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 |
|---|---|---|---|---|---|---|---|
P54756 | P52803 | 2 | binding | up-regulates | 0.896 | Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor | SIGNOR-52476 |
O60282 | Q9Y3R0 | 2 | binding | up-regulates activity | 0.324 | HAP1 and GRIP1 are kinesin-1 adaptors that have been implicated individually in the transport of vesicular cargoes in the dendrites of neurons. We find that HAP1a and GRIP1 form a protein complex in the brain, and co-operate to activate the kinesin-1 subunit KIF5C in vitro | SIGNOR-264061 |
P05067 | Q13564 | 2 | binding | up-regulates activity | 0.732 | Alzheimer's disease (AD) is the gradual loss of the cognitive function due to neuronal death. Currently no therapy is available to slow down, reverse or prevent the disease. Here we analyze the existing data in literature and hypothesize that the physiological function of the Amyloid Precursor Protein (APP) is activating the AppBp1 pathway and this function is gradually lost during the progression of AD pathogenesis. | SIGNOR-251577 |
Q01813 | O15294 | 0 | glycosylation | down-regulates activity | 0.257 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267583 |
Q04917 | Q7Z418 | 2 | binding | down-regulates activity | 0.309 | Phosphorylation of serine 264 in mouse TRESK was required for the binding of 14-3-3η. In the present study, we report that 14-3-3 proteins directly bind to the intracellular loop of TRESK and control the kinetics of the calcium-dependent regulation of the channel. Coexpression of 14-3-3η with TRESK blocked, whereas the coexpression of a dominant negative form of 14-3-3η accelerated the return of the K+ current to the resting state after the activation mediated by calcineurin in Xenopus oocytes. | SIGNOR-263155 |
O15194 | Q15796 | 1 | dephosphorylation | down-regulates activity | 0.498 | Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity | SIGNOR-248310 |
P07948 | P42679 | 0 | phosphorylation | down-regulates activity | 0.333 | In vitro phosphorylation assays showed that Chk suppressed Lyn activity by phosphorylating its C-terminal negative regulatory tyrosine. | SIGNOR-250177 |
Q9H3D4 | Q16539 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.307 | P38α phosphorylates and destabilizes p63. | SIGNOR-277414 |
Q99426 | Q13618 | 0 | ubiquitination | down-regulates quantity | 0.245 | Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B. | SIGNOR-268945 |
P46937 | Q9P289 | 0 | phosphorylation | down-regulates activity | 0.2 | Further, and consistent with our aforementioned finding that MST4 inactivates YAP in response to serum starvation, this stress condition enhanced the YAP\u2013MST4 interaction ( xref ).|Here, we revealed that the MST4 kinase-mediated Thr83 phosphorylation of YAP represents such an additional mechanism of YAP inactivation. | SIGNOR-278994 |
Q8NFZ4 | Q9Y4C0 | 2 | binding | up-regulates activity | 0.825 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264166 |
P48431 | Q9UGL1 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.309 | Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes. | SIGNOR-273450 |
Q9BV68 | P38936 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.331 | E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation.We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner. | SIGNOR-272033 |
Q9H4A3 | P31749 | 0 | phosphorylation | up-regulates | 0.393 | Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt. | SIGNOR-252481 |
P01106 | P25490 | 2 | binding | down-regulates activity | 0.544 | Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc.Yin-Yang-1 (YY1) regulates the transcription of many genes, including the oncogenes c-fos and c-myc. Depending on the context, YY1 acts as a transcriptional repressor, a transcriptional activator, or a transcriptional initiator. In cotransfections, c-Myc inhibits both the repressor and the activator functions of YY1, which suggests that one way c-Myc acts is by modulating the activity of YY1. | SIGNOR-268795 |
P01583 | P14778 | 2 | binding | up-regulates activity | 0.767 | Interleukin-1 receptor (il-1r) is a cytokine receptor which binds interleukin 1. | SIGNOR-35077 |
P46108 | P29320 | 2 | binding | up-regulates | 0.626 | Our results suggest that recruitment of crkii and activation of rho signalling are responsible for epha3-mediated cell rounding, blebbing and de-adhesion, and that ephrin-a5-mediated receptor clustering and epha3 tyrosine kinase activity are essential for this response | SIGNOR-115335 |
P20827 | Q15375 | 2 | binding | up-regulates | 0.812 | The best known function is their role in the guidance of migration of axons and cells in the nervous system through repulsive interactions | SIGNOR-56965 |
O43318 | O43318 | 2 | phosphorylation | up-regulates activity | 0.2 | Analyses of phosphorylation site mutants of the activation segment indicate that autophosphorylation of Ser-192 precedes TAB1 phosphorylation and is followed by sequential phosphorylation of Thr-178, Thr-187, and finally Thr-184. Finally, we present a model for the chronological order of events governing TAB1-induced TAK1 autoactivation. | SIGNOR-227544 |
P63000 | O15013 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.442 | 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-260536 |
P31749 | O14757 | 1 | phosphorylation | down-regulates | 0.43 | The chk1 protein phosphorylated by pkb on serine 280 does not enter into protein complexes after replication arrest. Moreover, chk1 phosphorylated by pkb fails to undergo activating phosphorylation on serine 345 by atm/atr. Phosphorylation by atm/atr and association with other checkpoint proteins are essential steps in activation of chk1. | SIGNOR-124365 |
P47736 | P19086 | 2 | binding | down-regulates activity | 0.35 | Biochemical analysis using purified recombinant proteins revealed that the physical interaction between Gaz and Rap1GAP blocks the ability of RGSs (regulators of G protein signaling) to stimulate GTP hydrolysis of the a subunit, and also attenuates the ability of activated Gaz to inhibit adenylyl cyclase. | SIGNOR-278053 |
P05771-2 | P62714 | 0 | dephosphorylation | down-regulates activity | 0.469 | Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme. | SIGNOR-248587 |
P34931 | P49137 | 0 | phosphorylation | up-regulates activity | 0.2 | We demonstrate that MK2 phosphorylates HspA1L solely on Ser241, a residue within the N-terminal nucleotide-binding domain of the enzyme. This phosphorylation event enhances the chaperone activity of HspA1L in vitro and renders male germ cells more resistant to heat stress-induced apoptosis. | SIGNOR-273674 |
P51452 | P27361 | 1 | dephosphorylation | down-regulates activity | 0.665 | The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase (14), protein-tyrosine phosphatase (ptp) (14, 15), or dual specificity phosphatases | SIGNOR-103035 |
P49841 | Q01974 | 1 | phosphorylation | down-regulates activity | 0.312 | We identify ror2 ser 864 as a critical residue phosphorylated by gsk3 and required for noncanonical receptor activation by wnt5a, analogous to the priming phosphorylation of low-density receptor-related protein 6 (lrp6) in response to wnt3a. | SIGNOR-169642 |
Q05397 | P49841 | 1 | phosphorylation | up-regulates activity | 0.365 | Inhibition of FAK by its small molecule inhibitor attenuated IL-33-induced tyrosine 216 phosphorylation of GSK3beta in a both time- and dose dependent manner (XREF_FIG).|The current study indicates that FAK activated GSK3beta modulates ST2L internalization and signaling. | SIGNOR-278986 |
P43146 | Q9HD67 | 2 | binding | up-regulates activity | 0.686 | Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites. Moreover, expression of DCC, but not neogenin, stimulates Myo X-mediated formation and elongation of filopodia, suggesting that Myo X function may be differentially regulated by DCC and neogenin. | SIGNOR-268281 |
P08047 | Q9UKX5 | 1 | null | up-regulates quantity by expression | 0.2 | We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors. | SIGNOR-253350 |
P54764 | P11362 | 1 | phosphorylation | up-regulates activity | 0.402 | EphA4 and FGFR1 heterodimer promotes FGFR1 signaling in glioma cell line.|Ligand stimulation of EphA4 stimulates FGFR1 phosphorylation and signaling. | SIGNOR-280007 |
P30622 | O75122 | 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 |
O96017 | P10636 | 1 | phosphorylation | down-regulates | 0.2 | Tau pseudophosphorylation at specific sites such as s262, s293, s324 and s356 was reported to induce tau conformational change and attenuate tau binding to microtubules (fischer et al., 2009). Then, newly soluble tau proteins are targeted by post-translational modifications that directly or indirectly alter tau conformation, promoting tau dimerization in an anti-parallel manner. Stable tau dimers form tau oligomers, which continue in the aggregation process | SIGNOR-171026 |
Q6UVJ0 | Q66GS9 | 2 | binding | up-regulates activity | 0.596 | In this study, we demonstrate that the human microcephaly protein, CEP135, directly interacts with hSAS-6 via its carboxyl-terminus and with MTs via its amino-terminus. Unexpectedly, CEP135 also interacts with another microcephaly protein CPAP via its amino terminal domain. Depletion of CEP135 not only perturbed the centriolar localization of CPAP, but also blocked CPAP-induced centriole elongation. We propose that CEP135 may serve as a linker protein that directly connects the central hub protein, hSAS-6, to the outer MTs, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP-mediated centriole elongation. | SIGNOR-269676 |
Q00535 | P07197 | 1 | phosphorylation | down-regulates quantity | 0.42 | Converse to the effect of PKA overexpression, overexpression of CDK5 and its activator, p35, decreased the association between spinophilin and NF-M as well as the expression of NF-M.|Moreover, CDK5 phosphorylates NF-M [ xref ], and this was also apparent in our data, given a dramatic molecular weight shift in the NF-M band following CDK5 overexpression. | SIGNOR-279683 |
Q9NZQ7 | Q9NX76 | 0 | stabilization | up-regulates quantity by stabilization | 0.47 | Furthermore, the observations that (i) CMTM6 affects PD-L1 protein stability at late time points after biosynthesis; (ii) CMTM6, CMTM4 and PD-L1 interact, as shown by co-immunoprecipitation; and that (iii) CMTM6 is largely located at the cell surface, collectively suggest a model in which CMTM6 interacts with PD-L1 at the tumour cell surface and thereby protects it from degradation | SIGNOR-274980 |
Q9BXH1 | Q16611 | 2 | binding | up-regulates | 0.382 | Bim, and puma bind with high affinity to all pro-survival proteins | SIGNOR-196929 |
P61244 | Q99583 | 2 | binding | up-regulates activity | 0.352 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240354 |
P19086 | P30550 | 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-257314 |
Q01668 | P43146 | 0 | null | up-regulates activity | 0.297 | DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. | SIGNOR-268292 |
Q12778 | P48729 | 0 | phosphorylation | down-regulates | 0.418 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity | SIGNOR-183658 |
Q13177 | P05412 | 1 | phosphorylation | up-regulates | 0.268 | P21-activated protein kinase (pak2)-mediated c-jun phosphorylation at 5 threonine sites promotes cell transformationour data showed that pak2 binds and phosphorylates c-jun at five threonine sites (thr2, thr8, thr89, thr93 and thr286) | SIGNOR-170772 |
Q9UHD2 | P31645 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, our data suggest that TBK1 expression promotes the general cellular clearance mechanism of soluble HTT and prevents its accumulation and aggregation by enhancing autophagy.|This confirmed that TBK1 phosphorylated endogenous HTT at S13 (Fig XREF_FIG G and H). | SIGNOR-278384 |
P01106 | P11802 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.569 | C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation | SIGNOR-102734 |
P43220 | P63092 | 2 | binding | up-regulates activity | 0.481 | The GPCRs are allocated in five families where the GLP-1R and GIPR are found within the secretin family, also classified as class B [31,32]. Upon stimulation by an extracellular stimuli (ligand), GPCRs undergo conformational changes, and triggers downstream intracellular signals by coupling with G proteins (or other intracellular proteins such as arrestins), causing a wide range of both physiological and pathological processes.To stimulate insulin secretion, and in the presence of elevated blood glucose concentrations, GLP-1R activation in pancreatic beta cells promote recruitment and activation of Gαs protein leading to adenylate cyclase-mediated cAMP production, elevation of Ca2+, and ERK1/2 phosphorylation (Fig. 3) | SIGNOR-278137 |
P68400 | P12821 | 1 | phosphorylation | up-regulates activity | 0.303 | CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine(1270) within the CK2 consensus sequence almost abolished ACE phosphorylation.|These results indicate that the CK2-mediated phosphorylation of ACE regulates its retention in the plasma membrane and may determine plasma ACE levels. | SIGNOR-264425 |
P53778 | P52564 | 0 | phosphorylation | up-regulates | 0.659 | Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub of the mitogen-activated protein kinase superfamily . the p38 mapkinasekinasemkk6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma mapkinaseisoforms . p38mapks are activated by dual phosphorylation on a t-x-y motif in the activation loop through the action of map kinase kinases | SIGNOR-184134 |
P63000 | Q96JJ3 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.583 | We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth. | SIGNOR-266821 |
P33032 | Q8TCY5 | 2 | binding | down-regulates activity | 0.396 | We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members. | SIGNOR-252368 |
Q08050 | P45974 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.351 | Wnt signaling activation inhibits FoxM1 phosphorylation by GSK3-Axin complex and leads to interaction between FoxM1 and deubiquitinating enzyme USP5, thereby deubiquitination and stabilization of FoxM1. | SIGNOR-277210 |
P07948 | P35354 | 1 | phosphorylation | up-regulates activity | 0.385 | We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro. | SIGNOR-276643 |
Q86Y13 | Q16777 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271754 |
Q7Z7A1 | Q96ED9 | 2 | binding | up-regulates | 0.353 | Hook2 localizes to the centrosome, binds directly to centriolin/cep110 and contributes to centrosomal function | SIGNOR-150956 |
P27487 | P51654 | 2 | binding | down-regulates | 0.352 | The interaction occurred with both the glycosylated and unglycosylated forms of gpc3 and led to the inhibition of cd26 peptidase activity. | SIGNOR-155527 |
P23458 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.767 | Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5. | SIGNOR-134620 |
P16591 | P10275 | 1 | phosphorylation | up-regulates | 0.259 | Fer is required for il-6 mediated ar activation by phosphorylating ar tyrosine 223 and binding via its sh2 domain. | SIGNOR-194749 |
P33981 | Q53HL2 | 1 | phosphorylation | up-regulates | 0.461 | First, we confirmed that wild-type borealin is phosphorylated at the previously described sites t88, t94, t169, and t230 when present in complex with survivin borealin might be a substrate for mps1. In the case of wild-type borealin, the fast exchange between the monomeric and dimeric forms may allow mps1 to phosphorylate the monomer. In turn, mps1 may regulate borealin function by unfolding the c-terminal domain and/or shifting the population to the monomeric form. | SIGNOR-186151 |
P04637 | P11166 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.597 | P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway. | SIGNOR-267464 |
O75822 | P68400 | 0 | phosphorylation | up-regulates activity | 0.326 | CK2 phosphorylates the eIF3j subunit at Ser127. CK2-phosphorylation of eIF3j triggers its association with the eIF3 complex. | SIGNOR-266402 |
P14921 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.309 | Treatment of ets1 by t-cell nuclear extract or phosphorylation of these four serines by calmodulin-dependent kinase ii (camk ii) has recently been reported to decrease ets1 dna binding by reinforcing autoinhibition | SIGNOR-96334 |
P42336 | P01111 | 2 | binding | up-regulates activity | 0.844 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k | SIGNOR-175222 |
P18084 | Q99704 | 2 | binding | down-regulates activity | 0.294 | Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation | SIGNOR-257691 |
P31751 | Q9UBK2 | 1 | phosphorylation | down-regulates | 0.348 | Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1? At ser?570 Is required for akt to inhibit recruitment of pgc-1? To chromatin. | SIGNOR-155536 |
Q04759 | P29350 | 1 | phosphorylation | down-regulates activity | 0.2 | SHP-1 phosphorylation is mediated through PKC-θ. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 'folded' state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in vivo. | SIGNOR-277590 |
P06493 | Q16512 | 1 | phosphorylation | up-regulates activity | 0.436 | CDK1 phosphorylates PKN1 at S533, S537, S562, and S916 in vitro and in cells during drug-induced mitotic arrest. Immunofluorescence staining further confirmed that PKN1 phosphorylation occurs during normal mitosis in a CDK1-dependent manner.Knockdown of PKN1 significantly inhibited anchorage-independent growth and migration without affecting proliferation in multiple cancer cell lines. | SIGNOR-276831 |
Q9UBY5 | O95837 | 2 | binding | up-regulates activity | 0.5 | 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-257357 |
Q16236 | P48637 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.31 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy | SIGNOR-279870 |
P07948 | P40763 | 1 | phosphorylation | up-regulates activity | 0.659 | An in vitro phosphorylation assay showed that Lyn directly phosphorylates STAT3. | SIGNOR-279062 |
Q13671 | P55196 | 2 | binding | up-regulates activity | 0.2 | Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors. | SIGNOR-220926 |
P49023 | Q9Y2U5 | 0 | phosphorylation | down-regulates quantity | 0.362 | As MEKK2 kinase activity is required for this function, our findings support a model of paxillin modification wherein MEKK2 directly phosphorylates and targets paxillin for ubiquitylation. | SIGNOR-278955 |
Q14289 | O43294 | 1 | phosphorylation | up-regulates activity | 0.71 | 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-262876 |
P68871 | Q86VB7 | 2 | binding | up-regulates activity | 0.442 | These data suggest that hemoglobin may mediate a stimulatory effect on erythropoiesis through the activation of CD163 on hematopoietic progenitor cells. | SIGNOR-251746 |
Q99542 | P16112 | 1 | cleavage | down-regulates quantity by destabilization | 0.4 | Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)|In this study we investigated the ability of MMP-19 and MMP-20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well-described MMP cleavage site between residues Asn(341) and Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development. | SIGNOR-266978 |
Q9HB90 | Q8NFG4 | 0 | gtpase-activating protein | up-regulates activity | 0.695 | The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur | SIGNOR-256503 |
P00540 | Q02750 | 1 | phosphorylation | up-regulates activity | 0.485 | Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222. | SIGNOR-260920 |
P06241 | Q00535 | 1 | phosphorylation | up-regulates activity | 0.608 | Constitutively active Fyn phosphorylated Tyr15 of Cdk5. Fyn Facilitates Kinase Activity of Cdk5 Via Tyr15 Phosphorylation | SIGNOR-251156 |
P10242 | P27361 | 0 | phosphorylation | down-regulates | 0.301 | Functional analysis of phosphorylation at serine 532 of human c-myb by map kinase. expression of a polypeptide containing the c-myb c-terminal domain stimulated c-myb activity. This effect is reduced upon mapk-dependent phosphorylation of serine 532. Our data suggest that the mapk-dependent state of phosphorylation modifies the cellular function of c-myb by modulating its interaction with a putative inhibitory factor | SIGNOR-45348 |
P53350 | Q9Y2Z0 | 1 | phosphorylation | up-regulates activity | 0.437 | Plk1 phosphorylates Sgt1 at the kinetochores to promote timely kinetochore-microtubule attachment|Plk1 is required for the kinetochore localization of Sgt1 and phosphorylates serine 331 of Sgt1 at the kinetochores. This phosphorylation event enhances the association of the Hsp90-Sgt1 chaperone | SIGNOR-265222 |
P03230 | Q92985 | 1 | sumoylation | down-regulates activity | 0.2 | One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. | SIGNOR-266951 |
Q9HCE7 | Q99717 | 1 | ubiquitination | down-regulates | 0.769 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-195663 |
O43379 | O14733 | 1 | relocalization | up-regulates activity | 0.294 | In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis | SIGNOR-271716 |
P27361 | Q15303 | 1 | phosphorylation | down-regulates activity | 0.534 | We also identified Ser-1026 as an ErbB4-specific ERK target site in the CYT-1 region. Moreover, double mutations (Thr-674/Ser-1026 to Ala) significantly upregulated ErbB4 activation, indicating that Thr-674 and Ser-1026 are cooperatively involved in negative feedback regulation. | SIGNOR-277448 |
P17181 | P01562 | 2 | binding | up-regulates | 0.651 | The present study describes a novel type i ifn receptor having the ability to bind and respond to several subtypes of ifn-a as well as to ifn-8. This 102 kda-51 kda receptor is essential for the activity of many type i ifns, as demonstrated with anti-receptor antibodies. | SIGNOR-36622 |
P35408 | P63092 | 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 |
Q96D96 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | HVCN1S is phosphorylated more by PKC-δ than HVCN1L. PKC-δ in vitro kinase assay showing phosphorylation of HVCN1 | SIGNOR-273827 |
P23409 | Q14814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.573 | Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. | SIGNOR-238715 |
Q13315 | Q03112 | 1 | phosphorylation | up-regulates activity | 0.2 | To investigate to what extent EVI1 function might be regulated by post-translational modifications we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif. | SIGNOR-273433 |
P59637 | O00560 | 1 | relocalization | up-regulates activity | 0.2 | Overall, these results support the hypothesis that the interaction of E protein PBM with syntenin facilitates the recruitment of syntenin in the cytosol and leads to p38 MAPK activation. | SIGNOR-260752 |
P12931 | Q8WTV0 | 2 | binding | up-regulates activity | 0.368 | Importantly, coimmunoprecipitation of SR-BI and Src demonstrated that the two proteins are directly associated in WT macrophages (Fig. 7B), suggesting that SR-BI plays a direct role in activation of Src in macrophages. | SIGNOR-260314 |
O60346 | P04049 | 1 | 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 |
O15105 | Q9HAU4 | 2 | relocalization | up-regulates activity | 0.87 | 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-104996 |
Q9UBR4 | P01215 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.387 | Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing hormone (TRH). P-Lim binds to CBP in TRH-dependent manner on this site and that these proteins synergistically activate the human α-GSU promoter during TRH stimulation. | SIGNOR-267207 |
P10721 | P62993 | 2 | binding | up-regulates activity | 0.65 | We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. | SIGNOR-248283 |
P06493 | P39748 | 1 | phosphorylation | down-regulates activity | 0.446 | Phosphorylation of human fen1 by cyclin-dependent kinase modulates its role in replication fork regulation.As a functional consequence of phosphorylation by cdk1-cyclin a in vitro, endo- and exonuclease activities of fen1 are reduced whereas its dna binding is not affected. | SIGNOR-103535 |
Q5VT25 | P53667 | 1 | phosphorylation | up-regulates activity | 0.404 | Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha. \ In vitro, MRCKalpha phosphorylated the protein kinase domain of LIM kinases, and the site in LIMK2 phosphorylated by MRCKalpha proved to be threonine 505 within the activation segment. | SIGNOR-250721 |
Q9NQC7 | Q12933 | 1 | deubiquitination | down-regulates activity | 0.677 | Cyld also interacts directly with tumour-necrosis factor receptor (tnfr)-associated factor 2 (traf2), an adaptor molecule involved in by members of the family of tnf/nerve growth factor receptors. (articolo-abstract) | SIGNOR-117860 |
Q03405 | P00749 | 2 | binding | up-regulates | 0.891 | The urokinase plasminogen activator binds to its cellular receptor with high affinity and initiates signaling cascades that are implicated in pathological processes including tumor growth, metastasis, and inflammation. | SIGNOR-144306 |
P08172 | P09471 | 2 | binding | up-regulates activity | 0.349 | 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-256964 |
P18848 | O43776 | 1 | 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-269422 |
Q14674 | P28482 | 0 | phosphorylation | down-regulates | 0.277 | Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro | SIGNOR-113130 |
Q9Y6Q6 | O14788 | 2 | binding | up-regulates activity | 0.896 | RANKL, a member of the tumour necrosis factor superfamily, is most abundantly expressed as a cell-surface protein by bone-marrow stromal cells. It interacts with its receptor RANK (which is encoded by Tnfrsf11a) on macrophages and mature osteoclasts. | SIGNOR-253042 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.