Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).src Homology Domains: Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Kinetics: The rate dynamics in chemical or physical systems.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Drug Residues: Drugs and their metabolites which are found in the edible tissues and milk of animals after their medication with specific drugs. This term can also apply to drugs found in adipose tissue of humans after drug treatment.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Pesticide Residues: Pesticides or their breakdown products remaining in the environment following their normal use or accidental contamination.Lysine: An essential amino acid. It is often added to animal feed.Histidine: An essential amino acid that is required for the production of HISTAMINE.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Bacterial Proteins: Proteins found in any species of bacterium.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Arginine: An essential amino acid that is physiologically active in the L-form.Nuclear Magnetic Resonance, Biomolecular: NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesLigands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Sulfhydryl Compounds: Compounds containing the -SH radical.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Molecular Weight: The sum of the weight of all the atoms in a molecule.Peptide Mapping: Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Asparagine: A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Hydrophobic and Hydrophilic Interactions: The thermodynamic interaction between a substance and WATER.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Static Electricity: The accumulation of an electric charge on a objectMass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes.SH2 Domain-Containing Protein Tyrosine Phosphatases: A subcategory of protein tyrosine phosphatases that contain SH2 type SRC HOMOLOGY DOMAINS. Many of the proteins in this class are recruited to specific cellular targets such as a cell surface receptor complexes via their SH2 domain.Enzyme Stability: The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.Diethyl Pyrocarbonate: Preservative for wines, soft drinks, and fruit juices and a gentle esterifying agent.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Carbohydrate Sequence: The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.PhosphoproteinsEnzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Oligosaccharides: Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form.Protein Interaction Domains and Motifs: Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Sequence Analysis, Protein: A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.Molecular Conformation: The characteristic three-dimensional shape of a molecule.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.PhosphopeptidesCercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Oligopeptides: Peptides composed of between two and twelve amino acids.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Chemical Phenomena: The composition, conformation, and properties of atoms and molecules, and their reaction and interaction processes.GRB2 Adaptor Protein: A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Structural Homology, Protein: The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN.Protein Denaturation: Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.Spectrophotometry, Ultraviolet: Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Epitopes: Sites on an antigen that interact with specific antibodies.Protein Engineering: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.Sulfhydryl Reagents: Chemical agents that react with SH groups. This is a chemically diverse group that is used for a variety of purposes. Among these are enzyme inhibition, enzyme reactivation or protection, and labelling.Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Carbohydrate Conformation: The characteristic 3-dimensional shape of a carbohydrate.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Cross-Linking Reagents: Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Phenylglyoxal: A reagent that is highly selective for the modification of arginyl residues. It is used to selectively inhibit various enzymes and acts as an energy transfer inhibitor in photophosphorylation.Bromosuccinimide: A brominating agent that replaces hydrogen atoms in benzylic or allylic positions. It is used in the oxidation of secondary alcohols to ketones and in controlled low-energy brominations. (From Miall's Dictionary of Chemistry, 5th ed; Hawley's Condensed Chemical Dictionary, 12th ed,).Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Proto-Oncogene Proteins pp60(c-src): Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.Dithionitrobenzoic Acid: A standard reagent for the determination of reactive sulfhydryl groups by absorbance measurements. It is used primarily for the determination of sulfhydryl and disulfide groups in proteins. The color produced is due to the formation of a thio anion, 3-carboxyl-4-nitrothiophenolate.Viral Proteins: Proteins found in any species of virus.Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Tetranitromethane: Corrosive oxidant, explosive; additive to diesel and rocket fuels; causes skin and lung irritation; proposed war gas. A useful reagent for studying the modification of specific amino acids, particularly tyrosine residues in proteins. Has also been used for studying carbanion formation and for detecting the presence of double bonds in organic compounds.Models, Structural: A representation, generally small in scale, to show the structure, construction, or appearance of something. (From Random House Unabridged Dictionary, 2d ed)Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Crystallization: The formation of crystalline substances from solutions or melts. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization: A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced, and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis.Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Protein PrecursorsLeucine: An essential branched-chain amino acid important for hemoglobin formation.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Solutions: The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed)Chromatography, Ion Exchange: Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.Proto-Oncogene Proteins c-abl: Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.Proto-Oncogene Proteins c-crk: Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. c-crk protein is closely related to ONCOGENE PROTEIN V-CRK and includes several alternatively spliced isoforms.Biocatalysis: The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.PolysaccharidesProtein Sorting Signals: Amino acid sequences found in transported proteins that selectively guide the distribution of the proteins to specific cellular compartments.Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Amino Acids, Basic: Amino acids with side chains that are positively charged at physiological pH.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Carbohydrates: The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Genes, Bacterial: The functional hereditary units of BACTERIA.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.
AdhesomeSH2) domain, which mediate interaction with phosphorylated tyrosine residues; armadillo (ARM) GUK and LIM domains, which ...
"SH2 domain specificity and activity modified by a single residue". Nature. 369 (6480): 502-505. doi:10.1038/369502a0. PMID ... He identified the phosphotyrosine-binding Src homology 2 (SH2 domain) as the prototypic non-catalytic interaction module. SH2 ... Since the discovery of SH2 domains, hundreds of different modules have been identified in many proteins. Born in Maidstone, ... "for identification of the phosphotyrosine binding SH2 domain and demonstrating its function in protein-protein interactions" ...
SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. c-Src can be activated by many transmembrane ... c-Src includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. c-Src stands for "cellular Src kinase" and should ... c-Src is made up of 6 functional regions: Src homology (SH) 4 domain (SH4 domain), unique region, SH3 domain, SH2 domain, ... When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 ...
The longer SH2 domain (~100 residues) binds phosphotyrosine (P-Tyr) residues in a sequence-specific manner. The P-Tyr interacts ... Both the SH2 and SH3 domains are important for a negative regulation of Src activity. Mutations in the SH2 and SH3 domains that ... ZAP70/Syk and JAKs The kinase activity of Syk is regulated by the SH2 domains. Binding of the two SH2 domains to the tyrosine- ... a region of positively charged residues, a short region with low sequence homology, SH3 and SH2 domains, a tyrosine kinase ...
When phosphate groups are added to the tyrosine (Y) residue of the ITAM by enzymes called tyrosine kinases, a signaling cascade ... Negative signaling through SHIP appears to inhibit the Ras pathway through SH2 domain competition with Grb2 and Shc and may ... This modification generates the binding site for the phosphatase, a SH2 recognition domain. The abrogation of ITAM activation ... Inhibitory actions of these receptors are controlled by enzymes that remove phosphate groups from tyrosine residues; the ...
Activated JAKs then phosphorylate tyrosine residues on the receptor, creating binding sites for proteins possessing SH2 domains ... SH2 domain containing STATs are recruited to the receptor where they are also tyrosine-phosphorylated by JAKs. These activated ...
The SH2 domain spans approximately 100 amino acid residues and binds phosphotyrosine-containing proteins such as kinases. The ... LNK contains 3 functional domains: a C-terminal Src homology 2 (SH2) domain, a pleckstrin homology (PH) domain, and a ... This motif is responsible for facilitating the homo- or heterodimerization of SH2-B family proteins as a mechanism for ... The dimerization domain spans approximately 70 amino acid residues and contains a central phenylalanine zipper motif, which is ...
Phosphotyrosine (P.Tyr) residues on activated RTKs are recognized by a phosphodependent-binding domain, the SH2 domain. The ... SH2 domain proteins may have a variety of functions, including adaptor proteins to recruit other signaling proteins, enzymes ... In response to EGF, PDGF, or FGF receptor activation, the SH2 domains of PLCγ bind to specific phosphotyrosines in the C- ... Phosphorylation on tyrosine residues, which are localized on membrane proteins, stimulates a cascade of signaling pathways that ...
"Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells". ... "Replacing two conserved tyrosines of the EphB2 receptor with glutamic acid prevents binding of SH2 domains without abrogating ...
The EGFR becomes phosphorylated on tyrosine residues. Docking proteins such as GRB2 contain an SH2 domain that binds to the ... phosphotyrosine residues of the activated receptor. GRB2 binds to the guanine nucleotide exchange factor SOS by way of the two ...
First, the protein Grb2 binds the P-Tyr residue of IRS-1 in its SH2 domain. Grb2 is then able to bind SOS, which in turn ... residues 471-595), FnIII-2 (residues 596-808) and FnIII-3 (residues 809-906). Additionally, an insert domain (ID, residues 638- ... residues 1-157), a cysteine-rich region (CR, residues 158-310), an additional leucine rich repeat domain (L2, residues 311-470 ... SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains". The Journal of Biological ...
The SH2 domains of the STAT5 proteins are once again used for this dimerization. STAT5 can also form homo-tetramers, usually in ... the stimulated kinases add a phosphate group to a specific tyrosine residue on the receptor; STAT5 then binds to these ... The inhibition of proper dimerization, on the other hand, is brought about by the use of small molecules that target the SH2 ... "Small molecule STAT5-SH2 domain inhibitors exhibit potent antileukemia activity". J. Med. Chem. 55 (3): 1047-55. doi:10.1021/ ...
The regulatory subunit p85 binds to phosphorylated tyrosine residues on the activated receptor via its Src homology 2 (SH2) ... Loss of PTEN function leads to over-activation of Akt and is common in cancer cells (PTEN is a tumour suppressor). SH2- ... S6K1 is also able to phosphorylate IRS-1 at multiple serine residues, preventing binding to RTKs. Another negative feedback ... causing receptor dimerization and cross-phosphorylation of tyrosine residues in the intracellular domains. ...
Both Itk and Lck are able to phosphorylate the tyrosine residues which then allow binding of SH2 containing proteins to CD28. ... The N172 residue (as part of the YMNM) is important for the binding of Grb2 and Gads and seems to be able to induce IL-2 mRNA ... The Y170 residue is important for the induction of Bcl-xL via mTOR and enhancement of IL-2 transcription via PKCθ, but has no ... The YMNM motif beginning at tyrosine 170 in particular is critical for the recruitment of SH2-domain containing proteins, ...
The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the ... PLCg1 binds to LAT through its n-terminal SH2 domain and to SLP-76 via its SH3 domain. Has been shown to interact with CISH ... Specific to the PLCG isozymes is a large separation between the X and Y domains consisting of a split PH domain, tandem SH2 ... Jhun BH, Rivnay B, Price D, Avraham H (April 1995). "The MATK tyrosine kinase interacts in a specific and SH2-dependent manner ...
A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its ... SH2 domains ); therefore phosphatases are integral to many signal transduction pathways. Phosphate addition and removal do not ... Proteins are phosphorylated predominantly on Ser, Thr and Tyr residues, which account for 79.3, 16.9 and 3.8% respectively of ... CDK, for example, can be either activated or deactivated depending on the specific amino acid residue being phosphorylated. ...
SLP-76 also contains a central proline-rich domain and a COOH-terminal SH2 domain. A number of additional proteins have been ... The PDB file 1H3H depicts the SH3 domain of GRAP2 in complex with an RSTK-containing peptide representing residues 226-235 of ... Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa), also known as LCP2 or SLP-76, is a gene that ... The NH2-terminus contains an acidic region that includes a PEST domain and several tyrosine residues that are phosphorylated ...
"SH2" domain stands for src-homology 2 domain, which is a three-dimensional domain structure of about 100 amino acid residues. ... A deletion in the SH2D1A gene leads to a non-functional SH2 domain on the SAP protein, making it unable to bind to SLAM. This ... The amino acid residues adjacent to the phosphotyrosine on the target protein are what determine the unique binding specificity ... At this position, there is a deletion in the SH2D1A gene, which codes for an SH2 domain on a signal transducing protein called ...
Arginine residue (R609) on the N-SH2 domain forms a salt bridge to aspartate 755 (D755) on the FGFR1 domain. The acid base ... The phosphorylation of tyrosine residue 766 on FGFR1 kinase forms hydrogen bonds with the n-SH2 to stabilize the complex. ... The N-SH2 domain makes an additional polar contact through water-mediated interaction that takes place between the N-SH2 domain ... Interestingly, the arginine residue 609 (R609) on the FGFR1 kinase also forms a salt bridge to the aspartate residue (D594) on ...
A PKA/PKG phosphorylation site has been identified in CASS4 on residue S305 in the unstructured domain containing SH2-binding ... and substantial similarity within 432-591 residues of CASS4 and 449-610 residues of p130Cas/BCAR1 at the level of secondary and ... Further to the carboxy-terminus, they have a four-helix bundle rich in serine residues, and a second highly conserved four- ... In addition, human CASS4 has a limited number of candidate SH2-binding sites, estimated at 10, which is similar to EFS ( ...
... or may form part of a signaling cascade via SH2 domain binding. A tyrosine residue also plays an important role in ... Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine ... Some of the tyrosine residues can be tagged (at the hydroxyl group) with a phosphate group (phosphorylated) by protein kinases ...
The remaining carboxy-terminal sequence contains a bipartite Src-binding domain (residues 681-713) able to bind both the SH2 ... Mayer BJ, Hirai H, Sakai R (1995). "Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases". ...
In addition, SOCE-induced Pyk2 activation mediates disassembly of endothelial adherens junctions, via tyrosine (Y1981-residue) ... and the SH2 domain of GRB2. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks ...
Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB, Chin YE (November 2004). "Central role of the threonine residue within the p+1 loop ... Li W, Hu P, Skolnik EY, Ullrich A, Schlessinger J (December 1992). "The SH2 and SH3 domain-containing Nck protein is oncogenic ... As a result, autophosphorylation of several tyrosine (Y) residues in the C-terminal domain of EGFR occurs. These include Y992, ... The kinase domain of EGFR can also cross-phosphorylate tyrosine residues of other receptors it is aggregated with, and can ...
SH2 domains recognise specific amino acid sequences within proteins containing phosphotyrosine residues and SH3 domains ... SH2 domain containing 3A SH2D3C - SH2 domain containing 3C SHB - Src homology 2 domain containing adaptor protein B SLC4A1AP - ... Adaptor proteins usually contain several domains within their structure (e.g., Src homology 2 (SH2) and SH3 domains) that allow ...
Kinases are either phosphorylated on serine and/or threonine residues, or solely on tyrosine residues.[5] This serves as a ... 4. The constitutive activation of src kinase observed in cancer can be due to deletion of tyr-527, displacement of SH3 and SH2- ... The phosphorylated tyrosine residue can then serve as a docking site for downstream signaling proteins.[21] (Fig. 1). ... In eukaryotes, this process occurs by the addition of a phosphate group to serine, threonine or tyrosine residues within ...
RCSB PDB - 1LCJ: SH2 (SRC HOMOLOGY-2) DOMAIN OF HUMAN P56-LCK TYROSINE KINASE COMPLEXED WITH THE 11 RESIDUE PHOSPHOTYROSYL...DOMAIN OF HUMAN P56-LCK TYROSINE KINASE COMPLEXED WITH THE 11 RESIDUE PHOSPHOTYROSYL PEPTIDE EPQPYEEIPIYL ... SH2 (SRC HOMOLOGY-2) DOMAIN OF HUMAN P56-LCK TYROSINE KINASE COMPLEXED WITH THE 11 RESIDUE PHOSPHOTYROSYL PEPTIDE EPQPYEEIPIYL ... The Src homology-2 (SH2) domains are modules of about 100 amino-acid residues that are found in many intracellular signal- ... The Src homology-2 (SH2) domains are modules of about 100 amino-acid residues that are found in many intracellular signal- ...
The pTyr binding site of Grb2 SH2 was similar to those of other SH2 domains. In contrast, the amino acid residues C-terminal to ... the peptide formed a turn-structure on the surface of Grb2 SH2. The asparagine residue at the pTyr+2 position of the Shc- ... Finally, the structure of Grb2 SH2 domain was compared with those of the complexes of Src and phospholipase C-gamma1 with their ... Solution structure of the SH2 domain of Grb2 complexed with the Shc-derived phosphotyrosine-containing peptide.. Ogura, K., ...
Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis. - PubMed - NCBIA) Cartoon diagram of the active SH2-kinase domain unit of Abl. Critical residues involved in the SH2-kinase domain interface ... The SH2 domain is shown as a white surface model.. (E) Orthogonal views of HA4-Abl SH2 and 7c12sm-Abl SH2 complexes ... defined as Abl SH2 domain residues within 5 Å of a monobody) are colored in blue and 7c12sm interface residues are colored in ... Residues Tyr88, Tyr172, and Phe197 were mutated to abolish binding to the Abl SH2 domain. See also .. (E) In vitro kinase ...
SH2 Protein Domain | Phospho-Tyr Binding | CSTA scientific resource for the SH2 protein domain containing information on structure, function, and domain binding to phospho- ... SH2. domain recognizes Y as well as pY in the context of residues N and C terminal, suggesting that an alternate 3-pronged ... SH2. domains have a conserved pocket that recognizes pY, and a more variable pocket that binds 3-6 residues C-terminal to the ... Phospho-lipase C-γ C-terminal SH2. PDGF β receptor. pTyr. -Ile-Ile-Pro-Leu-Pro-Asp. Cys ΒD5. ...
Filamin-C (D3ZHA0) | InterPro | EMBL-EBIPer-residue features. Residue annotation. Colour by help domain relationship. source database. ...
Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be ... Tyrosine-protein kinase SYK/ZAP-70, inter-SH2 domain superfamily (IPR023420). Short name: Kinase_SYK/ZAP-70_inter-SH2_sf ... The N-terminal region of ZAP-70 consists of two SH2 domains that are connected by an helical region. The overall fold is Y ... shaped, with the intervening residues forming the stem [PMID: 7659156]. This superfamily represents the inter-SH2 domain found ...
A shift in the salt bridge interaction of residues D620 and E621 mediates the constitutive activation of Jak2-H538Q/K539L |...Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta. Mol Cell Biol 24:4557-4570 ... A shift in the salt bridge interaction of residues D620 and E621 mediates the constitutive activation of Jak2-H538Q/K539L. * ... Gnanasambandan, K., Magis, A.T. & Sayeski, P.P. A shift in the salt bridge interaction of residues D620 and E621 mediates the ... Dusa A, Mouton C, Pecquet C, Herman M, Constantinescu SN (2010) JAK2 V617F constitutive activation requires JH2 residue F595: a ...
The binding specificity of SH2 domains are primarily dictated by binding sites that interact with the amino acid residues on ... chain ITAM-2 C terminal phosphotyrosine residues. Such selectivity of SH2 domain is essential for a proper cellular activation ... Accordingly, Lck SH2 domain is a potential target for immunosuppressive drugdevelopment.. Based on the vast knowledge of SH2 ... Although there are numerous signaling proteins with SH2 domains in T cells, only a few bind to the ITAM via their SH2 domains. ...
The SH3 domain in both p190- and p210-BCR-ABL activates p95Vav (Vav1). Y177/Y412, tyrosine residues that can be phosphorylated ... Dbl, Rac GTPase exchange factor; SH2/SH3, Src homology domains; DD; dimerization domain; DBD, DNA-binding domain; ABD, actin- ...
SH3BP2 - SH3 domain binding protein 2 - Canis lupus familiaris (Dog) - SH3BP2 gene & proteinphosphotyrosine residue binding Source: Ensembl. *SH3/SH2 adaptor activity Source: InterPro. View the complete GO annotation on ... SH2InterPro annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, without manual ... SH2 domainPROSITE-ProRule annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, ...
Anti-BLNK antibody (ab2230) | AbcamContains 1 SH2 domain.. * Post-translational. modifications. Following BCR activation, phosphorylated on tyrosine residues by ... Src homology [SH2] domain-containing leukocyte protein of 65 kD antibody. *Src homology 2 domain containing leukocyte protein ...
Short Linear Motifs recognized by SH2, SH3 and Ser/Thr Kinase domains are conserved in disordered protein regions | BMC...... we systematically studied the evolutionary conservation of SLiMs recognized by SH2, SH3 and Ser/Thr Kinase domains in both ... Invariant amino acid residues in SLiMs recognized by SH2, SH3 and Ser/Thr Kinase domains. ... Some SH2 domains (e.g., Crk SH2 domain) contain specific SH3 domain-binding sites [29], thus linking together SH2- and SH3- ... A) SH2 binding Tyr-SLiMs are significantly more conserved than those that do not bind to SH2 domains in both order and disorder ...
C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domainsMutations that impair sem-5 activity alter residues that are highly conserved among different SH2 and SH3 domains. Our results ... C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains Nature. 1992 Mar 26;356(6367):340-4. doi: ... On the basis of its DNA sequence, sem-5 encodes a novel 228-amino-acid protein which consists almost entirely of one SH2 (SH, ... SH2 and SH3 domains are present in many signalling proteins regulated by receptor and non-receptor tyrosine kinases. ...
Residue enrichment at positions relative to tyrosine that contribute to the recruitment of SH2 domains. A, representative plots ... B, each receptor or adaptor was assessed for enrichment or depletion of binding sites for a given SH2 or PTB domain and is ... Color-coded heat maps represent KD values for FP interactions between SH2 and PTB domains and phosphopeptides representing all ... Sequences of peptides used are indicated for each receptor site, where d denotes the pre-charged Asp residue on the peptide ...
JCI -
H7N9 influenza virus neutralizing antibodies that possess few somatic mutations... in Sh2/H7 HA (gray) highlighting antibody residues contacting HA. The relative location of RBS is labeled. (B) The ... HA1 is shown in gray, and the epitope residues are shown as green sticks. The weighted percentage of identity of each residue ... B) Close-up view of the interaction between H7.167 and Sh2/H7 HA. The coloring is similar to that shown in A, but H7.167 is ... At this resolution, the heavy chain appears to bind to numerous residues, including R131 and N157 to N158B close to the 150- ...
Molecular docking studies indicated that YL064 may interact with STAT3 in its SH2 domain, thereby inhibiting the dimerization ... the interaction of STAT3 with phosphorylated tyrosine residues on cytoplasmic receptor kinases through targeting the SH2 domain ... a, b Predicted conformation of YL064 in the pocket of STAT3 SH2 domain (a). The molecular surface of STAT3 SH2 domain is shown ... b Residues of STAT3 are shown in cyan sticks and labeled with residue names. The dashed lines in black represent hydrogen bonds ...
Temperature-Sensitive Transformation by an Abelson Virus Mutant Encoding an Altered SH2 Domain | Journal of VirologyResidues within the SH2 domain that contact residues C terminal to the phosphotyrosine on the target protein are one way in ... 1993) Binding of the Src SH2 domain to phosphopeptides is determined by residues in both the SH2 domain and the phosphopeptides ... 1989) A mutation in v-src that removes a single conserved residue in the SH-2 domain of pp60v-src restricts transformation in a ... 1994) SH2 domain specificity and activity modified by a single residue. Nature (London) 369:502-505. ...
... the SH2 and PTB domains, which recognize phosphotyrosine and contiguous residues; and PDZ domains (reviewed in ref. 1). Because ... 2b). Specificity is determined on the opposite side of the groove by interaction of side chain residues at the -2 position (S/T ... Stereoscopic images depicting hydrogen bonding (dashed white lines) between residues of the PDZ domains (blue) and the peptide ... PDZ domains recognizing S/T or a hydrophobic residue at the -2 position have been termed class I and class II, respectively. ...
SMART: SH2 domain annotationSH2 domains recognise between 3-6 residues C-terminal to the phosphorylated tyrosine in a fashion that differs from one SH2 ... The blk SH2 domain adopts the prototypical SH2 fold. Structurally, blk SH2 is most similar to the crystal structure of the v- ... The glutamate residues are in solvent-exposed environments in the vicinity of basic side chains of the SH2 domain, and the two ... C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(3-BUTYLPIPERIDINE). 1a81. CRYSTAL STRUCTURE OF THE TANDEM SH2 DOMAIN OF ...
SH2) domain, which mediate interaction with phosphorylated tyrosine residues; armadillo (ARM) GUK and LIM domains, which ...
ELM - Detail for LIG SH2 STAT5Src Homology 2 (SH2) domains recognize small motifs containing a phosphorylated Tyrosine residue. Additional specificity ... LIG_SH2_CRK LIG_SH2_GRB2like LIG_SH2_PTP2 LIG_SH2_SRC LIG_SH2_STAT3 LIG_SH2_STAT5 LIG_SH2_STAT6 ... Sh2-Domain Binding (also annotated in these classes: LIG_SH2_GRB2like LIG_SH2_PTP2 LIG_SH2_SRC LIG_SH2_STAP1 LIG_SH2_STAT3 LIG_ ... SH2_CRK LIG_SH2_GRB2like LIG_SH2_PTP2 LIG_SH2_SRC LIG_SH2_STAT3 LIG_SH2_STAT6 LIG_SH3_1 LIG_SH3_2 LIG_SH3_3 LIG_SH3_4 LIG_SH3_5 ...
... which is rich in docking sites for SH2 domain-containing proteins, was O-GlcNAc-modified at multiple residues. Rat IRS-1 was O- ... SH2. Src homology 2. SHP2. SH2 domain-containing tyrosine phosphatase 2. PUGNAc. O-(2-acetamido-2-deoxy-d-glucopyranosylidene) ... Human IRS-1 was O-GlcNAc-modified at Ser984 or Ser985, at Ser1011, and possibly at multiple sites within residues 1025-1045. O- ... O-Linked N-Acetylglucosamine Modification of Insulin Receptor Substrate-1 Occurs in Close Proximity to Multiple SH2 Domain ...
Investigation of Early Events in FcεRI-Mediated Signaling Using a Detailed Mathematical Model | The Journal of ImmunologySH2 domains bound to phosphotyrosines protect the sites they are bound to from dephosphorylation (29). Because SH2-bound Lyn ... The construct, with 492 residues total, consists of a 24-aa leader sequence, residues 10-261 from human Syk, and GST from ... On the representations of the kinases, notches indicate SH2 domains. The tandem SH2 domains of Syk are lumped together in the ... SH2) domain with the phosphorylated β ITAM (11, 15). The cytosolic PTK Syk binds with high affinity, through its two SH2 ...
Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma | Science SignalingSH2, PI, PTB, and Cbl-like PTB domain-containing proteins are indicated by gene name and a star. Log2 ratios of fold change of ... Each square indicates a median SILAC ratio for the indicated ALK tyrosine residue. (C) Functional association network based on ... C) Sequence motif analysis by iceLogo of the ±6 amino acid residues flanking the regulated phosphorylation site (left: tyrosine ... Only proteins containing SH2, PTB, and PI domains are included. ...
FGR Gene - GeneCards | FGR Protein | FGR AntibodyInteracts (via SH2 domain) with SYK (tyrosine phosphorylated). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). ... Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2A and/or FCGR2B engagement, cell adhesion ... Binding (via SH2 domain) of HCLS1 that is already phosphorylated by SYK strongly increases kinase activity. *FGR_HUMAN,P09769 ... Interacts (via SH2 domain) with HCLS1 (tyrosine phosphorylated by SYK). Interacts with SIRPA and PTPNS1. Interacts (not ...
Amino-acid residuesProteinsReceptorMotifsSpecific tyrosine residuesBindsSpecificityInteractionPhosphorylatesBindPhosphorylated on tyrosine residuesKinasesMultiple tyrosine residuesInteractsPTyrMotifSerineInteractSequenceHydrophobicGrb2LigandSubstratesCytoplasmic tailLeucineSelectivityFibronectin typePhosphatasesSitesAffinityPMIDSuperfamily
- The Src homology-2 (SH2) domains are modules of about 100 amino-acid residues that are found in many intracellular signal-transduction proteins. (rcsb.org)
- In contrast, the amino acid residues C-terminal to pTyr did not form an extended structure because of steric hindrance caused by a bulky side-chain of Trp121 (EF1). (rcsb.org)
- Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (ebi.ac.uk)
- The binding specificity of SH2 domains are primarily dictated by binding sites that interact with the amino acid residues on the C-terminal side of the pY, especially the third residue (pY+3 sites). (patentgenius.com)
- Because binding specificities are based on a few amino acid residues, these domains are uniquely suited to permit evolution of new protein interactions by coordinate mutations in the domain and target peptide sequence. (jci.org)
- The amino-terminal domain spans up to 125 amino acid residues and is involved in the formation of homotypic dimers among unphosphorylated STATs in resting cells. (hindawi.com)
- The catalytic domains comprise of a characteristic signature of conserved amino acid residues. (nature.com)
- SH2 and SH3 domains are small, independent domains of about 100 or 70 amino acid residues respectively. (perkinelmer.com)
- The compounds were prepared by using trans-cyclopropane-containing amino acid mimics, macrocyclization, or [alpha,alpha]-disubstituted amino acid residues. (utexas.edu)
- Since SH2 is a functional domain that binds to specific tyrosine phosphorylated sites of proteins, studies have been focused on the relevant portions of the SH2 domain structures, i.e., the region to which the phosphorylated tyrosine (pY) targetpeptides bind. (patentgenius.com)
- Since the discovery of SH2 domains, hundreds of different modules have been identified in many proteins. (wikipedia.org)
- This protein phosphorylates specific tyrosine residues in other proteins. (wikipedia.org)
- SH2 and SH3 domains are present in many signalling proteins regulated by receptor and non-receptor tyrosine kinases. (nih.gov)
- Relative binding energy and site enrichment for SH2 and PTB domains by signaling proteins. (mcponline.org)
- Three adapter proteins, IRS1, IRS2 and Shc, become phosphorylated on tyrosine residues following insulin receptor activation. (abcam.com)
- These three phosphorylated proteins then interact with SH2 domain containing signaling proteins. (abcam.com)
- replacing Arg βB5, located at the base of the pocket, with a Lys or other residues drastically affects the ability of activated c-Abl proteins and Bcr/Abl proteins to transform immortalized fibroblast lines ( 1 , 28 ). (asm.org)
- Consistent with the idea that signals requiring an intact SH2 domain pass through Ras and lead to c-Myc ( 52 ), transformation of RAT-1 cells by Bcr/Abl proteins containing an altered FLVRES motif is complemented by expression of c-Myc ( 1 , 25 ). (asm.org)
- There are 58927 SH2 domains in 53279 proteins in SMART's nrdb database. (embl-heidelberg.de)
- Taxonomic distribution of proteins containing SH2 domain. (embl-heidelberg.de)
- The complete taxonomic breakdown of all proteins with SH2 domain is also avaliable . (embl-heidelberg.de)
- Click on the protein counts, or double click on taxonomic names to display all proteins containing SH2 domain in the selected taxonomic class. (embl-heidelberg.de)
- 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)
- Because of overlapping specificities amongst SH2 domains, it is unlikely to be clear which proteins bind to a new pTyr candidate SH2-binding motif. (eu.org)
- Tandem mass spectrometric analysis of IRS-1, exogenously expressed in HEK293 cells, revealed that the C terminus, which is rich in docking sites for SH2 domain-containing proteins, was O -GlcNAc-modified at multiple residues. (mcponline.org)
- Structural studies revealed that all STAT family proteins have seven structurally and functionally conserved domains including the amino-terminal domain (NH2), coiled-coil domain, DNA-binding domain (DBD), linker domain (Lk), SH2 domain, tyrosine activation domain (Y), and transactivation domain (TAD) that have distinct roles [ 3 ]. (hindawi.com)
- When phosphorylated, they can become ligands for proteins with SH2 domains. (antievolution.org)
- What makes ITAMs special is that there are proteins such as ZAP70 that contain dual SH2 domains and bind to the ITAM phosphorylated tyrosines as a unit. (antievolution.org)
- If proteins with these dual SH2 domains are found in tunicates, then it becomes a good argument. (antievolution.org)
- as for the SH2-containing proteins, i should point out that homologues for syk and ZAP70 have been discovered in organisms as distant as hydra , and as similar (to tunicates) as sea urchin . (antievolution.org)
- The SH2 domains of the STAT5 proteins are once again used for this dimerization. (wikipedia.org)
- The human genome encodes 120 SH2 domains embedded in a variety of proteins ( Fig. 1A ). (sciencemag.org)
- Most SH2 domain-containing proteins are recruited to sites of tyrosine phosphorylation to aid in the construction of molecular machines ( 3 ). (sciencemag.org)
- These noncatalytic organizing proteins contain a domain that selectively recognizes the activated receptor (an SH2 domain in the case of receptor tyrosine kinases), linked to domains such as SH3, that engage specific downstream targets, typically by binding to proline-rich sequences. (sciencemag.org)
- Multivalent modular proteins such as Grb2 (SH3-SH2-SH3) and Nck (SH3-SH3-SH3-SH2) exemplify this strategy ( Fig. 1A ). (sciencemag.org)
- These proteins consist of two conserved motifs, a central SH2 domain and a C-terminal SOCS box (Figure 1 ) [ 1 ]. (hindawi.com)
- The SH2 domain of SOCS proteins is a crucial component for association of SOCS proteins with phosphorylated tyrosine residues on tyrosine kinases or cytokine receptors [ 1 ]. (hindawi.com)
- These phosphotyrosine residues can then interact with a variety of intracellular mediators by a process involving binding to SH2 domains in the effector proteins. (springer.com)
- The immunoreceptor tyrosine-based inhibitory motif of FcγRIIB1 represents a docking site for the SH2 domains of at least two proteins, the tyrosine phosphatase SHP1 (( 16 )) and the inositide phosphatase SHIP (( 17 )), either of which may mediate inhibitory effects. (rupress.org)
- These changes facilitate the recruitment of specific adapter proteins such as the insulin receptor substrate proteins (IRS) in addition to SH2-B ( Src Homology 2 - B ), APS and protein phosphatases, such as PTP1B , eventually promoting downstream processes involving blood glucose homeostasis. (wikidoc.org)
- These proteins share a highly conserved NH 2 -terminal pleckstrin homology (PH) domain, a central proline-rich domain, and multiple tyrosine residues that are recognized by SH2 domain-containing proteins. (pubmedcentralcanada.ca)
- Phosphorylation of insulin receptor substrate (IRS) proteins on serine residues has emerged as a key step in these control processes under both physiological and pathological conditions. (physiology.org)
- Prolonged insulin stimulation and other stimuli triggered by inducers of insulin resistance activate IRS kinases that phosphorylate the IRS proteins, such as IRS-1, on Ser/Thr residues. (physiology.org)
- Binding of insulin to its receptor activates the intrinsic tyrosine kinase activity of the receptor (IRK), which phosphorylates Tyr residues of target proteins such as the insulin receptor substrates (IRS-1 to -6), Shc proteins, Cbl, p60dok, APS, and Gab-1 ( 92 , 112 ). (physiology.org)
- Tyr-phosphorylated IRS proteins, the major insulin receptor substrates, function as signaling scaffolds that propagate insulin action through binding of Src homology 2 (SH2) domain-containing proteins. (physiology.org)
- SH2 is a domain present in many signal-transduction proteins. (wikibooks.org)
- SH2 domains are host to specific phosphotyrosine sequences, such as those in activated IRS proteins. (wikibooks.org)
- A large group of lipid kinases have SH2 domains that are attracted to IRS proteins. (wikibooks.org)
- This is mediated by binding of proteins with src homology 2 (SH2) domains to receptor autophosphorylation sites. (royalsocietypublishing.org)
- Among the proteins involved in complex formation is phosphatidylinositol (PI) 3-kinase, a heterodimeric enzyme composed of 85 kDa and 110 kDa subunits, which binds to receptor (and non-receptor) phosphotyrosine residues through the two SH2 domains in the p85 subunit. (royalsocietypublishing.org)
- Expression of these domains in E. coli as GST-fusion proteins has allowed definition by nuclear magnetic resonance (NMR) of three-dimensional structures for the SH2 and SH3 domains. (royalsocietypublishing.org)
- These sites are multifunctional- they can regulate kinase activity, or serve as binding sites for adapters (such as SH2) or other signaling proteins. (novusbio.com)
- Many signaling proteins carry SH2 domains plus one or more small protein modules such as SH3, PH, PTB, WW or FYVE domains. (yale.edu)
- (rcsb.org)
- Comprehensive SH2 domain recruitment potential of the adaptor protein GAB1, the MET and KIT receptor tyrosine kinases, and the human AR as determined by high throughput fluorescence polarization. (mcponline.org)
- Sequences of peptides used are indicated for each receptor site, where d denotes the pre-charged Asp residue on the peptide synthesis resin and not a naturally occurring Asp. (mcponline.org)
- B, each receptor or adaptor was assessed for enrichment or depletion of binding sites for a given SH2 or PTB domain and is depicted by Z -score transformation of raw data. (mcponline.org)
- Receptor activation occurs through ligand binding, which facilitates receptor dimerization and autophosphorylation of specific tyrosine residues in the cytoplasmic portion. (abcam.com)
- A single phosphotyrosine residue of the prolactin receptor is responsible for activation of gene transcription. (eu.org)
- Identification of tyrosine residues in the intracellular domain of the growth hormone receptor required for transcriptional signaling and Stat5 activation. (eu.org)
- For example, when activated, fibroblast growth factor receptor 1 and epidermal growth factor receptor are RTKs that have phosphorylated tyrosines, which provide docking sites for PLCG1 SH2 domains . (wikipedia.org)
- Because the sequence surrounding the N-terminal tyrosine fulfills the requirement of ITIM, identified in the cytoplasmic region of immunoinhibitory receptors such as IgG Fc receptor type IIB (FcγRIIB), killer Ig-like receptor (KIR), CD22, and the paired Ig-like receptor B, it is quite natural to speculate that PD-1 mediates its negative signal by means of this tyrosine residue. (pnas.org)
- Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. (nih.gov)
- Rather, its signal transduction is mediated by JAK2 (Janus kinase) which phosphorylates tyrosine residues and thereby generates SH2 recognition sites at the EPO-receptor. (ahajournals.org)
- Src SH2 interacts with phosphotyrosine 537 of oestradiol receptor α and the Src SH3 domain with a proline‐rich stretch of the androgen receptor. (embopress.org)
- Glycan microarray and kinetic analyses of recombinant A(H7N9) HAs were performed to compare the receptor binding profile of wild-type receptor binding site variants at position 217, a residue analogous to one of two positions known to switch avian to human receptor preference in H2N2 and H3N2 viruses. (asm.org)
- Two recombinant A(H7N9) HAs were structurally characterized, and a mutational study of the receptor binding site was performed to analyze important residues that can affect receptor preference and affinity. (asm.org)
- 5-10 ⇓ ⇓ ⇓ ⇓ ⇓ The N- and C-terminal SH2 domains bind to tyrosine-phosphorylated insulin receptor substrate (IRS)-1, 11 suggesting that SHP2 is involved in positive signaling pathways serving multiple hormone receptors. (ahajournals.org)
- The binding of ligand to the α-chains of the IR ectodomain induces structural changes within the receptor leading to autophosphorylation of various tyrosine residues within the intracellular TK domain of the β-chain. (wikidoc.org)
- The tyrosine-phosphorylated receptor provides for docking sites for SH2 domain containing signal transducing molecules such as Grb2 and phospholipase-Cγ1. (rupress.org)
- TITLE Interaction of fibroblast growth factor receptor 3 and the adapter protein SH2-B. A role in STAT5 activation JOURNAL J. Biol. (genome.jp)
- TITLE SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase JOURNAL Biochem. (genome.jp)
- Those residues are then picked up by phosphotyrosine-binding domains known as PTB, such as insulin receptor substrate, SHC and Cbl. (wikibooks.org)
- The steroid receptor Zinc fingers have only cysteines and no histidine residues in their Zinc binding sites. (highveld.com)
- The activated JAKs then phosphorylate the cytoplasmic tail of gp130 on specific tyrosine residues, generating binding sites for STAT transcription factors including STAT3. (deepdyve.com)
- An 11-residue phosphopeptide derived from the hamster polyoma middle-T antigen, EPQpYEEIPIYL, binds with an approximately 1 nM dissociation constant to the Lck SH2 (ref. 17), an affinity equivalent to that of the tightest known SH2-phosphopeptide complex. (rcsb.org)
- Insulin binds to a-subunit and changes the conformation causing autophosphorylation of tyrosine residues. (wikibooks.org)
- The model shows that the tyrosine moiety binds Shc in a rather similar way to that observed for other SH2-peptide complexes, but that the residue in position +3 does not seem to make specific contact with the protein. (proteopedia.org)
- The modules typically recognize a linear motif in their ligands, with a few residues in the motif determining the specificity. (pnas.org)
- Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. (embl-heidelberg.de)
- Mutational analysis demonstrated that this interaction required the COOH-terminal sequence (T/S)XV, where serine or threonine are permitted at the -2 position, any residue could substitute at the -1, and valine or a hydrophobic side chain must be present at the 0 (or COOH-terminal) position. (jci.org)
- An invariant arginine and several nearby hydrophobic residues are solvent exposed and are predicted to be the site of interaction with ARFs. (embl-heidelberg.de)
- Once activated, STAT dimerizes to other STATs by reciprocal SH2 phosphotyrosine interaction, leading to its translocation into the nucleus followed by its binding to the specific enhancer elements for initiation of transcription [ 2 , 3 ] (Figure 1 ). (hindawi.com)
- HuGE Navigator) REFERENCE 7 (residues 1 to 683) AUTHORS Jones RB, Gordus A, Krall JA and MacBeath G. TITLE A quantitative protein interaction network for the ErbB receptors using protein microarrays JOURNAL Nature 439 (7073), 168-174 (2006) PUBMED 16273093 REFERENCE 8 (residues 1 to 683) AUTHORS Nishi M, Werner ED, Oh BC, Frantz JD, Dhe-Paganon S, Hansen L, Lee J and Shoelson SE. (genome.jp)
- Upon interaction, the leucine residues of the two bZIPs interdigitate through hydrophobic interactions such that the two helices wrap around each other to form a coiled-coil. (highveld.com)
- An intermolecular crystallographic interaction occurs between the pY-binding site and the C-terminal residues of a symmetry-related molecule. (proteopedia.org)
- According to the multistep model for BCR signaling ( 15 ), BCR stimulation first activates Lyn, which, in turn, phosphorylates the tyrosine residue in the immunoreceptor tyrosine-based activation motif of the Igα and Igβ, resulting in recruitment of another protein tyrosine kinase, Syk. (pnas.org)
- Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). (nih.gov)
- Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). (nih.gov)
- Recruitment of a STAT3 to the phosphorylated gp130 brings the STAT3 close to the activated JAK, which then phosphorylates a tyrosine residue of the STAT3 (10, 11). (deepdyve.com)
- Zinc fingers bind DNA through loops (fingers) that are formed when non-contiguous histidine and/or cysteine residues become associated by coordinating a Zinc ion. (highveld.com)
- Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. (abcam.com)
- Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. (ebi.ac.uk)
- Like other growth factor receptors, upon ligand binding, VEGFR2 dimerizes and is autophosphorylated on multiple tyrosine residues. (novusbio.com)
- The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit. (wikipathways.org)
- The asparagine residue at the pTyr+2 position of the Shc-peptide interacted with the main-chain carbonyl groups of Lys109 and Leu120. (rcsb.org)
- The ITAM motif is based on four residues. (antievolution.org)
- Mutagenesis studies indicated that these inhibitory effects do not require the N-terminal tyrosine in the immunoreceptor tyrosine-based inhibitory motif-like sequence, but do require the other tyrosine residue in the C-terminal tail. (pnas.org)
- PD-1 contains two tyrosine residues in its cytoplasmic region, the N-terminal of which is embedded in a sequence defined as the immunoreceptor tyrosine-based inhibitory motif (ITIM), I/L/VXYXXL/V ( 1 - 4 ). (pnas.org)
- There are also splice variants that arise from alternative usage of splice acceptor site resulting in the presence or absence of a serine residue (Crosier et al. (wikipathways.org)
- This circuit is broken by altering the charge of residues along the solvent-exposed face of the JH2 αC, which is predicted to interact with the SH2-JH2 linker and JH1. (biochemj.org)
- The residue change on the sequence. (expasy.org)
- Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown. (expasy.org)
- Both residues are medium size and hydrophobic. (expasy.org)
- As a result, the peptide formed a turn-structure on the surface of Grb2 SH2. (rcsb.org)
- The present solution structure was similar to the crystal structure reported for Grb2 SH2 complexed with a BCR-Abl-derived phosphotyrosine-containing peptide. (rcsb.org)
- RTKs are single pass transmembrane receptors that possess intrinsic cytoplasmic enzymatic activity, catalyzing the transfer of the gamma phosphate of ATP to tyrosine residues in protein substrates. (abcam.com)
- Deletion of the four C-terminal residues of the beta3 cytoplasmic tail [beta3(759X)] decreased Syk binding and disrupted its physical association with integrin alphaIIbbeta3. (nih.gov)
- They are characterized by a leucine zipper, which is a stretch of amino acids where every 7th residue is a leucine. (highveld.com)
- There is selectivity for the residues Glu, Glu and Ile in the three positions C-terminal to the phosphotyrosine. (rcsb.org)
- An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. (nih.gov)
- These findings explain how PTPROt both positively and negatively influences Src activity and suggest a potential switch function for C-terminal tyrosine residues in other tyrosine phosphatases. (sciencemag.org)
- On stimulation, tyrosine residues of ITIMs are usually phosphorylated to recruit Src homology 2 (SH2)-containing phosphatases that play critical roles in negative regulation of cellular activities. (pnas.org)
- Human IRS-1 was O -GlcNAc-modified at Ser 984 or Ser 985 , at Ser 1011 , and possibly at multiple sites within residues 1025-1045. (mcponline.org)
- Our high-affinity complex shows the presence of a second pocket for the residue (pY + 3) three positions C-terminal to the phosphotyrosine (pY). (rcsb.org)
- PD-1 is an immunoreceptor that belongs to the immunoglobulin (Ig) superfamily and contains two tyrosine residues in the cytoplasmic region. (pnas.org)