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 |
|---|---|---|---|---|---|---|---|
P24522 | Q9UQ88 | 2 | binding | down-regulates activity | 0.2 | GADD45alpha inhibits CDK11p58 kinase activity|We identified CDK11p58 as an interaction partner of GADD45α by co-immunoprecipitation analysis. We corroborated these data by co-immunoprecipitation in vitro translation assays, showing that all three members of the GADD45 family interact with CDK11p58. | SIGNOR-273023 |
Q15797 | O15194 | 0 | dephosphorylation | down-regulates activity | 0.498 | Smad proteins transduce bone morphogenetic protein (BMP) and transforming growth factor-beta (TGFbeta) signals upon phosphorylation of their C-terminal SXS motif by receptor kinases.|Phosphatases that dephosphorylate the linker region are therefore likely to play an integral part in the regulation of Smad activity. We reported previously that small C-terminal domain phosphatases 1, 2, and 3 (SCP1-3) dephosphorylate Smad1 C-terminal tail, thereby attenuating BMP signaling. |The linker region of Smad1 consists of four MAPK phosphorylation sites (Ser-187, Ser-195, Ser-206, and Ser-214) | SIGNOR-248314 |
P06239 | P20963 | 1 | phosphorylation | up-regulates | 0.764 | During tcr signaling, lck interacts with numerous molecules, including tcr-zeta. The binding of lck to the tyrosine-phosphorylated zeta chain of the tcr would serve to strengthen the interaction of the associated cd4 and the tcr complex, leading to increased avidity for the antigen-major histocompatibility protein complex. | SIGNOR-41361 |
Q9NPG1 | Q14344 | 2 | binding | up-regulates | 0.244 | Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families. | SIGNOR-122892 |
P14635 | P50539 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.266 | Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression | Mxi1 inhibits the promoter activity of the cyclin B1 gene. | SIGNOR-266064 |
P50281 | Q13443 | 1 | cleavage | down-regulates quantity by destabilization | 0.341 | Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top). | SIGNOR-260301 |
P42336 | Q9UQC2 | 2 | binding | up-regulates | 0.466 | The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival | SIGNOR-204966 |
Q13322 | P07949 | 2 | binding | up-regulates | 0.543 | Grb7 and grb10, likely relay signals emanating from ret to other, as yet, unidentified targets within the cell | SIGNOR-41699 |
O15350 | O15111 | 0 | phosphorylation | up-regulates activity | 0.336 | IKK-alpha had an ability to stabilize p73 by inhibiting its polyubiquitination, and enhanced p73 mediated transcriptional activation as well as proapoptotic activity.|In addition, IKK-alpha phosphorylated the NH 2 -terminal portion of p73 and a kinase deficient mutant form of IKK-alpha had undetectable effect on p73. | SIGNOR-279697 |
P48729 | Q5T0W9 | 2 | binding | up-regulates quantity | 0.344 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273746 |
P15056 | Q92911 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer. BRAF induces TGFβ secretion leading to NIS repression in a MEK-ERK–independent manner but cooperating with the MEK-ERK pathway to induce strong tumor invasion, two major traits acquired during PTC progression. | SIGNOR-251989 |
Q96GD4 | O15392 | 1 | phosphorylation | down-regulates | 0.795 | Phosphorylation by aurora-b negatively regulates survivin function . hat survivin is phosphorylated at t117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphaseduring mitosis | SIGNOR-154569 |
O43353 | O14733 | 1 | phosphorylation | up-regulates activity | 0.44 | Collectively, the results suggest that RIPK2 binds to and activates MKK7.|Radioactive in vitro kinase assay showed that RIPK2 can directly phosphorylate kinase-dead (K149A) MKK7 (Fig.\u00a0 xref ). | SIGNOR-280105 |
P29803 | Q15120 | 0 | phosphorylation | down-regulates | 0.563 | Pdh2 was found to be very similar to pdh1 / in the mechanism of inactivation by phosphorylation of three sites;and (iv) in the phosphorylation of sites 1 and 2 by pdk3 / (ser-264 (site 1), ser-271 (site 2), and ser-203 (site 3) | SIGNOR-143974 |
Q07812 | P31749 | 0 | phosphorylation | down-regulates activity | 0.486 | Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophilsWe suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members | SIGNOR-252538 |
Q7Z6E9 | P67809 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.317 | RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain, leading to ubiquitination and proteosomal degradation of YB-1 | SIGNOR-271773 |
Q13114 | Q96PU5 | 0 | ubiquitination | up-regulates activity | 0.27 | Nedd4l promotes TRAF3 to interact with cIAP1/2 and HECTD3.|Ubiquitination of TRAF3 by Nedd4l promotes interaction of TRAF3 with proteins such as cIAP1/2, HECTD3, and TBK1. | SIGNOR-278587 |
P63096 | O95379 | 2 | binding | up-regulates activity | 0.2 | TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation | SIGNOR-256491 |
P78426 | P52945 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.503 | In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1. | SIGNOR-255542 |
Q86UT6 | Q15366 | 2 | binding | up-regulates activity | 0.4 | Moreover, poly(rC) binding protein 2 (PCBP2) interacts with NLRX1 to participate in the NLRX1-induced degradation of MAVS and the inhibition of antiviral responses during HCV infection. | SIGNOR-260359 |
P35372 | P35626 | 0 | phosphorylation | down-regulates activity | 0.2 | These results demonstrate that the T180A mutation probably blocks GRK3- and arr3-mediated desensitization of MOR by preventing a critical agonist-dependent receptor phosphorylation and suggest a novel GRK3 site of regulation not yet described for other G-protein-coupled receptors | SIGNOR-247915 |
P43405 | Q8WV28 | 1 | phosphorylation | up-regulates | 0.806 | The phosphorylation of multiple tyrosine residues not only amplifies plcgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex. | SIGNOR-96044 |
P35579 | Q96QB1 | 2 | binding | down-regulates activity | 0.2 | Our study has shown that Dlc1 interacts with non-muscle myosin heavy chain II-A (Myh9), plectin and spectrin proteins in different multiprotein complexes. Overexpression of Dlc1 led to increased phosphorylation of Myh9 protein and activation of Rac1 GTPase. Dlc1 interacts with phosphorylated Myh9 (Ser-1943). This association of Dlc1 with S1943 phosphorylated Myh9, suggests that Dlc1 may be involved in reduced Myh9 filament stability. | SIGNOR-269283 |
Q14865 | O75151 | 2 | binding | up-regulates activity | 0.56 | We found that phosphorylated PHF2 then associates with ARID5B, a DNA-binding protein, and induce demethylation of methylated ARID5B. Assembly of the PHF2–ARID5B complex, its recruitment to target promoters, and its H3H9Me2 demethylase activity were dependent on PKA activity. | SIGNOR-264515 |
Q9NPH5 | P06241 | 0 | phosphorylation | down-regulates activity | 0.271 | We found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. | SIGNOR-277273 |
P31749 | P26678 | 1 | phosphorylation | down-regulates activity | 0.289 | Akt interacts with and phosphorylates PLN at Thr(17), the Ca(2+)-calmodulin-dependent kinase IIdelta site, whereas silencing Akt signaling, through the knock-out of phosphatidylinositol-dependent kinase-1, resulted in reduced phosphorylation of PLN at Thr(17). | SIGNOR-252578 |
P20042 | P78344 | 2 | binding | up-regulates activity | 0.753 | Unlike eIF4GI/II, DAP5 binds eIF2β, a subunit of the eIF2 complex that delivers methionyl-tRNA to ribosomes. | SIGNOR-266385 |
P37840 | P53350 | 0 | phosphorylation | down-regulates activity | 0.351 | Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. | SIGNOR-189045 |
Q8WXE1 | Q92547 | 2 | binding | up-regulates | 0.796 | Topbp1 directly activates atr/atrip and promotes atr-mediated chk1 phosphorylation. | SIGNOR-163214 |
Q9BUB5 | P67775 | 0 | dephosphorylation | down-regulates | 0.514 | Moreover, a dephosphorylation assay revealed that pp2a could directly dephosphorylate mnk1 and eif4e. | SIGNOR-168314 |
Q13873 | P12644 | 2 | binding | up-regulates | 0.78 | Bmp-4 bound to alk-3 and alk-6 efficiently | SIGNOR-35763 |
P55040 | Q08289 | 2 | binding | down-regulates activity | 0.2 | 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-261720 |
Q06330 | Q96K30 | 2 | binding | down-regulates | 0.417 | Thus, we propose that rita acts as a negative modulator of the notch signalling pathway, controlling the level of nuclear rbp-j/cbf-1, where its amounts are limiting. | SIGNOR-170089 |
Q12837 | P03372 | 2 | binding | up-regulates activity | 0.571 | the POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3-ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect. | SIGNOR-241208 |
Q9NRC8 | P68431 | 1 | deacetylation | up-regulates activity | 0.2 | SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. | SIGNOR-275874 |
Q05513 | P08047 | 1 | phosphorylation | up-regulates | 0.484 | Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 binding to the platelet-derived growth factor-d promoter. | SIGNOR-160774 |
O43541 | P51817 | 0 | phosphorylation | up-regulates activity | 0.431 | In vitro phosphorylation assays demonstrated that PrKX phosphorylates Smad6 at a serine residue. | SIGNOR-279270 |
P35573 | Q6VVB1 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.56 | The E3 ubiquitin ligase Malin interacts with and promotes the ubiquitination of AGL. | SIGNOR-271669 |
P11802 | Q9NS23 | 1 | phosphorylation | down-regulates | 0.409 | This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4. | SIGNOR-159849 |
Q9UHD0 | Q9UHF4 | 2 | binding | up-regulates | 0.745 | Il-19 signals only through the type i il-20r complex. | SIGNOR-110671 |
Q9HCK8 | Q9BT81 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268922 |
P36897 | O15105 | 2 | binding | down-regulates activity | 0.789 | SMAD7 functions as an antagonist to TGFB by binding to the TBRI and thus inhibiting activation of SMAD2 and SMAD3. | SIGNOR-64088 |
Q15303 | P42338 | 2 | binding | up-regulates | 0.485 | Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4. | SIGNOR-146882 |
P27361 | P14921 | 1 | phosphorylation | up-regulates | 0.672 | We found that hgf/sf activates the erk1 map kinase, leading to the phosphorylation of the threonine 38 residue of ets1 | SIGNOR-116494 |
Q15910 | P31269 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.396 | These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression. | SIGNOR-260068 |
P36507 | P67775 | 0 | dephosphorylation | down-regulates | 0.493 | In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a. | SIGNOR-166652 |
Q9BZS1 | P13501 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.434 | Given its role as a potent chemoattractant for T cells, CCL5 can be utilized to attract Tregs to malignant epithelial cells. Wang et al. demonstrated that Forkheadbox protein 3 (FOXP3), a key transcription factor for Tregs, was highly ex- pressed in pancreatic cancer cell lines, which, in turn, upregulated CCL5 expression | SIGNOR-277727 |
P10398 | P01111 | 2 | binding | up-regulates | 0.835 | The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175216 |
P0DP23 | O00418 | 2 | binding | up-regulates | 0.465 | The calmodulin-binding region is located between amino acids 51 and 96 | SIGNOR-82505 |
Q15116 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.659 | Related to the latter notion, we recently showed that SHP2 dephosphorylates PD-1 to disassemble the PD-1:SHP2 complex ( xref ). | SIGNOR-277052 |
P07948 | P14317 | 1 | phosphorylation | up-regulates activity | 0.714 | Lyn and Syk synergistically phosphorylate HS1, and that Tyr-378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis. PMID: 9104825 PMCID: PMC2196252 | SIGNOR-251401 |
Q13363 | Q13131 | 0 | phosphorylation | down-regulates | 0.2 | We found that an activated amp-activated protein kinase (ampk) phosphorylates ctbp1 on ser-158 upon metabolic stresses. Moreover, ampk-mediated phosphorylation of ctbp1 (s158) attenuates the repressive function of ctbp1 | SIGNOR-200250 |
P78543 | Q16236 | 2 | binding | up-regulates activity | 0.2 | BTG2 stimulation of antioxidant gene expression is also NFE2L2-dependent. We further demonstrate that BTG2 is a binding partner for NFE2L2 and increases its transcriptional activity. | SIGNOR-254647 |
O14966 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.581 | In an attempt to mimic phosphorylation of Rab29 by LRRK2, we mutated the phosphorylation sites to Glu and observed that the Rab29[T71E,S72E] mutant failed to activate LRRK2 (Fig\u00a0 xref B).|To test whether phosphorylation of Rab29 at Thr71 and Ser72 by LRRK2 was required for activation of LRRK2, we mutated these sites both to Ala. | SIGNOR-279474 |
P49418 | O76039 | 0 | phosphorylation | down-regulates activity | 0.36 | This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293.| The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis | SIGNOR-245881 |
Q9Y237 | P68400 | 0 | phosphorylation | down-regulates activity | 0.326 | As proved by MALDI-TOF mass spectrometry and MS/MS fragmentation, hPar14 is phosphorylated at Ser19 in vitro and in vivo. In human HeLa cells the protein is most likely modified by casein kinase 2 (CK2). |In contrast to wild-type hPar14, the in vitro DNA-binding affinity of the Glu19 mutant is strongly reduced, suggesting that only the dephosphorylated protein is the active DNA-binding form of hPar14 in the nucleus. | SIGNOR-265753 |
P52333 | O15524 | 2 | binding | down-regulates activity | 0.708 | SOCS proteins bind to janus kinase and to certain cytokine receptors and signaling molecules, thereby suppressing further signaling events. Studies have shown that SOCS proteins are key physiological regulators of inflammation. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of adaptive immunity.Both SOCS1 and SOCS3 can inhibit JAK tyrosine kinase activity directly through their kinase inhibitory regions (KIR). | SIGNOR-238642 |
Q8WV44 | P05771 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.317 | RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear. | SIGNOR-271667 |
Q9Y625 | O95644 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.251 | NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. | SIGNOR-264022 |
P27361 | O14994 | 1 | phosphorylation | up-regulates | 0.2 | A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. | SIGNOR-121402 |
O60674 | P10721 | 2 | binding | up-regulates activity | 0.614 | C-Kit stimulates rapid and transient tyrosine phosphorylation of JAK2. JAK2 was found to be constitutively associated with c-Kit, with increased association after ligand stimulation of c-Kit | SIGNOR-254954 |
P63241 | P49366 | 0 | post translational modification | up-regulates activity | 0.933 | Deoxyhypusine synthase (DHPS) utilizes spermidine and NAD as cofactors to incorporate a hypusine modification into the eukaryotic translation initiation factor 5A (eIF5A). Hypusine is essential for eIF5A activation, which, in turn, plays a key role in regulating protein translation of selected mRNA that are associated with the synthesis of oncoproteins, thereby enhancing tumor cell proliferation. | SIGNOR-266374 |
Q8WZ42 | P28482 | 0 | phosphorylation | up-regulates quantity | 0.387 | ERK2 phosphorylates three serines in titin\u2019s N2B-Us: S3918, S3960, and S4010 (the latter of which is well conserved) (). | SIGNOR-279636 |
P63092 | P30968 | 2 | binding | up-regulates activity | 0.444 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256792 |
P68366 | P43405 | 0 | phosphorylation | up-regulates activity | 0.33 | Syk, Activated by Cross-linking the B-cell Antigen Receptor, Localizes to the Cytosol Where It Interacts with and Phosphorylates alpha-Tubulin on Tyrosine | SIGNOR-246626 |
P27361 | Q96Q27 | 1 | phosphorylation | up-regulates activity | 0.265 | Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. |Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation. | SIGNOR-272241 |
Q9UQB8 | Q9Y6W5 | 2 | binding | up-regulates activity | 0.802 | Here we demonstrate that IRSp53, a substrate for insulin receptor with unknown function, is the 'missing link' between Rac and WAVE. Activated Rac binds to the amino terminus of IRSp53, and carboxy-terminal Src-homology-3 domain of IRSp53 binds to WAVE to form a trimolecular complex. From studies of ectopic expression, we found that IRSp53 is essential for Rac to induce membrane ruffling, probably because it recruits WAVE, which stimulates actin polymerization mediated by the Arp2/3 complex. | SIGNOR-265556 |
P23510 | P43489 | 2 | binding | up-regulates | 0.921 | Activation of nf-kappab in ox40-transfected hsb-2 cells was detected by electrophoretic mobility shift assay within 30 min after the binding of the ligand gp34. | SIGNOR-54927 |
Q07820 | P27361 | 0 | phosphorylation | up-regulates | 0.436 | We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1. | SIGNOR-179812 |
P43629 | P17252 | 0 | phosphorylation | down-regulates activity | 0.2 | Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. | SIGNOR-276080 |
Q66K64 | Q14498 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.377 | Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. | SIGNOR-272203 |
P58400 | P58417 | 2 | binding | up-regulates | 0.548 | Purification of neurexin ialpha revealed that it is tightly complexed to a secreted glycoprotein called neurexophilin 1 | SIGNOR-62699 |
P53350 | P14635 | 1 | phosphorylation | up-regulates activity | 0.922 | Phosphorylation of cyclin b1 is central to its nuclear translocationduring cell-cycle progression in hela cells, a change in the kinase activity of endogenous plk1 toward s147 and/or s133 correlates with a kinase activity in the cell extractsa mutant cyclin b1 in which s133 and s147 are replaced by alanines remains in the cytoplasm, whereas wild-type cyclin b1 accumulates in the nucleus during prophase.Together, these results suggest that phosphorylation of s133 and s147 is necessary for the nuclear translocation of cyclin b1 during prophase, and that phosphorylation of s126 and s128 may stimulate the nuclear translocation. | SIGNOR-105719 |
P42574 | Q9BQQ3 | 1 | cleavage | up-regulates activity | 0.396 | In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein | SIGNOR-260613 |
P40763 | P29350 | 0 | dephosphorylation | down-regulates | 0.457 | Stat3 may also be a substrate of shp1 | SIGNOR-178699 |
P06493 | Q14674 | 1 | phosphorylation | down-regulates | 0.572 | Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro | SIGNOR-113126 |
O14965 | O95983 | 1 | phosphorylation | up-regulates | 0.286 | These results suggest that the biochemical changes of mbd3 may be intimately related to the targeting of mbd3 to centrosomes. aurora-a phosphorylates mbd3 | SIGNOR-93693 |
O95837 | Q96RI0 | 2 | binding | up-regulates activity | 0.429 | 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-257419 |
P07101 | Q8IW41 | 0 | 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 |
Q16620 | P22001 | 1 | phosphorylation | down-regulates | 0.377 | Previously we have shown that acute brain-derived neurotrophic factor (bdnf) activation of neurotrophin receptor tyrosine kinase b (trkb) suppresses the shaker voltage-gated potassium channel (kv1.3) via phosphorylation of multiple tyrosine residues in the n and c terminal aspects of the channel protein. | SIGNOR-183515 |
P63096 | P20309 | 2 | binding | up-regulates activity | 0.277 | 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-256739 |
Q05086 | Q8IXH7 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.326 | In this paper, we identify here trihydrophobin 1 (TH1), an integral subunit of the human negative transcription elongation factor (NELF) complex, as a novel E6-AP interaction protein and a target of E6-AP-mediated degradation. Overexpression of E6-AP results in degradation of TH1 in a dose-dependent manner, whereas knock-down of endogenous E6-AP elevates the TH1 protein level. | SIGNOR-271404 |
P22736 | P45983 | 0 | phosphorylation | down-regulates | 0.5 | We also identified the exact phosphorylation site of jnk to be serine 95 at the n terminus of tr3, around which a classical jnk phosphorylation motif exists. Furthermore, we demonstrated that tr3 phosphorylation by jnk coincided with its ubiquitination and degradation, resulting in the loss of its mitogenic activity. | SIGNOR-149998 |
P27694 | P54727 | 2 | binding | up-regulates activity | 0.575 | GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo | SIGNOR-275698 |
P63092 | Q92847 | 2 | binding | up-regulates activity | 0.283 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256782 |
Q9NZN5 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.905 | 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-260539 |
P25445 | Q13546 | 2 | binding | up-regulates activity | 0.651 | Fas associates with rip. Rip is a novel form of apoptosis-inducing protein | SIGNOR-235430 |
Q15391 | P08754 | 2 | binding | up-regulates activity | 0.403 | 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-256866 |
Q13459 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.774 | 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-260509 |
P41208 | O43303 | 2 | binding | up-regulates activity | 0.698 | We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis. | SIGNOR-265967 |
Q8IWJ2 | P51151 | 0 | null | up-regulates activity | 0.54 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253087 |
Q13177 | P19105 | 1 | phosphorylation | up-regulates activity | 0.495 | In this study we report that gamma-PAK, which is activated by the GTP-binding proteins Cdc42 and Rac, catalyses phosphorylation of intact non-muscle myosin II and isolated recombinant RLC. Phosphopeptide maps and phosphoamino acid analysis revealed that gamma-PAK phosphorylates Ser-19 but does not phosphorylate Thr-18.Taken together, these data suggest that myosin II activation by the p21-activated family of kinases may be physiologically important in regulating cytoskeletal organization. | SIGNOR-263020 |
O14543 | P42224 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.677 | Expression of SOCS1 and SOCS3 is regulated primarily by activation of STAT1 and STAT3, respectively, although their expression can be mediated through other signaling cascades, including the mitogen activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) pathways. | SIGNOR-249565 |
P27707 | P06493 | 2 | binding | down-regulates activity | 0.378 | We demonstrate that dCK interacts with cyclin-dependent kinase 1 (Cdk1) after IR and that the interaction inhibits Cdk1 activity both in vitro and in vivo. | SIGNOR-275805 |
P16220 | O75676 | 0 | phosphorylation | up-regulates | 0.605 | Msk1 and msk2 directly phosphorilate and activete transcription factors such as creb1, atf1 msk was the kinase responsible for phosphorylation of the transcription factor creb in response to tcr stimulation. | SIGNOR-157158 |
P00519 | P17844 | 1 | phosphorylation | up-regulates | 0.357 | These results suggested that p68 was phosphorylated by c-abl in ht-29 cells under stimulation of pdgf. we demonstrated that tyrosine phosphorylation of p68 at y593 mediated pdgf-stimulated epithelial-mesenchymal transition (emt). We showed that pdgf treatment led to phosphorylation of p68 at y593 in the cell nucleus. The y593-phosphorylated p68 (referred to as phosphor-p68) promotes beta-catenin nuclear translocation via a wnt-independent pathway. | SIGNOR-149988 |
Q01130 | Q13627 | 0 | phosphorylation | down-regulates activity | 0.408 | Dyrk1A inhibits SC35\u2032s activity to promote tau exon 10 inclusion.|Dyrk1A interacts with and phosphorylates SC35 and inhibits its activity to promote tau exon 10 inclusion. | SIGNOR-278307 |
P00533 | Q96TA1 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras. | SIGNOR-273637 |
P31751 | P98170 | 1 | phosphorylation | up-regulates | 0.42 | Here, we demonstrate that akt, including akt1 and akt2, interacts with and phosphorylates x-linked inhibitor of apoptosis protein (xiap) at residue serine-87 in vitro and in vivo. Phosphorylation of xiap by akt protects xiap from ubiquitination and degradation in response to cisplatin. Moreover, autoubiquitination of xiap is also inhibited by akt. | SIGNOR-119492 |
P49674 | P56645 | 1 | phosphorylation | down-regulates activity | 0.74 | The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. Moreover, CKIepsilon and CKIdelta are able to induce nuclear translocation of mPer3, which requires its nuclear localization signal. The mutation in potential phosphorylation sites on mPer3 decreased the extent of both nuclear translocation and degradation of mPer3 that are stimulated by CKIepsilon. | In mut7 in which all of the conserved serine and threonine residues in this region were mutated, the ratio of the shifted band was greatly reduced reproducibly. | SIGNOR-250816 |
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