• Homologs of both the Src homology 2 and Src homology 3 domains are found in numerous other proteins. (wikipedia.org)
  • In terms of initiating the cell cycle when growth factor signals are present, "Src homology domains" are found on Grb2 proteins, allowing them to bind Receptor Tyrosine Kinases (RTKs), and also on SOS proteins allowing them to interact with Grb2. (wikipedia.org)
  • Based on primary sequence comparisons, β subunits are predicted to be modular structures composed of five domains (A-E) that are related to the large family of membrane-associated guanylate kinase proteins. (jneurosci.org)
  • Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. (sdbonline.org)
  • 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)
  • The bacterial SH2 domains are not only capable of binding proteins or peptides in a Tyr phosphorylation-dependent manner, some bind pTyr itself with micromolar affinities, a property not observed for mammalian SH2 domains. (rcsb.org)
  • Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signalling pathways. (eu.org)
  • Mutations identified in many SH2 domain-containing proteins as well as the SH2 domain itself are associated with human diseases ranging from cancers, diabetes, to immunodeficiencies. (eu.org)
  • SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
  • SH2 (Src Homology 2) is a protein domain found in many intracellular signal-transducing proteins. (nersc.gov)
  • Different growth factor receptors were known to bind different constellations of SH2 domain-containing proteins. (the-scientist.com)
  • The ECM proteins bind to the extracellular domains of integrin heterodimers, whereas the actin stress fibers link to integrin cytoplasmic tails via large molecular complexes. (rupress.org)
  • 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)
  • Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS. (genscript.com)
  • Domain commonly found in eukaryotic signalling proteins. (embl.de)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
  • Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)
  • There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
  • Next-generation sequencing identified two de novo truncating variants in the Src-family tyrosine kinase, LYN , p.Y508*, p.Q507* and a de novo missense variant, p.Y508F, that result in constitutive activation of Lyn kinase. (nature.com)
  • The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)
  • Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.de)
  • c-Src tyrosine kinase plays an important role in signal transduction pathways, where its activity is regulated by phosphorylation of the two tyrosine residues. (intechopen.com)
  • To investigate the conformational change of c-Src tyrosine kinase, we applied network analysis to time series of correlation among residues. (intechopen.com)
  • With centrality measures such as betweenness centrality, degree centrality, and closeness centrality, we observed a few important residues that significantly contribute to the conformational change of c-Src tyrosine kinase for the different time steps. (intechopen.com)
  • c-Src (cellular Src), encoded by Src gene, is a non-receptor tyrosine kinase first isolated as the normal cellular homolog to the potent avian sarcoma viral transforming oncogene v-Src [ 4 ]. (intechopen.com)
  • c-Src tyrosine kinase consists of the N-terminal unique region, the Src homology 3 (SH3), SH2, linker, kinase domain, and the regulatory C-terminal tail. (intechopen.com)
  • Gene expression of Sh3d19, a novel adaptor protein with five Src homology 3 domains, in anagen mouse hair follicles. (atlasgeneticsoncology.org)
  • Noonan syndrome (NS) and NS with multiple lentigines (NSML) cognitive dysfunction are linked to SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) gain-of-function (GoF) and loss-of-function (LoF), respectively. (sdbonline.org)
  • Oncogenic protein tyrosine phosphatases have long been viewed as drug targets of interest, and recently developed allosteric inhibitors of SH2 domain-containing phosphatase-2 (SHP2) have entered clinical trials. (aacrjournals.org)
  • Here we identify 93 SH2 domains from Legionella that are distinct in sequence and specificity from mammalian SH2 domains. (rcsb.org)
  • The Legionella SH2 domains feature the SH2 fold and a pTyr-binding pocket, but lack a specificity pocket found in a typical mammalian SH2 domain for recognition of sequences flanking the pTyr residue. (rcsb.org)
  • Different families of SH2 domains may have different binding specificity, which is usually determined by a few residues C-terminal with respect to the pY (positions +1 to +4). (eu.org)
  • The human NCK1 (Nckα) and NCK2 (Nckβ/GRB4) SH2 domains show a degree of partner specificity but share the same mode of ligand binding ( Frese,2006 ) and belong to the class IA family which contains an aromatic residue (Phe) at the specificity-determining βD5 position ( Kaneko,2010 ). (eu.org)
  • Three loops surround the peptide binding pocket and are important for specificity: Because these loops can be flexible, considerable variation in peptide binding can apply for any given SH2 domain. (eu.org)
  • Adam Kashishian (Fred Hutchinson Cancer Research Center, Seattle): "The question of the specificity of Src homology 2 (SH2) domain/phosphotyrosine interactions has been an important one since the ability of the SH2 domains to bind phosphotyrosine- containing peptides was first shown. (the-scientist.com)
  • Was this a function of differences in receptor primary sequence, their locations in the cell, or, possibly, the specificity of the protein kinase domain of the receptor? (the-scientist.com)
  • The catalytic domain of this dual-specificity phosphatase has recently been mapped to the 180 most C-terminal amino acids. (embl.de)
  • The Src homology 1 domain was an early name of the protein kinase domain. (wikipedia.org)
  • Pleckstrin homology domain. (embl.de)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • We have previously shown that after T-cell antigen receptor stimulation, Lck binds to ZAP-70 via its Src homology 2 (SH2) domain (LckSH2) and, more recently, that Tyr319 of ZAP-70 is phosphorylated in vivo and plays a positive regulatory role. (pasteur.fr)
  • The Tir protein of EPEC binds NCK1/NCK2 SH2 domains through a high affinity pYDEV motif ( Frese,2006 ). (eu.org)
  • We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction. (rupress.org)
  • We propose that the overlap ligand motifs are a new class of ligands with innate ability to dictate SH3 domain orientation and to facilitate the rate, strength, and stereospecificity of receptor interactions. (tmu.edu.tw)
  • The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. (cancerindex.org)
  • 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)
  • Recombinant expressed p85 α and p85β associate with and are phosphorylated by both platelet-derived growth factor receptor and Polyoma middle T antigen;pp60c-src complexes in vitro. (ucl.ac.uk)
  • An extensive search and analysis for Src homology domain 3 (SH3) ligand motifs revealed a myriad of broadly distributed SH3 ligand motifs, with the highest density in the PEVK segments of human titin. (tmu.edu.tw)
  • The binding affinity of an SH2 domain to a pTyr containing ligand is moderate, with the typical affinity range between 0.1 µМ to 10 µМ for equilibrium dissociation constant values (Kd) ( Kaneko,2012 ). (eu.org)
  • Two patients with truncating mutations had liver fibrosis that in one patient resolved on treatment with the Src kinase inhibitor dasatinib. (nature.com)
  • A role of Src family kinase members in causing sterile inflammation and human disease is only recently recognized. (nature.com)
  • Several different binding motifs are known, for example: pYEEI (Src-family SH2 domains), pY [IV]. (eu.org)
  • The C-terminal half of the SH2 domain exhibits greater structural variability and provides a platform for accommodating different kinds of SH2-binding motifs. (eu.org)
  • Isoform gamma contains two PH domains, the second one is split into two parts separated by about 400 residues. (embl.de)
  • Based on the amino acid sequence homology and biological activity in macrophages, Shimamoto et al ( 15 ) identified that HLP was identical to MSP ( 15 ). (spandidos-publications.com)
  • The predicted sequence of p85α and the related p85β (for which no tryptic peptides were obtained) show the presence of an SH3 domain, two SH2 domains and a bcr-related sequence. (ucl.ac.uk)
  • Apart from a few isolated cases in viruses, no functional SH2 domain has been identified to date in prokaryotes. (rcsb.org)
  • Functional diversity between PTPases is endowed by regulatory domains and subunits. (embl.de)
  • 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)
  • PTPase domains consist of about 300 amino acids. (embl.de)
  • The cytoplasmic region generally contains two copies of the PTPase domain. (embl.de)
  • The N-terminal A domain differs among the four subtypes of Ca 2+ channel β subunits (β 1 -β 4 ) primarily as the result of two duplications of an ancestral gene containing multiple alternatively spliced exons. (jneurosci.org)
  • [ 4 ] The genetic defect appears to be a region of the gene encoding the KRT14 nonhelical head (E1/V1) domain located between the microsatellite markers D17S798 and D17S957, which are separated by approximately 26.97 cM. (medscape.com)
  • In NCK SH2 domains, the EF loop is positioned away from the BG loop, exposing the pY+3 binding pocket where the side chain of Val forms tight interactions. (eu.org)
  • The residue at pY+2 does not make direct side chain interactions with the SH2 domain, but aromatic residues are not allowed. (eu.org)
  • Heat map of the average magnitude of interaction energies projected onto a structural representation of SH2 domains (white) in complex with phosphopeptide (green). (nersc.gov)
  • The structure of the SH2 domain consists of a central antiparallel β-sheet formed by three or four β strands flanked by two α helices. (eu.org)
  • MacDonald, SM & Vonakis, BM 2002, ' Association of the Src homology 2 domain-containing inositol 5′ phosphatase (SHIP) to releasability in human basophils ', Molecular Immunology , vol. 38, no. 16-18, pp. 1323-1327. (johnshopkins.edu)
  • Over 120 SH2 domains are predicted in the human genome ( Liu,2011 ). (eu.org)
  • In biology, a Src homology domain is one of the two small protein binding domains found in the Src oncoprotein. (wikipedia.org)
  • This entry represents the PTPase domain found in several tyrosine-specific protein phosphatases (PTPases). (embl.de)
  • A nonsense mutation in a corresponding region of KRT5 has been found in Dowling-Degos disease and a missense mutation in the V1 domain of KRT5 has been described in patients with epidermolysis bullosa with mottled pigmentation. (medscape.com)
  • PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. (embl.de)
  • Positively charged residues are disfavoured at pY-1 and pY-2 due to the positively charged SH2 domain surface, but are tolerated when pY+1 and pY+3 are strong residues. (eu.org)
  • There are no totally invariant residues within the PH domain. (embl.de)
  • The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)
  • The inactive domains of tandem phosphatases can be divided into two classes. (embl.de)
  • Src homology 2 (SH2) domains play a critical role in signal transduction in mammalian cells by binding to phosphorylated Tyr (pTyr). (rcsb.org)
  • HGF forms a family with HGF-like protein (HLP), a unique protein with a domain structure similar to that of HGF ( 12 ). (spandidos-publications.com)
  • The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2) and phosphotyrosine binding domain-containing focal adhesion molecule that may function as a tumor suppressor. (rupress.org)
  • Collectively, our findings indicate that Tyr319-mediated binding of the SH2 domain of Lck is crucial for ZAP-70 activation and consequently for the propagation of the signaling cascade leading to T-cell activation. (pasteur.fr)
  • This may involve significant role of "shank," named for SRC-homology (SH3) and multiple ankyrin repeat domains, in nitric oxide synthesis. (frontiersin.org)
  • Tyrosine 319 in the interdomain B of ZAP-70 is a binding site for the Src homology 2 domain of Lck. (pasteur.fr)
  • however, little is known about the structures of the A and E domains. (jneurosci.org)