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 |
|---|---|---|---|---|---|---|---|
P00519 | P12004 | 1 | phosphorylation | up-regulates activity | 0.333 | In the current study, we are able to establish a new pathway in which the Ron receptor tyrosine kinase activates c-Abl which in turn catalyzes Y211 phosphorylation of PCNA.|We previously showed that Y211 phosphorylation stabilized chromatin bound PCNA, which in turn promoted cell proliferation, and that c-Abl functioned to enhance chromatin association of PCNA in cancer cells. | SIGNOR-279389 |
P35568 | P23458 | 0 | phosphorylation | up-regulates activity | 0.708 | Janus kinase-dependent activation of insulin receptor substrate 1 | SIGNOR-251343 |
Q5VUA4 | P10275 | 2 | binding | down-regulates activity | 0.372 | Using different promoters and cells, we confirmed that AR-mediated transactivation was repressed by TZF in a dose-dependent manner (Fig. 1A and B). Endogenous ARmediated transactivation was also inhibited by expression of TZF; These results indicate that amino acid residues 512–663 are essential for the repressive effect of TZF on AR-mediated transactivation. | SIGNOR-261187 |
Q9BVV6 | Q86YT6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Conversely, expression of active, but not inactive, Mib1 likewise drastically reduced the levels of centriolar Talpid3 (XREF_FIG).|Mib1 promotes the poly-ubiquitylation of Talpid3, Cep131, and PCM1. | SIGNOR-278829 |
P00519 | P42684 | 1 | phosphorylation | up-regulates | 0.517 | The results show that arg is stabilized in response to 0.1 mm h2o2 by autophosphorylation of y-261, consistent with involvement of the arg kinase function in regulating arg levels. The results further demonstrate that c-abl-mediated phosphorylation of arg on y-261 similarly confers arg stabilization | SIGNOR-134396 |
O14965 | P35222 | 1 | phosphorylation | up-regulates quantity | 0.346 | In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic \u03b2-catenin expression in esophageal squamous cell carcinoma tissues.|We also demonstrate for the first time that Aurora-A directly interacts with \u03b2-catenin and phosphorylates \u03b2-catenin at Ser552 and Ser675. | SIGNOR-278468 |
P63096 | Q96RI0 | 2 | binding | up-regulates | 0.385 | Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13) | SIGNOR-151162 |
P05771 | P09211 | 1 | phosphorylation | up-regulates activity | 0.2 | Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently | SIGNOR-276023 |
Q16690 | Q16539 | 1 | dephosphorylation | down-regulates | 0.537 | The activity of mapks can be also regulated by a family of dusps, which dephosphorylates bot phosphotyrosine and phopsphothreonine residues. | SIGNOR-166574 |
Q00987 | P38936 | 2 | binding | down-regulates quantity by destabilization | 0.643 | MDM2 facilitates p21 degradation independent of ubiquitination and the E3 ligase function of MDM2. Instead, MDM2 promotes p21 degradation by facilitating binding of p21 with the proteasomal C8 subunit. The physical interaction between p21 and MDM2 was demonstrated both in vitro and in vivo with the binding region in amino acids 180-298 of the MDM2 protein. | SIGNOR-272954 |
P15260 | P01579 | 2 | binding | up-regulates | 0.886 | Ifn-g Binds to the ifn-g Receptor binding subunit (ifn-gR1;receptor chain 1), a species-specific cell surface transmembrane receptor chain (41, 42). A second transmembrane protein (ifn-gR2) (4345) is required for signal transduction | SIGNOR-95626 |
P23497 | Q12834 | 2 | binding | down-regulates quantity by destabilization | 0.2 | Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. | SIGNOR-272724 |
P68400 | P42575 | 1 | phosphorylation | down-regulates | 0.309 | Here we show that protein kinase (pk) ck2 phosphorylates procaspase-2 directly at serine-157. When intracellular pkck2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a piddosome-independent manner. | SIGNOR-140836 |
P58012 | Q96EB6 | 0 | deacetylation | down-regulates | 0.501 | We find that foxl2 activity is repressed by the sirt1 deacetylase. | SIGNOR-182306 |
P51149 | Q8NEB9 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.484 | The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7 | SIGNOR-261302 |
Q05516 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.311 | UTX catalytic activity has been reported to upregulate expression of the master transcription factor PLZF and to modulate superenhancer accessibility in invariant natural killer T cells. | SIGNOR-260038 |
Q7Z434 | Q14790 | 1 | relocalization | up-regulates | 0.587 | Another protein suggested to play a role in caspase-8 translocation to mitochondria is the mitochondrial membrane protein cardif | SIGNOR-143572 |
P46527 | Q86TM6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | The E3 ligase activity of Hrd1 is required for p27 kip1 ubiquitination, because co-expression of Hrd1 containing an alanine point mutation at the critical cysteine within the RING E3 ligase region (Hrd1/CA) failed to enhance p27 kip1 ubiquitination (XREF_FIG).|Therefore, our study identifies Hrd1 as an E3 ligase of p27 kip1 and establishes that Hrd1 mediated p27 kip1 degradation plays an important role in T-cell immunity. | SIGNOR-278786 |
O60346 | P49841 | 0 | phosphorylation | down-regulates | 0.353 | In addition, we show that the beta-trcp-mediated degradation requires phosphorylation of phlpp1 by casein kinase i and glycogen synthase kinase 3beta (gsk-3beta), and activation of the phosphatidylinositol 3-kinase/akt pathway suppresses the degradation of phlpp1 by inhibiting the gsk-3beta activity. | SIGNOR-188330 |
Q6NXT2 | Q92831 | 0 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269617 |
P84022 | P27361 | 0 | phosphorylation | down-regulates | 0.623 | These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3. | SIGNOR-66781 |
P27361 | P47712 | 1 | phosphorylation | up-regulates | 0.658 | Activated map kinase phosphorylates cpla2 at ser-505, causing increased enzymatic activity of cpla2, which is only realized upon translocation of cpla2 to the membrane. | SIGNOR-38434 |
Q16584 | P06493 | 0 | phosphorylation | down-regulates activity | 0.2 | Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases. | SIGNOR-277603 |
P14651 | P09429 | 2 | binding | up-regulates activity | 0.298 | We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein. | SIGNOR-219902 |
Q13233 | Q92918 | 0 | phosphorylation | up-regulates | 0.455 | Hpk1 binds and phosphorylates mekk1 directly, | SIGNOR-43996 |
P30305 | Q15418 | 0 | phosphorylation | up-regulates | 0.253 | Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b. | SIGNOR-202125 |
Q12933 | P61088 | 2 | binding | up-regulates activity | 0.428 | Traf2, ubc13, and ikkgamma were required for complex assembly and activation of mekk1 and mapk cascades. | SIGNOR-179479 |
Q15759 | P15923 | 1 | phosphorylation | up-regulates | 0.436 | Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription, while the nonphosphorylatable e47 mutant ser140ala fails to heterodimerize with myod and displays impaired myogenic potentia | SIGNOR-134190 |
Q92547 | Q9UIF7 | 2 | binding | up-regulates | 0.373 | Binding of myh directly participates in atr and topbp1 activation in dna damage signaling, leading to apoptosis. | SIGNOR-173972 |
O14757 | Q53H47 | 1 | phosphorylation | down-regulates activity | 0.49 | We previously found that Chk1 phosphorylation of Metnase on S495 enhanced its DNA DSB repair activity but decreased its ability to re-start stalled replication forks. Here we show that phosphorylated Metnase feeds back to increase the half-life of Chk1. Chk1 half-life is regulated by DDB1 targeting it to Cul4A for ubiquitination and destruction. Metnase decreases Chk1 interaction with DDB1, and decreases Chk1 ubiquitination. | SIGNOR-273610 |
Q15418 | Q07352 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the Messenger RNA destabilization activity of ZFP36L1.|These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the mRNA destabilization activity of ZFP36L1. | SIGNOR-279280 |
P25116 | Q14344 | 2 | binding | up-regulates | 0.599 | The protease-activated receptors (PAR)2 are a class of G protein-coupled receptors (GPCR) that are activated by the proteolysis of the N-terminal exodomain. Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13). | SIGNOR-196006 |
O14775 | P35462 | 2 | binding | up-regulates activity | 0.452 | The D2-class dopamine receptors (D2, D3, and D4) couple to the Gi/o family of G proteins and thus induce inhibition of AC | SIGNOR-264994 |
Q13490 | P55060 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.333 | We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase-8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation. | SIGNOR-272812 |
P0DMV9 | Q96M98 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Our in vitro data suggest that CHIP competes with Hsp70 in binding to Parkin, probably via suppression of the ATPase activity of Hsc/Hsp70 (Figure 4E).In fact, it acts as an inhibitory factor that suppresses the ubiquitination of Pael-R mediated by Parkin in vitro, and Hsp70 enhances the efficiency of folding of overexpressed Pael-R in vivo. | SIGNOR-272891 |
Q14242 | P16109 | 2 | binding | up-regulates | 0.927 | The major ligand for p-selectin on leukocytes is p-selectin glycoprotein ligand-1 (PSGL-1) | SIGNOR-47625 |
P0DP23 | Q8N5S9 | 2 | binding | up-regulates | 0.754 | The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases | SIGNOR-232178 |
P36956 | P17612 | 0 | phosphorylation | down-regulates | 0.2 | Sterol regulatory element-binding protein 1 is negatively modulated by pka phosphorylation. ser338 of srebp-1a and ser314 of srebp-1c are pka phosphorylation sites. | SIGNOR-143392 |
P49588 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269414 |
P68036 | P46934 | 1 | ubiquitination | up-regulates activity | 0.544 | Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1). | SIGNOR-272735 |
P43405 | P00519 | 0 | phosphorylation | up-regulates activity | 0.253 | Abl kinases modulate Syk kinase activation.|Expression of constitutively active Abl (AblPP) increased Syk Y346 phosphorylation, whereas the phosphorylation was unaffected in cells expressing kinase inactive form of Abl (AblKR) (XREF_FIG). | SIGNOR-279665 |
P35625 | P50281 | 2 | binding | down-regulates activity | 0.568 | FAP cilia regulated the expression of TIMP3, a secreted metalloproteinase inhibitor, that inhibited MMP14 to block adipogenesis. | SIGNOR-255908 |
P63000 | Q70Z35 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.609 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260571 |
Q86UR1 | P10415 | 1 | null | down-regulates activity | 0.2 | BH3-only proteins containing only a single BH domain and including Puma, Noxa, Bid and Bad as well as other factors are particularly important for such neutralisation, binding and regulating the anti-apoptotic Bcl-2 proteins to promote apoptosis | SIGNOR-209684 |
Q9Y397 | P01112 | 1 | palmitoylation | up-regulates activity | 0.435 | Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein. | SIGNOR-261352 |
Q13043 | P17252 | 1 | phosphorylation | up-regulates activity | 0.2 | Mst1 and Mst2 activate PKC\u03b1 to disrupt the LyGDI-Rac complex.|Thus, the phosphorylation of PKC\u03b1 at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKC\u03b1. | SIGNOR-280146 |
O14920 | Q9Y4G8 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Taken together, these results indicate that IKK\u03b2-dependent phosphorylation of RAPGEF2 is required for RAPGEF2 degradation induced by HGF and mediated by \u03b2TrCP. | SIGNOR-279807 |
P46531 | Q9NYJ7 | 2 | binding | up-regulates activity | 0.491 | Notch signaling is a highly conserved pathway involved in cell fate choice during development with Delta and Jagged constituting the two evolutionary conserved families of Notch ligands. These ligands are transmembrane proteins with conserved biochemical structure that share their receptors and signal through a common mechanism. Upon ligand binding Notch receptors are proteoliticaly cleaved, the intracellular domain of Notch (NICD) is released and translocated to the nucleus, where it activates target genes. In mammals, four receptors and five ligands have been described. Delta-1, Delta-3 and Delta-4 are homologues to Drosophila Delta and Jagged-1 and Jagged-2 to Drosophila Serrate. | SIGNOR-209738 |
P12931 | P01112 | 1 | 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 |
Q15722 | O95837 | 2 | binding | up-regulates activity | 0.435 | 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-257086 |
O95837 | Q15722 | 2 | binding | up-regulates activity | 0.435 | 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-257086 |
Q14686 | Q4ZG55 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Herein, using growth-regulating estrogen receptor binding 1 (GREB1) as an ERα target gene in Ishikawa cells, we demonstrate that nuclear receptor co-activator 6 (NCOA6) is essential for estradiol (E2)/ERα-activated GREB1 transcription. We found that NCOA6 associates with the GREB1 promoter and enhancer in an E2-independent manner and that NCOA6 knockout reduces chromatin looping, enhancer-promoter interactions, and basal GREB1 expression in the absence of E2. | SIGNOR-265883 |
Q06124 | P42224 | 1 | dephosphorylation | down-regulates activity | 0.743 | SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei|In SHP-2-/- mouse fibroblast cells, Stat1 phosphorylation at both the tyrosine residue Tyr(701) and the serine residue Ser(727) |Overexpression of SHP-2 in 293T cells inhibited IFNgamma-dependent Stat1 phosphorylation and suppressed Stat1-dependent induction of luciferase activity. | SIGNOR-248673 |
P48058 | P05129 | 0 | phosphorylation | up-regulates | 0.702 | We found that pka phosphorylation of the ampa receptor subunits glur4 and glur1 directly controlled the synaptic incorporation of ampa receptors in organotypic slices from rat hippocampus. | SIGNOR-97558 |
P63000 | Q53QZ3 | 0 | gtpase-activating protein | down-regulates activity | 0.581 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260470 |
Q02447 | P27361 | 0 | phosphorylation | up-regulates | 0.299 | 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. | SIGNOR-157276 |
P48736 | Q15303 | 2 | binding | up-regulates | 0.319 | Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4. | SIGNOR-146888 |
Q68D86 | P51955 | 0 | phosphorylation | down-regulates activity | 0.2 | CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis. | SIGNOR-275626 |
P46934 | Q14457 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.46 | BECN1 stability was increased by NEDD4 via K6 and K27 ubiquitination during autophagy induction, thereby promoting autophagy activation.|Further, NEDD4 mediated K6- and K27- linkage ubiquitination of BECN1, leading to elevated stability of BECN1 and increased autophagy. | SIGNOR-278558 |
Q9BXL7 | O15530 | 0 | phosphorylation | up-regulates | 0.55 | We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts. | SIGNOR-134866 |
P31749 | Q6PKG0 | 1 | phosphorylation | down-regulates activity | 0.288 | LARP1 is a direct substrate of Akt/S6K1 and mTORC1. Akt is a physiologically relevant primary kinase for S770/S979 phosphorylation of LARP1|Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5’UTRs and relieves its inhibitory activity on RP mRNA translation. | SIGNOR-260992 |
O15530 | P17252 | 1 | phosphorylation | up-regulates | 0.417 | One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. | SIGNOR-126066 |
O14713 | P05107 | 2 | binding | down-regulates activity | 0.313 | Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation | SIGNOR-257649 |
Q80H93 | Q14653 | 2 | binding | down-regulates activity | 0.2 | Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3.We also found that proteins 8b and 8ab could physically interact with IRF3. This counteracting effect was partially mediated by protein 8b/8ab-induced degradation of IRF3 in a ubiquitin-proteasome-dependent manner. Taken together, we propose that SARS-CoV may exploit the unique functions of proteins 8b and 8ab as novel mechanisms to overcome the effect of IFN response during virus infection.. | SIGNOR-260240 |
P02679 | P04275 | 2 | binding | down-regulates activity | 0.499 | Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a). | SIGNOR-251968 |
Q04721 | P21741 | 2 | binding | up-regulates | 0.491 | We showed that mk binds to the notch2 receptor in hacat keratinocytes. We further found that mk activates notch2 | SIGNOR-161427 |
P45984 | P05412 | 2 | binding | up-regulates | 0.884 | C-jun is targeted for ubiquitination by its association with inactive c-jun nh2-terminal kinase (jnk).Phosphorylation By activated jnk protects c-jun from ubiquitination. | SIGNOR-53791 |
P43250 | P30411 | 1 | phosphorylation | down-regulates activity | 0.288 | Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration. | SIGNOR-251207 |
O75381 | O00628 | 2 | binding | up-regulates activity | 0.89 | The peroxisomal docking complex is a key component of the import machinery for matrix proteins. The core protein of this complex, Pex14, is thought to represent the initial docking site for the import receptors Pex5 and Pex7. | SIGNOR-253028 |
P11308 | O60216 | 0 | relocalization | down-regulates activity | 0.2 | Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity. | SIGNOR-261515 |
Q9HAW8 | Q99626 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.257 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253968 |
Q9HCU9 | Q09472 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.363 | BRMS1 suppresses lung cancer metastases through an E3 ligase function on histone acetyltransferase p300. BRMS1 induces polyubiquitination of p300, resulting in its proteasome-mediated degradation. | SIGNOR-266408 |
O60674 | Q9NRF2 | 2 | binding | up-regulates activity | 0.692 | The SH2B adaptor protein 1 (SH2B1) is a key regulator of leptin, as it enhances leptin signalling by both stimulating Janus kinase 2 (JAK2) activity and assembling a JAK2/IRS1/2 signalling complex | SIGNOR-253078 |
O15327 | P60484 | 1 | dephosphorylation | down-regulates activity | 0.632 | In support, the increase in PTEN caused by INPP4B knockdown was associated with increased phosphorylation of the Ser380, Thr382, Thr383 and Ser385 cluster of the protein (XREF_FIG), which is known to increase PTEN half-life, in colon cancer cells.|Exogenous INPP4B could pull down and dephosphorylate endogenous PTEN, suggesting that effect of INPP4B on PTEN in colon cancer cells is not due to cell-type-specific characteristics of INPP4B per se.|INPP4B downregulates PTEN in colon cancer cells. | SIGNOR-277018 |
P63096 | P25021 | 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-257049 |
Q14157 | Q99496 | 2 | binding | up-regulates activity | 0.385 | UBAP2L associates with BMI1 and RNF2. UBAP2L, BMI1, RNF2, and PHC1 define a novel Polycomb subcomplex | SIGNOR-261316 |
Q8N2I9 | P17676 | 2 | binding | down-regulates quantity by destabilization | 0.28 | The COP1-interacting protein STK40 (Durzynska et al., 2017), which was detected in c/EBPβ complexes from BMDMs (Figure 1B), also appeared to contribute to the suppression of c/EBPβ in microglia. Specifically, deletion of the STK40 pseudokinase increased the amount of c/EBPβ protein without increasing the amount of Cebpb mRNA | SIGNOR-261925 |
Q9Y5S8 | P05771 | 0 | phosphorylation | up-regulates activity | 0.2 | Site-directed mutagenesis and isothermal titration calorimetry indicated that protein kinase C-beta1 phosphorylates Nox1 at threonine 429. Moreover, Nox1 threonine 429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly | SIGNOR-264729 |
P35462 | P63096 | 2 | binding | up-regulates activity | 0.548 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256702 |
O14640 | Q13467 | 2 | binding | up-regulates activity | 0.659 | Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. | SIGNOR-258957 |
P56945 | P12931 | 0 | phosphorylation | up-regulates activity | 0.803 | Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of CasBased on these data, 11 tyrosine residues (132, 169, 183, 196, 238, 253, 271, 291, 301, 391, and 414) were phosphorylated by Src|the biological activity of Cas depends on its phosphorylation by Src (16–18). After phosphorylation, Cas associates with a number of proteins, including Crk, Src, phosphatidylinositol 3-kinase, Nck, and phospholipase Cgamma, via SH2 binding motifs | SIGNOR-246393 |
P35240 | Q9UKE5 | 0 | phosphorylation | up-regulates activity | 0.2 | Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3). | SIGNOR-278386 |
P12004 | Q149N8 | 0 | ubiquitination | up-regulates | 0.553 | We provide evidence that similar to rad5, shprh physically interacts with the human rad6rad18 and mms2ubc13 protein complexes, and importantly, we show that it exhibits an ubiquitin ligase activity and mediates mms2ubc13-dependent polyubiquitylation of pcna. Thus, shprh is a functional homolog of rad5. | SIGNOR-187757 |
P01111 | P48736 | 2 | binding | up-regulates | 0.722 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. It was also described that ras interacts with pi3k in a direct manner.llysine residue 227 is essential for the interaction of ras with pi3k | SIGNOR-175228 |
P53350 | Q96R06 | 1 | phosphorylation | up-regulates activity | 0.394 | Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate. | SIGNOR-279423 |
P55211 | P27361 | 0 | phosphorylation | down-regulates activity | 0.535 | Inhibition of caspase-9 through phosphorylation at thr 125 by erk mapk | SIGNOR-101548 |
P54646 | Q13393 | 1 | phosphorylation | up-regulates | 0.2 | Ampk-wild type (wt) stimulates pld activity, while ampk-dominant negative (dn) inhibits it. Ampk regulates pld1 activity through phosphorylation of the ser-505 and this phosphorylation is increased by the presence of amp. | SIGNOR-164293 |
P19784 | Q99801 | 1 | phosphorylation | up-regulates | 0.315 | In vitro kinase assays followed by mass spectrometric analyses demonstrated that ck2 phosphorylated recombinant nkx3.1 on thr89 and thr93. We have also determined that nkx3.1 is degraded primarily through a proteasomal pathway, suggesting that phosphorylation by ck2 protects nkx3.1 from degradation. | SIGNOR-145501 |
Q13418 | P31751 | 1 | phosphorylation | up-regulates activity | 0.615 | ILK mediated activation of Akt2 is required for Tbeta4 inducible expression of MMP-2 and EC motility.|Our experiments suggest that ILK phosphorylates Akt2 at Ser474, that Akt2 is a better substrate than Akt1, and that a post-translational modification to ILK is required for its activity. | SIGNOR-279055 |
Q13315 | Q04206 | 1 | phosphorylation | down-regulates activity | 0.502 | Interestingly, another group has identified that in the VP-16 induced NF-\u03baB activation, ATM binds to RelA directly and phosphorylates RelA on Ser 547, a post-translational modification that represses a subset of NF-\u03baB-dependent genes ( xref ).|Our findings that ablation of ATM reduces RelA serine 276 phosphorylation, suggests a mechanism for how ROS mediates RelA serine 276 phosphorylation in the TNF pathway (Figure -D). | SIGNOR-279006 |
P25098 | Q13188 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, these studies support a role for GRK2 phosphorylation of Mst2 residues Ser-18 and Ser-316 in EGF-promoted centrosome separation.|Thus GRK2 appears to mediate EGF promoted cleavage and activation of Mst2. | SIGNOR-278206 |
P59594 | O00303 | 2 | binding | down-regulates activity | 0.2 | Coronavirus spike protein inhibits host cell translation by interaction with eIF3f | SIGNOR-260255 |
P01189-PRO_0000024969 | P33032 | 2 | binding | up-regulates activity | 0.2 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268716 |
O43353 | Q676U5 | 2 | binding | down-regulates activity | 0.384 | In human monocyte-derived dendritic cells, NOD2 activation by MDP induced physical interaction between ATG16L1 and RIPK2 and negatively regulated NF-κB activation. It is important to note that ATG16L1 acts synergistically with IRF4 to inhibit RIPK2 polyubiquitination. | SIGNOR-280457 |
P09603 | P15509 | 2 | binding | up-regulates | 0.337 | Granulocyte-macrophage colony-stimulating factor (gm-csf) is an important hematopoietic cytokine that exerts its effects by interaction with the gm-csf receptor (gmr) on the surface of responsive cells. The gm-csf receptor consists of two subunits: gmralpha, which binds gm-csf with low affinity, and gmrbeta, which lacks intrinsic ligand-binding capability but complexes with gmralpha to form a high-affinity receptor (gmralpha/beta). | SIGNOR-72455 |
P17676 | P17174 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells. Deletion studies revealed that regions P2 and P4 are critical for promoter activity. In gel retardation experiments, the P4 region bound different C/EBP-related proteins in different tissues | SIGNOR-254051 |
Q92793 | P22087 | 1 | acetylation | down-regulates activity | 0.27 | Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206) | SIGNOR-275897 |
Q16695 | Q9UIF8 | 2 | binding | down-regulates activity | 0.2 | The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation. | SIGNOR-266620 |
Q15139 | O95251 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | We show that PKD1 directly interacts and phosphorylates KAT7 at Thr97 and Thr331 in vitro and in vivo. PKD1-mediated phosphorylation of KAT7 enhances its expression levels and stability by reducing its ubiquitination-mediated degradation. | SIGNOR-277828 |
O43255 | P55036 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.432 | S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. | SIGNOR-272748 |
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