Editing Post-translational modification

{{short description|Chemical changes in proteins following their translation from mRNA}}
[[File:Insulin path.svg|right|thumb|upright=1.35|Post-translational 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.]]

In [[molecular biology]], '''post-translational modification''' ('''PTM''') is the [[covalent]] process of changing [[protein]]s following [[protein biosynthesis]]. PTMs may involve [[enzymes]] or occur spontaneously. Proteins are created by [[ribosomes]], which [[translation (biology)|translate]] [[mRNA]] into [[polypeptide chain]]s, which may then change to form the mature protein product. PTMs are important components in cell [[signal transduction|signalling]], as for example when [[prohormone]]s are converted to [[hormone]]s.

Post-translational modifications can occur on the [[amino acid]] [[side chain]]s or at the protein's [[C-terminus|C-]] or [[N-terminus|N-]] termini.<ref>{{cite book|last1=Pratt|first1=Charlotte W.|authorlink1=Charlotte W. Pratt|authorlink2=Judith G. Voet|authorlink3=Donald Voet|first2=Judith G.|last2=Voet|last3=Voet|first3=Donald|url=https://books.google.com/books?id=h0FCAQAAIAAJ|title=Fundamentals of Biochemistry: Life at the Molecular Level|date=2006|publisher=Wiley|location=Hoboken, NJ|oclc=1280801548|isbn=9780471214953|archive-date=13 July 2012|archive-url=https://archive.org/details/fundamentalsofbi00voet_0|edition=2nd }}</ref> They can expand the chemical set of the 22 [[proteinogenic amino acid|amino acids]] by changing an existing [[functional group]] or adding a new one such as phosphate. [[Phosphorylation]] is highly effective for controlling the enzyme activity and is the most common change after translation. <ref name="khoury">{{cite journal|vauthors=Khoury GA, Baliban RC, Floudas CA|author-link3=Christodoulos Floudas|date=September 2011|title=Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database|journal=[[Scientific Reports]]|volume=1|pages=90|bibcode=2011NatSR...1...90K|doi=10.1038/srep00090|pmc=3201773|pmid=22034591}}</ref> Many [[eukaryotic]] and [[prokaryotic]] proteins also have [[carbohydrate]] molecules attached to them in a process called [[glycosylation]], which can promote [[protein folding]] and improve stability as well as serving regulatory functions. Attachment of [[lipid]] molecules, known as [[lipidation]], often targets a protein or part of a protein attached to the [[cell membrane]].

Other forms of post-translational modification consist of cleaving [[peptide bond]]s, as in processing a [[propeptide]] to a mature form or removing the initiator [[methionine]] residue. The formation of [[disulfide bond]]s from [[cysteine]] residues may also be referred to as a post-translational modification.<ref name=lodish>{{cite book|vauthors=Lodish H, Berk A, Zipursky SL|display-authors=etal|chapter=17.6, Post-Translational Modifications and Quality Control in the Rough ER|title=Molecular Cell Biology|date=2000|publisher=W. H. Freeman|location=New York|isbn=978-0-7167-3136-8|edition=4th|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK21741/|url=https://archive.org/details/molecularcellbio00lodi}}</ref> 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.

Some types of post-translational modification are consequences of [[oxidative stress]]. [[Carbonylation]] is one example that targets the modified protein for degradation and can result in the formation of protein aggregates.<ref>{{cite journal|vauthors=Dalle-Donne I, Aldini G, Carini M, Colombo R, Rossi R, Milzani A|year=2006|title=Protein carbonylation, cellular dysfunction, and disease progression|journal=[[Journal of Cellular and Molecular Medicine]]|volume=10|issue=2|pages=389–406|doi=10.1111/j.1582-4934.2006.tb00407.x|pmc=3933129|pmid=16796807}}</ref><ref>{{cite journal|vauthors=Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA|date=August 2008|title=Oxidative stress and covalent modification of protein with bioactive aldehydes|journal=[[The Journal of Biological Chemistry]]|volume=283|issue=32|pages=21837–41|doi=10.1074/jbc.R700019200|pmc=2494933|pmid=18445586|doi-access=free}}</ref> Specific amino acid modifications can be used as [[biomarker]]s indicating oxidative damage.<ref>{{cite journal | vauthors = Gianazza E, Crawford J, Miller I | title = Detecting oxidative post-translational modifications in proteins | journal = Amino Acids | volume = 33 | issue = 1 | pages = 51–6 | date = July 2007 | pmid = 17021655 | doi = 10.1007/s00726-006-0410-2 | s2cid = 23819101 }}</ref>
PTMs and metal ions play a crucial and reciprocal role in regulating protein function, influencing cellular processes such as signal transduction and gene expression, with dysregulated interactions implicated in diseases like cancer and neurodegenerative disorders.<ref>{{cite journal |last1=Peana |first1=Massimiliano |title=Interplay of Metal Ions and Posttranslational Modifications in Proteins |journal=European Journal of Inorganic Chemistry |date=19 August 2024 |volume=27 |issue=27 |doi=10.1002/ejic.202400175 |url=https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/ejic.202400175|url-access=subscription }}</ref>

Sites that often undergo post-translational modification are those that have a functional group that can serve as a [[nucleophile]] in the reaction: the [[hydroxyl]] groups of [[serine]], [[threonine]], and [[tyrosine]]; the [[amine]] forms of [[lysine]], [[arginine]], and [[histidine]]; the [[thiolate]] [[anion]] of [[cysteine]]; the [[carboxylate]]s of [[aspartate]] and [[glutamate]]; and the N- and C-termini. In addition, although the [[amide]] of [[asparagine]] is a weak nucleophile, it can serve as an attachment point for [[glycan]]s. Rarer modifications can occur at oxidized [[methionine]]s and at some [[methylene group]]s in side chains.<ref name=walsh>{{cite book|last1=Walsh|first1=Christopher T.|title=Posttranslational modification of proteins : expanding nature's inventory|date=2006|publisher=Roberts and Co. Publ.|location=Englewood|isbn=9780974707730}} {{rp|12–14}}</ref>

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

== PTMs involving addition of functional groups ==
<!-- removed from display. See Talk [[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.]]-->

===Addition by an enzyme ''in vivo''===

====Hydrophobic groups for membrane localization====
* [[myristoylation]] (a type of [[acylation]]), attachment of [[myristate]], a C<sub>14</sub> saturated acid
* [[palmitoylation]] (a type of acylation), attachment of [[palmitate]], a C<sub>16</sub> saturated acid
* [[isoprenylation]] or [[prenylation]], the addition of an [[isoprenoid]] group (e.g. [[farnesol]] and [[geranylgeraniol]])
** [[farnesylation]]
** [[geranylgeranylation]]
* [[glypiation]], [[GPI anchor|glycosylphosphatidylinositol (GPI) anchor]] formation via an amide bond to C-terminal tail

====Cofactors for enhanced enzymatic activity====
* [[lipoylation]] (a type of acylation), attachment of a [[lipoate]] (C<sub>8</sub>) functional group
* [[flavin group|flavin]] moiety ([[flavin mononucleotide]] (FMN) or [[flavin adenine dinucleotide]] (FAD)) may be covalently attached
* [[heme C]] attachment via [[thioether]] bonds with [[cysteine]]s
* [[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

====Modifications of translation factors====
* [[diphthamide]] formation (on a histidine found in [[eEF2]])
* [[ethanolamine phosphoglycerol]] attachment (on glutamate found in [[Eukaryotic translation elongation factor 1 alpha 1|eEF1α]])<ref name="pmid2569467">{{cite journal | vauthors = Whiteheart SW, Shenbagamurthi P, Chen L, Cotter RJ, Hart GW | title = 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 | journal = The Journal of Biological Chemistry | volume = 264 | issue = 24 | pages = 14334–41 | date = August 1989 | doi = 10.1016/S0021-9258(18)71682-7 | pmid = 2569467 | display-authors = etal | doi-access = free }}</ref>
* [[hypusine]] formation (on conserved lysine of [[eIF5A]] (eukaryotic) and [[aIF5A]] (archaeal))
* [[beta-Lysine]] addition on a conserved lysine of the [[elongation factor P]] (EFP) in most bacteria.<ref>{{cite journal | vauthors = Roy H, Zou SB, Bullwinkle TJ, Wolfe BS, Gilreath MS, Forsyth CJ, Navarre WW, Ibba M | title = The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-β-lysine | journal = Nature Chemical Biology | volume = 7 | issue = 10 | pages = 667–9 | date = August 2011 | pmid = 21841797 | pmc = 3177975 | doi = 10.1038/nchembio.632 }}</ref> EFP is a homolog to [[eIF5A]] (eukaryotic) and [[aIF5A]] (archaeal) (see above).

====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]] of the protein or at [[lysine]] residues.<ref name="pmid29405707">{{cite journal | vauthors = Ali I, Conrad RJ, Verdin E, Ott M | title = Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics | journal = Chem Rev | volume = 118 | issue = 3 | pages = 1216–1252 | date = February 2018 | pmid = 29405707 | pmc = 6609103 | doi = 10.1021/acs.chemrev.7b00181 }}</ref> The reverse is called [[deacetylation]].
** [[formylation]]
* [[alkylation]], the addition of an [[alkyl]] group, e.g. [[methyl]], [[ethyl group|ethyl]]
** [[methylation]] the addition of a [[methyl]] group, usually at [[lysine]] or [[arginine]] residues. The reverse is called [[demethylation]].
* <span id="amidation">amidation</span> at C-terminus. Formed by oxidative dissociation of a C-terminal Gly residue.<ref name="amidation">{{cite journal | vauthors = Bradbury AF, Smyth DG | title = Peptide amidation | journal = Trends in Biochemical Sciences | volume = 16 | issue = 3 | pages = 112–5 | date = March 1991 | pmid = 2057999 | doi = 10.1016/0968-0004(91)90044-v }}</ref>
* [[amide]] bond formation
** [[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.<ref name="pmid1967194">{{cite journal | vauthors = 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 | date = January 1990 | pmid = 1967194 | doi = 10.1126/science.1967194 | bibcode = 1990Sci...247...83E }}</ref> (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]]<ref>{{cite journal | vauthors = Walker CS, Shetty RP, Clark K, Kazuko SG, Letsou A, Olivera BM, Bandyopadhyay PK | title = On a potential global role for vitamin K-dependent gamma-carboxylation in animal systems. Evidence for a gamma-glutamyl carboxylase in Drosophila | journal = The Journal of Biological Chemistry | volume = 276 | issue = 11 | pages = 7769–74 | date = March 2001 | pmid = 11110799 | doi = 10.1074/jbc.M009576200 | display-authors = etal | doi-access = free }}</ref>
* [[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.
** [[O-GlcNAc|''O''-GlcNAc]], addition of ''N''-acetylglucosamine to serine or threonine residues in a β-glycosidic linkage
** polysialylation, addition of [[polysialic acid]] (PSA) to [[neural cell adhesion molecule]] (NCAM)
* [[malonylation]]
* [[protein hydroxylation|hydroxylation]]: addition of an oxygen atom to the side-chain of a Pro or Lys residue
* [[iodination]]: addition of an iodine atom to the aromatic ring of a tyrosine residue (e.g. in [[thyroglobulin]])
* [[ADP-ribosylation|nucleotide addition]] such as [[ADP-ribosylation]]
* [[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)
** uridylylation, the addition of an uridylyl-group (i.e. [[uridine monophosphate]] (UMP)), usually to tyrosine
* [[propionylation]]
* [[pyroglutamate]] formation
* [[S-glutathionylation|''S''-glutathionylation]]
* [[S-nitrosylation|''S''-nitrosylation]]
* ''S''-sulfenylation (''aka'' ''S''-sulphenylation), reversible covalent addition of one oxygen atom to the [[thiol]] group of a [[cysteine]] residue<ref name="CysOx">{{cite journal | vauthors = Chung HS, Wang SB, Venkatraman V, Murray CI, Van Eyk JE | title = Cysteine oxidative posttranslational modifications: emerging regulation in the cardiovascular system | journal = Circulation Research | volume = 112 | issue = 2 | pages = 382–92 | date = January 2013 | pmid = 23329793 | pmc = 4340704 | doi = 10.1161/CIRCRESAHA.112.268680 | display-authors = 1 }}</ref>
<!-- old ref{{Cite journal|title = MDD–SOH: exploiting maximal dependence decomposition to identify S-sulfenylation sites with substrate motifs|date = 26 September 2015|journal = Bioinformatics|doi = 10.1093/bioinformatics/btv558|pmid = 26411868|vauthors = Bui VM, Lu CT, Ho TT, Lee TY|volume = 32|issue = 2|pages = 165–72}}-->
* ''S''-sulfinylation, normally irreversible covalent addition of two oxygen atoms to the [[thiol]] group of a [[cysteine]] residue<ref name="CysOx" />
* ''S''-sulfonylation, normally irreversible covalent addition of three oxygen atoms to the [[thiol]] group of a [[cysteine]] residue, resulting in the formation of a [[cysteic acid]] residue<ref name="CysOx" />
* [[succinylation]] addition of a [[succinyl]] group to [[lysine]]
* [[tyrosine sulfation|sulfation]], the addition of a sulfate group to a [[tyrosine]].

===Non-enzymatic modifications ''in vivo''===
Examples of non-enzymatic PTMs are glycation, glycoxidation, nitrosylation, oxidation, succination, and lipoxidation.<ref>"The Advanced Lipoxidation End-Product Malondialdehyde-Lysine in Aging and Longevity" PMID 33203089 PMC7696601</ref>
* [[glycation]], the addition of a sugar molecule to a protein without the controlling action of an enzyme.
* [[carbamylation]] the addition of [[Isocyanic acid]] to a protein's N-terminus or the side-chain of Lys.<ref name="pmid21768218">{{cite journal | vauthors = Jaisson S, Pietrement C, Gillery P | title = Carbamylation-derived products: bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis | journal = Clinical Chemistry | volume = 57 | issue = 11 | pages = 1499–505 | date = November 2011 | pmid = 21768218 | doi = 10.1373/clinchem.2011.163188 | doi-access = free }}</ref>
* [[carbonylation]] the addition of carbon monoxide to other organic/inorganic compounds.
* spontaneous [[isopeptide bond]] formation, as found in many surface proteins of [[Gram-positive bacteria]].<ref name="pmid21055949">{{cite journal | vauthors = Kang HJ, Baker EN | title = Intramolecular isopeptide bonds: protein crosslinks built for stress? | journal = Trends in Biochemical Sciences | volume = 36 | issue = 4 | pages = 229–37 | date = April 2011 | pmid = 21055949 | doi = 10.1016/j.tibs.2010.09.007 }}</ref>

===Non-enzymatic additions ''in vitro''===
* [[biotinylation]]: covalent attachment of a biotin moiety using a biotinylation reagent, typically for the purpose of labeling a protein.
* carbamylation: the addition of isocyanic acid to a protein's N-terminus or the side-chain of Lys or Cys residues, typically resulting from exposure to urea solutions.<ref name="stark_1960">{{cite journal |vauthors=Stark GR, Stein WH, Moore X | title = Reactions of the Cyanate Present in Aqueous Urea with Amino Acids and Proteins | journal = J Biol Chem | volume = 235 | issue = 11 | pages = 3177–3181 | year = 1960 | doi = 10.1016/S0021-9258(20)81332-5 | doi-access = free }}</ref>
* oxidation: addition of one or more oxygen atoms to a susceptible side-chain, principally of Met, Trp, His or Cys residues. Formation of [[disulfide]] bonds between Cys residues.
* [[pegylation]]: covalent attachment of [[polyethylene glycol]] (PEG) using a pegylation reagent, typically to the N-terminus or the side-chains of Lys residues. Pegylation is used to improve the efficacy of protein pharmaceuticals.

==Conjugation with other proteins or peptides==
* [[ubiquitin]]ation, the [[covalent]] linkage to the protein ubiquitin.
* [[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''] {{webarchive|url=https://web.archive.org/web/20050209075122/http://horizonpress.com/hsp/books/sumo.html |date=2005-02-09 }}. Horizon Bioscience. {{ISBN|0-9545232-8-8}}.</ref>
* [[neddylation]], the covalent linkage to the [[NEDD8|Nedd protein]]
* ISGylation, the covalent linkage to the [[ISG15]] protein (interferon-stimulated gene 15)<ref>{{cite journal | vauthors = Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, Peterson LF, Shuai K, Zhang DE | title = Protein ISGylation modulates the JAK-STAT signaling pathway | journal = Genes & Development | volume = 17 | issue = 4 | pages = 455–60 | date = February 2003 | pmid = 12600939 | pmc = 195994 | doi = 10.1101/gad.1056303 }}</ref>
* [[pupylation]], the covalent linkage to the [[prokaryotic ubiquitin-like protein]]

== Chemical modification of amino acids ==
* [[citrullination]], or deimination, the conversion of [[arginine]] to [[citrulline]]<ref>{{cite journal | vauthors = Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L | title = Immunity to citrullinated proteins in rheumatoid arthritis | journal = Annual Review of Immunology | volume = 26 | pages = 651–75 | year = 2008 | pmid = 18173373 | doi = 10.1146/annurev.immunol.26.021607.090244 | url = https://zenodo.org/record/894124 }}</ref>
* [[deamidation]], the conversion of [[glutamine]] to [[glutamic acid]] or [[asparagine]] to [[aspartic acid]]
* [[eliminylation]], the conversion to an [[alkene]] by [[Elimination reaction|beta-elimination]] of [[phosphothreonine]] and [[phosphoserine]], or [[Dehydration reaction|dehydration]] of [[threonine]] and [[serine]]<ref>{{cite journal | vauthors = Brennan DF, Barford D | title = Eliminylation: a post-translational modification catalyzed by phosphothreonine lyases | journal = Trends in Biochemical Sciences | volume = 34 | issue = 3 | pages = 108–14 | date = March 2009 | pmid = 19233656 | doi = 10.1016/j.tibs.2008.11.005 }}</ref>

== Structural changes ==
* [[disulfide bridge]]s, the covalent linkage of two [[cysteine]] amino acids
* [[lysine-cysteine bridge]]s, the covalent linkage of 1 lysine and 1 or 2 cystine residues via an oxygen atom (NOS and SONOS bridges)<ref>{{cite journal |last1=Rabe von Pappenheim |first1=Fabian |last2=Wensien |first2=Marie |last3=Ye |first3=Jin |last4=Uranga |first4=Jon |last5=Irisarri |first5=Iker |last6=de Vries |first6=Jan |last7=Funk |first7=Lisa-Marie |last8=Mata |first8=Ricardo A. |last9=Tittmann |first9=Kai |title=Widespread occurrence of covalent lysine–cysteine redox switches in proteins |journal=Nature Chemical Biology |date=April 2022 |volume=18 |issue=4 |pages=368–375 |doi=10.1038/s41589-021-00966-5 |doi-access=free|pmid=35165445 |pmc=8964421 }}</ref>
* [[proteolytic cleavage]], cleavage of a protein at a peptide bond
* [[isoaspartate]] formation, via the cyclisation of asparagine or aspartic acid amino-acid residues
* [[racemization]]
** of [[serine]] by [[protein-serine epimerase]]
** of [[alanine]] in [[dermorphin]], a frog [[opioid peptide]]
** of [[methionine]] in [[deltorphin]], also a frog opioid peptide
* [[protein splicing]], self-catalytic removal of [[intein]]s analogous to mRNA processing

== Statistics ==
===Common PTMs by frequency===
In 2011, statistics of each post-translational modification experimentally and putatively detected have been compiled using proteome-wide information from the Swiss-Prot database.<ref>{{cite journal | vauthors = Khoury GA, Baliban RC, Floudas CA | title = Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database | journal = Scientific Reports | volume = 1 | issue = 90 | pages = 90 | date = September 2011 | pmid = 22034591 | pmc = 3201773 | doi = 10.1038/srep00090 | bibcode = 2011NatSR...1E..90K }}</ref> The 10 most common experimentally found modifications were as follows:<ref>{{cite web|url=http://selene.princeton.edu/PTMCuration/|title=Proteome-Wide Post-Translational Modification Statistics|website=selene.princeton.edu|access-date=2011-07-22|archive-url=https://web.archive.org/web/20120830234041/http://selene.princeton.edu/PTMCuration/|archive-date=2012-08-30|url-status=dead}}</ref>
{| class="wikitable"
!Frequency
!Modification
|-
|58383
|[[Phosphorylation]]
|-
|6751
|[[Acetylation]]
|-
|5526
|[[N-linked glycosylation]]
|-
|2844
|[[#amidation|Amidation]]
|-
|1619
|[[Hydroxylation]]
|-
|1523
|[[Methylation]]
|-
|1133
|[[O-linked glycosylation]]
|-
|878
|[[Ubiquitin|Ubiquitylation]]
|-
|826
|[[Pyroglutamic acid|Pyrrolidone carboxylic acid]]
|-
|504
|[[Sulfation]]
|}

=== Common PTMs by residue ===
Some common post-translational modifications to specific amino-acid residues are shown below. Modifications occur on the side-chain unless indicated otherwise.

{| class="wikitable sortable" style="text-align: left"   
|-   
! Amino Acid !! Abbrev. !! Modification
|-   
! [[Alanine]]
| Ala or A
| [[Acetylation|N-acetylation]] (N-terminus)
|-   
! [[Arginine]]
| Arg or R
| deimination to [[Citrullination|citrulline]], [[Protein methylation|methylation]]
|-   
! [[Asparagine]]
| Asn or N
| [[deamidation]] to Asp or iso(Asp), [[N-linked glycosylation]], [[Isopeptide bond|spontaneous isopeptide bond formation]]
|-   
! [[Aspartic acid]]
| Asp or D
| [[deamidation|isomerization]] to isoaspartic acid, spontaneous isopeptide bond formation
|-   
! [[Cysteine]]
| Cys or C
| [[disulfide]]-bond formation, oxidation to sulfenic, sulfinic or sulfonic acid, [[palmitoylation]], N-acetylation (N-terminus), [[S-nitrosylation]]
|-   
! [[Glutamine]]
| Gln or Q
| cyclization to [[pyroglutamic acid]] (N-terminus), deamidation to [[glutamic acid]] or [[isopeptide bond]] formation to a [[lysine]] by a [[transglutaminase]]
|-   
! [[Glutamic acid]]
| Glu or E
| cyclization to [[pyroglutamic acid]] (N-terminus), [[gamma-carboxylation]]
|-   
! [[Glycine]]
| Gly or G
| N-[[myristoylation]] (N-terminus), N-acetylation (N-terminus)
|-   
! [[Histidine]]
| His or H
| [[Histidine kinase|phosphorylation]]
|-   
! [[Isoleucine]]
| Ile or I
|
|-   
! [[Leucine]]
| Leu or L
|
|-   
! [[Lysine]]
| Lys or K
| [[acetylation]], [[ubiquitylation]], [[SUMO protein|SUMOylation]], [[Protein methylation|methylation]], [[hydroxylation]] leading to [[allysine]], spontaneous isopeptide bond formation
|-   
! [[Methionine]]
| Met or M
| N-acetylation (N-terminus), N-linked ubiquitination, oxidation to [[sulfoxide]] or [[sulfone]]
|-   
! [[Phenylalanine]]
| Phe or F
|
|-   
! [[Proline]]
| Pro or P
| [[hydroxylation]]
|-   
! [[Serine]]
| Ser or S
| [[phosphorylation]], [[O-linked glycosylation]], N-acetylation (N-terminus)
|-   
! [[Threonine]]
| Thr or T
| phosphorylation, O-linked glycosylation, N-acetylation (N-terminus)
|-   
! [[Tryptophan]]
| Trp or W
| mono- or di-oxidation, formation of [[kynurenine]], [[tryptophan tryptophylquinone]]
|-   
! [[Tyrosine]]
| Tyr or Y
| [[Tyrosine sulfation|sulfation]], phosphorylation
|-   
! [[Valine]]
| Val or V
| N-acetylation (N-terminus)
|}

== Databases and tools ==

[[File:Image for Wiki 2.jpg|alt=|thumb|Flowchart of the process and the data sources to predict PTMs.<ref name="ReferenceA">{{cite journal | vauthors = Lee TY, Huang HD, Hung JH, Huang HY, Yang YS, Wang TH | title = dbPTM: an information repository of protein post-translational modification | journal = Nucleic Acids Research | volume = 34 | issue = Database issue | pages = D622-7 | date = January 2006 | pmid = 16381945 | pmc = 1347446 | doi = 10.1093/nar/gkj083 }}</ref>  |440x440px]]

Protein sequences contain sequence motifs that are recognized by modifying enzymes, and which can be documented or predicted in PTM databases. With the large number of different modifications being discovered, there is a need to document this sort of information in databases. PTM information can be collected through experimental means or predicted from high-quality, manually curated data. Numerous databases have been created, often with a focus on certain taxonomic groups (e.g. human proteins) or other features.

=== List of resources ===
* [http://www.phosphosite.org/ PhosphoSitePlus]<ref>{{cite journal | vauthors = Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E | title = PhosphoSitePlus, 2014: mutations, PTMs and recalibrations | journal = Nucleic Acids Research | volume = 43 | issue = Database issue | pages = D512-20 | date = January 2015 | pmid = 25514926 | pmc = 4383998 | doi = 10.1093/nar/gku1267 }}</ref> – A database of comprehensive information and tools for the study of mammalian protein post-translational modification
* [[ProteomeScout]]<ref name="ReferenceB">{{cite journal | vauthors = Goel R, Harsha HC, Pandey A, Prasad TS | title = Human Protein Reference Database and Human Proteinpedia as resources for phosphoproteome analysis | journal = Molecular BioSystems | volume = 8 | issue = 2 | pages = 453–63 | date = February 2012 | pmid = 22159132 | pmc = 3804167 | doi = 10.1039/c1mb05340j }}</ref> – A database of proteins and post-translational modifications experimentally
* [[Human Protein Reference Database]]<ref name="ReferenceB"/> – A database for different modifications and understand different proteins, their class, and function/process related to disease causing proteins
* [[PROSITE]]<ref>{{cite journal | vauthors = Sigrist CJ, Cerutti L, de Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A, Hulo N | title = PROSITE, a protein domain database for functional characterization and annotation | journal = Nucleic Acids Research | volume = 38 | issue = Database issue | pages = D161-6 | date = January 2010 | pmid = 19858104 | pmc = 2808866 | doi = 10.1093/nar/gkp885 }}</ref> – A database of Consensus patterns for many types of PTM's including sites
* [[Protein Information Resource|RESID]]<ref>{{cite journal | vauthors = Garavelli JS | title = The RESID Database of Protein Modifications: 2003 developments | journal = Nucleic Acids Research | volume = 31 | issue = 1 | pages = 499–501 | date = January 2003 | pmid = 12520062 | pmc = 165485 | doi = 10.1093/nar/gkg038 }}</ref> – A database consisting of a collection of annotations and structures for PTMs.
* [https://research.bioinformatics.udel.edu/iptmnet/ iPTMnet] <ref>{{cite journal | vauthors = Huang H, Arighi CN, Ross KE, Ren J, Li G, Chen SC, Wang Q, Cowart J, Vijay-Shanker K, Wu CH | title = iPTMnet: an integrated resource for protein post-translational modification network discovery | journal = Nucleic Acids Research | volume = 46 | issue = 1 | pages = D542–D550 | date = January 2018 | pmid = 2914561 | pmc = 5753337 | doi = 10.1093/nar/gkx1104}}</ref>– A database that integrates PTM information from several knowledgbases and text mining results. 
* [[dbPTM]]<ref name="ReferenceA"/> – A database that shows different PTM's and information regarding their chemical components/structures and a frequency for amino acid modified site
* [https://www.uniprot.org/help/post-translational_modification Uniprot] has PTM information although that may be less comprehensive than in more specialized databases.[[File:Image for Wiki 1.jpg|alt=|thumb|Effect of PTMs on protein function and physiological processes.<ref>{{cite journal | vauthors = Audagnotto M, Dal Peraro M | title = In silico prediction tools and molecular modeling | journal = Computational and Structural Biotechnology Journal | volume = 15 | pages = 307–319 | date = 2017-03-31 | pmid = 28458782 | pmc = 5397102 | doi = 10.1016/j.csbj.2017.03.004 }}</ref>|440x440px]]
* [https://www.oglcnac.mcw.edu/ The ''O''-GlcNAc Database]<ref>{{cite journal | vauthors = Wulff-Fuentes E, Berendt RR, Massman L, Danner L, Malard F, Vora J, Kahsay R, Olivier-Van Stichelen S | title = The human ''O''-GlcNAcome database and meta-analysis | journal = Scientific Data | volume = 8 | date = January 2021 | issue = 1 | page = 25 | pmid = 33479245 | pmc = 7820439 | doi = 10.1038/s41597-021-00810-4 | bibcode = 2021NatSD...8...25W }}</ref><ref>{{cite journal | vauthors = Malard F, Wulff-Fuentes E, Berendt RR, Didier G, Olivier-Van Stichelen S | title = Automatization and self-maintenance of the O-GlcNAcome catalog: a smart scientific database | journal = Database (Oxford) | volume = 2021 | date = July 2021 | page = 1 | pmid = 34279596 | doi = 10.1093/database/baab039 | pmc = 8288053 }}</ref> - A curated database for protein O-GlcNAcylation and referencing more than 14 000 protein entries and 10 000 ''O''-GlcNAc sites.

=== Tools ===
List of software for visualization of proteins and their PTMs
* [[PyMOL]]<ref>{{cite journal | vauthors = Warnecke A, Sandalova T, Achour A, Harris RA | title = PyTMs: a useful PyMOL plugin for modeling common post-translational modifications | journal = BMC Bioinformatics | volume = 15 | issue = 1 | pages = 370 | date = November 2014 | pmid = 25431162 | pmc = 4256751 | doi = 10.1186/s12859-014-0370-6 | doi-access = free }}</ref> – introduce a set of common PTM's into protein models
* [[AWESOME]]<ref>{{cite journal | vauthors = Yang Y, Peng X, Ying P, Tian J, Li J, Ke J, Zhu Y, Gong Y, Zou D, Yang N, Wang X, Mei S, Zhong R, Gong J, Chang J, Miao X | title = AWESOME: a database of SNPs that affect protein post-translational modifications | journal = Nucleic Acids Research | volume = 47 | issue = D1 | pages = D874–D880 | date = January 2019 | pmid = 30215764 | pmc = 6324025 | doi = 10.1093/nar/gky821 }}</ref> – Interactive tool to see the role of single nucleotide polymorphisms to PTM's
* [[UCSF Chimera|Chimera]]<ref>{{cite journal | vauthors = Morris JH, Huang CC, Babbitt PC, Ferrin TE | title = structureViz: linking Cytoscape and UCSF Chimera | journal = Bioinformatics | volume = 23 | issue = 17 | pages = 2345–7 | date = September 2007 | pmid = 17623706 | doi = 10.1093/bioinformatics/btm329 | doi-access = free }}</ref> – Interactive Database to visualize molecules

== Case examples ==
{{more citations needed section|date=January 2016}}
* Cleavage and formation of [[disulfide bridge]]s during the production of [[insulin]]
* PTM of [[histone]]s as regulation of [[Transcription (genetics)|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<ref>{{cite web|url=http://www.proteopedia.org/wiki/index.php/1tp8|title=1tp8 - Proteopedia, life in 3D|website=www.proteopedia.org}}</ref>
* Influence of Ni(II) in the Acetylation of Histones H4 Protein <ref>{{cite journal |last1=Peana |first1=Massimiliano |title=Interplay of Metal Ions and Posttranslational Modifications in Proteins |journal=European Journal of Inorganic Chemistry |date=19 August 2024 |volume=27 |issue=27 |doi=10.1002/ejic.202400175 |url=https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/ejic.202400175|url-access=subscription }}</ref>

==See also==
* [[Protein targeting]]
* [[Post-translational regulation]]

==References==
{{reflist|30em}}

==External links==
* [https://ftp.uniprot.org/pub/databases/uniprot/current_release/knowledgebase/complete/docs/ptmlist.txt Controlled vocabulary of post-translational modifications] in [[Uniprot]]
* [https://www.uniprot.org/docs/ptmlist List of posttranslational modifications in ExPASy]
* [http://supfam.org/SUPERFAMILY/cgi-bin/dcbo.cgi?type=KW;po=9991 Browse SCOP domains by PTM] — from the [[dcGO]] database
* [http://www.cytoskeleton.com/about-signal-seeker-ptm-detection Overview and description of commonly used post-translational modification detection techniques]

{{Protein topics}}
{{Protein primary structure}}
{{Posttranslational modification}}
{{Gene expression}}
{{Portal bar|Biology}}

{{DEFAULTSORT:Posttranslational Modification}}
[[Category:Gene expression]]
[[Category:Protein structure]]
[[Category:Protein biosynthesis]]
[[Category:Post-translational modification| ]]
[[Category:Cell biology]]