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 |
|---|---|---|---|---|---|---|---|
Q14457 | Q9P2Y5 | 2 | binding | up-regulates activity | 0.861 | UVRAG interacts with Beclin 1, leading to activation of autophagy and thereof inhibition of tumorigenesis. | SIGNOR-150825 |
Q5U5R9 | O75925 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.389 | We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. | SIGNOR-272421 |
P24386 | Q92696 | 2 | binding | down-regulates activity | 0.77 | Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. | SIGNOR-265570 |
O15492 | P12931 | 0 | phosphorylation | up-regulates | 0.346 | Src-mediated rgs16 tyrosine phosphorylation promotes rgs16 stability. / this result suggests src phosphorylates native rgs16 at residue tyr177 in vitro. | SIGNOR-98271 |
O96013 | P16949 | 1 | phosphorylation | down-regulates activity | 0.283 | Indeed, we show here that inactivating phosphorylation of the endogenous stathmin on serine-16 is also induced by the active PAK4 in mitotic egg extract and is likely to participate in the observed stabilization of the MT asters ( xref , right). | SIGNOR-280058 |
Q06418 | O43524 | 1 | phosphorylation | down-regulates activity | 0.2 | However, the present study in tPA and NMDA treated neurons establishes the link between PS mediated activation of Tyro3 and FKHRL1 phosphorylation which inactivates pro apoptotic FKHRL1 and mediates PS 's beneficial effects.|We also show that inhibition of the extrinsic apoptotic cascade by PS requires Tyro3 mediated phosphorylation of FKHRL1 which in turn inhibits FasL production and FasL dependent caspase-8 activation in the extrinsic pathway. | SIGNOR-279669 |
P17252 | P55273 | 1 | phosphorylation | up-regulates | 0.2 | Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation. | SIGNOR-197285 |
O15067 | P28482 | 0 | phosphorylation | up-regulates | 0.2 | T619 in PFAS is required to mediate ERK2-dependent purine synthesis stimulation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation. | SIGNOR-267306 |
Q92837 | Q92997 | 2 | binding | up-regulates | 0.454 | These results indicate that cki epsilon-dependent phosphorylation of dvl enhances the formation of a complex of dvl-1 with frat-1 and that this complex leads to the activation of the wnt signaling pathway. | SIGNOR-97877 |
P35813 | P46937 | 1 | dephosphorylation | up-regulates activity | 0.269 | Although the authors show an in vitro kinase assay where PPM1A supposedly dephosphorylates YAP on Ser127, Fig. 4A lacks a positive control to ensure that PPM1A purified from cells is active.|The protein phosphatase PPM1A dephosphorylates and activates YAP to govern mammalian intestinal and liver regeneration. | SIGNOR-276984 |
P38405 | P41231 | 2 | binding | up-regulates activity | 0.2 | 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-256902 |
P07355 | P07947 | 0 | phosphorylation | up-regulates activity | 0.2 | Activated YES1 interacts with ANXA2 andphosphorylates ANXA2 at Tyr24 site that induces ANXA2 activation and increases ANXA2 nuclear distribution , leading to activation of the tumorpromoting transcription factors ( such as Myc , Stat3 , Stat6 ) that promotes GC invasion and metastasis .|YES1 phosphorylates ANXA2 at Tyr24 site that leads to ANXA2 activation and increased ANXA2 nuclear distribution. | SIGNOR-279435 |
P04049 | O60346 | 0 | dephosphorylation | down-regulates activity | 0.272 | PHLPP1 and PHLPP2 dephosphorylate RAF1 to reduce its signaling, increase the invasive and migratory activities of CRC cells, and activate the epithelial-mesenchymal transition. In Apc(Min) mice, loss of PHLPP1 promotes tumor progression. | SIGNOR-237449 |
Q13315 | O94874 | 2 | phosphorylation | up-regulates activity | 0.2 | Furthermore, ATM phosphorylates UFL1 at serine 462, enhancing UFL1 E3 ligase activity and promoting ATM activation in a positive feedback loop. | SIGNOR-265075 |
Q8ND76 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.2 | Our in vitro and cellular analyses supported the mass spectrometry data that implicated serine 326 (S326) as the phospho-acceptor site on CCNY by AMPK. |Mechanistically the S326 phosphorylation by AMPK promotes the interaction of CCNY with CDK16, which in turn autophosphorylates S336, which serves as a marker for active CCNY-CDK16 | SIGNOR-273011 |
Q9ULU4 | Q8IVL1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We also confirmed transcriptional coactivator functions of ZMYND8 in ERα-driven reporter assays and on endogenous E2-dependent genes (Figure 5F,G). siRNA knockdown of ZMYND8 showed markedly decreased transcription at the presumptive ERα/Z3 target genes ADORA1 and NAV2, while the classical ERα targets pS2/TFF1 and GREB1 appear to be less affected (Figure 5G), suggesting likely gene-specificity of ZMYND8. | SIGNOR-266209 |
O43791 | Q9HCU9 | 1 | ubiquitination | down-regulates quantity | 0.402 | Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells. | SIGNOR-268857 |
P30411 | P09471 | 2 | binding | up-regulates activity | 0.2 | 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-256974 |
P49327 | Q6Y1H2 | 0 | chemical activation | up-regulates activity | 0.2 | Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, | SIGNOR-267761 |
P53355 | Q16623 | 1 | phosphorylation | down-regulates activity | 0.339 | Syntaxin-1A phosphorylation by DAP kinase or its S188D mutant, which mimics a state of complete phosphorylation, significantly decreases syntaxin binding to Munc18-1, a syntaxin-binding protein that regulates SNARE complex formation and is required for synaptic vesicle docking. | SIGNOR-251083 |
Q13616 | P63208 | 2 | binding | up-regulates | 0.959 | The human f box protein beta-trcp associates with the cul1/skp1 complex and regulates the stability of beta-catenin. | SIGNOR-64511 |
Q99490 | Q00535 | 0 | phosphorylation | up-regulates | 0.262 | Here, we demonstrate that cyclin dependent kinase 5 (cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates pike-a at ser-279 in its gtpase domain in glioblastoma cells. This phosphorylation event stimulates pike-a gtpase activity and the activity of its downstream effector akt. | SIGNOR-178660 |
Q07890 | P01116 | 1 | guanine nucleotide exchange factor | up-regulates | 0.713 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. | SIGNOR-175265 |
Q9UQ26 | Q01668 | 2 | binding | up-regulates activity | 0.347 | Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs). In conclusion, we propose that RIM2α and RIM3γ directly interact with the C-terminus of the pore-forming subunit of CaV1.3 Ca2+ channels and positively regulate their plasma membrane expression in HEK293 cells. | SIGNOR-264356 |
Q00987 | P10914 | 1 | ubiquitination | down-regulates quantity | 0.388 | HIV-1 Tat Recruits HDM2 E3 Ligase To Target IRF-1 for Ubiquitination and Proteasomal Degradation.|IRF-1 ubiquitination by HDM2 is specifically increased during HIV-1 infection in the presence of increasing amounts of Tat and is mediated by the formation of a trimeric complex between Tat, IRF-1, and HDM2, as demonstrated by coimmunoprecipitation analysis (XREF_FIG). | SIGNOR-278590 |
Q96IF1 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.256 | The Rac effector PAK1 was also transiently activated upon cell-cell adhesion and directly phosphorylated Ajuba (Thr172). | SIGNOR-278449 |
P04792 | P30793 | 2 | binding | up-regulates quantity by stabilization | 0.2 | GTP cyclohydrolase I (GCH), an oligomeric protein composed of 10 identical subunits, is required for the synthesis of neurotransmitters; mutations in GCH are associated with dopa-responsive dystonia (DRD) and hyperphenylalaninemia. Mutated GCH proteins are unstable and prone to dominant-negative effect. We show herein that expression of the GCH mutant GCH-201E or the splicing variant GCH-II caused intracellular inclusion bodies. When Hsp27 was expressed together with the GCH mutants, Hsp27 expression decreased the formation of inclusion bodies by GCH (as assessed by immunofluorescence) and decreased the amount of insoluble GCH mutant proteins (as assessed by Western blot). we demonstrated that Hsp27 increases the expression of the wild-type GCH protein, causes the appearance of the soluble GCH-II protein, and decreases the quantities of insoluble mutated GCH protein. Therefore, it is likely that Hsp27 improves the folding of mutated GCH proteins, so they can stay in free cytosolic compartment. | SIGNOR-252222 |
Q15121 | Q9UQM7 | 0 | phosphorylation | up-regulates | 0.2 | Pea-15 is a phosphoprotein containing a ser-104 phosphorylated by protein kinase c and a ser-116 phosphorylated by camkii (calcium/calmodulin-dependent protein kinase ii) or akt. Phosphorylation of ser-104 is implicated in the regulation of glucose metabolism, while phosphorylation at ser-116 is required for pea-15 recruitment to the disc (death-initiation signalling complex) | SIGNOR-137614 |
Q9NPG1 | Q93097 | 2 | binding | up-regulates | 0.63 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131777 |
O14490 | Q9UQM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.397 | CaMKIIα activated by the NMDA receptor phosphorylates GKAP Ser54 to induce polyubiquitination of GKAP. | SIGNOR-276429 |
Q9HC98 | Q9P0K8 | 1 | phosphorylation | up-regulates activity | 0.2 | Additionally, we found that NEK6 phosphorylated FOXJ2 at Thr23 and Ser254 ( xref , lanes 3 and 5), and NCOA5 at Ser21 and Ser151 ( xref , lanes 3 and 4). | SIGNOR-278965 |
Q9UM11 | P04183 | 2 | binding | down-regulates quantity by destabilization | 0.342 | We show that hTK1 is degraded via a ubiquitin-proteasome pathway in mammalian cells and that anaphase-promoting complex/cyclosome (APC/C) activator Cdh1 is not only a necessary but also a rate-limiting factor for mitotic degradation of hTK1. By in vitro ubiquitinylation assays, we demonstrated that hTK1 is targeted for degradation by the APC/C-Cdh1 ubiquitin ligase dependent on this KEN box motif. | SIGNOR-272945 |
P27361 | P16949 | 1 | phosphorylation | down-regulates activity | 0.577 | Stress-induced stathmin phosphorylation is not de- pendent on ERK. Stathmin is also known to be phos- phorylated by ERK on Ser-25 and Ser-38 (17). Thus, it is possible that ERK phosphorylates stathmin in 293 cells|In subsequent reports (28, 29) it was shown that phosphorylation of stathmin blocks its ability to destabilize MTs. | SIGNOR-249483 |
P09769 | Q05397 | 1 | phosphorylation | up-regulates | 0.552 | Phosphorylated on tyrosine residues upon activation. Phosphorylation at tyr-925 is important for interaction with grb2 and depends on the complex formation between fak and the src-kinase fgr. | SIGNOR-94405 |
P31749 | Q13363 | 1 | phosphorylation | down-regulates quantity | 0.483 | Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation. | SIGNOR-278304 |
Q8WXG6 | P20336 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.396 | Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP). | SIGNOR-265579 |
Q92934 | P51812 | 0 | phosphorylation | down-regulates | 0.385 | The rsks catalyze the phosphorylation of the pro-apoptotic protein bad at serine 112 to promote cell survival. | SIGNOR-184595 |
Q9P2Y5 | Q9HCE7 | 0 | ubiquitination | down-regulates activity | 0.2 | Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux. | SIGNOR-273652 |
P12931 | Q13009 | 1 | phosphorylation | up-regulates | 0.657 | Tiam1 cooperated with src to induce activation of rac1 in vivo and the formation of membrane ruffles. | SIGNOR-102354 |
P36897 | O00459 | 2 | binding | up-regulates | 0.343 | These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells. | SIGNOR-227531 |
Q66K89 | P04637 | 1 | ubiquitination | up-regulates activity | 0.608 | E4F1 Has an Intrinsic Ubiquitin E3 Ligase Activity that Drives K48-type Ubiquitylation of p53. These data demonstrate that E4F1 stimulates the ubiquitylation of p53 on the lysine cluster K319–K321, i.e., at sites distinct from those targeted by Hdm2. p53 forms Ubiquitylated by E4F1 Are Localized on Chromatin. In striking contrast with Ub-p53 forms stimulated by Hdm2, which are mainly cytosoluble and targeted to the proteasome, we found that E4F1-stimulated Ub-p53 forms are tightly associated with chromatin, suggesting that they could be involved in transcription. | SIGNOR-271394 |
P24941 | P22674 | 2 | phosphorylation | up-regulates activity | 0.453 | Phosphorylation of cyclin O, a novel cyclin family protein containing a cyclin-like domain, is involved in the activation of cyclin-dependent kinase 2|This activity was reduced in cells overexpressing cyclin O, in which the 81st serine had been replaced with alanine (S81A). These results suggest that cyclin O is a novel cyclin family protein that regulates CDK2 kinase activity, which is mediated by the phosphorylation of the 81st serine residue of cyclin O|CKD2 phosphorylates the 81st serine residue of cyclin O | SIGNOR-275615 |
Q9ULU4 | P30542 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We also confirmed transcriptional coactivator functions of ZMYND8 in ERα-driven reporter assays and on endogenous E2-dependent genes (Figure 5F,G). siRNA knockdown of ZMYND8 showed markedly decreased transcription at the presumptive ERα/Z3 target genes ADORA1 and NAV2, while the classical ERα targets pS2/TFF1 and GREB1 appear to be less affected (Figure 5G), suggesting likely gene-specificity of ZMYND8. | SIGNOR-266208 |
P14921 | O75444 | 2 | binding | down-regulates | 0.425 | Full-length c-maf binds to the c-myb and ets-1. / c-maf inhibits c-myb and ets-1 transcriptional activity. | SIGNOR-56808 |
P25445 | Q9UER7 | 2 | binding | down-regulates | 0.703 | A c-terminal portion of daxx interacts with the fas death domain. The fas-binding domain of daxx is a dominant-negative inhibitor of both fas-induced apoptosis and jnk activation. | SIGNOR-49473 |
P22415 | P49841 | 0 | phosphorylation | up-regulates activity | 0.286 | Both MITF and USF1 were activated by glycogen synthase kinase (GSK) 3, with GSK3 phosphorylation sites on USF1 identified as the previously described activating site threonine 153 as well as serine 186. | SIGNOR-276355 |
P05106 | Q03405 | 2 | binding | up-regulates activity | 0.471 | Recent evidence suggests that the activation of b3 integrin in podocytes mediates uPAR-induced cellular events leading to proteinuria | SIGNOR-253333 |
Q6PI48 | 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-269418 |
P35568 | P19525 | 0 | phosphorylation | down-regulates activity | 0.339 | First, PKR induces phosphorylation of IRS1 at Ser312 and suppresses tyrosine phosphorylation of IRS1, mediated by the insulin receptor substrates kinases, JNK and I\u03baB kinase.|These results suggest that PKR induces the inhibitory phosphorylation of IRS1 at Ser312 in HepG2 cells, thereby suppressing the phosphorylation at Tyr941. | SIGNOR-278310 |
P18089 | P08754 | 2 | binding | up-regulates activity | 0.47 | 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-256857 |
P63279 | Q13485 | 1 | sumoylation | up-regulates | 0.626 | The mh1 domain of smad4 was shown to associate physically with ubc9, the ubiquitin carrier protein (e2) conjugating enzyme in sumoylation. In cultured cells, smad4 is modified by sumo-1 at the endogenous level. The sumoylation sites were identified as two evolutionarily conserved lysine residues, lys-113 and lys-159, in the mh1 domain. We found that the mutations at lys-113 and lys-159 did not alter the ability of smad4 to form a complex with smad2 and fast on the mix.2 promoter. Importantly, sumo-1 overexpression enhanced tgf-beta-induced transcriptional responses. These findings identify sumoylation as a unique mechanism to modulate smad4-dependent cellular responses | SIGNOR-98997 |
P15735 | P06737 | 1 | phosphorylation | up-regulates activity | 0.656 | It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15 | SIGNOR-267401 |
P26367 | Q9H2X6 | 0 | phosphorylation | up-regulates activity | 0.463 | HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373. | SIGNOR-251271 |
O95786 | P19784 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response.Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of RIG-I are phosphorylated by casein kinase II (CK2) in the resting state of the cell and dephosphorylated when cells are infected by RNA virus. | SIGNOR-276285 |
Q9Y281 | Q15569 | 0 | 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-246719 |
P04637 | P49757 | 2 | binding | up-regulates | 0.515 | Numb can actually interact in vivo with endogenous mdm2 and p53, resulting in a trimeric complex between the three proteins [10]. This interaction appears to regulate the stability of p53, as reduction of numb levels by rna interference (rnai) causes a decrease in the half-life of p53 and consequently a reduction in steady-state levels of the protein. Consistent with this observation, overexpression of numb increases the level of p53 in both unstressed and stressed cells. | SIGNOR-178668 |
P06239 | Q9H204 | 1 | phosphorylation | up-regulates | 0.439 | Y64 of magicin is phosphorylated by lck creating a sh2-grb2 binding motif | SIGNOR-148704 |
Q8TAS1 | Q15637 | 1 | phosphorylation | up-regulates | 0.406 | Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding. | SIGNOR-199797 |
Q6NXT2 | Q9NRC8 | 0 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275879 |
Q9Y281 | P53667 | 0 | phosphorylation | down-regulates activity | 0.703 | Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3;. Here we show that lim-kinase 1 (limk-1), a serine/threonine kinase containing lim and pdz domains, phosphorylates cofilin at ser 3, both in vitro and in vivo | SIGNOR-58596 |
P08151 | O14920 | 0 | phosphorylation | up-regulates activity | 0.356 | Active IKKbeta promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.|Herein, we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL. | SIGNOR-279194 |
P35222 | P55287 | 2 | binding | up-regulates activity | 0.654 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265851 |
P05129 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.27 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275445 |
Q9H2P0 | Q9GZQ8 | 2 | binding | up-regulates activity | 0.369 | Here, we show for the first time that hippocampal ADNP deficiency paralleled reduced beclin1 expression which, in turn, parallels increased tauopathy and cell death. We now show that ADNP directly interacts with LC3B, implicating the requirement of a healthy ADNP system for the apoptotic/autophagy processes. | SIGNOR-266759 |
P68400 | Q12913 | 1 | phosphorylation | up-regulates activity | 0.2 | CK2-dependent phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation upon VEGF stimulation. | SIGNOR-277876 |
Q03933 | P35227 | 0 | sumoylation | down-regulates activity | 0.325 | MEL-18, in contrast to the polycomb protein PC2/CBX4, in which SUMO E3 activity stimulates sumoylation of certain proteins, actually functions like an anti-SUMO E3 protein, interacting with both HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity and thereby decreasing sumoylation of a target protein, in this case that of HSF2. sumoylation of HSF2 is up-regulated during mitosis and is important for the interaction of this factor with a subunit of the condensin complex during the bookmarking process | SIGNOR-226245 |
Q13131 | P04049 | 1 | phosphorylation | down-regulates | 0.342 | Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259. The catalytic subunit of PKA also phosphorylated Ser621 in vitro, while its overexpression in intact cells resulted in increased phosphorylation of Ser621 and decreased activity of Raf-1. These results suggest that phosphorylation of Ser621 inactivates Raf-1, but do not prove that PKA is responsible for this in vivo. | SIGNOR-47148 |
O94804 | P26038 | 1 | phosphorylation | up-regulates activity | 0.385 | Evidence in jurkat cells that lok phosphorylates erm and that erm phosphorylation impedes migration. | SIGNOR-184433 |
P14921 | Q13554 | 0 | phosphorylation | down-regulates activity | 0.309 | Increased Transactivation of the GM-CSF Promoter/Enhancer by Ets1 with Mutated CaMK II Sites | Significantly, phosphorylation of Ets1 by Ca2+-dependent pathways is thought to inhibit DNA binding in vitro. To analyze the role of these four serines, S251, S257, S282, and S285, in transcription, we constructed three mutant derivatives of human Ets1 | SIGNOR-250684 |
Q96HS1 | Q14145 | 2 | binding | down-regulates quantity by destabilization | 0.552 | Keap1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5. Keap1 is a Bric-a-Brac (BTB) 2 -Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. | SIGNOR-272645 |
P51812 | Q92934 | 1 | phosphorylation | down-regulates | 0.385 | The rsks catalyze the phosphorylation of the pro-apoptotic protein bad at serine 112 to promote cell survival. | SIGNOR-184595 |
Q96N16 | P33176 | 0 | relocalization | up-regulates activity | 0.2 | Marlin-1 is associated with kinesin-I and suggest that the movement of Marlin-1 is mediated by plus end microtubuledependent molecular motors | SIGNOR-260989 |
Q8WVD3 | Q9UJU2 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.307 | Here, we show that NARF induces the ubiquitylation of TCF/LEF in vitro and in vivo, and functions as an E3 ubiquitin-ligase that specifically cooperates with the E2 conjugating enzyme E2-25K. We found that NLK augmented NARF binding and ubiquitylation of TCF/LEF, and this required NLK kinase activity. The ubiquitylated TCF/LEF was subsequently degraded by the proteasome. | SIGNOR-271595 |
P17252 | O60500 | 1 | phosphorylation | up-regulates activity | 0.2 | Binding of _-arrestin2 to the nephrin intracellular domain depended on phosphorylation of nephrin threonine residues 1120 and 1125 by pkc_. | SIGNOR-172056 |
Q14541 | Q92819 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.337 | Transcription was activated by HNF4G in reporter assays using the promoter/enhancer region of the HAS2 gene. The endogenous expression of the HAS2 gene was suppressed by knockdown of HNF4G. | SIGNOR-261626 |
P63027 | P37840 | 2 | binding | down-regulates quantity | 0.401 | The normal function of the small presynaptic protein α-synuclein (α-syn) is of exceptional interest, not only in the context of neurodegeneration, but also as a cytosolic regulator of neurotransmission. we show that α-syn-VAMP2 interactions are necessary for α-syn-induced synaptic attenuation. Our data connect divergent views and suggest a unified model of α-syn function. the data indicate that α-syn–VAMP2 binding is essential for α-syn function and advocate an “interlocking model” where α-syn multimers on the SV surface interact with VAMP2 on adjacent SVs, helping to maintain physiologic SV clustering. | SIGNOR-264104 |
P02763 | P16066 | 0 | phosphorylation | up-regulates activity | 0.2 | On TORC1 inhibition by rapamycin treatment or nutrient limitation, Npr1 phosphorylates and activates Orm1 and Orm2, which in turn promotes synthesis of complex sphingolipids downstream of SPT.|Thus Npr1 directly phosphorylates Orm1 and Orm2 downstream of TORC1. | SIGNOR-278966 |
Q9GZQ8 | O95352 | 2 | binding | up-regulates | 0.873 | These results indicated that the fap motif of atg7 is indispensable for formation of the atg3-lc3 e2-substrate intermediate through the interaction of atg7 with atg3. | SIGNOR-195239 |
P17676 | P42684 | 0 | phosphorylation | up-regulates | 0.274 | The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells | SIGNOR-186427 |
P84022 | Q9GZV5 | 2 | binding | up-regulates | 0.555 | Taz has been shown to interact with smad2 and smad3 through its coiled-coil region, and to be important in maintaining the nuclear localization of smad2 and smad3 as well as the expression of their target genes in response to tgf-b signaling and, thus, in the maintenance of human esc self-renewal. | SIGNOR-169841 |
Q12778 | Q9UBE8 | 0 | phosphorylation | down-regulates activity | 0.613 | Here, we report that the transforming growth factor-beta-activated kinase (TAK1)-Nemo-like kinase (NLK) pathway negatively regulates FOXO1. We show that NLK binds and phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain. The phosphorylation by TAK1-NLK pathway inhibits the transcriptional activity of FOXO1 and excludes FOXO1 from the nucleus, which is independent of phosphatidylinositol 3-kinase/Akt pathway. | SIGNOR-273907 |
Q99942 | P11142 | 2 | binding | up-regulates activity | 0.387 | JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex | SIGNOR-271493 |
P12830 | O15379 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.257 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. | SIGNOR-275662 |
Q92859 | Q96B86 | 2 | binding | down-regulates activity | 0.787 | Netrin-1-neogenin interactions mediate chemoattractive axon guidance, while RGMa-neogenin interactions repel axons. | SIGNOR-268388 |
P08754 | Q15722 | 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-256834 |
Q12778 | P06493 | 0 | phosphorylation | down-regulates | 0.511 | Overexpression of cdk1 inhibits the transcriptional activity of foxo1 in pca cells through s249 phosphorylation on foxo1. | SIGNOR-178202 |
Q2M1Z3 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.566 | 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-260489 |
P28329 | P05129 | 0 | phosphorylation | up-regulates | 0.321 | We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation. | SIGNOR-129320 |
Q01082 | P36897 | 0 | phosphorylation | up-regulates | 0.522 | This suggests that, upon stimulation with tgf-beta1, phosphorylation of elf could induce a conformational change that reduces its affinity for ankyrin and tropomyosin and facilitates an association with smad3 and smad4 instead. | SIGNOR-97626 |
Q8NHY2 | O00763 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1. Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D). | SIGNOR-271599 |
P38936 | P31749 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.84 | Pim-1, PKC, and Akt1 kinases phosphorylate Thr-145 and Ser-146 sites on p21 protein. Phosphorylation at Thr-145 promotes cytoplasmic translocation and stability of p21. Ser-146 phosphorylation mediated by Akt1 enhances p21 stabilization and promotes cell survival. | SIGNOR-157790 |
P07949 | P18848 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We observed that RET physically interacted with and phosphorylated ATF4 at tyrosine and threonine residues. Indeed, RET kinase activity was required to inhibit the ATF4-dependent activation of the NOXA gene because the site-specific substitution mutations that block threonine phosphorylation increased ATF4 stability and activated its targets NOXA and PUMA. | SIGNOR-276448 |
Q9NYV6 | P27361 | 0 | phosphorylation | up-regulates | 0.2 | Erk-dependent phosphorylation of the transcription initiation factor tif-ia is required for rna polymerase i transcription and cell growth. phosphopeptide mapping and mutational analysis reveals two serine residues (s633 and s649) that are phosphorylated by erk and rsk kinases. Replacement of s649 by alanine inactivates tif-ia, inhibits pre-rrna synthesis, and retards cell growth. | SIGNOR-98984 |
P51679 | P13500 | 2 | binding | up-regulates activity | 0.489 | CCR2 and CCR4 are two cell surface receptors that bind CCL2 | SIGNOR-237555 |
Q9Y625 | Q14934 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | 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-264023 |
P31749 | P42345 | 2 | phosphorylation | up-regulates | 0.929 | Once phosphorylated, Akt can act on a broad spectrum of substrates that can influence cell survival and proliferation and protein synthesis (65). Phosphorylation of mTOR by Akt leads to mTOR activation (40, 52) and the subsequent activation of p70S6K | SIGNOR-255107 |
Q15051 | Q9H992 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH7 induces K48 ubiquitination of NPHP5 and protein degradation, while BBS11 triggers K63 ubiquitination and protein delocalization.|Unlike the catalytically inactive mutant , wild type MARCH7 was able to trigger NPHP5 ubiquitination (XREF_FIG). | SIGNOR-278585 |
Q13309 | O60729 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.357 | The activity of SCF(Skp2) is regulated by the Cyclin-dependent kinase (CDK)2-mediated phosphorylation of Skp2 on Ser64 allows its expression in mid-G1 phase, even in the presence of active APC(Cdh1). Reciprocally, dephosphorylation of Skp2 by the mitotic phosphatase Cdc14B at the M --> G1 transition promotes its degradation by APC(Cdh1). | SIGNOR-248333 |
O75592 | P01106 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.415 | We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop. | SIGNOR-267147 |
P31749 | Q5VWQ8 | 1 | phosphorylation | down-regulates activity | 0.497 | DAB2IP can be phosphorylated by RIP1 on Ser 604 within the PER domain, and by AKT1 on Ser 847 within the proline-rich domain. Although RIP1-mediated phosphorylation is stimulatory,40 a recent study reported that AKT-mediated phosphorylation inhibits DAB2IP functions | SIGNOR-254780 |
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