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 |
|---|---|---|---|---|---|---|---|
P15311 | P43405 | 0 | phosphorylation | up-regulates activity | 0.447 | Phospho-SYK has also been shown to specifically activate ezrin upon CD81 engagement.|We found that the activated SYK led to a time dependent phosphorylation of ezrin (pY354 and pThr567) and radixin (pThr564) (XREF_FIG). | SIGNOR-279129 |
Q16445 | Q8TAB3 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. | SIGNOR-267221 |
Q06413 | Q9Y3R0 | 2 | binding | up-regulates | 0.403 | The cofactors grip-1, cbp/p300 and pcaf have hat activity and function as co-activators for mef-2c during myogenesis. | SIGNOR-83883 |
Q9BYH8 | Q16552 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.381 | In cooperation with RORγt and RORα, IκBζ enhances Il17a expression by binding directly to the regulatory region of the Il17a gene. | SIGNOR-266210 |
Q08209 | Q969Q1 | 0 | ubiquitination | down-regulates quantity | 0.26 | First, downregulation of MuRF1 significantly attenuates degradation of CnA in cardiomyocytes in vitro, indicating that endogenous MuRF1 negatively regulates the stability of CnA in a cell-autonomous manner.|Furthermore, MuRF1 directly ubiquitinated CnA in vitro.|These results suggest that MuRF1 directly polyubiquitinates CnA. | SIGNOR-278736 |
Q14739 | P06493 | 0 | phosphorylation | down-regulates | 0.396 | The binding of the nk fragment to chromatin pretreated with an s-phase extract was suppressed by incubation with an m-phase extract. Enzyme inhibitor experiments revealed that multiple kinases participate in the suppression. One of these kinases was shown to be cdc2 experiments involving a mutant nk fragment showed that the phosphorylation of serine 71 by cdc2 kinase is responsible for the suppression. | SIGNOR-121335 |
O75888 | O14836 | 2 | binding | up-regulates | 0.71 | Tumor necrosis factor (tnf) receptor superfamily member taci is a high affinity receptor for tnf family members april and blys. | SIGNOR-81308 |
P67775 | P56524 | 1 | dephosphorylation | up-regulates | 0.35 | Different signal-regulated serine/threonine kinases phosphorylate class ii histone deacetylases (hdacs) to promote nuclear export, cytosolic accumulation, and activation of gene transcriptionhere we show that hdac4 forms a complex with the pp2a holoenzyme c alpha, a alpha, b/pr55 alpha. In vitro and in vivo binding studies demonstrate that the n-terminus of hdac4 interacts with the catalytic subunit of pp2a. Hdac4 is dephosphorylated by pp2a | SIGNOR-159492 |
P31269 | P11309 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells. | SIGNOR-261632 |
O95999 | O14920 | 0 | phosphorylation | up-regulates activity | 0.772 | Here we show that the putative downstream kinase IKKbeta is required for initial CBM complex formation. Further, upon engagement of IKKbeta/Malt1/Bcl10 with Carma1, IKKbeta phosphorylates Bcl10 in the C terminus and thereby interferes with Bcl10/Malt1 association and Bcl10-mediated IKKgamma ubiquitination. Since only mutation of all serines 134, 136, 138, 141, and 144 completely prevented signal-induced Bcl10 phosphorylation, the Bcl10 5×S/A mutant was used to elucidate the effects of C-terminal Bcl10 phosphorylation on downstream signaling. | SIGNOR-276292 |
P04637 | P53355 | 0 | phosphorylation | up-regulates | 0.558 | Dna damage-activated protein kinases like chk1/2 modify the box-i domain of p53 at thr18 and ser20 (46) by an allosteric mechanism (10). | SIGNOR-153491 |
Q8NBJ5 | P02461 | 1 | glycosylation | up-regulates activity | 0.404 | Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues. | SIGNOR-261154 |
P68400 | Q9H257 | 1 | phosphorylation | down-regulates activity | 0.346 | PVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2 | SIGNOR-257601 |
Q86TM6 | P10909 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.32 | We also report that the ER-associated ubiquitin ligase Hrd1/synoviolin can interact with, and ubiquitinate clusterin. The fact that cleaved endogenous clusterin appears, under certain conditions, to be subject to polyubiquitination (Figure 2C) and proteasomal degradation (1, 2) strongly suggests that it passed through the secretory pathway before reaching the cytosol. | SIGNOR-272629 |
P15927 | P78527 | 0 | phosphorylation | down-regulates activity | 0.579 | We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. | we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13 | SIGNOR-248981 |
P48740 | P0C0L5 | 1 | cleavage | up-regulates activity | 0.676 | The classical complement activation pathway, like the MELinitiated pathway, involves the generation of a C3-converting complex, C4b2b, through enzymatic activation of C4 and C2. In the C1 complex (C1qr2s2), this specific protease activity is exhibited by C1s after activation of this enzyme by C1r. When C4 is activated, its reactive thiol ester is exposed and C4b binds covalently to nearby amino or hydroxyl groups. The C4-activating abilities of MASP-1 and MASP-2 were compared.|Activation of C4 by Ct sand MASP-2 on western blots. | SIGNOR-263426 |
P61088 | Q13404 | 2 | binding | up-regulates activity | 0.854 | Ubc13, the partner of rnf8 and rnf168, usually cooperates with an e2-like protein, uev1 (also known as ube2v1) or mms2 (also known as ube2v2), for the synthesis of lys63-linked polyubiquitin chains. | SIGNOR-166177 |
P08754 | P32249 | 2 | binding | up-regulates activity | 0.431 | 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-256858 |
P12931 | P29323 | 2 | binding | up-regulates | 0.566 | We propose src kinase as a downstream effector that mediates the neuron's response to eph receptor activation | SIGNOR-58142 |
P45984 | Q9UIG0 | 1 | phosphorylation | up-regulates | 0.2 | Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target | SIGNOR-188168 |
P43360 | Q5T6F0 | 2 | binding | down-regulates quantity by destabilization | 0.2 | The CRL4‐DCAF12 E3 ubiquitin ligase degrades MAGE‐A3/6 | SIGNOR-272255 |
Q08209 | P21333 | 1 | dephosphorylation | down-regulates | 0.259 | We report that a purified c-terminal recombinant region of filamin is a suitable substrate for calcineurin in vitro. Furthermore, 1 microm cyclosporin a (csa), a specific calcineurin inhibitor, reduced the dephosphorylation of the recombinant fragment in 293ft cells | SIGNOR-143979 |
Q00535 | A0A1B0GVQ0 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Cdk5 also phosphorylates PSD-95-interacting protein Spine Associated RapGAP (SPAR), resulting in its degradation ([98], Table 2). | SIGNOR-280219 |
O75116 | P55040 | 2 | binding | down-regulates activity | 0.29 | Two functions for Gem have been demonstrated, including inhibition of voltage-gated calcium channel activity and inhibition of Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation and neurite retraction. These functions for Gem have been ascribed to its interaction with the calcium channel Β subunit and Rho kinase Β, respectively. | SIGNOR-261711 |
Q13501 | Q9GZQ8 | 2 | binding | up-regulates | 0.837 | Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation. | SIGNOR-184255 |
Q99558 | Q13114 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.668 | TRAF2 and TRAF3 mediate NIK ubiquitination by forming a complex with the E3 ligase cIAP (cIAP1 or cIAP2).|We demonstrated further that TRAF3 mediates the degradation of NIK and thereby serves as a pivotal negative regulator of noncanonical NF-kappaB signaling. | SIGNOR-278673 |
Q8TDC3 | P20810 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that an AZ cytomatrix protein CAST and an AZ-associated protein kinase SAD-B coordinately regulate STD by controlling reloading of the AZ with release-ready synaptic vesicles. SAD-B phosphorylates the N-terminal serine (S45) of CAST, and S45 phosphorylation increases with higher firing rate. | SIGNOR-263051 |
O43315 | Q05513 | 0 | phosphorylation | up-regulates | 0.2 | Wt-pkc_-mediated phosphorylation of wt aqp9 in vitro. In the experiments, substitution of ser11 to ala markedly inhibited phosphorylation. the s11a mutation in fibroblasts caused a smoother cell periphery with fewer aqp9-induced filopodia | SIGNOR-176278 |
P29350 | P00533 | 1 | dephosphorylation | down-regulates | 0.415 | The sh2-domain ptpase shp-1 binds to and dephosphorylates autophosphorylated egfr and may participate in modulation of egfr signaling in epithelial cells. Reduced shp-1 binding to the egfr y1173f mutant resulted in a reduced receptor dephosphorylation by coexpressed shp-1 and less interference with egf-dependent mitogen-activated protein kinase stimulation. | SIGNOR-59965 |
P19086 | P18089 | 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-257109 |
Q05086 | O43166 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.365 | the purified E6AP enhanced the ubiquitination and degradation of E6TP1 in the presence of E6 in vitro. Additionally, the expression of a dominant-negative E6AP mutant (C833A) in cells inhibited the E6-induced degradation of E6TP1. These findings demonstrate that the E6-induced decrease in the levels of E6TP1 protein involves the E6AP-mediated ubiquitination followed by proteasome-dependent degradation. | SIGNOR-272608 |
Q9BQG0 | Q10571 | 2 | binding | up-regulates activity | 0.2 | Taken together, our results indicate that MN1 is a transcription coactivator rather than a sequence-specific transcription factor, and that it may stimulate RAR/RXR-mediated transcription through interaction with p160 and p300. | SIGNOR-256021 |
Q13464 | P04637 | 1 | phosphorylation | up-regulates quantity | 0.409 | Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level. | SIGNOR-280108 |
Q04206 | Q14164 | 0 | phosphorylation | up-regulates | 0.439 | Overexpressed ikkepsilon and tbk1 phosphorylate ser-536 in vivo and in vitro. | SIGNOR-129943 |
P78362 | P31946 | 2 | binding | down-regulates | 0.33 | 14-3-3 interacts with akt-phosphorylated srpk2 and blocks its nuclear translocation. kt phosphorylates SRPK2 on Thr-492 and promotes its nuclear translocation leading to cyclin D1 up-regulation, cell cycle reentry, and neuronal apoptosis. In addition, SRPK2 phosphorylates SC35 and, thus, inactivates p53, resulting in cyclin D1 up-regulation. 14-3-3 binding to SRPK2, regulated by Akt phosphorylation, inhibits these events. | SIGNOR-186767 |
P10398 | Q13153 | 0 | phosphorylation | up-regulates | 0.267 | Phosphorylation of endogenous a-raf, b-raf and raf-1 on the homologous pak phosphorylation sites (serine 299, serine 445, or serine 338 respectively)we found that the phosphorylation of a-raf on serine 299 was also stimulated by egf, although the duration of phosphorylation on this site was much shorter than for raf-1. Thus, by analogy with raf-1, phosphorylation of this site may play an important role in the a-raf activation mechanism. | SIGNOR-236342 |
Q00975 | Q01484 | 2 | binding | up-regulates quantity | 0.263 | Here, we demonstrate that ankyrin-B associates with Cav2.1 and Cav2.2 in cortex, cerebellum, and brain stem. Additionally, using in vitro and in vivo techniques, we demonstrate that ankyrin-B, via its membrane-binding domain, associates with a highly conserved motif in the DII/III loop domain of Cav2.1 and Cav2.2. Collectively, our findings identify an interaction between ankyrin-B and both Cav2.1 and Cav2.2 at the amino acid level that is necessary for proper Cav2.1 and Cav2.2 targeting in vivo. | SIGNOR-266707 |
P12931 | P52735 | 1 | phosphorylation | up-regulates activity | 0.527 | Since we find that Vav2 is necessary for cell spreading and Src activity is necessary for Vav2 activation of Rac and lamellipodia formation, our data suggest a model of Rac activation by integrins that depends on Src phosphorylation of Vav2.|We did not detect increased Rac activation when Vav2 was cotransfected with activated Src, although Vav2 tyrosine phosphorylation was increased (data not shown), indicating that endogenous Src activity is sufficient to fully activate Vav2. | SIGNOR-280138 |
Q8IVH8 | Q8IVH8 | 2 | phosphorylation | up-regulates | 0.2 | We identify a transautophosphorylation site in the map4k3 kinase activation segment (ser170) that is required for map4k3 activity and its activation of mtorc1 signaling. | SIGNOR-164103 |
P48023 | P25445 | 2 | binding | up-regulates activity | 0.903 | The death-inducing receptor fas is activated when cross-linked by the type ii membrane protein faslg (fasl) | SIGNOR-49688 |
Q9HC29 | Q676U5 | 2 | binding | up-regulates activity | 0.755 | By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease. | SIGNOR-252405 |
P00533 | Q9UKV8 | 1 | phosphorylation | up-regulates activity | 0.534 | Furthermore, AGO2 function is directly modulated by EGFR signaling in ERalpha negative breast cancer under states of hypoxic stress.|Here, EGFR can directly bind and phosphorylate residue Y393 of AGO2[ xref ]. | SIGNOR-278931 |
Q969H0 | P06748 | 2 | binding | up-regulates quantity | 0.482 | We report here that NPM regulates turnover of the c-Myc oncoprotein by acting on the F-box protein Fbw7 , a component of the E3 ligase complex involved in the ubiquitination and proteasome degradation of c-Myc. NPM was required for nucleolar localization and stabili- zation of Fbw7 | SIGNOR-245084 |
Q4L180 | Q14315 | 2 | binding | down-regulates quantity by destabilization | 0.252 | We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKCα. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells. | SIGNOR-262618 |
P55085 | O95837 | 2 | binding | up-regulates activity | 0.461 | 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-257359 |
O96013 | P07954 | 1 | phosphorylation | down-regulates quantity | 0.2 | FH is massively phosphorylated at the Ser 46 by PAK4 in non-small cell lung cancer (NSCLC) cells, and PAK4-phosphorylated FH binds to 14-3-3, resulting in cytosolic detention of FH and prohibition of FH/CSL/p53 complex formation. | SIGNOR-266315 |
Q9BX63 | P54132 | 2 | binding | up-regulates quantity by stabilization | 0.656 | In this work, FANCJ and BLM were found to interact physically and functionally in human cells and co-localize to nuclear foci in response to replication stress. The cellular level of BLM is strongly dependent upon FANCJ, and BLM is degraded by a proteasome-mediated pathway when FANCJ is depleted. | SIGNOR-259186 |
P10636 | P19525 | 0 | phosphorylation | up-regulates quantity | 0.2 | Interestingly, PKR phosphorylated tau directly and no detectable labeling occurred when tau was incubated with 32 P\u2010ATP alone (Figure\u00a0 xref right).|PKR kinase directly regulates tau expression and Alzheimer's disease-related tau phosphorylation. | SIGNOR-279735 |
O75925 | Q12888 | 1 | sumoylation | up-regulates | 0.494 | Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation. | SIGNOR-162156 |
O43597 | Q15139 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.324 | PKD negatively affects the stability of Spry2 WT but not of mutant Spry2 S112A.|Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. | SIGNOR-280091 |
Q02156 | P35236 | 1 | phosphorylation | up-regulates activity | 0.2 | HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient. | SIGNOR-276050 |
Q92630 | O43255 | 1 | phosphorylation | up-regulates | 0.41 | In the present study, we identify the serine/threonine kinase dyrk2 as siah2 interaction partner that phosphorylates siah2 at five residues (ser16, thr26, ser28, ser68, and thr119). accordingly, phosphorylated siah2 is more active than the wild-type e3 ligase and shows an increased ability to trigger the hif-1?-Mediated transcriptional response and angiogenesis. | SIGNOR-198729 |
P46937 | Q13950 | 2 | binding | down-regulates | 0.449 | Here we show that the endogenous yes-associated protein (yap), a mediator of src/yes signaling, interacts with the native runx2 protein, an osteoblast-related transcription factor, and suppresses runx2 transcriptional activity in a dose-dependent manner. | SIGNOR-195221 |
O43541 | P36897 | 2 | binding | down-regulates activity | 0.74 | The inhibitory Smads (I-Smads), i.e. Smad6 and Smad7, are negative regulators of transforming growth factor-_ (TGF-_) family signaling. I-Smads inhibit TGF-_ family signaling principally through physical interaction with type I receptors (activin receptor-like kinases), so as to compete with receptor-regulated Smads (R-Smads) for activation. | SIGNOR-167160 |
P42229 | Q13568 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.287 | The GM-CSF receptor forms a dodecamer structure and recruits JAK2, leading to the activation of STAT5, extracellular signal-regulated kinase (ERK), V-Akt murine thymoma viral oncogene homolog 1 (AKT), and the nuclear translocation of NF-kappaB and IRF5 | SIGNOR-249508 |
P40424 | P55075 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.271 | Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription | SIGNOR-265803 |
Q8TBB1 | P49757 | 1 | ubiquitination | down-regulates | 0.74 | Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation. | SIGNOR-112201 |
Q86Y07 | P04406 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation. | SIGNOR-277840 |
Q13485 | Q9HCE7 | 0 | ubiquitination | down-regulates activity | 0.745 | Smurfs, which otherwise cannot directly bind to smad4, mediated poly-ubiquitination of smad4 in the presence of smad6 or smad7. Smad signaling is negatively regulated by inhibitory (i) smads and ubiquitin-mediated processes. | SIGNOR-236096 |
P14316 | P42224 | 2 | binding | up-regulates activity | 0.547 | We show that IRF-2 forms a complex with STAT1 and the cytokine-responsive region of the TAP1 promoter in any TPO or IFN-gamma target cells tested. Interaction of IRF-2 and STAT1 on the promoter depends on the DNA-binding domain of IRF-2. | SIGNOR-254532 |
Q02447 | P49585 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 function as transcriptional activators of the Ctpct promoter | SIGNOR-266232 |
Q13131 | O75925 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanically, we found that AMPKα1 directly phosphorylated protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, at serine 510, to promote its SUMO E3-ligase activity. Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed m | SIGNOR-259866 |
Q9H4A3 | Q8N9I0 | 1 | phosphorylation | up-regulates activity | 0.603 | Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. . In contrast, WNK1 phosphorylated Syt2 on T202 and T386 within the C2 domains (Figure 6B). | SIGNOR-263049 |
P00533 | P17706 | 0 | dephosphorylation | down-regulates | 0.635 | Here, we report that the 45-kda variant of the protein tyrosine phosphatase tcptp (tc45) can recognize delta egfr as a cellular substrate | SIGNOR-132316 |
P63000 | Q14185 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth. | SIGNOR-266822 |
P54257 | Q13562 | 2 | binding | up-regulates activity | 0.328 | We identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2). Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2 | SIGNOR-234602 |
Q9UBW7 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.376 | PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis|Similar analyses with ZNF198 identified two clusters of putative Plk1 phosphorylation sites in vitro. A cluster of serine residues at the N-terminus of ZNF198, S303, S305, and S309, and a cluster at the C-terminus, S1056 and S1064. The triple Ser to Ala mutant, S303A/S305A/S309A, consistently exhibited the lowest level of phosphorylation in vitro, in comparison to the double S1056A/S1064A mutant | SIGNOR-275560 |
Q9HBY0 | P14598 | 2 | binding | up-regulates activity | 0.626 | Stimulus-induced phosphorylation of p47phox causes a conformational change, by which both PX and SH3 domains become accessible to their membranous targets, phosphoinositides and p22phox, respectively. Cooperation of these two interactions, each being indispensable, enables p47phox to form a stable complex with cytochrome b558 (composed of the two subunit gp91phox and p22phox), leading to activation of the phagocyte NADPH oxidase. | SIGNOR-276624 |
P12931 | P49407 | 1 | phosphorylation | down-regulates | 0.684 | Using fluorescently tagged proteins combined with resonance energy transfer and image cross-correlation spectroscopy approaches, we show in live cells that beta2-adaptin phosphorylation is an important regulatory process for the dissociation of beta-arrestin-AP-2 complexes in CCPs. Finally, we show that beta2-adaptin phosphorylation is involved in the early steps of receptor internalization. Our findings not only unveil beta2-adaptin as a new Src target during AT1R internalization, but also support the role of receptor-mediated signaling in the control of clathrin-dependent endocytosis of receptors. | SIGNOR-154564 |
Q13882 | Q13017 | 1 | phosphorylation | up-regulates | 0.2 | Breast tumor kinase phosphorylates p190rhogap to regulate rho and ras and promote breast carcinoma growth, migration, and invasion. Brk phosphorylates p190 at the y(1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120rasgap (p120). As a consequence, brk stimulates p190 and attenuates p120 functions, leading to rhoa inactivation and ras activation, respectively. | SIGNOR-181452 |
O14981 | Q14919 | 2 | binding | up-regulates activity | 0.504 | We present evidence that the NC2alpha subunit interacts with BTAF1. Addition of NC2alpha or the NC2 complex can stimulate the ability of BTAF1 to interact with TBP. | SIGNOR-263918 |
Q9Y5H3 | Q9Y5I2 | 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-265704 |
P00533 | Q92952 | 1 | phosphorylation | up-regulates activity | 0.2 | These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus. | SIGNOR-276490 |
Q96BD8 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.736 | Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments. | SIGNOR-262662 |
P04818 | Q9HCK8 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.283 | In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes. | SIGNOR-268805 |
Q13131 | Q8WUI4 | 1 | phosphorylation | down-regulates | 0.273 | Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs). | SIGNOR-176491 |
P41134 | P15172 | 2 | binding | down-regulates activity | 0.478 | Id1 and Id2 interacted strongly with MyoD and Myf-5.Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-240265 |
Q9H3D4 | Q96SW2 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | CRBN functions as a substrate receptor of the E3 ubiquitin ligase CRL4, whose substrate specificity is modulated by thalidomide and its analogs.When thalidomide binds to CRBN, substrate specificity of CRL4CRBN is altered and CRBN neomorphically binds to ∆Np63, TAp63 and other neosubstrates and ubiquitinates them for proteasomal degradation. | SIGNOR-272214 |
P49137 | P11831 | 1 | phosphorylation | up-regulates | 0.584 | Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2 | SIGNOR-166640 |
Q9Y616 | P04150 | 0 | transcriptional regulation | up-regulates quantity | 0.36 | We show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter | SIGNOR-259287 |
Q14289 | Q9ULH1 | 1 | phosphorylation | down-regulates activity | 0.458 | The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. Pyk2 directly phosphorylates ASAP1 on tyrosine residues in vitro and increases ASAP1 tyrosine phosphorylation when co-expressed in HEK293T cells.Phosphorylation of tyrosine 308 and 782 affects the phosphoinositide binding profile of ASAP1, and fluorimetric Arf-GTPase assays with purified proteins revealed an inhibition of ASAP1 GTPase-activating protein activity by Pyk2-mediated tyrosine phosphorylation. | SIGNOR-263186 |
P10415 | Q99933 | 2 | binding | up-regulates activity | 0.415 | Cloning and functional analysis of BAG-1: A novel Bcl-2-binding protein with anti-cell death activity| | SIGNOR-254118 |
Q9UPP1 | P28482 | 0 | phosphorylation | down-regulates activity | 0.2 | Upon IFNgamma treatment, PHF8 is phosphorylated by ERK2 and evicted from the promoters, which correlates with an increase in H4K20me1 and H3K4me3 levels. | SIGNOR-279745 |
P12931 | Q96RD7 | 1 | phosphorylation | up-regulates activity | 0.379 | We recently identified amino acids 198-200 (YLK) on the PANX1 intracellular loop that are critical for α1-AR-mediated vasoconstriction and PANX1 channel function. We report herein that the YLK motif is contained within an SRC homology 2 domain and is directly phosphorylated by SRC proto-oncogene, nonreceptor tyrosine kinase (SRC) at Tyr198 | SIGNOR-277817 |
O00712 | P08651 | 2 | binding | down-regulates activity | 0.362 | Coexpression of NFI-B3 with other isoforms of the NFI-B, -C, and -X family, however, led to a strong reduction of transcriptional activation compared with the expression of these factors alone. NFI-B3 apparently forms heterodimers with other NFI proteins thereby interfering with their function. | SIGNOR-240880 |
P40763 | Q9UM73 | 2 | binding | up-regulates | 0.439 | Npm-alk has been shown to activate signal transducer and activator of transcription (stat) 3, a transcriptional regulator of cyclin d3.Proteins that interact with alk tyrosine kinase play important roles in mediating downstream cellular signals. Previously reported proteins in the alk signal pathway were identified including pi3-k, jak2, jak3, stat3, grb2, irs, and plcgamma1. | SIGNOR-139460 |
Q02156 | O94925 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCε is the kinase that phosphorylates GAC at Ser314. | SIGNOR-277387 |
Q99816 | P17542 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | These data suggest that Tal mediates polyubiquitylation of the lysine residues in the VPS28-binding region of TSG101, leading to subsequent degradation of TSG101. | SIGNOR-271636 |
Q96T58 | Q06330 | 2 | binding | down-regulates | 0.703 | We identified sharp as an rbp-jkappa/cbf-1-interacting corepressor in a yeast two-hybrid screen. | SIGNOR-94201 |
P27361 | Q92934 | 1 | phosphorylation | down-regulates | 0.483 | Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells. | SIGNOR-188172 |
P18848 | P05198 | 0 | transcriptional regulation | down-regulates quantity | 0.64 | ER stress, viral infection, and other cellular stress signals activate PERK, PKR, HRI, and GCN2 kinases that converge on phosphorylation of eIF2alpha, the core of ISR. This leads to global attenuation of Cap Âdependent translation while concomitantly initiates the preferential translation of ISR Âspecific mRNAs, such as ATF4. ATF4 is the main effector of the ISR. eIF2alpha phosphorylation causes a reduction in global protein synthesis while allowing the translation of selected genes including activating transcription factor 4 (ATF4), aiding cell survival and recovery | SIGNOR-260169 |
Q8N6P7 | P23458 | 2 | binding | up-regulates | 0.523 | Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain. | SIGNOR-124489 |
P35227 | Q03933 | 1 | sumoylation | down-regulates activity | 0.325 | MEL-18, in contrast to the polycomb protein PC2/CBX4, in which SUMO E3 activity stimulates sumoylation of certain proteins, actually functions like an anti-SUMO E3 protein, interacting with both HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity and thereby decreasing sumoylation of a target protein, in this case that of HSF2. sumoylation of HSF2 is up-regulated during mitosis and is important for the interaction of this factor with a subunit of the condensin complex during the bookmarking process | SIGNOR-226245 |
Q04206 | P25963 | 2 | binding | up-regulates activity | 0.891 | Nf-kappa b is an inducible transcription factor comprised of a 50-kd (p50) and a 65-kd (p65) subunit. Induction of nf-kappa b activity, which is a critical event in many signal transduction pathways, involves release from a cytoplasmic inhibitory protein, i kappa b, followed by translocation of the active transcription factor complex into the nucleus. we demonstrate by in vitro and in vivo methods that the recently cloned i kappa b/mad-3 interacts with both the p50 and p65 subunits of nf-kappa b. | SIGNOR-17691 |
Q04759 | O43516 | 1 | phosphorylation | up-regulates activity | 0.324 | TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation. | These results suggest that phosphorylation at S488 disrupts WIP binding to WASP. | SIGNOR-249181 |
P20396 | P34981 | 2 | binding | up-regulates activity | 0.762 | When TRH reaches the pars distalis of the pituitary, it regulates cells that express TRH receptor-1 (TRH-R1), such as the thyrotrophs. These cell types are subject to a multifactorial regulation that determines the extent and specificity of their response to TRH. | SIGNOR-267200 |
O96017 | Q01094 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.487 | We report that checkpoint kinase 2 (chk2) regulates e2f-1 activity in response to the dna-damaging agent etoposide. A chk2 consensus phosphorylation site in e2f-1 is phosphorylated in response to dna damage | SIGNOR-100898 |
P06493 | Q99638 | 1 | phosphorylation | up-regulates activity | 0.361 | Here we present evidence that thr292 of hrad9 is subject to cdc2-dependent phosphorylation in mitosis. Furthermore, our data are also consistent with four other hrad9 phosphorylation sites (ser277, ser328, ser336, and thr355) being regulated in part by cdc2. We also identify ser387 as a novel site of hrad9 constitutive phosphorylation and show that phosphorylation at ser387 is a prerequisite for one form of dna damage-induced hyperphosphorylation of hrad9. | SIGNOR-101055 |
P08754 | P30872 | 2 | binding | up-regulates activity | 0.475 | 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-256822 |
Q5T1M5 | O43516 | 2 | binding | up-regulates activity | 0.2 | However, we did detect WAFL binding to bothWIP and actin by immunoprecipitation (Fig. 4). In conclusion, we propose a model whereby WAFL associates toendocytic vesicles by its coiled-coil domain and is involved in actin-based movement of early endosomes via WIP and binding to actin. | SIGNOR-260596 |
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