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 |
|---|---|---|---|---|---|---|---|
P56178 | Q9Y458 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.307 | the main function of TBX22 as shown in misexpression experiments is to decrease proliferation. We subsequently uncovered three targets of TBX22, DLX5, MSX2, and TBX22 itself. All are downregulated in the presence of viral-derived hTBX22. | SIGNOR-265566 |
Q9NZQ7 | Q13451 | 0 | catalytic activity | up-regulates quantity by expression | 0.2 | FKBP51s upregulated PD-L1 expression on the plasma membrane by catalysing the protein folding required for subsequent glycosylation. Inhibition of FKBP51s isomerase activity by SAFit decreased PD-L1 levels | SIGNOR-274973 |
P04049 | Q6VAB6 | 2 | binding | up-regulates activity | 0.606 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273879 |
P14784 | Q13261 | 2 | binding | up-regulates | 0.8 | The il-15 receptor comprises a heterotrimeric complex consisting of the common ?cytokine Receptor (?c), the il-2 ? Receptor subunit (il-2r?), And an il-15-specific ? Receptor (il-15r?) | SIGNOR-157418 |
Q9Y243 | P35226 | 1 | phosphorylation | up-regulates activity | 0.258 | the polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate | SIGNOR-249583 |
Q16566 | Q99623 | 1 | phosphorylation | down-regulates | 0.338 | Here we show that calcium/calmodulin-dependent kinase iv (camk iv) specifically binds to the c terminus of phb2 and phosphorylates phb2 at serine 91. Camk iv effectively decreased phb2-mediated repression of mef2 activity through phosphorylation | SIGNOR-174437 |
P14136 | Q13464 | 0 | phosphorylation | down-regulates activity | 0.312 | We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by aurora-b;thr-7/ser-13/ser-38 of gfap, and thr-16 of desmin are common with those related to rho-associated kinase (rho-kinase), which has been reported to phosphorylate gfap and desmin at cleavage furrow during cytokinesis. We identified ser-59 of desmin to be a specific site phosphorylated by aurora-b in vitro. | SIGNOR-100192 |
P07949 | Q99748 | 2 | binding | up-regulates | 0.715 | A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling | SIGNOR-49122 |
O00401 | P20929 | 2 | binding | up-regulates | 0.352 | Igf1-akt signaling, by inhibiting gsk3b, allows the interaction of n-wasp with the unphosphorylated nebulin;the consequent recruitment of n-wasp to the z-disk promotes actin nucleation and elongation of actin filaments. | SIGNOR-175671 |
P05019 | P08069 | 2 | binding | up-regulates activity | 0.956 | Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor. | SIGNOR-175662 |
P49757 | Q96J02 | 2 | binding | up-regulates | 0.615 | Numb activates the catalytic activity of itch, releasing it from an inhibitory intramolecular interaction between its homologous to e6-ap c-terminus and ww domains. | SIGNOR-167844 |
P98172 | Q12923 | 0 | dephosphorylation | up-regulates activity | 0.708 | Loss of PTPN13 function increases EFNB1 phosphorylation, enhances EFNB1 's interaction with ERBB1 and correlates with potentiated ERK1/2 activation.|Moreover, acquisition of PTPN13 loss-of-function mutations or its decreased expression (due to HPV infection or epigenetic silencing) may further enhance ERBB1 and EFNB1 mediated signals. | SIGNOR-277002 |
Q96GD4 | Q8NEM2 | 1 | phosphorylation | up-regulates activity | 0.372 | AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing. | SIGNOR-273552 |
Q13485 | Q8N2W9 | 2 | binding | down-regulates | 0.558 | Piasy binds most strongly with smad3 and also associates with other receptor-regulated smads and smad4. smad3, smad4, and piasy can form a ternary complex. Piasy does not inhibit smad complex binding to dna, but it represses smad transcriptional activity. | SIGNOR-104541 |
Q9H492 | Q9BQS8 | 2 | binding | up-regulates activity | 0.561 | The preferential binding to LC3A and -B was confirmed in vivo by co-immunoprecipitation experiments of Myc-tagged FYCO1 and GFP fusions of human ATG8 family pro-teins expressed in HEK293 cells (Fig. 2B). GFP-LC3A and GFP-LC3B were efficiently co-precipitated with Myc-FYCO1,whereas GFP-LC3C, GFP-GABARAP, GFP-GABARAPL1 and-L2 were not. The effects we see on late steps of basal autophagy on mutation of the FYCO1 LIR motif correlate with a role of FYCO1 in regulating kinesin-mediated transport of LC3-positive autophagic structures. | SIGNOR-260598 |
P35222 | Q9UPN9 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.457 | TRIM33 ubiquitylates nuclear beta-catenin.|Tumour suppressor TRIM33 targets nuclear beta-catenin degradation. | SIGNOR-278578 |
P68400 | Q14493 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.328 | Phosphorylation of Thr61 is necessary for subsequent phosphorylation of Thr60 by CK2 in vitro. Inhibitors of CK2 also prevent degradation of SLBP at the end of S phase. Thus, phosphorylation of Thr61 by cyclin A/Cdk1 primes phosphorylation of Thr60 by CK2 and is responsible for initiating SLBP degradation. | SIGNOR-265260 |
Q13464 | Q15746 | 2 | binding | up-regulates | 0.315 | Rock proteins are known to regulate mlc-phosphorylation, and apoptotic cells exhibit a gradual increase in levels of phosphorylated mlc concomitant with rock i cleavage. | SIGNOR-106552 |
Q96J02 | Q8N0X7 | 2 | binding | up-regulates activity | 0.2 | SPG20 Protein Spartin Is Recruited to Midbodies by ESCRT-III Protein Ist1 and Participates in Cytokinesis. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells significantly decreases the number of cells where spartin is present at midbodies. | SIGNOR-261308 |
Q9NWZ5 | Q6ZMZ0 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.583 | We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and has as one of its substrates, URKL-1, thus defining this cytolytic protein as an E3 ubiquitin ligase. | SIGNOR-271590 |
O75581 | Q8N752 | 0 | phosphorylation | up-regulates | 0.254 | Ck1 also phosphorylates lrp6 at the second ser residue in the pppspxs motif ck1_ in the lrp5/e-cadherin/p120-catenin complex temporally coincides with p120-catenin phosphorylation in ser268. moreover, and considering the close similarity between the catalytic domains of ck1_ and ck1_, it is possible that ck1_ is indeed responsible for the phosphorylation at ser1420 and ser1430 in lrp5/6 that negatively affects wnt signaling by still not defined mechanisms | SIGNOR-173853 |
Q06124 | Q15116 | 1 | dephosphorylation | down-regulates activity | 0.659 | Related to the latter notion, we recently showed that SHP2 dephosphorylates PD-1 to disassemble the PD-1:SHP2 complex ( xref ). | SIGNOR-277052 |
P22607 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276181 |
Q9ULZ3 | Q07812 | 1 | relocalization | up-regulates | 0.353 | Asc directly induces bax-mediated apoptosis. Asc induces the translocation of bax to the mitochondria, bax-dependent cycs release from the mitochondria and casp9 activation. | SIGNOR-149522 |
Q96A56 | Q9BXW4 | 2 | binding | up-regulates | 0.28 | These data indicate that cell death observed after tp53inp1-lc3 interaction depends on both autophagy and caspase activity. We conclude that tp53inp1 could act as a tumor suppressor by inducing cell death by caspase-dependent autophagy. | SIGNOR-196676 |
Q9HB63 | Q92859 | 2 | binding | up-regulates activity | 0.536 | Experiments have demonstrated that Neogenin also mediates Netrin-1 attractive functions. Both DCC and Neogenin are type I transmembrane receptors that belong to the immunoglobulin superfamily proteins. | SIGNOR-268170 |
P35790 | Q99541 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In addition, as a protein kinase, CHKalpha2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth | SIGNOR-267649 |
P00748 | P01009 | 2 | binding | down-regulates activity | 0.33 | C1INH is a serine protease inhibitor (serpin) that acts on both the complement pathway and the contact system and is the main inhibitor of the contact system by targeting both FXIIa and PK 9. Additionally, FXIIa can be inhibited by α1‐antitrypsin and plasminogen activator inhibitor‐1 (PAI‐1). | SIGNOR-263515 |
O60260 | P38936 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Next, we defined whether pJNK is involved in parkin mediated p21 degradation.|Parkin ubiquitinates p21 in vivo and in vitro in an E3 ligase-substrate dependent manner. | SIGNOR-278640 |
Q04206 | Q68CZ1 | 0 | demethylation | down-regulates | 0.2 | Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation. | SIGNOR-163320 |
P12830 | O60729 | 0 | dephosphorylation | up-regulates activity | 0.313 | Cdc14B activates APC/C Cdh1 after DNA damage in G2.|Importantly, after DNA damage, thein vivo phosphorylation of wild type Cdh1 - but not that of Cdh1 (4xA) - increased after Cdc14B silencing (XREF_FIG), indicating that in response to genotoxic stress, Cdc14B dephosphorylates Cdh1 on the four sites phosphorylated by Cdk2. | SIGNOR-277017 |
P41240 | P07948 | 1 | phosphorylation | down-regulates | 0.538 | Lyn tyr507 kinase, csk, is recruited by pag, which targets lipid rafts by palmitoylation.Thus, our data suggest that il-6 treatment induces the translocation of cd45 to lipid rafts sequentially, followed by the association of cd45 with lyn and pag;dephosphorylation of lyn tyr507 and pag tyr314;lyn activation;and csk release from lipid rafts | SIGNOR-132912 |
A1X283 | P12931 | 0 | phosphorylation | up-regulates activity | 0.521 | C-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells|Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation. | SIGNOR-264705 |
O00213 | P49841 | 0 | phosphorylation | up-regulates quantity | 0.293 | In this regards, GSK3beta may promote amyloidogenic processing of APP by regulating the cellular level of monomeric FE65 for the formation of LRP1, FE65, and APP complex.|In this study, we showed that FE65 is phosphorylated at T579 by GSK3beta. | SIGNOR-278359 |
Q6ZSZ5 | Q9UHD8 | 2 | binding | down-regulates | 0.2 | In transient expression analyses, sept9b inhibited sa-rhogef-dependent rho activation in cos7 and hela cells. | SIGNOR-131184 |
P17302 | P27361 | 0 | phosphorylation | down-regulates activity | 0.637 | These studies confirm that connexin-43 is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279, and/or Ser282 initiates the down-regulation of gap junctional communication. Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional intercellular communication. | SIGNOR-249466 |
Q15262 | O43490 | 1 | dephosphorylation | down-regulates activity | 0.2 | PTPRK dephosphorylates CD133, which is a stem cell marker; phosphorylated CD133 accelerates xenograft tumor growth of colon cancer cells through the activation of AKT, but the functional significance of this has remained elusive.|Together, these observations suggest that PTPRK suppresses CD133\u2010mediated colon cancer growth both in\u00a0vitro and in\u00a0vivo. | SIGNOR-277133 |
P10636 | P05186 | 0 | dephosphorylation | down-regulates activity | 0.2 | TNAP dephosphorylates overphosphorylated tau once it is released upon neuronal death. | SIGNOR-277097 |
P35222 | Q9UKB1 | 2 | binding | down-regulates | 0.746 | We conclude that beta-trcp is a component of an e3 ubiquitin ligase that is responsible for the targeted degradation of phosphorylated beta-catenin. we found that the binding of beta-trcp to beta-catenin was direct. | SIGNOR-65429 |
P12931 | P00519 | 1 | phosphorylation | up-regulates activity | 0.538 | c-Src-induced c-Abl activation involves phosphorylation of Y245 and Y412, two residues required for c-Abl mitogenic function. | SIGNOR-246311 |
O75122 | P30622 | 2 | binding | up-regulates activity | 0.771 | CLASPs were originally identified as CLIP-170-interacting proteins and later found to be required for microtubule stabilisation at the cortical regions of epithelial cells|the C-terminal region of CLASP2 is known to interact with CLIP-170 | SIGNOR-264827 |
P08069 | P01308 | 2 | binding | up-regulates | 0.89 | Because of the sequence homology and tertiary structure similarities between proinsulin (pi) and insulin-like growth factor-i (igf-i), it is possible that pi interacts with the igf-i receptor with higher affinity than insulin. | SIGNOR-22083 |
P08754 | O60755 | 2 | binding | up-regulates activity | 0.45 | 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-256862 |
P05771 | P29474 | 1 | phosphorylation | down-regulates activity | 0.309 | 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-251630 |
Q9UJV3 | Q5S007 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity. | SIGNOR-278763 |
Q9H2X6 | P04637 | 1 | phosphorylation | up-regulates | 0.797 | Based on all these observations, it is legitimate to suggest that axin and daxx seem to adopt both parallel routes and a convergent means to activate p53. In either case, hipk2 seems to be the protein kinase that catalyzes the ser46 phosphorylation. | SIGNOR-151930 |
P01031 | P21730 | 2 | binding | up-regulates activity | 0.757 | The chemotactic receptor for human C5a anaphylatoxin|The human C5a receptor was cloned from U937 and HL-60 cells and identified by high affinity binding when expressed in COS-7 cells. | SIGNOR-263457 |
P39880 | P06493 | 0 | phosphorylation | down-regulates | 0.357 | Phosphorylation of serines 1237 and 1270 caused inhibition of dna binding in vitro. In cotransfection studies, cyclin a-cdk1 inhibited cdp/cux stable dna binding and prevented repression of the p21(waf1) reporter. | SIGNOR-110912 |
P63096 | Q96LB2 | 2 | binding | up-regulates activity | 0.249 | 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-257058 |
Q9NY33 | P01019-PRO_0000032458 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Human dipeptidyl-peptidase III (hDPP III) is capable of specifically cleaving dipeptides from the N-terminal of small peptides with biological activity such as angiotensin II (Ang II, DRVYIHPF), and participates in blood pressure regulation, pain modulation, and the development of cancers in human biological activities. The binding of Ang II to hDPP III may lead to changes in the shape and size of subsite S1, an important catalytic site, so as to promote the decomposition of the substrate. | SIGNOR-268463 |
Q9HB75 | Q9UPS8 | 0 | relocalization | up-regulates activity | 0.2 | Here, we demonstrate that PIDD1 is recruited to mature centrosomes by the centriolar distal appendage protein ANKRD26.|We propose that PIDDosome activation can in both cases be promoted by an ANKRD26-dependent local increase in PIDD1 concentration close to the centrosome. | SIGNOR-266068 |
P06239 | P24666 | 1 | phosphorylation | up-regulates activity | 0.354 | In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Site-directed mutagenesis showed that Tyr-131 is important for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activation. | SIGNOR-251367 |
P35222 | Q9H159 | 2 | binding | up-regulates activity | 0.315 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265858 |
Q05397 | Q13164 | 0 | phosphorylation | up-regulates activity | 0.291 | Remarkably, the reduction in ERK5 expression correlated with decreased p-FAK(Tyr397) staining, consistent with the requirement of ERK5 for mediating FAK activation in vivo (Fig. 6C).|We confirmed that JWG-045, a novel pharmacological inhibitor of ERK5 exhibiting significantly reduced affinity for BRD4 compared with XMD8-92 (25, 26), did not suppress FAK phosphorylation at Tyr397 in MDA-MB-231 cells (Supplementary Fig. S3B and C). | SIGNOR-279304 |
Q9NQU5 | P10275 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Furthermore, AR phosphorylation at Ser-578 by PAK6 promotes AR-E3 ligase murine double minute-2 (Mdm2) association, causing AR degradation upon androgen stimuli. | SIGNOR-279247 |
Q9UKV5 | P11441 | 1 | polyubiquitination | down-regulates activity | 0.52 | USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding. | SIGNOR-272856 |
Q5VST9 | Q01484 | 1 | relocalization | up-regulates quantity | 0.498 | Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins. | SIGNOR-266726 |
P51692 | P06239 | 0 | phosphorylation | up-regulates activity | 0.643 | A constitutively active Lck kinase promotes cell proliferation and resistance to apoptosis through signal transducer and activator of transcription 5b activation.|Expression of the active Lck kinase induces both tyrosine phosphorylation and DNA binding activity of signal transducer and activator of transcription 5b (STAT5b), a STAT family member activated in a variety of tumor cells. | SIGNOR-279056 |
P06493 | P27816 | 1 | phosphorylation | down-regulates activity | 0.497 | We have shown that MAP4 is phosphorylated in vivo in mitotic HeLa cells at eight sites. Five of these were phosphorylated by p34cdc2 kinase. Two of the five p34cdc2 kinase phosphorylation sites were shown to be Ser696 and Ser787 in the proline-rich region. Mutation of Ser787 to Glu strikingly reduced the MAP4's MT-polymerization activity, while Glu-mutation at Ser696 did not. These results suggest that Ser787 could be the critical phosphorylation site causing MTs to be dynamic at mitosis. | SIGNOR-277459 |
P31749 | P29401 | 1 | phosphorylation | up-regulates activity | 0.282 | Akt phosphorylates TKT on Thr382, markedly enhancing enzyme activity and increasing carbon flow through the nonoxidative PPP, thereby increasing purine synthesis. | SIGNOR-265101 |
Q92831 | P04150 | 0 | relocalization | up-regulates activity | 0.549 | NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase | SIGNOR-269233 |
P51955 | P51955 | 2 | phosphorylation | up-regulates | 0.2 | Enzymatic activity, induced; | SIGNOR-151763 |
P00519 | P03372 | 1 | phosphorylation | up-regulates | 0.446 | Eralpha can be phosphorylated on two sites, tyrosine 52 (y-52) and tyrosine 219 (y-219). Eralpha phosphorylation by c-abl stabilizes eralpha, resulting in enhanced eralpha transcriptional activity and increased expression of endogenous eralpha target genes. | SIGNOR-163562 |
Q03135 | O75581 | 2 | binding | up-regulates | 0.676 | Overall, our data suggest that wnt-3a triggers the interaction of lrp6 with caveolin and promotes recruitment of axin to lrp6 phosphorylated by glycogen synthase kinase-3beta and that caveolin thereby inhibits the binding of beta-catenin to axin. | SIGNOR-148665 |
O75096 | O00468 | 2 | binding | up-regulates activity | 0.849 | AGRN is released by the nerve and binds to LRP4, which then binds to MuSK. This interaction leads to MuSK autophosphorylation and activation of its kinase function, leading to anterograde signalling by subsequent phosphorylation of DOK7 (not shown), which binds MuSK as a dimer. | SIGNOR-273849 |
P08183 | P53041 | 0 | dephosphorylation | down-regulates activity | 0.2 | Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function|P-gp is known to be phosphorylated at Ser667, Ser671, and Ser683 by PKA; at Ser661, Ser667, and Ser671 by PKC; and at Ser683 by Pim-1|simultaneous expression of PP5 and PPP2R3C reduced the phosphorylation detected by the antibodies that specifically recognize serine/threonine phosphorylated by PKA or serine phosphorylated by PKC. These results suggest that the PP5/PPP2R3C complex dephosphorylates PKA- and PKC-phosphorylated serine residues on P-gp | SIGNOR-272507 |
Q13315 | Q9NS23 | 1 | phosphorylation | up-regulates | 0.549 | We show that, upon dna damage, rassf1a is phosphorylated by atm on ser131 and is involved in the activation of both mst2 and lats1, leading to the stabilization of p73. | SIGNOR-161934 |
P04049 | P17612 | 0 | phosphorylation | down-regulates activity | 0.5 | Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). | SIGNOR-250041 |
P50148 | O14842 | 2 | binding | up-regulates activity | 0.573 | 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-257272 |
P21462 | P63096 | 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-256682 |
Q13555 | O60266 | 1 | phosphorylation | down-regulates activity | 0.353 | Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo. | Site-directed mutagenesis of a CaM kinase II consensus site (Ser-1076 to Ala-1076) in III-AC greatly reduced Ca2+-stimulated phosphorylation and inhibition of III-AC in vivo. | SIGNOR-250691 |
P08254 | P10451 | 1 | cleavage | up-regulates activity | 0.67 | In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA. | SIGNOR-253320 |
P06213 | Q8WU20 | 1 | phosphorylation | up-regulates activity | 0.371 | We found that insulin receptor can directly phosphorylate FRS2. | SIGNOR-278945 |
Q969H0 | P01106 | 1 | ubiquitination | down-regulates quantity | 0.762 | We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1. Whereas wild-type Fbw7 promoted c-Myc turnover in cells, an Fbw7 mutant lacking the F-box domain delayed it. | SIGNOR-243545 |
O00141 | Q99759 | 1 | phosphorylation | down-regulates activity | 0.2 | Inhibition of mitogen-activated kinase kinase kinase 3 activity through phosphorylation by the serum- and glucocorticoid-induced kinase 2 | SIGNOR-101216 |
Q9GZM8 | P06493 | 0 | phosphorylation | up-regulates activity | 0.66 | In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites | SIGNOR-274074 |
P30530 | Q8NB16 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6). | SIGNOR-274119 |
P62837 | Q8IYM9 | 2 | binding | up-regulates activity | 0.3 | It was found that TRIM22 underwent self-ubiquitylation in vitro in combination with the E2 enzyme UbcH5B and the ubiquitylation was dependent on its RING finger domain. Further evidences showed that TRIM22 could also be self-ubiquitylated in vivo. Importantly, TRIM22 was conjugated with poly-ubiquitin chains and stabilized by the proteasome inhibitor in 293T cells, suggesting that TRIM22 targeted itself for proteasomal degradation through the poly-ubiquitylation. We also found that TRIM22 was located in the nucleus, indicating that TRIM22 might function as a nuclear E3 ubiquitin ligase. | SIGNOR-271779 |
Q16539 | P06400 | 1 | phosphorylation | down-regulates | 0.539 | P38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates rb on ser567, which is not phosphorylated during the normal cell cycle. Phosphorylation by p38, but not cdks, triggers an interaction between rb and the human homolog of murine double minute 2 (hdm2), leading to degradation of rb, release of e2f1 and cell death. | SIGNOR-168178 |
P48730 | P46937 | 1 | phosphorylation | down-regulates | 0.421 | LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP) | SIGNOR-230738 |
Q9NZ42 | P34925 | 1 | cleavage | up-regulates | 0.2 | Ryk activity is modulated through cleavage of its icd by gamma-secretase | SIGNOR-182145 |
Q01860 | O00308 | 0 | ubiquitination | down-regulates quantity | 0.453 | WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells|Here, we report that human WWP2, an E3 ubiquitin (Ub)-protein ligase, interacts with OCT4 specifically through its WW domain and enhances Ub modification of OCT4 both in vitro and in vivo. | SIGNOR-268850 |
Q9NXV6 | P04637 | 2 | binding | up-regulates | 0.382 | In the nucleoplasm, carf interacts with p53 and enhances its function. | SIGNOR-147360 |
Q18PE1 | O15146 | 2 | binding | up-regulates | 0.721 | In addition, dok7, a cytoplasmic adaptor protein, is also required for musk activation in vivo. This review focuses on the physical interplay between these proteins and musk for activation and downstream signaling, which culminates in nmj formation. | SIGNOR-192264 |
Q01094 | Q16531 | 2 | binding | up-regulates | 0.351 | We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription | SIGNOR-54096 |
P04637 | Q66K89 | 0 | 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 |
P84077 | O43150 | 0 | gtpase-activating protein | up-regulates activity | 0.655 | Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro. | SIGNOR-269705 |
Q9NR80 | P12931 | 0 | phosphorylation | up-regulates | 0.312 | This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1. | SIGNOR-179601 |
O60229 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.4 | We then demonstrated that Cdk5 phosphorylates Kalirin 7 on Thr 1590 , increasing its GEF activity slightly and changing its solubility properties. | SIGNOR-279603 |
P22681 | P06241 | 0 | phosphorylation | up-regulates activity | 0.812 | Fyn associates with cbl and phosphorylates tyrosine 731 in cbl, a binding site for phosphatidylinositol 3-kinasecbl represents a substrate for src-like kinases that are activated in response to the engagement of cell surface receptors, and that src-like kinases are responsible for the phosphorylation of a tyrosine residue in cbl that may regulate activation of phosphatidylinositol 3-kinase | SIGNOR-63968 |
P40763 | P17706 | 0 | dephosphorylation | down-regulates | 0.735 | The nuclear isoform of protein-tyrosine phosphatase tc-ptp regulates interleukin-6-mediated signaling pathway through stat3 dephosphorylation. | SIGNOR-90818 |
Q8IVS8 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability | SIGNOR-280258 |
P05067 | O75116 | 0 | phosphorylation | up-regulates quantity | 0.386 | Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms. | SIGNOR-280109 |
O15265 | O43186 | 2 | binding | down-regulates activity | 0.607 | We found that ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation. | SIGNOR-223226 |
Q17R89 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.589 | 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-260498 |
Q03135 | P48664 | 2 | binding | down-regulates activity | 0.2 | EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers. | SIGNOR-264810 |
Q9H444 | Q6DKK2 | 2 | binding | up-regulates activity | 0.417 | We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis. On the basis of these data and the high-content microscopy described above, we propose that PtdIns(3)P controls the KIF13A-dependent recruitment of FYVE-CENT and TTC19 to the midbody, and that TTC19 is the most downstream effector of the three, possibly controlling the function of CHMP4B. | SIGNOR-265541 |
P07948 | Q7L591 | 1 | phosphorylation | up-regulates activity | 0.409 | 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-268447 |
Q9H6E5 | Q8IXQ5 | 2 | binding | down-regulates quantity by destabilization | 0.2 | Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. | SIGNOR-272318 |
Q13315 | P50542 | 1 | phosphorylation | up-regulates activity | 0.497 | Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. | SIGNOR-262792 |
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