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 |
|---|---|---|---|---|---|---|---|
Q96F46 | P49840 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation. | SIGNOR-277206 |
Q8TF68 | P03956 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.307 | Luciferase activity driven by the MMP-1 promoter also increased by 2.5- to 3-fold. In contrast, CIZ had no effect on the luciferase activity from the MMP-1 promoter that was mutated at the CIZ binding consensus sequence. These results show that the CIZ transactivates the MMP-1 promoter through this sequence. | SIGNOR-266229 |
P29279 | Q15561 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter | SIGNOR-277686 |
O75807 | P35638 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.454 | ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress. | SIGNOR-260173 |
P00533 | P43115 | 0 | relocalization | up-regulates quantity | 0.332 | These results demonstrate that PGE2 -mediated EGFR nuclear translocation requires the EP3 receptor. | SIGNOR-278884 |
Q09472 | P84243 | 1 | acetylation | down-regulates activity | 0.2 | These results highlight the substrate and site specificities of hats in cells, demonstrate the distinct roles of gcn5/pcaf- and cbp/p300-mediated histone acetylations in gene activation, and suggest an important role of cbp/p300-mediated h3k18/27ac in nr-dependent transcription. | SIGNOR-170266 |
Q676U5 | Q9H2C0 | 0 | ubiquitination | down-regulates quantity | 0.2 | Here we identify Gigaxonin24, an E3 ligase mutated in a fatal neurodegenerative disease called giant axonal neuropathy (GAN)25, as the first regulator of ATG16L1. Gigaxonin poly-ubiquitinates and controls the degradation of ATG16L1, and is essential to activate autophagy. | SIGNOR-268948 |
P51813 | Q08881 | 0 | phosphorylation | up-regulates activity | 0.334 | Itk phosphorylated Bmx-SH3 to a low extent. pY positions correspond to the residues Y215 and Y223 in Bmx. Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. | SIGNOR-251331 |
P21580 | Q13546 | 1 | ubiquitination | down-regulates quantity | 0.655 | The amino-terminal domain of A20, which is a de-ubiquitinating (DUB) enzyme of the OTU (ovarian tumour) family, removes lysine-63 (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex. The carboxy-terminal domain of A20, composed of seven C2/C2 zinc fingers, then functions as a ubiquitin ligase by polyubiquitinating RIP with K48-linked ubiquitin chains, thereby targeting RIP for proteasomal degradation. | SIGNOR-259978 |
P17252 | P29474 | 1 | phosphorylation | down-regulates activity | 0.3 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251620 |
Q99683 | Q969S3 | 1 | phosphorylation | up-regulates | 0.487 | Ask1 directly phosphorylated zpr9 at ser(314) and thr(318), suggesting that zpr9 can act as an ask1 substrate. Ask1-mediated phosphorylation of zpr9 at ser(314) and thr(318) was also responsible for zpr9-induced apoptosis. | SIGNOR-175113 |
Q96PX1 | P24941 | 0 | phosphorylation | up-regulates activity | 0.287 | CDK2 promotes phosphorylation of RNF157 at the same Ser 660-663 residues that become phosphorylated downstream of combined PI3K and MAPK pathway activity. | SIGNOR-279016 |
Q8IYW5 | Q8WYQ5 | 2 | binding | up-regulates activity | 0.2 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277309 |
P31943 | Q15554 | 1 | post transcriptional regulation | down-regulates quantity | 0.334 | During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels. | SIGNOR-266807 |
P15923 | Q02779 | 0 | phosphorylation | down-regulates | 0.2 | Mlk2 inhibits e47 transactivation activity on the trkb promote | SIGNOR-161544 |
Q9BSA4 | Q96PU5 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.286 | Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein. | SIGNOR-272632 |
P48436 | O76039 | 0 | phosphorylation | down-regulates activity | 0.2 | Based on these studies, we hypothesized that Cdkl5 dependent phosphorylation at Ser 199 suppresses Sox9 function during AKI.|We also found that Cdkl5 phosphorylates Sox9 at Ser 199 residue during kidney injury in vivo. | SIGNOR-279457 |
O14733 | P45984 | 1 | phosphorylation | up-regulates | 0.637 | Here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1). These results indicate that hgk, a novel activator of the jnk pathway, may function through tak1, and that the hgk --> tak1 --> mkk4, mkk7 --> jnk kinase cascade may mediate the TNF-alphalpha signaling pathway. | SIGNOR-83744 |
P08754 | P29274 | 2 | binding | up-regulates activity | 0.263 | 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-257151 |
Q9NR48 | Q16620 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Depletion of ASH1L decreases neurite outgrowth and decreases expression of the gene encoding the neurotrophin receptor TrkB whose signaling pathway is linked to neuronal morphogenesis. | SIGNOR-269058 |
Q13621 | Q9BYP7 | 0 | phosphorylation | up-regulates activity | 0.498 | 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-264626 |
P62136 | Q12972 | 2 | binding | down-regulates activity | 0.622 | We have purified two of these nuclear inhibitors of PP-1 (NIPP-1a and NIPP-1b) until homogeneity. | SIGNOR-255657 |
Q9Y478 | Q13586 | 1 | phosphorylation | down-regulates activity | 0.2 | STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE | SIGNOR-277298 |
P46531 | Q9UBE8 | 0 | phosphorylation | down-regulates | 0.382 | Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex. | SIGNOR-163697 |
P0DMV8 | Q8NFG4 | 2 | binding | up-regulates quantity by stabilization | 0.2 | These data suggest that inhibition of Hsp70 does not lead to an increase in misfolded FLCN but instead to its degradation. | SIGNOR-256506 |
P49840 | O75030 | 1 | phosphorylation | up-regulates | 0.294 | Glycogen synthase kinase 3 (gsk3) was found to phosphorylate ser298 in vitro, thereby enhancing the binding of mitf to the tyrosinase promoter | SIGNOR-72878 |
P04637 | Q14694 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.662 | Since USP10 is known as a deubiquitinating protease of p53 (Yuan et al., 2010), inhibition of USP10 by spautin-1 may promote the degradation of p53. | SIGNOR-260297 |
P49585 | P28482 | 0 | phosphorylation | down-regulates | 0.45 | Oxysterols inhibit phosphatidylcholine synthesis via erk docking and phosphorylation of ctp:phosphocholine cytidylyltransferase. Mutagenesis of ser315 within cctalpha was both required and sufficient to confer significant resistance to 22-hc/9-cis-ra inhibition of ptdcho synthesis. | SIGNOR-134837 |
P31249 | P09429 | 2 | binding | up-regulates activity | 0.298 | We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein. | SIGNOR-219980 |
Q13153 | Q12778 | 1 | phosphorylation | down-regulates activity | 0.358 | Pak1 efficiently phosphorylated GST-FKHR. | SIGNOR-279242 |
Q92831 | P46531 | 1 | acetylation | up-regulates | 0.602 | In earlier studies, we demonstrated that maml1 enhanced p300 acetyltransferase activity, which increased the acetylation of notch by p300.Acetylation controls notch stability and function in t-cell leukemia. | SIGNOR-199024 |
P51149 | P63000 | 2 | binding | up-regulates activity | 0.277 | Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments | SIGNOR-261304 |
Q9UI95 | Q96JM3 | 2 | binding | up-regulates activity | 0.497 | Here, we report a novel regulator for accurate chromosome segregation, chromosome alignment-maintaining phosphoprotein (CAMP). We identified CAMP as a MAD2L2-interacting protein. Spindle localization of MAD2L2 was abrogated by CAMP depletion (Supplementary Figure S2A) | SIGNOR-264904 |
Q08209 | O95644 | 1 | dephosphorylation | up-regulates | 0.825 | Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat. | SIGNOR-176370 |
O95271 | O15234 | 1 | ADP-ribosylation | down-regulates quantity by destabilization | 0.2 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263383 |
Q9UBV4 | O75581 | 2 | binding | up-regulates | 0.542 | 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-131677 |
Q8IW41 | Q99497 | 1 | phosphorylation | up-regulates activity | 0.469 | PRAK preferentially colocalizes with DJ-1 and leads to DJ-1 activation, which in turn facilitates DJ-1 to sequester Daxx in the nucleus, preventing oxidative stress induced cell death.|These data clearly demonstrate a PRAK dependent phosphorylation of DJ-1. | SIGNOR-279746 |
Q16621 | P45983 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.411 | Through use of different approaches including nano-scale proteomics, we show that activated-JNK, or Phospho-JNK (P-JNK), physically interacts with p45/NF-E2 and phosphorylates its Ser157 residue. This reaction leads to the poly-ubiquitination of p45/NF-E2 at one or more of six Lys residues, one of which being also a sumoylation site, and its degradation through the proteasome pathway. | SIGNOR-275552 |
P63000 | Q13464 | 2 | binding | up-regulates activity | 0.404 | Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK) | SIGNOR-258972 |
O75581 | P56703 | 2 | binding | up-regulates | 0.649 | 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-131823 |
P42574 | Q16539 | 0 | phosphorylation | down-regulates | 0.775 | Consequently, p38-mapk can directly phosphorylate and inhibit the activities of caspase-8 and caspase-3 and thereby hinder neutrophil apoptosis, and, in so doing, regulate the inflammatory response. | SIGNOR-122099 |
O43426 | Q12965 | 2 | binding | up-regulates activity | 0.427 | We describe binding of two PRD-containing endocytic proteins, dynamin and synaptojanin-1, to the SH3 domain of Myo1E. This interaction was detected both in vitro, using pull-downs of purified proteins, and in vivo, using immunoprecipitation of protein complexes from synapse-enriched brain extract and immunolocalization of Myo1E and dynamin. Our observation of the interaction between human Myo1E and endocytic proteins suggests that this longtailed myosin may play a role in clathrin-dependent endocytosis.Interaction between Myo1E SH3 domain and PRD-containing endocytic proteins may promote recruitment of Myo1E to clathrin-coated structures since an inactivating mutation in the SH3 domain reduced Myo1E localization to clathrin-containing puncta. | SIGNOR-265423 |
P60510 | O75531 | 1 | dephosphorylation | up-regulates | 0.2 | Herein, we demonstrate we demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. We have identified the major phosphatase responsible for dephosphorylation of ser-4 to be protein phosphatase 4 catalytic subunit. | SIGNOR-203281 |
P38405 | P50406 | 2 | binding | up-regulates activity | 0.375 | 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-256944 |
Q9H2X9 | Q9H4A3 | 0 | phosphorylation | down-regulates activity | 0.461 | The activity of the neuronal specific KCC2 had recently been shown to be regulated by the WNK1 kinase, where phosphorylation decreased KCC2 activation .|WNK1 phosphorylation of KCC2 occurs in immature neurons but is absent in adult neurons , , emphasizing a developmental role. | SIGNOR-280163 |
O14733 | O43353 | 0 | 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 |
Q96HE7 | Q8IXL6 | 0 | phosphorylation | up-regulates activity | 0.2 | We further show that ER oxidoreductin 1α (Ero1α), the pivotal sulfhydryl oxidase that catalyzes disulfide formation in the ER, is phosphorylated by Fam20C in the Golgi apparatus and retrograde-transported to the ER mediated by ERp44. The phosphorylation of Ser145 greatly enhances Ero1α oxidase activity and is critical for maintaining ER redox homeostasis and promoting oxidative protein folding. | SIGNOR-277395 |
P36897 | Q9HAU4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.71 | Smad7 Recruits Smurf2 to the TGFβ Receptor Complex. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where it causes degradation of receptors and Smad7 via proteasomal and lysosomal pathways. | SIGNOR-272938 |
P18850 | P17861-2 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.654 | Apart from ER protein chaperones, ATF6 also induces the expression of CHOP and XBP1, thereby connecting the three UPR branches into an integrated signaling network | SIGNOR-260184 |
P63244 | Q13308 | 2 | binding | up-regulates | 0.2 | Here, we identify rack1 as a novel interaction partner of ptk7. Mechanistically, rack1 is necessary for the ptk7-mediated membrane localization of dishevelled (dsh). Rack1 facilitates the ptk7-dsh interaction by recruiting pkcdelta1, a known effector of dsh membrane translocation. | SIGNOR-172322 |
Q92945 | P38936 | 1 | post transcriptional regulation | down-regulates quantity by destabilization | 0.252 | Importantly, KSRP knockdown in C2C12 GM cells (Figure 2D) stabilized endogenous my- ogenin and p21 transcripts (Figure 2E). Furthermore, stable knockdown of KSRP, using shRNA, induced the accumulation of p21 mRNA in C2C12 GM while it did not affect the expression of late myogenic markers (MHC and muscle-creatine kinase [MCK]) | SIGNOR-235859 |
P27986 | Q13191 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.517 | Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells.Here it is shown that Cbl-b interacts with and induces ubiquitin conjugation to the p85 regulatory subunit of phosphatidylinositol 3-kinase, an upstream regulator of Vav. | SIGNOR-272583 |
Q9HCI7 | Q16778 | 1 | monoubiquitination | down-regulates activity | 0.2 | MSL1/2 ubiquitylates histone H2B on K 34. Importantly, only mono-ubiquitylation of H2B by MSL1/2 was detected in cells (data not shown), suggesting that MSL1/2, like RNF20/RNF40, was mainly a mono-ubiquitylase under physiological conditions.the MOF-MSL complex functions to promote both H4 K16ac and H2B K34ub. H2B K34ub, in turn, promotes H2B K120ub, H3 K4me3 and K79me2 to facilitate transcription elongation. | SIGNOR-271976 |
P0DMV8 | O94826 | 2 | binding | up-regulates activity | 0.2 | The Tom70 receptor is a membrane-localized cochaperone that integrates the Hsp70/Hsp90 chaperones with mitochondrial preprotein targeting and translocation. In mammals, preprotein in the cytosol is associated with both Hsp90 and Hsp70 in a multichaperone complex, and docking of Hsp90 and/or Hsp70 onto Tom70 is essential for preprotein targeting. | SIGNOR-261380 |
Q9UHC7 | P46783 | 1 | ubiquitination | up-regulates activity | 0.2 | We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates. | SIGNOR-272216 |
Q9Y243 | Q13188 | 1 | phosphorylation | down-regulates | 0.271 | Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation. | SIGNOR-164306 |
P11021 | Q9UBS3 | 2 | binding | up-regulates activity | 0.542 | When BAP was added to BiP (2:1 molar ratio of BAP:BiP), it increased the ATPase activity of BiP by about 2-fold, which was similar to the increase observed when the J domain of ERdj4 was added to BiP (Fig.5). When both BAP and the J domain were added to BiP, the rate of ATP hydrolysis by BiP was stimulated by about 4-fold over basal levels, indicating that both BAP and ERdj4 positively regulate the ATPase activity of BiP | SIGNOR-261044 |
P19447 | P50613 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.895 | These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation. | SIGNOR-277433 |
P45973 | Q9C0F0 | 2 | binding | down-regulates activity | 0.251 | Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression. | SIGNOR-266763 |
P22001 | Q16620 | 0 | 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 |
Q9NX24 | O14746 | 2 | binding | up-regulates activity | 0.656 | A complex of four proteins (GAR1, NHP2, NOP10, and the putative pseudouridine synthase dyskerin) associates with snoRNAs to form small nucleolar ribonucleoprotein particles (snoRNPs), and the binding of this complex to the H/ACA domain of TERC may have a role in the biogenesis of the telomerase RNP | SIGNOR-263330 |
P05305 | P25101 | 2 | binding | up-regulates | 0.881 | Endothelin-1 (et-1) and angiotensin ii (angii), two potent vasoactive peptides involved in the regulation of cardiovascular homeostasis, also induce mitogenic and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme and angiotensin-converting enzyme, respectively) and activate two subtypes of membrane receptors (eta-r and etb-r for et-1, at1r and at2r for angii) that all belong to the superfamily of g-protein coupled receptors. | SIGNOR-145759 |
P05412 | Q99986 | 0 | phosphorylation | up-regulates | 0.512 | Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription | SIGNOR-127073 |
P12757 | Q9HAU4 | 0 | ubiquitination | down-regulates activity | 0.738 | Tgf-beta also induces the association of smurf2 with the transcriptional co-repressor snon and we show that smad2 can function to mediate this interaction. This allows smurf2 hect domain to target snon for ubiquitin-mediated degradation by the proteasome. | SIGNOR-236090 |
O43504 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.336 | Strikingly, we found that the kinase ataxia telangiectasia mutated (ATM) phosphorylated HBXIP at Ser (108).|The knockdown of ATM by siRNA remarkably decreased the levels of serine phosphorylation and blocked the nuclear import of HBXIP. | SIGNOR-279791 |
P50539 | P23443 | 0 | phosphorylation | down-regulates activity | 0.351 | Phosphorylation of Mxi1 by S6K1 at S160 site promotes its binding to beta-Trcp and ubiquitin mediated degradation.|The above findings demonstrate that S6K1 and beta-Trcp negatively regulates the stability of Mxi1 through ubiquitin proteasome pathway. | SIGNOR-278231 |
Q12972 | P68400 | 0 | phosphorylation | up-regulates activity | 0.471 | Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2. | SIGNOR-250931 |
Q14493 | O60814 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265383 |
Q9P2F6 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.436 | 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-260473 |
Q15465 | Q96F81 | 2 | binding | up-regulates activity | 0.729 | We show that the vertebrate homologue, dispatched-a (dispa) interacts with human sonic hedgehog (hshh) via its cholesterol anchor, and that this interaction is necessary for hshh secretion. binding to dispa is necessary but not sufficient for hshh secretion | SIGNOR-191888 |
P16104 | Q99502 | 0 | dephosphorylation | down-regulates | 0.2 | Tyr142 is dephosphorylated by the tyr phosphatases eya1 and eya3. | SIGNOR-168879 |
Q99717 | O96004 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268941 |
P00533 | P12931 | 0 | phosphorylation | up-regulates activity | 0.625 | Revealed that peptides derived from egfr residues y992, y1086, y1101, and y1148 bound directly to the sh2 domain of c-src (figure 8c). These experiments demonstrate that a specific subset of egfr receptor c-src phosphorylation sites are also ligands for the sh2 domain of c-src.Cellular src functions as a co-transducer of transmembrane signals emanating from a variety of growth factor receptors, including egfr | SIGNOR-44251 |
O14490 | Q9UPX8 | 1 | relocalization | up-regulates activity | 0.827 | 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-264587 |
P27361 | O60885 | 1 | null | down-regulates activity | 0.312 | The MYC stabilizing kinase, ERK1, regulates MYC levels directly and indirectly by inhibiting BRD4 kinase activity. | SIGNOR-262048 |
P06241 | O43294 | 1 | phosphorylation | up-regulates activity | 0.34 | Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5. | SIGNOR-262875 |
Q9NRA0 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway. | SIGNOR-278660 |
P09958 | P06213 | 1 | cleavage | up-regulates activity | 0.283 | Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. | SIGNOR-260365 |
P45983 | Q7Z6J0 | 2 | binding | up-regulates | 0.371 | Posh activates jnk1 in cos-1 cells. | SIGNOR-55759 |
Q15661 | O75030 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription of tryptase gene in human mast cells is regulated by mi transcription factor |Using mutant constructs of tryptase promoter, we observed that two E-box (CANNTG) motifs including between -817 to -715 and -421 to -202 are able to involve in the transactivation of tryptase gene by MITF-A. | SIGNOR-251725 |
Q9NYL2 | O14733 | 1 | phosphorylation | up-regulates activity | 0.2 | We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling. | SIGNOR-243345 |
O95096 | Q8TAM6 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.249 | Further study revealed that Nkx2.2 could bind JN promoter and its overexpression increase the promoter activity of JN. | SIGNOR-268965 |
P11021 | Q9H173 | 2 | binding | up-regulates activity | 0.577 | BAP, a Mammalian BiP-associated Protein, Is a Nucleotide Exchange Factor That Regulates the ATPase Activity of BiP. In addition,BAP was associated with BiP in mammalian cells and inter-acted with BiP functionallyin vitro. BAP stimulated the ATPase activity of BiP when added alone or together with the ER DnaJ protein, ERdj4, by promoting the release of ADP from BiP. Together, these data demonstrate that BAP serves as a nucleotide exchange factor for BiP and provide insights into the mechanisms that control protein folding in the mammalian ER. | SIGNOR-261045 |
O15111 | Q07666 | 1 | phosphorylation | up-regulates activity | 0.2 | Sam68 is phosphorylated by IKK\u03b1 in the nucleus. | SIGNOR-278439 |
P30679 | Q969V1 | 2 | binding | up-regulates activity | 0.435 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257390 |
Q15759 | P04637 | 1 | phosphorylation | up-regulates | 0.611 | We show that prak activates p53 by direct phosphorylation. | SIGNOR-152843 |
Q96ST3 | Q9Y2Y9 | 2 | binding | up-regulates activity | 0.432 | detailed biochemical and functional analyses have demonstrated that the TIEG2 _-HRM domain interacts specifically with the PAH2 domain of mSin3A to repress transcription. our data suggest the presence of a conserved _-helical repression motif (_-HRM) in the TIEG and BTEB subfamilies of Sp1-like proteins that mediates transcriptional repression activity through interaction with the corepressor mSin3A. | SIGNOR-222437 |
P20042 | Q9GZT9 | 1 | translation regulation | up-regulates quantity | 0.2 | DAP5 is involved in PHD2 translation. Distinct responses to DAP5 depletion (under hypoxia) of primary MEFs versus malignant glioma cells suggest that DAP5-mediated control of PHD2 may have special significance in cancer. Neoplastic cells may exploit DAP5 for managing chronic oxygen deprivation, possibly contributing to their adaptation to growth/proliferation under hypoxia. | SIGNOR-266386 |
Q14493 | Q99877 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265392 |
Q9UJY5 | P68400 | 0 | phosphorylation | down-regulates activity | 0.504 | Serine-355 of GGA1 is phosphorylated in vivo and in vitro. This inhibition is caused by the binding of an AC-LL sequence present in the hinge segment to the ligand-binding site in the VHS domain. The inhibition depends on the phosphorylation of a serine located three residues upstream of the AC-LL motif. The serine is phosphorylated by casein kinase 2 in in vitro assays. | SIGNOR-273623 |
P49959 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1. The MRE11-PIH1D1 interaction is dependent on casein kinase 2 (CK2) phosphorylation of two acidic sequences within the MRE11 C terminus containing serines 558/561 and 688/689. | SIGNOR-265893 |
P20809 | P40189 | 2 | binding | up-regulates | 0.714 | Some of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-4 | SIGNOR-48033 |
P41231 | P30679 | 2 | binding | up-regulates activity | 0.408 | 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-257031 |
P46531 | Q13627 | 0 | phosphorylation | down-regulates | 0.396 | Dyrk1a physically interacts with the nicd inducing its phosphorylation in the ankyrin domain, thereby attenuating notch . | SIGNOR-185494 |
Q99062 | P08631 | 0 | phosphorylation | up-regulates activity | 0.385 | Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling. the ability of Hck to phosphorylate the G-CSF-R in vitro, both Y728 and Y763 fit the Src consensus phosphorylation site. we investigated the activation of Hck by the G-CSF-R in intact cells as well as in vitro. These studies revealed recruitment of Hck to activated G-CSF-R, mediated by direct binding via its SH2 domain to multiple phosphotyrosines of the receptor. In addition, we show that Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling. | SIGNOR-251264 |
Q9NZQ7 | Q9UNE7 | 0 | destabilization | down-regulates quantity by destabilization | 0.2 | Deletion of STUB1 resulted in a more profound increase in PD-L1 levels in CMTM6 deficient than in CMTM6 proficient cells, identifying STUB1 as an E3 ligase that causes destabilization of PD-L1 (Fig. 4f,g), either by direct modification of one of the lysines in the PD-L1 cytoplasmic domain or indirectly | SIGNOR-274979 |
O95837 | Q92847 | 2 | binding | up-regulates activity | 0.435 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257429 |
P43403 | P43403 | 2 | phosphorylation | up-regulates activity | 0.2 | Zap-70 is modified by auto-phosphorylation of various tyrosine residues and is activated by specific phosphorylation of the tyrosine residue y-493 | SIGNOR-139098 |
P63092 | P35408 | 2 | binding | up-regulates activity | 0.491 | 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-256760 |
P27986 | P08069 | 2 | binding | up-regulates | 0.718 | Igf-1 activated both the pi3k and the extracellular signal-regulated kinase [?] (erk [?]) Pathways as evidenced by phosphorylation of either akt or erk1 [?]/2 (respectively) | SIGNOR-179386 |
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