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 |
|---|---|---|---|---|---|---|---|
P06493 | Q8WWK9 | 1 | phosphorylation | up-regulates | 0.288 | Among these, thr-622 was specifically phosphorylated by cdk1-cyclin b1 both in vitro and in vivo. these findings suggest that cdk1-cyclin b1-mediated phosphorylation of tmap is important for and contributes to proper regulation of microtubule dynamics and establishment of functional bipolar spindles during mitosis. | SIGNOR-185317 |
Q9HBI1 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.965 | These results indicate that affixin directly associates with \u03b1-actinin only when its CH2 domain is phosphorylated by ILK.|This may indicate that phosphorylation of the CH2 domain by ILK induces a conformational change of the CH2 domain of affixin, which enables affixin to interact with alpha-actinin to evoke the subsequent maturation of the FA complex. | SIGNOR-278259 |
P17612 | Q02952 | 2 | phosphorylation | up-regulates activity | 0.2 | Following receptor activation, gravin binding to the receptor increases, a process dependent upon PKA-catalyzed phosphorylation of two canonical PKA sites (Ser696–698 and Ser772) located within the AKAP domain of gravin. | SIGNOR-271844 |
Q9BXL7 | P31749 | 0 | phosphorylation | up-regulates activity | 0.522 | Akt phosphorylates S637 and S645 in the linker region of Carma1 | SIGNOR-276621 |
O14965 | Q13158 | 1 | phosphorylation | up-regulates | 0.343 | Here, we report that aur-a phosphorylates s203 of the fas associated with death domain protein (fadd)phosphorylation of s203 by aur-a serves to prime fadd for plk1-mediated phosphorylation at s194 | SIGNOR-176739 |
Q9BZL6 | Q8WYL5 | 1 | phosphorylation | down-regulates | 0.291 | Phosphorylation of ser 402 impedes phosphatase activity of slingshot 1. | SIGNOR-173441 |
Q8TD19 | Q9GZQ8 | 1 | phosphorylation | down-regulates activity | 0.2 | LC3B is phosphorylated at Thr-50 within the LDS by serine/threonine kinase (STK) 3 and STK4. Here, we identified LIR motifs in STK3 and atypical protein kinase Cζ (PKCζ) and never in mitosis A (NIMA)-related kinase 9 (NEK9). All three kinases phosphorylated LC3B Thr-50 in vitro A phospho-mimicking substitution of Thr-50 impaired binding of several LIR-containing proteins, such as ATG4B, FYVE, and coiled-coil domain-containing 1 (FYCO1), and autophagy cargo receptors p62/sequestosome 1 (SQSTM1) and neighbor of BRCA1 gene (NBR1). | SIGNOR-273904 |
Q9Y5I2 | Q9Y5H1 | 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-265713 |
P68400 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.34 | Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase | SIGNOR-250927 |
P29474 | P05771 | 0 | phosphorylation | down-regulates activity | 0.309 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251630 |
Q08334 | Q9NPH9 | 2 | binding | up-regulates | 0.601 | See table 2 | SIGNOR-151917 |
P42684 | O14818 | 1 | phosphorylation | down-regulates | 0.607 | Proteasome-mediated proteolysis is a primary protein degradation pathway in cells. The present study demonstrates that c-abl and arg (abl-related gene) tyrosine kinases associate with and phosphorylate the proteasome psma7 (alpha4) subunit at tyr-153. Consequently, proteasome-dependent proteolysis is compromised | SIGNOR-146589 |
P48048 | Q05655 | 0 | null | up-regulates activity | 0.307 | To determine whether this channel is a substrate for PKA, ROMK tagged with the hemagglutinin epitope was transiently transfected into HEK293 cells. In vitro labeling of immunoprecipitated proteins from transfected cells showed that ROMK could be phosphorylated by PKA. | Taken together, these results provide strong evidence that direct phosphorylation of the channel polypeptide by PKA is involved in channel regulation and PKA-dependent phosphorylation is essential for ROMK channel activity. | SIGNOR-248943 |
P22415 | P78527 | 0 | phosphorylation | up-regulates | 0.293 | Feeding induces the recruitment of dna-pk to usf-1 and its phosphorylation, which then allows recruitment of p/caf, resulting in usf-1 acetylation and fas promoter activation. | SIGNOR-184849 |
Q6ZMU5 | P35568 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.477 | Here, we demonstrate that MG53 induces IRS-1 ubiquitination with the help of the E2 enzyme UBE2H during skeletal myogenesis by examining MG53 disrupted skeletal muscle cells and tissues.|The IRS-1 protein level was decreased by MG53 in a concentration dependent manner and was restored by the addition of MG132, a proteasome inhibitor (XREF_FIG; XREF_SUPPLEMENTARY). | SIGNOR-278520 |
P30556 | P08754 | 2 | binding | up-regulates activity | 0.25 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256881 |
Q16828 | P28482 | 2 | dephosphorylation | down-regulates activity | 0.904 | Dual-specificity phosphatase six (DUSP6, MKP3, or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on ERK-2 (MAPK1) to inactivate the ERK-2 kinase. | SIGNOR-277006 |
P15036 | Q15131 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.528 | Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines. | SIGNOR-260914 |
P01112 | P12931 | 0 | phosphorylation | down-regulates activity | 0.775 | Src binds to and phosphorylates GTP-, but not GDP-, loaded Ras on a conserved Y32 residue within the switch I region in vitro and that in vivo, Ras-Y32 phosphorylation markedly reduces the binding to effector Raf and concomitantly increases binding to GTPase-activating proteins and the rate of GTP hydrolysis | SIGNOR-252093 |
Q15653 | O14920 | 0 | phosphorylation | down-regulates | 0.765 | We described the purification of a 900 kda protein kinase complex, the ikb kinase (ikk), that phosphorylates ikbalfa and ikbbeta at the sites that mediate their ubiquitination and degradation | SIGNOR-52932 |
Q14344 | P35348 | 2 | binding | up-regulates activity | 0.623 | 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-257279 |
P15311 | P17252 | 0 | phosphorylation | up-regulates | 0.547 | Phosphorylation of ezrin is required for both conformational activation and for signaling to downstream events. The activating c-terminal threonine phosphorylation on t567 was first described to be downstream of the rho pathway (matsui et al., 1998). Additional studies have implicated protein kinase c (pkc) in the phosphorylation of ezrin t567. | SIGNOR-133223 |
Q12982 | Q4KMG0 | 2 | binding | up-regulates activity | 0.506 | Bnip-2 and jlp are brought together through mutual interaction with cdo. the cdo-bnip-2 interaction stimulates cdc42 activity, which in turn promotes p38alpha/beta activity and cell differentiation. | SIGNOR-179864 |
P13569 | P17612 | 0 | phosphorylation | up-regulates | 0.485 | Cftr, the protein associated with cystic fibrosis, is phosphorylated on serine residues in response to camp agonists. Serines 660, 737, 795, and 813 were identified as in vivo targets for phosphorylation by protein kinase a.mutagenesis of all four sites abolished the response. | SIGNOR-21312 |
Q9NRC8 | P62826 | 1 | deacetylation | down-regulates activity | 0.2 | N this study, we demonstrated that SIRT7 interacts with a small GTPase, Ras-related nuclear antigen (Ran), and deacetylates Ran at K37. |The nuclear export by CRM1 requires an interaction with the small GTPase Ras-related nuclear antigen (Ran), which cycles between GTP- and GDP-bound states. The binding of Ran GTP to CRM1 in the nucleus increases the affinity of CRM1 for cargo proteins [[18], [19], [20]]. Interestingly, Ran is a lysine-acetylated protein | SIGNOR-275849 |
Q03112 | P15976 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.319 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266061 |
P42771 | P35226 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.455 | In HEK293A cells transfected with luciferase reporter constructs, necdin relieves Bmi1-dependent repression of p16 promoter activity, | SIGNOR-253385 |
P43119 | 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-257078 |
O43903 | P42574 | 0 | cleavage | up-regulates | 0.451 | We now demonstrate that gas2 is a substrate of caspase-3 but not of caspase-6. Proteolytic processing both in vitro and in vivo is dependent on aspartic residue 279. | SIGNOR-72347 |
Q05193 | Q12965 | 2 | binding | up-regulates activity | 0.333 | We describe binding of two PRD-containing endocytic proteins, dynamin and synaptojanin-1, to the SH3 domain of Myo1E. This interaction was detected both in vitro, using pull-downs of purified proteins, and in vivo, using immunoprecipitation of protein complexes from synapse-enriched brain extract and immunolocalization of Myo1E and dynamin. Our observation of the interaction between human Myo1E and endocytic proteins suggests that this longtailed myosin may play a role in clathrin-dependent endocytosis.Interaction between Myo1E SH3 domain and PRD-containing endocytic proteins may promote recruitment of Myo1E to clathrin-coated structures since an inactivating mutation in the SH3 domain reduced Myo1E localization to clathrin-containing puncta. | SIGNOR-265424 |
P35548 | P56178 | 2 | binding | down-regulates activity | 0.572 | We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities. | SIGNOR-240990 |
P49840 | Q14596 | 1 | phosphorylation | down-regulates activity | 0.322 | The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation. | SIGNOR-261794 |
Q08999 | P24941 | 0 | phosphorylation | down-regulates | 0.849 | When expressed in u2os cells, the phosphorylation-deficient mutant p130(delta)(cdk4), in which the cdk4 specific sites were mutated to alanine residues, imposed a more sustained g1 arrest than a constitutively active prb(delta)(cdk), known to repress all cellular e2f activity | SIGNOR-87492 |
Q9Y5H9 | Q9Y5F9 | 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-265684 |
P33032 | P50148 | 2 | binding | up-regulates activity | 0.25 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257337 |
Q13976 | P13569 | 1 | phosphorylation | up-regulates | 0.506 | Direct amino acid sequencing and peptide mapping of cf-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by pka and pkgcftr possesses a large cluster of strict dibasic consensus sites for phosphorylation by protein kinase a (pka) in the r-domain and an obligatory dependence on phosphorylation is a hallmark of cftr cl(-) channel function | SIGNOR-18249 |
Q9UH77 | Q9H4A3 | 2 | binding | down-regulates quantity by destabilization | 0.563 | CUL3 assembles with BTB proteins to form Cullin-RING E3 ubiquitin ligase complexes. To explore how a CUL3-KLHL3 complex might operate, we immunoprecipitated KLHL3 and found that it associated strongly with WNK isoforms and CUL3. These results suggest that the CUL3-KLHL3 E3 ligase complex regulates blood pressure via its ability to interact with and ubiquitylate WNK isoforms. | SIGNOR-272099 |
P48730 | O75581 | 1 | phosphorylation | up-regulates activity | 0.2 | Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 | SIGNOR-275402 |
Q6VVB1 | O14641 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.462 | We have also found that malin enhances K48- and K63-linked ubiquitination of dishevelled2 that could lead to its degradation through both proteasome and autophagy. Altogether, our results indicate that malin regulates Wnt signaling pathway through the degradation of dishevelled2 and suggest possible deregulation of Wnt signaling in Lafora disease. | SIGNOR-272005 |
P12931 | P19022 | 1 | phosphorylation | down-regulates | 0.397 | Src-mediated phosphorylation of the n-cadherin cytoplasmic domain results in a significant reduction in beta-catenin bindingbeta-catenin dissociates from n-cadherin and redistributes to the nucleus of transmigrating melanoma cells to activate gene transcription.Because there were only four tyrosine residues (y852, y860, y884, and y886) in this peptide, all of them were phosphorylated. | SIGNOR-143242 |
P38405 | P33032 | 2 | binding | up-regulates activity | 0.292 | 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-256941 |
P46977 | Q9NZQ7 | 1 | glycosylation | up-regulates quantity by stabilization | 0.2 | Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization. | SIGNOR-274975 |
Q9UPY3 | Q13148 | 0 | post transcriptional regulation | up-regulates quantity | 0.374 | Molecularly, we observed that TBPH regulates the expression levels of Dicer-2 by direct protein-mRNA interactions in vivo.|In agreement with this idea, we found that the suppression of TDP-43 induces the downregulation of Dicer in human neuroblastoma cell lines signifying that the TDP-43 function is required to prevent defects in Dicer protein expression or stability | SIGNOR-262114 |
Q16875 | Q9UM11 | 2 | binding | down-regulates quantity by destabilization | 0.262 | We have recently discovered that the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is degraded by the E3 ubiquitin ligase APC/C-Cdh1, which also degrades cell-cycle proteins. Cdh1 promotes PFKFB3 degradation in the nucleus. | SIGNOR-271436 |
Q9UBL0 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | The specificity of antibody G534 was examined using recombinant full-length rat ARPP-21 phosphorylated by PKA. Radiolabeled ARPP-21 from a reaction containing [γ32P]ATP correlated with the detection of phospho-Ser55-ARPP-21 by immunoblotting (Fig. 1A, left and middle panels). | SIGNOR-263107 |
Q92824 | P01178 | 1 | cleavage | down-regulates quantity | 0.248 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270327 |
O14640 | Q9NQ66 | 1 | null | up-regulates activity | 0.275 | Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin | SIGNOR-258978 |
O14746 | O60832 | 2 | binding | up-regulates activity | 0.815 | Dyskerin was recently found to be associated with active human telomerase (34), and mutations in dyskerin or NOP10 or deletion of the H/ACA motif of hTERC result in diminished telomerase activity | SIGNOR-263332 |
P42338 | P42338 | 2 | phosphorylation | down-regulates activity | 0.2 | Autophosphorylation sites of both pi3k isoforms were mapped to c-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma). autophosphorylation of p110 beta On serine 1070 results in down-regulation of the lipid kinase activity of pi3k beta | SIGNOR-96776 |
Q13237 | P00533 | 1 | phosphorylation | down-regulates activity | 0.2 | Recombinant PKG II inhibited the epidermal growth factor (EGF)-induced activation of the EGF receptor via phosphorylating the T406 of the extracellular domain and blocked EGF-triggered proliferation of various cancer cells. | SIGNOR-277589 |
O60285 | O95835 | 1 | phosphorylation | down-regulates | 0.389 | Moreover, we show that nuak1 phosphorylates lats1 at s464 and this has a role in controlling its stabilitycells that constitutively express nuak1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator lats1 | SIGNOR-161792 |
Q13263 | P60510 | 0 | dephosphorylation | down-regulates activity | 0.358 | PP4 dephosphorylated pKAP1 in vitro. | SIGNOR-277163 |
P28482 | Q07820 | 1 | phosphorylation | up-regulates | 0.527 | We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. | SIGNOR-92593 |
P15311 | P31751 | 0 | phosphorylation | up-regulates | 0.375 | Purified akt directly phosphorylates recombinant ezrin at threonine 567 in vitro in an atp-dependent manner. ezrin activation after initiation of na+-glucose cotransport requires akt2 expression | SIGNOR-130260 |
P11388 | P53350 | 0 | phosphorylation | up-regulates | 0.481 | Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin | SIGNOR-182844 |
Q09472 | Q14814 | 2 | binding | up-regulates | 0.743 | Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription. | SIGNOR-232162 |
O43474 | P04637 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.56 | Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. | SIGNOR-270544 |
Q14994 | P19793 | 2 | binding | up-regulates | 0.468 | Therefore, both car-rxr heterodimers and car monomers can contribute to the gene activating function of pbrems in car target genes. | SIGNOR-104441 |
P04637 | Q8IUQ4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.372 | P53 directly induces the expression of Siah-1 and in turn formation of a unique SCF-like complex (SCF(TBL1)) comprised of Siah-1, Siah-1-interacting protein (SIP), Skp1, transducin β-like 1 (TBL1), and APC | SIGNOR-271953 |
P21860 | P42338 | 2 | binding | up-regulates | 0.521 | Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4. | SIGNOR-146864 |
Q02763 | Q14449 | 1 | phosphorylation | up-regulates activity | 0.65 | Together these results suggest a role for the Grb14 SH2 domain in Tie2 mediated Grb14 signaling.|Tyrosine phosphorylation of Grb14 by Tie2. | SIGNOR-279300 |
O43660 | P52272 | 2 | binding | up-regulates activity | 0.747 | hnRNP-M interacts directly with CDC5L and PLRG1 in vivo. we investigated whether the function of hnRNP-M in alternative splicing was affected by the central region mapped as essential for binding to the CDC5L/PLRG1 proteins. We conclude that loss of the CDC5L/PLRG1 interaction domain in hnRNP-M correlates with a loss of ability to modulate alternative splice site selection in this assay. | SIGNOR-239444 |
Q9P286 | Q04206 | 1 | phosphorylation | up-regulates activity | 0.2 | PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo|We characterized that PAK5 could promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB, and demonstrated that p65 could directly bind to the promoter of Cyclin D1 | SIGNOR-275657 |
Q96RU7 | O00763 | 2 | binding | down-regulates quantity by destabilization | 0.258 | TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1. Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D). | SIGNOR-271601 |
P49336 | P51946 | 1 | phosphorylation | down-regulates | 0.645 | Cdk8 phosphorylates mammalian cyclin h in the vicinity of its functionally unique amino-terminal and carboxy-terminal alpha-helical domains. This phosphorylation represses both the ability of tfiih to activate transcription and its ctd kinase activity | SIGNOR-82033 |
Q16236 | P36969 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.383 | 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.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis. | SIGNOR-279874 |
P38936 | O14757 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.531 | Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21(Waf1) on T145 and S146 residues and induces its proteasome-dependent proteolysis. | SIGNOR-279325 |
P21860 | Q02297 | 2 | binding | up-regulates | 0.872 | The neuregulins (also called heregulins and neu differentiation factors) nrg-1 and nrg-2 bind erbb-3 and erbb-4;and nrg-3 and nrg-4 bind erbb-4 direct interaction between heregulin and the two proteins was demonstrated by chemical cross-linking experiments using 125i-heregulin followed by immunoprecipitation with antibodies specific for erbb2 or erbb3. | SIGNOR-26878 |
Q6IE81 | P48729 | 0 | phosphorylation | down-regulates activity | 0.277 | We demonstrate that the destruction complex component casein kinase 1α (CK1α) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit β-catenin signaling. | SIGNOR-273618 |
Q7Z460 | Q9UDT6 | 2 | binding | up-regulates activity | 0.594 | CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. | Both EB1- and cortex-binding domains of CLASP are required to promote MT stability. | SIGNOR-265092 |
Q9BQ95 | Q9Y4K3 | 0 | ubiquitination | down-regulates activity | 0.79 | Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation | SIGNOR-260370 |
P07900 | Q8NFG4 | 2 | 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 |
Q9UBN7 | Q01130 | 1 | deacetylation | up-regulates | 0.356 | Our data support a model in which hdac6 has a key role in the maintenance of srsf2 protein level by inhibiting tip60_mediated acetylation and proteasomal degradation. | SIGNOR-170590 |
P12931 | Q13308 | 1 | phosphorylation | up-regulates activity | 0.279 | Because Ptk7 lacks intrinsic kinase activitiy, we suggest a positive feedback model in which pre-existing active Src phosphorylates PTK7 enabling it to interact with the SH2 domain of additional Src molecules to result in further activation. | SIGNOR-279123 |
P45983 | Q96P20 | 1 | phosphorylation | up-regulates activity | 0.369 | Ethanol induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death.|However, recent studies suggested that Ser 194 phosphorylation of NLRP3 was essential for the control of inflammasome activation and that JNK1 directly phosphorylates NLRP3, which stimulates the self-association and oligomerization of NLRP3 [ xref , xref ]. | SIGNOR-280034 |
P56589 | P40855 | 2 | binding | up-regulates activity | 0.954 | PEX3 is required for PEX19 to dock at peroxisomes, interacts specifically with the docking domain of PEX19, and is required for recruitment of the PEX19 docking domain to peroxisomes. | SIGNOR-253026 |
P42345 | Q9BRS8 | 1 | phosphorylation | up-regulates activity | 0.2 | Binding of La ribonucleoprotein domain family, member 6 (LARP6) to collagen mRNAs regulates their translation and is necessary for high type I collagen expression. Here we show that mTORC1 phosphorylates LARP6 on S348 and S409. The S348A/S409A mutant of LARP6 acts as a dominant negative protein in collagen biosynthesis, which retards secretion of type I collagen and causes excessive posttranslational modifications. | SIGNOR-273679 |
P53350 | Q9NS56 | 1 | phosphorylation | up-regulates activity | 0.445 | Plk1-mediated phosphorylation of topors regulates p53 stabilityherein, we have identified topoisomerase i-binding protein (topors), a p53-binding protein, as a plk1 target. We show that plk1 phosphorylates topors on ser(718) in vivo. Significantly, expression of a plk1-unphosphorylatable topors mutant (s718a) leads to a dramatic accumulation of p53 through inhibition of p53 degradation. Topors is an ubiquitin and small ubiquitin-like modifier ubiquitin-protein isopeptide ligase (sumo e3) ligase. Plk1-mediated phosphorylation of topors inhibits topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. | SIGNOR-185838 |
P49137 | P34931 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrate that MK2 phosphorylates HspA1L solely on Ser241, a residue within the N-terminal nucleotide-binding domain of the enzyme. This phosphorylation event enhances the chaperone activity of HspA1L in vitro and renders male germ cells more resistant to heat stress-induced apoptosis. | SIGNOR-273674 |
P55089 | P10275 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | When cells were treated with DHT alone, AR was upregulated and translocated into the nuclei, which might repress UCN1 expression via a potential androgen-responsive element found in human CRF family promoter|These data suggest that DHT differentially influences UCN1 levels under normal and inflammatory conditions in human umbilical vein endothelial cells, which involves AR-dependent and -independent mechanisms respectively. | SIGNOR-253688 |
P49841 | P15941 | 1 | phosphorylation | down-regulates activity | 0.456 | GSK3beta binds directly to an STDRSPYE site in MUC1 and phosphorylates the serine adjacent to proline. Phosphorylation of MUC1 by GSK3beta decreases binding of MUC1 to beta-catenin in vitro and in vivo. | SIGNOR-249356 |
Q08209 | O00429 | 1 | dephosphorylation | up-regulates activity | 0.277 | When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. | SIGNOR-248676 |
Q02156 | Q86XR7 | 1 | phosphorylation | up-regulates | 0.573 | Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram. | SIGNOR-146991 |
Q9UK97 | Q9Y4R8 | 2 | binding | down-regulates quantity by destabilization | 0.441 | Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. The interaction between Tel2/Tti1 and Fbxo9 identified by mass spectrometry suggests that SCFFbxo9 is probably the ubiquitin ligase that mediates degradation of both proteins. | SIGNOR-271996 |
P57059 | Q53ET0 | 1 | phosphorylation | down-regulates | 0.644 | These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities. | SIGNOR-147707 |
P53671 | O43791 | 1 | phosphorylation | down-regulates activity | 0.2 | LIMK2 phosphorylates SPOP at S59, S171 and S226.|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability. | SIGNOR-278338 |
Q06609 | P24941 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.595 | Phosphorylation of the BRCA2 C-terminal RAD51 binding site by CDK2 promotes RAD51 filament disassembly, leading to nucleolitic cleavage of newly synthesized DNA and compromised fork integrity. | SIGNOR-280213 |
P29320 | P52803 | 2 | binding | up-regulates | 0.943 | Highly promiscuous for ephrin-a ligands it binds preferentially efna5 and became active. | SIGNOR-52470 |
P63092 | P43657 | 2 | binding | up-regulates activity | 0.323 | LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa. | SIGNOR-278873 |
Q9Y2R2 | P43403 | 1 | dephosphorylation | down-regulates | 0.706 | Native ptpn22 dephosphorylated lck and zap70 at their activating tyrosine residues tyr-394 and tyr-493, respectively, but not at the regulatory tyrosines tyr-505 (lck) or tyr-319 (zap70). | SIGNOR-144345 |
Q12772 | Q8NBP7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.465 | Recent studies have demonstrated that PCSK9 mRNA expression was upregulated to a greater extent than that of the LDL receptor in human hepatocytes in primary culture. Our findings also support the role of SREBP-2 as a transcriptional regulator of both the LDL receptor and PCSK9 in human enterocytes. | SIGNOR-254459 |
P06241 | P16885 | 1 | phosphorylation | up-regulates activity | 0.575 | The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors. | SIGNOR-249340 |
P09471 | P35462 | 2 | binding | up-regulates activity | 0.465 | 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-256981 |
Q9C0B5 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y | SIGNOR-261150 |
Q8IW41 | P07101 | 1 | phosphorylation | up-regulates | 0.2 | Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation of both ser40 and ser19 induced a high-affinity binding of 14-3-3 proteins, but only the interaction of 14-3-3 with ser19 increased the hth1 activity. | SIGNOR-95479 |
O76090 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.2 | We have identified a PKC phosphorylation site (S358) located in the C terminal region of hBest1 critical for channel rundown. Phosphorylation of this site by PKC activators and PP2A inhibitors reduces channel rundown. | SIGNOR-260880 |
Q9Y243 | P49841 | 1 | phosphorylation | down-regulates activity | 0.736 | Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1 | SIGNOR-245424 |
P59595 | P01100 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260726 |
P35414 | O95837 | 2 | binding | up-regulates activity | 0.253 | 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-256960 |
P31749 | Q53EL6 | 1 | phosphorylation | down-regulates | 0.435 | Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation. | SIGNOR-252505 |
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