NationMaster - Encyclopedia: SH2 domain

The Src homology 2 domain (or SH2 domain) is a protein domain of about 100 amino acid residues first identified as a conserved sequence region among the oncoproteins Src and Fps. Image File history File links Download high resolution version (948x1014, 233 KB) Summary Ribbon diagram of the SH2 domain from P56-Lck tyrosine kinase (PDB accession code 1lkk, chain A). ... Image File history File links Download high resolution version (948x1014, 233 KB) Summary Ribbon diagram of the SH2 domain from P56-Lck tyrosine kinase (PDB accession code 1lkk, chain A). ... Within a protein, a structural domain (domain) is an element of overall structure that is self-stabilizing and often folds independently of the rest of the protein chain. ... Phenylalanine is one of the standard amino acids. ... An oncogene is a modified gene that increases the malignancy of a tumor cell. ... Src is a family of proto-oncogenes that may lead to cancer. ...

Similar sequences were later found in many other intracellular proteins involved in signal transduction, such as Abl, ZAP70, STAT proteins,Grb2, and RasGAP. Overview of signal transduction pathways In biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another, most often involving ordered sequences of biochemical reactions inside the cell, that are carried out by enzymes and linked through second messengers resulting in... The abl gene is accociated with chronic myelogenous leukemia. ... ZAP-70 is an abbrevation for Zeta-chain-associated protein kinase 70 (70 is the molecular weight in kDa). ... The Signal Transducers and Activator of Transcription (STAT) protein regulates many aspects of cell growth, survival and differentiation. ... GRB2 is a cytosolic adapter protein that provides a key link between the binding of an EGF to an RTK and the activation of Ras. ... RasGAP (Ras GTPase activating protein) is a 120-kDa cytosolic protein that provides two principal activities: Inactivation of Ras from its active GTP-bound form to its unactive GDP-bound form by enhancing the endogenous GTPase activity of Ras, via its C-terminal GAP domain Mitogenic signal transmission towards downstream...

Binding and phosphorylation

SH2 domains typically bind a phosphorylated tyrosine residue in the context of a longer peptide motif within a target proteins, and SH2 domains represent the largest class of known pTyr-recognition domains^[1]. Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells to synthesize proteins. ...

Phosphorylation of tyrosine residues in a protein occurs during signal transduction and is carried out by tyrosine kinases. In this way, phosphorylation of a substrate by tyrosine kinases acts as a switch to trigger binding to an SH2 domain-containing protein. The intimate relationship between tyrosine kinases and SH2 domains is supported by their coordinate emergence during eukaryotic evolution. A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule or the introduction of a phosphate group into an organic molecule. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... In biochemistry, a substrate is a molecule upon which an enzyme acts. ...

Diversity

SH2 domains are not present in yeast and appear at the boundary between protozoa and animalia in organisms such as the social amoeba Dictyostelium discoideum^[2]. Typical divisions Ascomycota (sac fungi) Saccharomycotina (true yeasts) Taphrinomycotina Schizosaccharomycetes (fission yeasts) Basidiomycota (club fungi) Urediniomycetes Sporidiales Yeasts are a growth form of eukaryotic microorganisms classified in the kingdom Fungi. ... Wikisource has an original article from the 1911 EncyclopÃ¦dia Britannica about: Protozoa Protozoa (in Greek proto = first and zoa = animals) are single-celled eukaryotes (organisms whose cells have nuclei) that commonly show characteristics usually associated with animals, most notably mobility and heterotrophy. ... Phyla Subkingdom Parazoa Porifera (sponges) Subkingdom Agnotozoa Placozoa Orthonectida Rhombozoa Subkingdom Metazoa Radiata Cnidaria Ctenophora - Comb jellies Bilateria Protostomia Acoelomorpha Platyhelminthes - Flatworms Nemertina - Ribbon worms Gastrotricha Gnathostomulida - Jawed worms Micrognathozoa Rotifera - Rotifers Acanthocephala Priapulida Kinorhyncha Loricifera Entoprocta Nematoda - Roundworms Nematomorpha - Horsehair worms Cycliophora Mollusca - Mollusks Sipuncula - Peanut worms Annelida - Segmented...

A detailed bioinformatic examination of SH2 domains of human and mouse reveals 120 SH2 domains contained within 110 proteins encoded by the human genome^[3], representing a rapid rate of evolutionary expansion among the SH2 domains. Bioinformatics or computational biology is the use of techniques from applied mathematics, informatics, statistics, and computer science to solve biological problems. ... Trinomial name Homo sapiens sapiens Linnaeus, 1758 Humans, or human beings, are bipedal primates belonging to the mammalian species Homo sapiens (Latin: wise man or knowing man) in the family Hominidae (the great apes). ... Feral mouse A mouse (plural mice) is a rodent that belongs to one of numerous species of small mammals. ...

A large number of SH2 domain structures have been solved and many SH2 proteins have been knocked out in mouse.^[4]

The abl gene is accociated with chronic myelogenous leukemia. ... GRB2 is a cytosolic adapter protein that provides a key link between the binding of an EGF to an RTK and the activation of Ras. ... RasGAP (Ras GTPase activating protein) is a 120-kDa cytosolic protein that provides two principal activities: Inactivation of Ras from its active GTP-bound form to its unactive GDP-bound form by enhancing the endogenous GTPase activity of Ras, via its C-terminal GAP domain Mitogenic signal transmission towards downstream... The Signal Transducers and Activator of Transcription (STAT) protein regulates many aspects of cell growth, survival and differentiation. ... ZAP-70 is an abbrevation for Zeta-chain-associated protein kinase 70 (70 is the molecular weight in kDa). ... Phosphoinositide 3-kinases (PI 3-kinases or PI3Ks) are a family of related enzymes that are capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns)[1]. The various 3-phosphorylated phosphoinositides that are produced by PI 3-kinases (PtdIns3P, PtdIns(3,4)P2, PtdIns... Phospholipase C is a key enzyme in phosphatidylinositol (PIP2) metabolism and lipid signaling pathways. ... CRK is a gene which codes a protein exhibiting the SH2 domain. ... Wikipedia does not yet have an article with this exact name. ... Src is a family of proto-oncogenes that may lead to cancer. ...

Functions

Many biological signaling proteins use this mode of regulated protein-protein interactions as a means to localize proteins to various sub-cellular compartments, control enzymatic activities of proteins as well as nucleate multiprotein complexes, to name a few. Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ...

The SH2 domain has thus become a prototype for a large number of modular interaction domains that have been since identified.

The discovery of the SH2 domain and its many roles in signal transduction introduced the critical concept of how biology has exploited the use of modular interaction domains to create complex signaling networks.

References

External links

Categories: Protein domains | Signal transduction | Biochemistry stubs | Cell biology stubs In biochemistry, the tertiary structure of a protein is its overall shape. ... Within a protein, a structural domain (domain) is an element of overall structure that is self-stabilizing and often folds independently of the rest of the protein chain. ... Protein folding is the process by which a protein assumes its characteristic functional shape or tertiary structure, also known as the native state. ... A helix bundle is a small protein fold composed of three or four alpha helices and held together by nonlocal hydrophobic interactions. ... An example of the globin fold, the oxygen-carrying protein myoglobin (PDB ID 1MBA) from the mollusc Aplysia limacina. ... The Antennapedia homeodomain protein from Drosophila melanogaster bound to a fragment of DNA (PDB ID 1AHD). ... A trimer of the peridinin-chlorophyll-containing protein from the dinoflagellate Amphidinium carterae illustrating the alpha solenoid fold. ... Example of an immunoglobulin domain, the fibronectin type III domain from human tenascin (PDB accesion code 1TEN), colored from blue (N-terminus) to red (C-terminus). ... A beta barrel is a protein fold containing a series of beta sheets, typically arranged in an antiparallel fashion. ... Ribbon diagram of the C-terminal WD40 domain of Tup1 (a transcriptional co-repressor in yeast), which adopts a 7-bladed beta-propeller fold. ... Top view of a triosephosphateisomerase (TIM) barrel (PDB accession code 8TIM), colored from blue (N-terminus) to red (C-terminus). ... An example of a leucine-rich repeat protein, a porcine ribonuclease inhibitor (PDB ID 2BNH). ... Ribbon diagram of CheY (a regulator of the chemotactic response in bacteria, PDB accession code 3CHY), which adopts the flavodoxin fold. ... One molecule of human thioredoxin (PDB ID 1ERT), a canonical example of the thioredoxin fold class. ... A deep trefoil knot in a Thermus thermophilus RNA methyltransferase domain (PDB ID 1IPA). ... Ribbon diagram of acylphosphatase (PDB accession code 2ACY), which adopts a ferredoxin fold with an extra Î²-strand at the C-terminus (shown in red). ... Structure of RNase A Ribonuclease A (RNase A) is an endonuclease that cleaves single-stranded RNA. Bovine pancreatic RNase A is one of the classic model systems of protein science. ... A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail. ... A representation of the 3D structure of the Myoglobin protein. ... Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen and sulfur. ... In biochemistry, many proteins are actually assemblies of more than one protein (polypeptide) molecule, which in the context of the larger assemblage are known as protein subunits. ...

Contents

Diversity

Functions

References

External links