• It is found in the cytoplasm and binds to the intracellular domain of the Alzheimer's disease beta-amyloid precursor protein (APP) as well as to other APP-like proteins. (wikipedia.org)
  • This domain occurred 3 times on human genes ( 3 proteins). (umbc.edu)
  • 1) Characterize novel families of oncoproteins (Pbx and Meis) that dimerize with and regulate the DNA binding properties of Hox proteins. (stanford.edu)
  • Receptor dimerization and autophosphorylation attracts proteins containing Src homology 2 (SH2) or phosphotyrosine binding (PTB) domains including adaptor proteins like FRS2 and GRB2. (springer.com)
  • Despite the close relationship between the Drosophila and mammalian Shc proteins, dShc lacks the high-affinity Grb2-binding site found in mammalian Shc, suggesting that Shc proteins may have functions in addition to regulation of the Ras pathway. (elsevierpure.com)
  • There are 37989 PTPc domains in 29134 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing PTPc domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with PTPc domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing PTPc domain in the selected taxonomic class. (embl.de)
  • The resulting phosphotyrosines attract STAT proteins, such as the STAT1 and STAT2 shown here (dark blue, dark green), which bind via their SH2 domains and become phosphorylated on specific phosphotyrosines, indicated here as Y's (inset), by the Jaks. (shu.edu)
  • To do so, they coupled findings from 238 DNA-protein-binding experiments performed by the ENCODE project - a massive, multiyear international effort to identify the functional elements of the human genome - with a laboratory-based technique to identify binding patterns among the proteins themselves. (pharmaceuticalintelligence.com)
  • Proteins control gene expression by either binding to specific regions of DNA, or by interacting with other DNA-bound proteins to modulate their function. (pharmaceuticalintelligence.com)
  • They studied 128 proteins, called trans-acting factors , which are known to regulate gene expression by binding to regulatory regions within the genome. (pharmaceuticalintelligence.com)
  • In this way, they were able to tell which proteins interacted directly with one another, and which were seen together because their preferred DNA binding sites were adjoining. (pharmaceuticalintelligence.com)
  • Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)
  • Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (embl-heidelberg.de)
  • The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl-heidelberg.de)
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
  • There are 39736 RhoGEF domains in 38458 proteins in SMART's nrdb database. (embl-heidelberg.de)
  • The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (embl-heidelberg.de)
  • An amino-terminal portion conserved among a subset of Dbl family proteins is sufficient for the binding of Gbetagamma. (embl-heidelberg.de)
  • However, it remains unclear where these proteins bind on the AChR and how the interactions are regulated. (jneurosci.org)
  • Each subunit has a large intracellular loop between the third and fourth transmembrane domains that is the likely site for regulated interactions with postsynaptic scaffolding proteins. (jneurosci.org)
  • Breast cancers have got a high amount of genomic heterogeneity that includes a significant impact on treatment plans individual response to therapy patterns of metastasis and individual success [2 3 Breasts tumors are categorized into particular intrinsic subtypes predicated on the existence or lack of estrogen receptor (ER) progesterone receptor oncogene amplification the proliferation marker Ki-67 and the amount of claudins proteins involved with formation of restricted junctions [4]. (biospraysehatalami.com)
  • Phosphorylation creates sites for protein-protein connections between your phosphorylated proteins and signaling substances formulated with SH2 and phosphotyrosine binding domains that recognize phosphotyrosine [13]. (biospraysehatalami.com)
  • SH2 domains are around 100 amino acidity subunits that mediate the transduction of indicators via development of multiprotein complexes initiated by reputation and binding to choose phosphotyrosine residues on receptors and various other proteins [13]. (biospraysehatalami.com)
  • This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. (umbc.edu)
  • In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. (umbc.edu)
  • [8] Mutagenesis studies of type I IFNs, IFNAR1 and IFNAR2 demonstrated important binding residues, i.e. "hotspots", on the type I IFN subtypes which influenced its ability to bind to IFNAR2. (wikidoc.org)
  • Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. (embl.de)
  • IRS-1 contains no transmembrane domain but an amino-terminal pleckstrin homology (PH) and a phosphotyrosine-binding domain (PTB), followed by a carboxyl-terminal region which is enriched in Ser and Thr residues 28 . (nature.com)
  • Because positively charged residues in NT-3 are important for binding to trkB, two negatively charged aspartate residues within the 11 amino acid motif of FL trkB were mutated to examine the role of electrostatic interactions on ligand binding. (jneurosci.org)
  • The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so determine the sequence surrounding the phosphorylation site. (biomedcentral.com)
  • The second factor, termed peptide specificity, describes the interaction between amino acid residues in the catalytic domain of the protein kinase and the substrate residues that surround the phosphorylated residue. (biomedcentral.com)
  • Crystal structures of protein kinases with bound substrate peptides show that substrate residues at positions -3 to +3 relative to the phosphorylated serine, threonine or tyrosine residue adopt an extended conformation and bind to a pocket in the catalytic domain of the protein kinase [ 8 ]. (biomedcentral.com)
  • The heptapeptide sequence from -3 to +3 that best binds to the pocket is determined by the physicochemical nature of the residues in the catalytic domain that line the pocket and contact the substrate. (biomedcentral.com)
  • We identified a highly conserved, 13-residue segment (ADP-1) from adiponectin's collagen domain which comprises GXXG motifs and has one asparagine and two histidine residues that assist in oligomeric protein assembly. (phoenixpeptide.com)
  • In general, Janus family tyrosine kinases (JAKs) bind to the intracellular components of cytokine receptors, and are, in turn, bound by STATs upon cytokine signaling. (medscape.com)
  • Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. (embl-heidelberg.de)
  • Alternative splicing affects both the extracellular ligand-binding domains and the intracellular signal-transducing domains of the trks ( Barbacid, 1994 ). (jneurosci.org)
  • Using proteinCprotein connection assays, we shown that both SH2 and GEF domains of GIV are necessary for the forming of a ligand-activated ternary complicated between GIV, Gi, and development factor receptors as well as for activation of Gi after development factor stimulation. (bio-cavagnou.info)
  • Up coming we asked whether GIV's SH2-like domain is necessary for the recruitment of Gi3 to ligand-activated EGFR. (bio-cavagnou.info)
  • To the end, we examined receptor-bound immune system complexes (Body 4e) before and after ligand activation in GIV-depleted HeLa cells stably expressing little interfering RNA (siRNA)Cresistant, FLAG-tagged WT and mutant GIV (Supplemental Number S3, A and B). As demonstrated previously (Ghosh = 4). (bio-cavagnou.info)
  • Ligand binding to either subunit is required for and precedes dimerization and activation of the receptor. (wikidoc.org)
  • Each subunit of IFNAR contains an N-terminal ligand binding domain (with two or four fibronectin type II-like subdomains, for IFNAR2 and IFNAR1, respectively), a transmembrane (TM) domain, and a cytoplasmic domain. (wikidoc.org)
  • [7] Each type I IFN ligand contains a "hotspot", or a sequence of conserved amino acids that are involved in binding to the receptor, specifically the high affinity receptor IFNAR2, which determines the affinity of each ligand for the receptor. (wikidoc.org)
  • Structural analysis of type I IFN receptor with different type I IFN ligand subtypes revealed a similar binding site for the different agonists. (wikidoc.org)
  • RANKL is a ligand that binds to RANK, a receptor expressed on osteoclasts, dendritic cells, T cells, and other cells. (bvsalud.org)
  • Not shown here is the activation under certain conditions of Jaks that are bound to some G-protein-coupled receptors (GPCRs) and the phosphorylation of STATs directly by certain ligand-activated growth factor receptors (RTKs) as well as non-receptor tyrosine kinases. (shu.edu)
  • Mutations in the tyrosine kinase, whether in BCR-ABL in CML or a FLT3 mutation in AML, bypass control that comes from ligand binding. (shu.edu)
  • a deletion in close proximity to this domain is likely to affect ligand specificity. (jneurosci.org)
  • NMR structure of the interferon-binding ectodomain of the human interferon receptor. (wikidoc.org)
  • The interferon-α/β receptor (IFNAR) is a virtually ubiquitous membrane receptor which binds endogenous type I interferon (IFN) cytokines. (wikidoc.org)
  • [8] The evolutionary conservation of type I IFN subtypes binding the same IFNAR receptor at the same site with differing affinities suggests that type I IFNs are nonredundant and potentially regulate different cellular responses. (wikidoc.org)
  • In addition to a C-terminal Src homology 2 (SH2) domain, dShc contains an N-terminal phosphotyrosine-binding (PTB) domain, which associates in vitro with the autophosphorylated DER receptor tyrosine kinase and with phosphopeptides containing an Asn-Pro-X-pTyr motif, where pTyr stands for phosphotyrosine. (elsevierpure.com)
  • When GFLs bind with GFRα, they form complexes and associate with the RET receptor, subsequently activating downstream signaling. (medsci.org)
  • When cytokines bind to their cognate receptor, JAKs phosphorylate the cytokine receptor and subsequently the STATs, which then dissociate from the JAK-receptor complex. (medscape.com)
  • Structurally, all known receptor PTPases, are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. (embl.de)
  • Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region. (embl.de)
  • OPG is a decoy receptor that binds to RANKL and inhibits its signaling. (bvsalud.org)
  • Alternative splicing of the avian trkB receptor generates an extracellular deletion (ED) isoform missing 11 amino acids from the neurotrophin-binding domain of the full-length (FL) receptor. (jneurosci.org)
  • Here, we define a phosphorylation-dependent binding site on the receptor that mediates agrin-induced clustering. (jneurosci.org)
  • Together, these findings suggest that agrin-induced phosphorylation of the β subunit motif increases the stoichiometry of rapsyn binding to the AChR, thereby helping to stably cluster the receptor and anchor it at high density in the postsynaptic membrane. (jneurosci.org)
  • Insulin resistance, an important feature of type 2 diabetes, is manifested as attenuated insulin receptor (IR) signaling in response to insulin binding. (diabetesjournals.org)
  • Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)
  • Based on crystal structure of AdipoR1, we designed AdipoR1's peptide agonists using protein-peptide docking simulation and screened their receptor binding abilities and biological functions via surface plasmon resonance (SPR) and biological analysis. (phoenixpeptide.com)
  • the current presence of phosphotyrosine ligands. (bio-cavagnou.info)
  • The predominant expression pattern of either FL or ED isoforms in single embryonic DRG neurons establishes the existence of two subpopulations exhibiting differential responsiveness to trkB ligands, indicating that regulated splicing of the extracellular domain of trkB may serve as a mechanism to restrict neuronal responsiveness to the neurotrophins. (jneurosci.org)
  • Siglec-E, a mouse orthologue of human Siglec-9, is a sialic acid binding lectin predominantly expressed on the surface of myeloid cells to transduce inhibitory signal via recruitment of SH2-domain containing protein tyrosine phosphatase SHP-1/2 upon binding to its sialoglycan ligands. (biomedcentral.com)
  • Siglecs are a family of sialic acid-binding immunoglobulin-like receptors predominantly expressed on cells of immune system to regulate their functions through recognizing their glycan ligands [ 5 ]. (biomedcentral.com)
  • Although a high level of PDE10A gene expression is observed in the testis, information on the identity of the isoforms or on the cell type that express the PDE10 protein is lacking. (plos.org)
  • The VEE is a heterogeneous compartment containing the Adaptor Protein Phosphotyrosine Interacting with Pleckstrin homology Domain and Leucine Zipper 1 (APPL1) with distinct functions in regulating endosomal Gαs/cAMP signaling and rapid recycling. (frontiersin.org)
  • We also found that ADP-1 activates AMP-activated protein kinase (AMPK) in an adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)-dependent pathway and stimulates glucose uptake in rat skeletal muscle cells (L-6 myotubes). (phoenixpeptide.com)
  • The specific activity of the PI 3-kinase immunoprecipitated with anti-phosphotyrosine antibody was 3-fold higher than that with anti-PI 3-kinase antibody. (edrc2013.org)
  • Phosphorylated STATs dimerize within the cytosol via their phosphotyrosines and Src-homology 2 (SH2) domains. (medscape.com)
  • A model of Cdc25 phosphatase catalytic domain and Cdk-interaction surface based on the presence of a rhodanese homology domain. (embl.de)
  • Phosphorylation of the AChR β subunit is correlated with increased rapsyn/AChR binding, suggesting that the effect of βY390 phosphorylation on clustering is mediated by rapsyn. (jneurosci.org)
  • Indeed, we found that rapsyn associated with CD4-β loop chimeras in a phosphorylation-dependent manner, and that agrin increased the ratio of rapsyn binding to wild type AChR but not to AChR-β 3F/3F , which lacks β loop tyrosine phosphorylation sites. (jneurosci.org)
  • Phosphopeptide mapping revealed that the effect of TLK16998 on the IR was associated with increased tyrosine phosphorylation of the activation loop of the β-subunit tyrosine kinase domain. (diabetesjournals.org)
  • Overexpression of an inactive mutant of Cav-1 lacking the tyrosine phosphorylation site (Y14F) or an siRNA-mediated Cav-1 knock down also resulted in marked attenuation of IL-1β-induced iNOS gene expression and NO release from these cells, thus further implicating Cav-1 in this signaling cascade. (diabetesjournals.org)
  • Dimerized STATs then translocate to the nucleus, where they bind DNA in the promoter sequences of target genes to activate transcription. (medscape.com)
  • The researchers used 238 data sets generated by the ENCODE project to study the specific DNA sequences bound by each of the 128 trans-acting factors. (pharmaceuticalintelligence.com)
  • they bind many different sequences in a variety of protein-DNA combinations. (pharmaceuticalintelligence.com)
  • Spa gene: s - signal sequence, E, D, A, B, C sequences encoding IgG-binding domains, X - region which lacks IgG-binding activity and consists of repetitive region (Xr) and C-terminal region (Xc). (cftrpathway.com)
  • The enzymes that dephosphorylate these three amino acids are classified into four groups on the basis of specific catalytic signatures/domain sequences and substrate preference. (ac.be)
  • Type I IFN binding to IFNAR1 was less strongly impacted by mutating single amino acids to alanine. (wikidoc.org)
  • PTPase domains consist of about 300 amino acids. (embl.de)
  • The catalytic domain of this dual-specificity phosphatase has recently been mapped to the 180 most C-terminal amino acids. (embl.de)
  • The DH domain of Dbl has been shown to mediate oligomerisation that is mostly homophilic in nature. (embl-heidelberg.de)
  • often, there lacks to mediate dark-matter over degradation with the Phosphorylated mass bone country. (evakoch.com)
  • These results suggest that PI 3-kinase in signet ring cell carcinoma is recruited to the membrane and activated by the binding to the 200-kDa protein. (edrc2013.org)
  • Recently the SH2 domains of Grb7 [22] and STAT3 STAT5 have already been targeted with peptides and peptide mimetics [23 24 Developing practical drugs concentrating on SH2 domains has significant problems. (biospraysehatalami.com)
  • Regardless of the need for Th2 cells and their connected cytokines in the pathogenesis of sensitive respiratory disease, research of antigens regarded as causes of T-cell reactions have up to now been mostly limited by those recognized to bind IgE antibodies (7, 8) and induce IgE-mediated instant hypersensitivity reactions (9). (enmd-2076.com)
  • Thereafter, the STATs dimerize, each using its SH2 domain to bind to the phosphotyrosine of its partner, and then translocate to the nucleus, where they operate as transcription factors to activate expression of key genes, for example, the gene encoding an interferon. (shu.edu)
  • As the main component, extracellular structure contains some cysteine-rich repeats domains marked as D1-D2-D3 in GFRα1-3, and D2-D3 in GFRα4 ( Figure 1 a ). (medsci.org)
  • Since the protein lacks enzymatic activities, it will be difficult to develop chemical compounds capable to directly and specifically modulate Sprouty functions. (springer.com)
  • PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. (umbc.edu)
  • The constant management constitutively required to bind down the methylmalonic of aberrant plasma. (evakoch.com)
  • Arg/Abl2 modulates the affinity and stoichiometry of binding of cortactin to F-actin. (nih.gov)
  • However, demonstration of whether and how these genes cause pathology is largely lacking. (sdbonline.org)
  • Studies carried out in mice possess demonstrated the introduction of allergic airway hyperresponsiveness mediated by T cells in the lack of IgE (10, 11). (enmd-2076.com)
  • A collagen domain-derived short adiponectin peptide activates APPL1 and AMPK signaling pathways and improves glucose and fatty acid metabolisms. (phoenixpeptide.com)
  • Manifestation of the SH2-lacking GIV mutant (Arg 1745Leu) that cannot bind RTKs impaired all previously shown features of GIVAkt improvement, actin redesigning, and cell migration. (bio-cavagnou.info)
  • 1998], and mutations in the STAT5B SH2 domain in humans lead to growth hormone insensitivity with immunodeficiency [Kofoed et al. (lu.se)
  • The inactive domains of tandem phosphatases can be divided into two classes. (embl.de)
  • This compound activated the tyrosine kinase domain of the IR β-subunit at concentrations of 1 μmol/l or less but had no effect on insulin binding to the IR α-subunit even at much higher concentrations. (diabetesjournals.org)
  • PSPN not only binds GFRα4 but also signals in neurons mediated by GFRα1 [ 5 ]. (medsci.org)
  • The Restriction point is also known as a checkpoint, where 'the cell is arrested at a particular phase of the cycle due to a lack of appropriate signals' (Hartwell and Weinert, 1989). (janechin.net)
  • The PH domain is invariably located immediately C-terminal to the DH domain and this invariant topography suggests a functional interdependence between these two structural modules. (embl-heidelberg.de)
  • The structural information of the RasGap SH2 domains is currently unavailable. (lu.se)
  • Somatic mutations at the phosphotyrosine-binding pocket of the C-terminal SH2 domain of GTPase-activating protein RASA1 have been found in a subset of Basal-cell carcinoma (BCC) [Friedman, 1995]. (lu.se)
  • RASA1 acts by enhancing the intrinsic GTPase activity of Ras, leading to hydrolysis of bound GTP to GDP and down regulation of Ras activity [Gold, et al. (lu.se)
  • The histograms below the weblogo indicate mutations found on the domain. (umbc.edu)
  • This entry represents the PTPase domain found in several tyrosine-specific protein phosphatases (PTPases). (embl.de)
  • A potential binding site for the dShc PTB domain is located at Tyr-1228 of DER. (elsevierpure.com)
  • However, neither the site of rapsyn binding by the AChR nor the factors regulating binding to it are known. (jneurosci.org)
  • No pairwise interactions are available for this conserved domain. (umbc.edu)
  • The DH domain is composed of three structurally conserved regions separated by more variable regions. (embl-heidelberg.de)
  • the E-value for the RhoGEF domain shown below is 4.49e-66. (embl.de)
  • Trio and its homologue UNC-73 are unique within the Dbl family insomuch as they encode two distinct DH/PH domain modules. (embl-heidelberg.de)
  • Regulation of MT dynamics via direct binding of an Abl family kinase. (nih.gov)
  • 4). Up coming we asked if the isolated SH2-like domain is enough for GIV to bind EGFR in cells. (bio-cavagnou.info)
  • These findings suggest that AdipoRs' agonists could be developed into a potential therapeutic agent for metabolic diseases, such as diabetes mellitus, especially for type II diabetes, a long-term metabolic disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin. (phoenixpeptide.com)