | 2 | phosphorylation | up-regulates activity | 0.303 | ATM indeed mediated PPM1G phosphorylation at S183, and mutation of this residue (S183A) abrogated detection with the phospho-specific antibody | SIGNOR-255591 |
P05771 | P04004 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.303 | Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin. | SIGNOR-248963 |
Q05397 | Q9NZN5 | 1 | phosphorylation | up-regulates activity | 0.303 | These results suggest that LARG is phosphorylated on tyrosine by FAK after stimulation with RGMa. | SIGNOR-279310 |
Q96KB5 | P45983 | 1 | phosphorylation | up-regulates activity | 0.303 | Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo. | SIGNOR-280061 |
P00519 | Q96PH1 | 1 | phosphorylation | up-regulates activity | 0.303 | As shown in Fig. xref and c, c-Abl-phosphorylated NOX5 was mostly inhibited when c-Abl plasmid co-transfected with NOX5 Y476/Y478F mutant, then the NOX5 Y487F mutant, but not with NOX5 Y519F mutant.|Collectively, these results indicate that Pyk2 may act as a scaffolding protein for c-Abl stimulation of NOX5 activity in Pyk2 and NOX5 complex, and c-Abl-enhanced NOX5 activity is mainly dependent on phosphorylation of NOX5 Tyr 476/478 sites. | SIGNOR-280170 |
P24941 | Q96T88 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.303 | UHRF1 is phosphorylated by CDK2/cyclin A. In vitro kinase assay was performed with CDK2/cyclin A using recombinant wild-type UHRF1 or UHRF1-S674A mutant | SIGNOR-277192 |
P68400 | Q9UJU2 | 1 | phosphorylation | up-regulates | 0.303 | Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays. | SIGNOR-23958 |
Q9GZV5 | Q06710 | 1 | binding | up-regulates | 0.303 | Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation. | SIGNOR-182253 |
P68400 | P83916 | 1 | phosphorylation | down-regulates | 0.303 | Two recent papers suggest that hp1 recruitment to damage sites, rather than its rapid mobilization, is the predominant behaviour exhibited by this protein. Our findings reconcile recent findings in a new model, wherein rapid hp1beta mobilization from dsbs is mediated by its phosphorylation on thr51 by ck2 | SIGNOR-187450 |
Q9Y6C9 | P55957 | 1 | relocalization | up-regulates | 0.303 | Mtch2/mimp (mitochondrial carrier homologue 2/met-induced mitochondrial protein), a novel truncated bid (tbid)-interacting protein, is a surface-exposed outer mitochondrial membrane protein that facilitates the recruitment of tbid to mitochondria | SIGNOR-165081 |
P42684 | P09619 | 2 | phosphorylation | up-regulates activity | 0.303 | C-Abl phosphorylates three tyrosine residues on PDGFR-beta (Y686, Y934, Y970), while Arg only phosphorylatesY686. Y686 and Y934 reside in PDGFR-beta catalytic domains, while Y970 is in the C-terminal tail. Using site-directed mutagenesis, we show that Abl-dependent phosphorylation of PDGFR-beta activates PDGFR-beta activity, in vitro, but serves to downregulate PDGFR-mediated chemotaxis. | SIGNOR-276140 |
O15355 | Q13315 | 2 | dephosphorylation | down-regulates activity | 0.303 | After ionizing radiation, dephosphorylation of USP7S by the ATM-dependent protein phosphatase PPM1G leads to USP7S downregulation, followed by Mdm2 downregulation and accumulation of p53. |ATM Dependent Downregulation of USP7 and HAUSP by PPM1G Activates p53 Response to DNA Damage.|DNA Damage Leads to ATM Dependent USP7S Dephosphorylation by PPM1G. | SIGNOR-277158 |
P60900 | P17861 | 1 | binding | down-regulates quantity by destabilization | 0.303 | 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-239039 |
P68400 | P12821 | 1 | phosphorylation | up-regulates activity | 0.303 | CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine(1270) within the CK2 consensus sequence almost abolished ACE phosphorylation.|These results indicate that the CK2-mediated phosphorylation of ACE regulates its retention in the plasma membrane and may determine plasma ACE levels. | SIGNOR-264425 |
P63104 | P55040 | 1 | binding | up-regulates quantity by stabilization | 0.303 | In order to address whether Gem binds specific isoforms of 14-3-3, we determined the coassociation of Gem and 14-3-3 in the neuroblastoma cell line SY5Y. 14-3-3ζ, -γ, -τ, and -β were observed to bind to Gem. 14-3-3-bound Gem has a twofold-longer half-life than nonbound Gem (Fig. (Fig.6).6). A similar increase in protein stability following 14-3-3 binding has been described for the Wee1 kinase | SIGNOR-261715 |
P49137 | Q15717 | 1 | 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 |
Q9BWU1 | P46531 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.302 | Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues | SIGNOR-273135 |
P49841 | P12036 | 1 | phosphorylation | down-regulates | 0.302 | Gsk3beta was shown to phosphorylate at ser-493 in vitro by phosphopeptide mapping and site-directed mutagenesis, and in vivo in hek293 cells. The role of ser-493 phosphorylation is also a question to be addressed in the future. Because the e-segment appears to be involved in filament formation (27, 42), phosphorylation in that region may also play a regulatory role in filament formation. Secondary structure prediction suggests that phosphorylation of ser-493 in combination with following the pro residue interrupts _-helix of the e-segment | SIGNOR-90668 |
P10588 | P22888 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.302 | Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription. | SIGNOR-266216 |
Q9HCX3 | Q8N726 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.302 | Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells. | SIGNOR-266098 |
P17676 | P98066 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.302 | In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells. | SIGNOR-254055 |
O15550 | O43248 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.302 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260026 |
P68400 | P30307 | 1 | phosphorylation | down-regulates | 0.302 | Inhibition of protein kinase ck2 enzyme activity in vivo resulted in an enhanced nuclear localization of cdc25c. Thus, phosphorylation of cdc25c at threonine 236 is an important signal for the retention of cdc25c in the cytoplasm | SIGNOR-123713 |
Q16620 | P52735 | 1 | phosphorylation | up-regulates activity | 0.302 | Finally, the TrkB kinase dependent increase in P-Y172 Vav2 was largely independent of the Vav2 SH2 domain (XREF_FIG, right), which was previously shown to be important for activation by Eph receptors.|These findings reveal a strong kinase independent binding mechanism between Vav and TrkB in cells, and suggest that activation of TrkB kinase activity stimulates Vav2 tyrosine phosphorylation and GEF activity. | SIGNOR-280050 |
Q13976 | Q8N8S7 | 1 | phosphorylation | down-regulates activity | 0.302 | Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts. PKG may preferentially phosphorylate sites of Ena/VASP proteins that reduce or inactivate these proteins. Inactivated Ena/VASP proteins dissociate from actin filaments, allowing capping proteins to bind and block monomer addition to plus ends, resulting in filament retraction. | SIGNOR-268288 |
P50591 | P19838 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.302 | Treatment with TRAIL increased the NF-κB transcriptional activity by approximately twofold in MDA-MB-231 cells compared to the control. | SIGNOR-277936 |
P49841 | Q2M1Z3 | 1 | phosphorylation | up-regulates activity | 0.302 | We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation. | SIGNOR-262879 |
O76064 | O14773 | 1 | ubiquitination | up-regulates activity | 0.302 | Our data demonstrate that RNF8 directly ubiquitylates and stabilizes TPP1 at telomeres.|Taken together, these results suggest that RNF8 dependent K63 linked, but not K48 linked ubiquitin chain formation on TPP1 is required to promote TPP1 stability and function at telomeres. | SIGNOR-278574 |
Q14258 | P11308 | 1 | ubiquitination | down-regulates quantity | 0.301 | We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG.|Our previous discovery of USP9X as an ERG stabilizing deubiquitinase suggests that reduction of ERG protein levels by TRIM25 mediated proteasomal degradation is prevented by expression of USP9X in fusion positive prostate cancer cells.|Using several biochemical assays we show that TRIM25 mediates the polyubiquitination of full-length ERG as well as N-terminally truncated ERG. | SIGNOR-278732 |
P07948 | O15524 | 1 | phosphorylation | down-regulates activity | 0.301 | These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors. | SIGNOR-277888 |
P00734 | P08709 | 1 | null | up-regulates activity | 0.301 | Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind | SIGNOR-263529 |
P27361 | P10242 | 1 | phosphorylation | down-regulates | 0.301 | Functional analysis of phosphorylation at serine 532 of human c-myb by map kinase. expression of a polypeptide containing the c-myb c-terminal domain stimulated c-myb activity. This effect is reduced upon mapk-dependent phosphorylation of serine 532. Our data suggest that the mapk-dependent state of phosphorylation modifies the cellular function of c-myb by modulating its interaction with a putative inhibitory factor | SIGNOR-45348 |
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 |
P31314 | P62714 | 1 | binding | down-regulates activity | 0.301 | HOX11 also inhibited PP2A serine/threonine phosphatase activity concomitant with stimulation of the AKT/PKB signaling cascade. | SIGNOR-240722 |
P28482 | Q9HAV4 | 1 | phosphorylation | down-regulates activity | 0.301 | Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. | SIGNOR-262984 |
Q99576 | Q12778 | 1 | relocalization | down-regulates activity | 0.301 | GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells. | SIGNOR-256146 |
O14757 | P12830 | 1 | phosphorylation | down-regulates activity | 0.301 | Phosphorylation of Cdh1 by Chk1 promotes recognition of Cdh1 by SCF betaTRCP1.|These data suggest that Chk1 negatively regulates APC/C Cdh1 activity by both promoting Cdh1 destruction and by destabilizing its association with the APC/C. | SIGNOR-278396 |
P61244 | Q9Y6D9 | 1 | binding | up-regulates activity | 0.301 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240357 |
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