Posttranslational modification 164901 218210394 2008-06-09T17:29:47Z 195.113.47.212 adding czech iw '''Posttranslational modification''' (PTM) is the [[chemistry|chemical]] modification of a [[protein]] after its [[translation (biology)|translation]]. It is one of the later steps in [[protein biosynthesis]] for many proteins. [[image:Insulinpath.png|right|thumb|250px|The bottom of this diagram shows the modification of [[primary structure]] of insulin, as described.]] A protein (also called a [[polypeptide]]) is a chain of [[amino acid]]s. During protein synthesis, 20 different amino acids can be incorporated in proteins. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching to it other biochemical [[functional group]]s such as [[acetate]], [[phosphate]], various [[lipid]]s and [[carbohydrate]]s, by changing the chemical nature of an amino acid (e.g. [[citrulline|citrullination]]) or by making structural changes, like the formation of [[disulfide bridge]]s. Also, [[enzyme]]s may remove amino acids from the [[N-terminal end|amino end]] of the protein, or cut the peptide chain in the middle. For instance, the peptide [[hormone]] [[insulin]] is cut twice after disulfide bonds are formed, and a [[propeptide]] is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Other modifications, like [[phosphorylation]], are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme. == PTMs involving addition of functional groups == [[image:GeneticCode22.svg|right|thumb|300px|The genetic code diagram<ref>Gramatikoff K. in [[Abgent]] Catalog (2004-5) p.263</ref> showing the amino acid residues as target of modification.]] PTMs involving addition include: * [[acylation]] ** [[acetylation]], the addition of an [[acetyl]] group, usually at the [[N-terminus]] of the protein * [[alkylation]], the addition of an [[alkyl]] group (e.g. methyl, ethyl) ** [[methylation]] the addition of a [[methyl]] group, usually at [[lysine]] or [[arginine]] residues. (This is a type of alkylation.) ** [[demethylation]] * [[amidation]] at C-terminus * [[biotinylation]], acylation of conserved [[lysine]] residues with a biotin appendage * [[formylation]] * [[gamma-carboxylation]] dependent on [[Vitamin K]]<ref>{{cite journal |author=Walker CS, Shetty RP, Clark K, ''et al'' |title=On a potential global role for vitamin K-dependent gamma-carboxylation in animal systems. Evidence for a gamma-glutamyl carboxylase in Drosophila |journal=J. Biol. Chem. |volume=276 |issue=11 |pages=7769–74 |year=2001 |pmid=11110799 |doi=10.1074/jbc.M009576200}}</ref> * [[glutamylation]], covalent linkage of [[glutamic acid]] residues to tubulin and some other proteins.<ref>{{cite journal |author=Eddé B, Rossier J, Le Caer JP, Desbruyères E, Gros F, Denoulet P |title=Posttranslational glutamylation of alpha-tubulin |journal=Science |volume=247 |issue=4938 |pages=83–5 |year=1990 |pmid=1967194 |doi=10.1126/science.1967194}}</ref> (See [[tubulin polyglutamylase]]) * [[glycosylation]], the addition of a [[glycosyl]] group to either [[asparagine]], [[hydroxylysine]], [[serine]], or [[threonine]], resulting in a [[glycoprotein]]. Distinct from [[glycation]], which is regarded as a nonenzymatic attachment of sugars. * [[glycylation]], covalent linkage of one to more than 40 [[glycine]] residues to the [[tubulin]] C-terminal tail * [[heme]] moiety may be covalently attached * [[hydroxylation]] * [[iodination]] (e.g. of [[thyroid hormones]]) * [[isoprenylation]], the addition of an [[isoprenoid]] group (e.g. farnesol and geranylgeraniol) * [[lipoylation]], attachment of a lipoate functionality ** [[prenylation]] ** [[GPI anchor]] formation *** [[myristoylation]] *** [[farnesylation]] *** [[geranylgeranylation]] * [[nucleotide]]s or derivatives thereof may be covalently attached ** [[ADP-ribosylation]] ** [[flavin]] attachment * [[oxidation]] * [[palmitoylation]] * [[pegylation]] * [[phosphatidylinositol]] may be covalently attached * [[phosphopantetheinylation]], the addition of a 4'-phosphopantetheinyl moiety from [[coenzyme A]], as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis * [[phosphorylation]], the addition of a [[phosphate]] group, usually to [[serine]], [[tyrosine]], [[threonine]] or [[histidine]] * polysialylation, addition of [[polysialic acid]], PSA to [[NCAM]] * [[pyroglutamate]] formation * [[racemization]] of [[proline]] by [[prolyl isomerase]] * [[tRNA]]-mediation addition of amino acids such as [[arginylation]] * [[tyrosine sulfation|sulfation]], the addition of a sulfate group to a [[tyrosine]]. * [[selenoylation]] (co-translational incorporation of [[selenium]] in [[selenoproteins]]) * [[sulfation]] == PTMs involving addition of other proteins or peptides == * ISGylation, the [[covalent]] linkage to the ISG15 protein (Interferon-Stimulated Gene 15)<ref>{{cite journal |author=Malakhova, Oxana A.; Yan, Ming; Malakhov, Michael P.; Yuan, Youzhong; Ritchie, Kenneth J.; Kim, Keun Il; Peterson, Luke F.; Shuai, Ke; and Dong-Er Zhang |title=Protein ISGylation modulates the JAK-STAT signaling pathway |journal=Genes & Development |volume=17 |issue=4 |pages=455–60 |year=2003 |url=http://www.genesdev.org/cgi/content/full/17/4/455 |pmid=12600939 |doi=10.1101/gad.1056303}}</ref> * [[SUMOylation]], the [[covalent]] linkage to the [[SUMO protein]] (Small Ubiquitin-related MOdifier)<ref> Van G. Wilson (Ed.) (2004). [http://www.horizonpress.com/hsp/books/sumo.html ''Sumoylation: Molecular Biology and Biochemistry'']. Horizon Bioscience. ISBN 0-9545232-8-8.</ref> * [[Ubiquitin|ubiquitination]], the [[covalent]] linkage to the protein ubiquitin. == PTMs involving changing the chemical nature of amino acids == * [[citrullination]], or '''deimination''' the conversion of [[arginine]] to [[citrulline]] * [[deamidation]], the conversion of [[glutamine]] to [[glutamic acid]] or [[asparagine]] to [[aspartic acid]] == PTMs involving structural changes == * [[disulfide bridge]]s, the covalent linkage of two [[cysteine]] amino acids * [[Protease|proteolytic cleavage]], cleavage of a protein at a peptide bond == Case examples == * cleavage and formation of disulfide bridges during the production of [[insulin]] * PTM of [[histone]]s as regulation of transcription: [[RNA polymerase control by chromatin structure]] * PTM of RNA polymerase II as regulation of transcription: [[RNA polymerase II]] ==External links== * [http://www.posttranslational.com deltaMasses: Differential PTM Detection after mass spectrometry] * [http://www.natureprotocols.com/2007/03/23/automotif_server_a_computation.php AutoMotif Server: A Computational Protocol for Identification of Post-Translational Modifications in Protein Sequences] * [http://www.natureprotocols.com/2007/01/10/functional_analyses_for_sitesp.php Functional analyses for site-specific phosphorylation of a target protein in cells] == References == <references/> {{Protein primary structure}} {{Protein topics}} [[Category:Protein structure]] [[Category:Protein biosynthesis]] [[Category:Posttranslational modification]] [[Category:Cell biology]] [[cs:postranslační modifikace]] [[da:Posttranslationel modifikation]] [[de:Posttranslationale Modifikation]] [[es:Modificacion postraduccional]] [[it:Modificazione post traduzionale]] [[ja:翻訳後修飾]] [[pl:Modyfikacje posttranslacyjne]] [[pt:Modificação pós-traducional]] [[ru:Посттрансляционная модификация]] [[zh:翻译后修饰]]