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the grammatical relation that exists when a word qualifies the meaning of the phrase (同)qualifying, limiting
slightly modified copy; not an exact copy; "a modification of last years model"
of or relating to or characterized by covalence; "covalent bond"

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〈棟〉修正,変更)した(された)もの / 〈U〉〈C〉(文法で)修飾

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/11 21:09:56」(JST)

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Posttranslational modification (PTM) is a step in protein biosynthesis. Proteins are created by ribosomes translating mRNA into polypeptide chains. These polypeptide chains undergo PTM (such as folding, cutting and other processes) before becoming the mature protein product.

Posttranslational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated to become a protein. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching it to other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates), changing the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. formation of disulfide bridges).

Also, enzymes may remove amino acids from the 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. Also, most nascent polypeptides start with the amino acid methionine because the "start" n mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Post-translational modification of proteins can be detected by a variety of techniques, including mass spectrometry, Eastern blotting, and Western blotting.

1 PTMs involving addition of functional groups
- 1.1 PTMs involving addition by an enzyme in vivo
  - 1.1.1 PTMs involving addition of hydrophobic groups for membrane localization
  - 1.1.2 PTMs involving addition of cofactors for enhanced enzymatic activity
  - 1.1.3 PTMs involving unique modifications of translation factors
  - 1.1.4 PTMs involving addition of smaller chemical groups
- 1.2 PTMs involving non-enzymatic additions in vivo
- 1.3 PTMs involving non-enzymatic additions in vitro
2 PTMs involving addition of other proteins or peptides
3 PTMs involving changing the chemical nature of amino acids
4 PTMs involving structural changes
5 Post-translational modification statistics
6 Case examples
7 See also
8 External links
9 References

PTMs involving addition of functional groups

The genetic code diagram^[1] showing the amino acid residues as target of modification.

PTMs involving addition by an enzyme in vivo

PTMs involving addition of hydrophobic groups for membrane localization

myristoylation, attachment of myristate, a C₁₄ saturated acid
palmitoylation, attachment of palmitate, a C₁₆ saturated acid
isoprenylation or prenylation, the addition of an isoprenoid group (e.g. farnesol and geranylgeraniol)
- farnesylation
- geranylgeranylation
glypiation, glycosylphosphatidylinositol (GPI) anchor formation via an amide bond to C-terminal tail

PTMs involving addition of cofactors for enhanced enzymatic activity

lipoylation, attachment of a lipoate (C₈) functional group
flavin moiety (FMN or FAD) may be covalently attached
heme C attachment via thioether bonds with cysteins
phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety from coenzyme A, as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis
retinylidene Schiff base formation

PTMs involving unique modifications of translation factors

diphthamide formation (on a histidine found in eEF2)
ethanolamine phosphoglycerol attachment (on glutamte found in eEF1α)^[2]
hypusine formation (on conserved lysine of eIF5A (eukaryotic) and aIF5A (archeal))

PTMs involving addition of smaller chemical groups

acylation, e.g. O-acylation (esters), N-acylation (amides), S-acylation (thioesters)
- acetylation, the addition of an acetyl group, either at the N-terminus ^[3] of the protein or at lysine residues.^[4] See also histone acetylation.^[5]^[6] The reverse is called deacetylation.
- formylation
alkylation, the addition of an alkyl group, e.g. methyl, ethyl
- methylation the addition of a methyl group, usually at lysine or arginine residues. The reverse is called demethylation.
amide bond formation
- amidation at C-terminus
- amino acid addition
  - arginylation, a tRNA-mediation addition
  - polyglutamylation, covalent linkage of glutamic acid residues to the N-terminus of tubulin and some other proteins.^[7] (See tubulin polyglutamylase)
  - polyglycylation, covalent linkage of one to more than 40 glycine residues to the tubulin C-terminal tail
butyrylation
gamma-carboxylation dependent on Vitamin K^[8]
glycosylation, the addition of a glycosyl group to either arginine, asparagine, cysteine, hydroxylysine, serine, threonine, tyrosine, or tryptophan resulting in a glycoprotein. Distinct from glycation, which is regarded as a nonenzymatic attachment of sugars.
- polysialylation, addition of polysialic acid, PSA, to NCAM
malonylation
hydroxylation
iodination (e.g. of thyroglobulin)
nucleotide addition such as ADP-ribosylation
oxidation
phosphate ester (O-linked) or phosphoramidate (N-linked) formation
- phosphorylation, the addition of a phosphate group, usually to serine, threonine, and tyrosine (O-linked), or histidine (N-linked)
- adenylylation, the addition of an adenylyl moiety, usually to tyrosine (O-linked), or histidine and lysine (N-linked)
propionylation
pyroglutamate formation
S-glutathionylation
S-nitrosylation
succinylation addition of a succinyl group to lysine
sulfation, the addition of a sulfate group to a tyrosine.

PTMs involving non-enzymatic additions in vivo

glycation, the addition of a sugar molecule to a protein without the controlling action of an enzyme.

PTMs involving non-enzymatic additions in vitro

biotinylation, acylation of conserved lysine residues with a biotin appendage
pegylation

PTMs involving addition of other proteins or peptides

ISGylation, the covalent linkage to the ISG15 protein (Interferon-Stimulated Gene 15)^[9]
SUMOylation, the covalent linkage to the SUMO protein (Small Ubiquitin-related MOdifier)^[10]
ubiquitination, the covalent linkage to the protein ubiquitin.
Neddylation, the covalent linkage to Nedd
Pupylation, the covalent linkage to the Prokaryotic ubiquitin-like protein

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
eliminylation, the conversion to an alkene by beta-elimination of phosphothreonine and phosphoserine, or dehydration of threonine and serine, as well as by decarboxylation of cysteine ^[11]
carbamylation, the conversion of lysine to homocitrulline ^[12]

PTMs involving structural changes

disulfide bridges, the covalent linkage of two cysteine amino acids
proteolytic cleavage, cleavage of a protein at a peptide bond
racemization
- of proline by prolyl isomerase
- of serine by protein-serine epimerase
- of alanine in dermorphin, a frog opioid peptide
- of methionine in deltorphin, also a frog opioid peptide

Post-translational modification statistics

Recently, statistics of each post-translational modification experimentally and putatively detected have been compiled using proteome-wide information from the Swiss-Prot database.^[13] These statistics can be found at http://selene.princeton.edu/PTMCuration/.

Case examples

Cleavage and formation of disulfide bridges during the production of insulin
PTM of histones as regulation of transcription: RNA polymerase control by chromatin structure
PTM of RNA polymerase II as regulation of transcription
Cleavage of polypeptide chains as crucial for lectin specificity

External links

dbPTM - database of protein post-translational modifications
List of posttranslational modifications in ExPASy
Browse SCOP domains by PTM — from the dcGO database
Statistics of each post-translational modification from the Swiss-Prot database
AutoMotif Server - A Computational Protocol for Identification of Post-Translational Modifications in Protein Sequences
Functional analyses for site-specific phosphorylation of a target protein in cells
Detection of Post-Translational Modifications after high-accuracy MSMS

References

^ Gramatikoff K. in Abgent Catalog (2004-5) p.263
^ Whiteheart SW, Shenbagamurthi P, Chen L, et al. (1989). "Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha.". J. Biol. Chem. 264 (24): 14334–41. PMID 2569467.
^ Polevoda B, Sherman F (2003). "N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins". J Mol Biol 325 (4): 595–622. doi:10.1016/S0022-2836(02)01269-X. PMID 12507466.
^ Yang XJ, Seto E (2008). "Lysine acetylation: codified crosstalk with other posttranslational modifications". Mol Cell 31 (4): 449–61. doi:10.1016/j.molcel.2008.07.002. PMC 2551738. PMID 18722172.
^ Bártová E, Krejcí J, Harnicarová A, Galiová G, Kozubek S (2008). "Histone modifications and nuclear architecture: a review". J Histochem Cytochem 56 (8): 711–21. doi:10.1369/jhc.2008.951251. PMC 2443610. PMID 18474937.
^ Glozak MA, Sengupta N, Zhang X, Seto E (2005). "Acetylation and deacetylation of non-histone proteins". Gene 363: 15–23. doi:10.1016/j.gene.2005.09.010. PMID 16289629.
^ Eddé B, Rossier J, Le Caer JP, Desbruyères E, Gros F, Denoulet P (1990). "Posttranslational glutamylation of alpha-tubulin". Science 247 (4938): 83–5. Bibcode:1990Sci...247...83E. doi:10.1126/science.1967194. PMID 1967194.
^ Walker CS, Shetty RP, Clark K, et al. (2001). "On a potential global role for vitamin K-dependent gamma-carboxylation in animal systems. Animals can experience subvaginalhemototitis as a result of this linkage. Evidence for a gamma-glutamyl carboxylase in Drosophila". J. Biol. Chem. 276 (11): 7769–74. doi:10.1074/jbc.M009576200. PMID 11110799.
^ 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 (2003). "Protein ISGylation modulates the JAK-STAT signaling pathway". Genes & Development 17 (4): 455–60. doi:10.1101/gad.1056303. PMC 195994. PMID 12600939.
^ Van G. Wilson (Ed.) (2004). Sumoylation: Molecular Biology and Biochemistry. Horizon Bioscience. ISBN 0-9545232-8-8.
^ Brennan DF, Barford D (2009). "Eliminylation: a post-translational modification catalyzed by phosphothreonine lyases". Trends in Biochemical Sciences 34 (3): 108–114. doi:10.1016/j.tibs.2008.11.005. PMID 19233656.
^ Mydel P, et al. (2010). "Carbamylation-dependent activation of T cells: a novel mechanism in the pathogenesis of autoimmune arthritis". Journal of Immunology 184 (12): 6882–6890. doi:10.4049/jimmunol.1000075. PMC 2925534. PMID 20488785.
^ Khoury, George A.; Baliban, Richard C.; and Christodoulos A. Floudas (2011). "Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database". Scientific Reports 1 (90). Bibcode:2011NatSR...1E..90K. doi:10.1038/srep00090.

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