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 |
|---|---|---|---|---|---|---|---|
O76064 | P16403 | 1 | polyubiquitination | down-regulates | 0.2 | ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. | SIGNOR-272928 |
P17252 | Q9BZL6 | 1 | phosphorylation | up-regulates activity | 0.393 | Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta.|The position of PKD2 phosphorylated at Ser876 and Ser706/Ser710 is indicated by anarrowhead. | SIGNOR-275955 |
Q14493 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.419 | Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase | SIGNOR-265258 |
O00238 | P36894 | 2 | binding | up-regulates | 0.497 | Using several complementary approaches, we investigated the formation of homomeric and heteromeric complexes between the two known bmp type i receptors | SIGNOR-75649 |
Q9Y2H0 | Q9Y566 | 1 | relocalization | up-regulates activity | 0.696 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264595 |
P78347 | Q99856 | 2 | binding | up-regulates activity | 0.35 | In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels. | SIGNOR-268533 |
Q9NY61 | Q07812 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | We identify the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 as a critical regulator of the cellular outcome of the p53 response. Upon genotoxic stress, AATF is phosphorylated by the checkpoint kinase MK2. Phosphorylation results in the release of AATF from cytoplasmic MRLC3 and subsequent nuclear translocation where AATF binds to the PUMA, BAX and BAK promoter regions to repress p53-driven expression of these pro-apoptotic genes. | SIGNOR-259916 |
Q96PU5 | O15527 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We demonstrate that recombinant NEDD4L stimulates ubiquitylation of OGG1 in vitro, particularly on lysine 341, and that NEDD4L and OGG1 interact in U2OS cells. | SIGNOR-278639 |
Q8NEB9 | O75385 | 0 | phosphorylation | up-regulates activity | 0.713 | In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex. | SIGNOR-279670 |
Q86VB7 | P68871 | 2 | binding | up-regulates activity | 0.442 | These data suggest that hemoglobin may mediate a stimulatory effect on erythropoiesis through the activation of CD163 on hematopoietic progenitor cells. | SIGNOR-251746 |
P10244 | Q13309 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.378 | P19Skp1 and Cul-1 bind to the F-box protein p45Skp2 to form a complex (SCF) that functions as E3 ubiquitin ligase.We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle. | SIGNOR-272572 |
P07949 | P10586 | 0 | dephosphorylation | down-regulates | 0.426 | Lar expression significantly reduced tyrosine-1062 phosphorylation in ret-men2a but not in ret-men2b | SIGNOR-85170 |
Q13568 | P42229 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.287 | The GM-CSF receptor forms a dodecamer structure and recruits JAK2, leading to the activation of STAT5, extracellular signal-regulated kinase (ERK), V-Akt murine thymoma viral oncogene homolog 1 (AKT), and the nuclear translocation of NF-kappaB and IRF5 | SIGNOR-249508 |
Q7L590 | Q9Y4B6 | 2 | binding | down-regulates quantity by destabilization | 0.2 | By screening the known DDB1 interacting proteins, we discovered that VprBP is the substrate recognition subunit that targets Mcm10 for degradation. Hence, these results establish that Cul4-DDB1-VprBP ubiquitin ligase mediates the stress-induced proteolysis of replication factor, Mcm10. | SIGNOR-272046 |
O15111 | O75925 | 1 | phosphorylation | up-regulates activity | 0.38 | In addition, we show that IKKalpha is associated with PIAS1 and mediates the S90 phosphorylation of PIAS1.|Mutational studies indicate that Ser90 phosphorylation is required for PIAS1 to repress transcription. | SIGNOR-278926 |
P68400 | Q96FW1 | 1 | phosphorylation | up-regulates activity | 0.319 | Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. |Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec | SIGNOR-276527 |
Q96S53 | Q9Y281 | 1 | phosphorylation | down-regulates activity | 0.321 | Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin | SIGNOR-246711 |
O43293 | O43293 | 2 | phosphorylation | up-regulates | 0.2 | Mutational analysis showed that phosphorylation of thr180 in the kinase activation t-loop, thr225 in the substrate-binding groove, and thr265 in kinase subdomain x is essential for full zipk autophosphorylation and activity toward exogenous substrates. | SIGNOR-132463 |
P08754 | 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-256490 |
Q13387 | P45983 | 2 | binding | up-regulates | 0.638 | These experiments demonstrated that 10 different jnk isoforms bound to both jip proteins. | SIGNOR-70860 |
P30679 | Q9NQ66 | 2 | binding | up-regulates activity | 0.484 | This suggests that both Gal4 and Gal6 can activate PLC b1. | SIGNOR-278120 |
P48995 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | Taken together, these results indicate that store depletion induces interactions between TRPC1 and PKC\u03b4 in VSMCs, and that these interactions cause PKC\u03b4\u2010dependent phosphorylation of TRPC1. | SIGNOR-279559 |
P23515 | Q96FE5 | 2 | binding | up-regulates | 0.505 | Nogo-a, myelin-associated glycoprotein (mag), and oligodendrocyte myelin glycoprotein (omgp)...signal through a common receptor complex in neurons, which includes the ligand binding nogo-66 receptor (ngr), and two signal-transducing binding partners, p75 and lingo-1... | SIGNOR-133640 |
P60510 | Q13085 | 1 | dephosphorylation | up-regulates activity | 0.242 | PP4 was also found to directly interact with pACC1‑Ser79 in human HepG2 cells. In conclusion, the present study showed that PP4 may be a novel regulator in hepatic lipogenesis through dephosphorylating ACC1 on serine 79, suggesting that PP4 may be a promising therapeutic target in lipid metabolism disorders. | SIGNOR-267724 |
Q02763 | O15123 | 2 | binding | up-regulates | 0.924 | Angiopoietin-1 and -2, bound to tek with similar affinities, and angiopoietin-1 effectively induced tek phosphorylation in hematopoietic cells. Angiopoietin-2 also induced a low level of tek phosphorylation and weakened the phosphorylation induced by angiopoietin-1 | SIGNOR-59808 |
Q9H3M7 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.294 | ERK-dependent Txnip ubiquitination and proteasome degradation depended upon phosphorylation of a PXTP motif threonine (Thr349) located within the C-terminal α-arrestin domain and proximal to a previously characterized E3 ubiquitin ligase-binding site. | SIGNOR-277468 |
Q13129 | Q92963 | 2 | binding | up-regulates activity | 0.309 | Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors. | SIGNOR-220799 |
Q9P1Z0 | Q9H2X6 | 0 | phosphorylation | down-regulates activity | 0.379 | The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4. | SIGNOR-262882 |
Q9ULA0 | Q9P286 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. | PAK5 decreases DNPEP abundance via the ubiquitin-proteasome pathway. | SIGNOR-275651 |
P31785 | P60568 | 2 | binding | up-regulates | 0.866 | Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c). | SIGNOR-144543 |
P29475 | Q13424 | 0 | relocalization | up-regulates | 0.558 | biochemical studies showed that the N-terminal PDZ domain of nNOS binds to a similar PDZ domain of syntrophin (Fig. 1), a dystrophin-associated protein | SIGNOR-236916 |
Q9NRM7 | P00519 | 1 | phosphorylation | down-regulates activity | 0.362 | Inhibition of c-Abl by Lats2 was mediated through Lats2 interaction with and phosphorylation of c-Abl. Lats2 phosphorylates c-Abl at Thr197 in vitro. | SIGNOR-276497 |
Q03164 | O00255 | 2 | binding | up-regulates activity | 0.726 | However, menin dramatically increases the amount of MLL bound at the p27Kip1 and p18Ink4c loci, suggesting that it either directly or indirectly promotes MLL recruitment to these targets. Once recruited, MLL could enhance transcription by a number of mechanisms.Overall, the data suggest that transcriptional regulation by menin involves increasing MLL protein association with target loci. | SIGNOR-255890 |
P29350 | O15524 | 2 | binding | up-regulates | 0.325 | All together, our results indicate that shp-1 inhibits prlr and epor signaling by recruitment and targeting of socs-1 to jak2, highlighting a new mechanism of shp-1 regulation of cytokine-receptor signaling. | SIGNOR-118572 |
Q05086 | P00519 | 0 | phosphorylation | down-regulates activity | 0.273 | Our results suggest that c-Abl protects p53 from HPV-E6-E6AP complex-mediated degradation by phosphorylating E6AP and impairing its E3 ligase activity | SIGNOR-260930 |
P08151 | Q6PHR2 | 0 | phosphorylation | up-regulates activity | 0.673 | We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro. | Our data suggest that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins. | SIGNOR-260797 |
Q05923 | P31152 | 2 | dephosphorylation | down-regulates activity | 0.353 | DUSP2 can dephosphorylate both ERK3 and ERK4 when expressed in mammalian cells.|Finally, we demonstrate that DUSP2 inhibits ERK3 and ERK4 mediated activation of MK5. | SIGNOR-277068 |
O15524 | P42226 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.638 | We found that IL-4, like IFN-gamma, induces rapid de novo expression of SOCS-1 in primary macrophages. Induction of SOCS-1 gene expression by IL-4 is STAT6-dependent. | SIGNOR-249570 |
P14780 | P51684 | 0 | null | up-regulates activity | 0.2 | We hypothesized that MIP-3alpha promotes pancreatic cancer invasion through the up-regulation of MMP-9, a Type 4 collagenase. | SIGNOR-278042 |
P20962 | Q09472 | 2 | binding | up-regulates activity | 0.322 | Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells. | SIGNOR-268461 |
Q9Y490 | P05106 | 2 | binding | up-regulates activity | 0.793 | Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails. | SIGNOR-257625 |
O00213 | O00141 | 0 | phosphorylation | down-regulates activity | 0.345 | In the present study, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 attenuates the interaction between FE65 and APP (XREF_FIG).|In this regard, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 abolishes the effect of FE65 on APP processing and the amount of secreted Abeta is comparable to APP + Mock control (XREF_FIG). | SIGNOR-278220 |
O95180 | P51168 | 2 | binding | up-regulates activity | 0.2 | This study describes the functional interaction between Cav3.2 calcium channels and the Epithelial Sodium Channel (ENaC). β- and γ-ENaC subunits could be co-immunoprecipitated with Cav3.2 calcium channels from brain lysates, dorsal horn and lumbar dorsal root ganglia. Αβγ-ENaC channels enhanced Cav3.2 calcium channel trafficking to the plasma membrane in tsA-201 cells. This effect was reciprocal such that Cav3.2 channel expression also enhanced β-ENaC trafficking to the cell surface. these findings reveal ENaC as an interactor and potential regulator of Cav3.2 calcium channels expressed in neuronal tissues. | SIGNOR-269273 |
Q9NRI5 | Q9GZM8 | 2 | binding | up-regulates activity | 0.58 | Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3ε. 14-3-3ε is involved in the proper localization of NUDEL and LIS1 in axons. the association with NUDEL and LIS1 supports the notion that DISC1 contributes to the neuronal development and morphology | SIGNOR-252162 |
O15194 | Q15797 | 1 | 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 |
Q92734 | Q96JE7 | 2 | binding | up-regulates | 0.499 | We identify tfg-1, a new conserved regulator of protein secretion that interacts directly with sec-16 and controls the export of cargoes from the endoplasmic reticulum in caenorhabditis elegans. Hydrodynamic studies indicate that tfg-1 forms hexamers that facilitate the co-assembly of sec-16 with copii subunits. | SIGNOR-173279 |
P62993 | Q7L591 | 2 | binding | up-regulates activity | 0.554 | An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. | SIGNOR-268448 |
P23582 | Q15714 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.257 | TSC-22 significantly enhanced CNP promoter activity in GH3 cells. | SIGNOR-266226 |
Q86Y13 | P20671 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271753 |
P28482 | O94953 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | In addition, the phosphorylation of JMJD2B via p-ERK at Thr305, Ser352, Ser566 and Thr1065 contribute to JMJD2B stability. p-ERK stabilizes the JMJD2B protein level by protecting JMJD2B from ubiquitination and proteasome degradation. | SIGNOR-276744 |
Q13950 | P10451 | 1 | transcriptional regulation | up-regulates quantity | 0.488 | Ets-1 and Runx2 are critical transcriptional regulators of OPN expression in CT26 colorectal cancer cells. Suppression of these transcription factors results in significant down-regulation of the OPN metastasis protein. | SIGNOR-245336 |
O43464 | Q9BXM7 | 0 | phosphorylation | up-regulates | 0.607 | Htra2 is phosphorylated on activation of the p38 pathway, occurring in a pink1-dependent mannerwe suggest that pink1-dependent phosphorylation of htra2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress. | SIGNOR-158052 |
Q8IXJ6 | P06493 | 0 | phosphorylation | down-regulates | 0.412 | Here, we demonstrate that sirt2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1. Overexpression of sirt2 mediates a delay in cellular proliferation that is dependent on serine 368 phosphorylation. | SIGNOR-154681 |
Q15256 | P27361 | 0 | phosphorylation | up-regulates activity | 0.67 | Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL. | SIGNOR-249477 |
Q92934 | O14757 | 0 | phosphorylation | down-regulates activity | 0.2 | Chkl binds and phosphorylates BAD protein.|Taken together, our results suggest that Chk1 may inactivate BAD by associating with and phosphorylating residues critical for BAD function in response to DNA damage. | SIGNOR-279159 |
P21731-2 | P25098 | 0 | phosphorylation | down-regulates activity | 0.2 | These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization. | SIGNOR-274088 |
Q9NRA8 | P45983 | 0 | phosphorylation | up-regulates | 0.322 | Identification of 4e-t phosphorylation sites regulated by jnk. identification of these residues as phosphorylation sites (ser301, ser374, ser513, ser587, ser693, and ser752) was obtained by ms/ms sequencing, these results demonstrate that jnk activity is required to stimulate the assembly of pbs in response to oxidative stress. | SIGNOR-199004 |
Q96MU8 | O94907 | 2 | binding | up-regulates | 0.838 | Dkk1 has been shown to inhibitwnt by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to blockwnt/betBeta-catenin. Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of thewntreceptor lrp6 from the plasma membrane. | SIGNOR-88838 |
P10275 | P55317 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.766 | FOXA1 directly inhibits AR expression and thus the transcription of its target genes. FOXA1 inhibits AR gene expression in prostate cancer. oss of FOXA1 may lead to androgen-independent AR signaling and thus castration-resistant prostate cancer progression. Indeed, we have recently reported that FOXA1 is downregulated in CRPC | SIGNOR-251541 |
P19086 | P28223 | 2 | binding | up-regulates activity | 0.312 | 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-257021 |
P22736 | P28482 | 0 | phosphorylation | up-regulates activity | 0.669 | NGFI-B is an inducible orphan nuclear receptor that initiates apoptosis. Growth factors such as EGF activate the MAP kinase ERK, whose activity may determine if a cell survives or undergoes apoptosis. EGF stimulation of cells leads to phosphorylation of threonine in NGFI-B. Thr-142 of NGFI-B is comprised in a consensus MAP kinase site and was identified as a preferred substrate for ERK2 (but not ERK1) in vitro. | SIGNOR-249430 |
P51452 | P04626 | 1 | dephosphorylation | down-regulates activity | 0.268 | Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. | We found that VHR decreased ErbB2 phosphorylation in vitro and in a cellular context, and the dephosphorylation of ErbB2 was more evident at Tyr-877 and Tyr-1221 than those at Tyr-1139 and Tyr-1248 (supplemental Fig. S1). Our data indicated that VHR was a cellular PTP against EGFR and ErbB2. | SIGNOR-248533 |
Q05086 | Q9H2S1 | 1 | ubiquitination | up-regulates activity | 0.286 | UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. | SIGNOR-278527 |
P09471 | P35372 | 2 | binding | up-regulates activity | 0.64 | 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-256990 |
P35222 | Q9Y297 | 0 | ubiquitination | down-regulates | 0.872 | Here we show that fwd1 (the mouse homologue of slimb/betatrcp), an f-box/wd40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, axin, gsk-3beta and apc. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with fwd1. Fwd1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. | SIGNOR-67374 |
Q96G91 | P63092 | 2 | binding | up-regulates activity | 0.385 | 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-256788 |
Q96GD4 | Q9NQG5 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, we revealed that CREPT/RPRD1B interacted with Aurora B to regulate the expression of Cyclin B1 in gastric cancer cells. Interestingly, Aurora B phosphorylates S145 in a well-conserved motif of CREPT/RPRD1B. We proposed that phosphorylation of CREPT/RPRD1B by Aurora B is required for promoting the transcription of Cyclin B1 | SIGNOR-265499 |
Q13490 | Q01094 | 1 | ubiquitination | up-regulates activity | 0.336 | The ability of cIAP1 to promote wt E2F1 transcriptional activity was retained by all E2F1 mutants, except the K161R/164R mutant for which cIAP1 was completely inactive and the K185R whose basal transactivation activity was weakly enhanced by cIAP1 (XREF_FIG).|Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. | SIGNOR-278688 |
O43683 | P04637 | 1 | phosphorylation | up-regulates activity | 0.484 | In addition, purified Bub1 directly phosphorylates p53 on Ser-37 in vitro , possibly inducing cellular senescence [ xref ].|Studies have shown that depletion and inhibition of Aurora A, Aurora B, Plk1, or Bub1 induces cellular senescence or cell death in a p53 dependent or -independent but p73 dependent manner in many different cell types , - ]. | SIGNOR-280199 |
Q9Y3C5 | O95630 | 2 | binding | down-regulates quantity by destabilization | 0.531 | RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome. | SIGNOR-272953 |
Q8N264 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.433 | ROCK phosphorylates FilGAP, and this phosphorylation stimulates its RacGAP activity and is a requirement for FilGAP-mediated bleb formation. | As shown in Fig. 5b, ROCK stimulated the incorporation of phosphate into FilGAP. We identified seven potential phosphorylation sites in FilGAP that was isolated by preparative SDSPAGE and subjected to trypsin digestion and mass spectrometry: Ser 391, Ser 402, Ser 413, Ser 415, Ser 437, Thr 452, and a cluster of serine and threonine residues (SSTTT) at position 573577 (see Supplementary Information, Table S2). | SIGNOR-249302 |
Q9BXW9 | Q9NW38 | 0 | ubiquitination | up-regulates activity | 0.9 | Thus, eight of the nine components of the FA core complex are FA proteins (FANC‐A, B, C, E, F, G, L, and M). Furthermore, two of the newly discovered FA proteins have enzymatic activities: FANCL is a ubiquitin ligase essential for FANCD2 monoubiquitination in vivo | SIGNOR-263250 |
Q9UQL6 | O94806 | 0 | phosphorylation | up-regulates activity | 0.265 | Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67]. | SIGNOR-275926 |
P00519 | Q4KMG0 | 2 | binding | up-regulates activity | 0.518 | Abl binds a proline-rich motif in cdo via its sh3 domain, and these regions of abl and cdo are required for their promyogenic effects. Cdo is important for full abl kinase activity | SIGNOR-185762 |
O15530 | P53350 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency | SIGNOR-243519 |
Q14738 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.297 | In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth. | SIGNOR-276319 |
P0DMS8 | P63096 | 2 | binding | up-regulates activity | 0.461 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256671 |
Q00535 | P37231 | 1 | phosphorylation | down-regulates activity | 0.574 | CDK5 in turn phosphorylates PPARgamma at Ser273 and prevents the transcription of specific PPARgamma target genes that have anti-diabetic effects . | SIGNOR-278189 |
P25116 | P07384 | 0 | cleavage | up-regulates activity | 0.376 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus | SIGNOR-263559 |
P60484 | P98170 | 0 | ubiquitination | down-regulates quantity | 0.691 | Finally, we found that XIAP can directly ubiquitinate PTEN in vitro.|Overexpression of XIAP induces polyubiquitination of PTEN and proteasome dependent decrease of PTEN protein levels. | SIGNOR-278751 |
P55265 | P31749 | 0 | phosphorylation | down-regulates activity | 0.281 | AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively | SIGNOR-276193 |
P16410 | P06241 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.77 | CTLA-4 can associate with the Src kinases Fyn and Lck and that transfection of Fyn or Lck, but not the unrelated kinase ZAP70, can induce tyrosine phosphorylation of CTLA-4 on residues Y201 and Y218.  Phosphorylation of CTLA-4 Y201 in Jurkat cells correlated with cell surface accumulation of CTLA-4. | SIGNOR-251161 |
P42345 | Q9BY84 | 0 | dephosphorylation | down-regulates activity | 0.274 | MKP7 represses mTOR function.|These results suggest that MKP7 could directly dephosphorylate pmTOR and pPRAS40 and forming complexes with these two proteins ( xref ). | SIGNOR-277067 |
P31749 | O60825 | 1 | phosphorylation | up-regulates activity | 0.654 | These findings suggest that PKB-dependent binding of 14-3-3s to phospho-Ser483 of cardiac PFK-2 mediates the stimulation of glycolysis by growth factor. | SIGNOR-252555 |
P49841 | Q00653 | 1 | phosphorylation | down-regulates activity | 0.271 | More recently, phosphorylation of S707 and S711 by GSK3beta has been shown to promote complete proteasomal degradation of p100 involving the E3 ligase Fbw7 .|These studies suggest that a pool of p100 is constitutively phosphorylated by GSK3beta at S707 and S711, triggering the Fbw7 mediated ubiquitination and proteasomal degradation of p100 which controls the levels of p100 available for the non canonical pathway. | SIGNOR-279186 |
Q13535 | Q01831 | 2 | binding | up-regulates | 0.477 | Atrand atm physically interacted with xpc and promptly localized to the uv damage sites. | SIGNOR-201112 |
P68400 | Q13547 | 1 | phosphorylation | up-regulates | 0.62 | Human hdac1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, ser(421) and ser(423), were unambiguously identified. Loss of phosphorylation at ser(421) and ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of hdac1. | SIGNOR-111015 |
Q13882 | P40763 | 1 | phosphorylation | up-regulates activity | 0.622 | 29 PTK6 promotes activating phosphorylation of STAT3 at tyrosine residue 705.|STAT3 has been shown to promote tumor initiation of different tumor types, including those of the gastrointestinal tract and skin, and PTK6 was previously shown to promote STAT3 activation and tumorigenesis in mouse models of colon and skin cancer. | SIGNOR-278346 |
Q9GZY6 | P43405 | 0 | phosphorylation | up-regulates activity | 0.592 | Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.The dramatic reduction in phosphorylation of the LAB Y233F mutant suggested that Tyr233 is a primary target of the Syk family kinases. | SIGNOR-273576 |
P55017 | Q9BYP7 | 0 | phosphorylation | up-regulates activity | 0.455 | We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs | SIGNOR-264624 |
O15344 | P67775 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.453 | MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation | SIGNOR-271467 |
Q96A00 | P62140 | 2 | binding | down-regulates activity | 0.505 | We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin | SIGNOR-265742 |
Q96SN8 | Q12834 | 2 | binding | down-regulates activity | 0.313 | We show here that inhibition of CDK5RAP2 expression causes chromosome mis-segregation, fails to maintain the spindle checkpoint, and is associated with reduced expression of the spindle checkpoint proteins BUBR1 and MAD2 and an increase in chromatin-associated CDC20.|We found that the APC activator CDC20, but not others we exam-ined, was present in the CDK5RAP2 immunocomplex in HeLa cell extracts (Fig. 3A). CDK5RAP2 was detected in the CDC20 immunocomplex as well (Fig. 3B). | SIGNOR-260311 |
P49810 | Q14790 | 0 | cleavage | up-regulates activity | 0.332 | In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329. | SIGNOR-261752 |
Q9Y572 | Q13263 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that TRIM28 phosphorylation at S473 is RIPK3-dependent and suggest that RIPK1/RIPK3 activation induces TRIM28 phosphorylation at S473, which may play an important role in the regulation of transcriptional activity. | SIGNOR-279107 |
P28329 | Q05513 | 0 | phosphorylation | up-regulates | 0.288 | Finally, basal chat phosphorylation in neurons is mediated predominantly by pkc at ser-476, with pkc activation increasing phosphorylation at ser-440 and enhancing chat activity. | SIGNOR-129340 |
P07814 | P23443 | 0 | phosphorylation | up-regulates activity | 0.2 | Our studies reveal an unexpected adipogenic pathway resulting from mTORC1-S6K1 activation of EPRS ( xref ).|These results establish the requirement for mTORC1-activated S6K1 to phosphorylate EPRS at Ser 999 ( xref ). | SIGNOR-279483 |
P28482 | P10275 | 1 | phosphorylation | down-regulates | 0.511 | Map kinase-dependent phosphorylation at ar ser-515 was supported by the decrease in intensity of the slower migrating 23-kda band after treatment with both egf and increasing concentrations of the map kinase inhibitor, u0126 | SIGNOR-178718 |
P00742 | P00734 | 1 | cleavage | up-regulates activity | 0.459 | The present data point to key roles of FVIII and FIX in FX activation at the site of a platelet thrombus by supporting: (i) thrombin generation, (ii) thrombus growth and platelet phosphatidylserine exposure, and (iii) fibrin formation at the platelet surface. The likely mechanism is that tenase activity via FVIIIa and FIXa, which is confined to the sites of platelet thrombi, generates FXa that directly catalyzes the conversion of prothrombin into thrombin. | SIGNOR-263539 |
P36888 | P48735 | 1 | phosphorylation | down-regulates activity | 0.421 | FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment, | SIGNOR-267632 |
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