Post-translational modification

• myristoylation (a type of acylation), attachment of myristate, a C₁₄ saturated acid
• palmitoylation (a type of acylation), 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

• lipoylation (a type of acylation), attachment of a lipoate (C₈) functional group
• flavin moiety (flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD)) may be covalently attached
• heme C attachment via thioether bonds with cysteines
• 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

• diphthamide formation (on a histidine found in eEF2)
• ethanolamine phosphoglycerol attachment (on glutamate found in eEF1α){{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 }}
• 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.{{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 }} EFP is a homolog to eIF5A (eukaryotic) and aIF5A (archaeal) (see above).

• 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.{{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 }} 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.
• amidation at C-terminus. Formed by oxidative dissociation of a C-terminal Gly residue.{{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 }}
• 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.{{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 }} (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{{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 }}
• 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, 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
• 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)
• 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-nitrosylation
• S-sulfenylation (aka S-sulphenylation), reversible covalent addition of one oxygen atom to the thiol group of a cysteine residue{{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 }}

• S-sulfinylation, normally irreversible covalent addition of two oxygen atoms to the thiol group of a cysteine residue
• 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
• succinylation addition of a succinyl group to lysine
• sulfation, the addition of a sulfate group to a tyrosine.

Examples of non-enzymatic PTMs are glycation, glycoxidation, nitrosylation, oxidation, succination, and lipoxidation."The Advanced Lipoxidation End-Product Malondialdehyde-Lysine in Aging and Longevity" PMID 33203089 PMC7696601

• 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.{{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 }}
• 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.{{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 }}

• 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.{{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 }}
• 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.

• ubiquitination, the covalent linkage to the protein ubiquitin.
• SUMOylation, the covalent linkage to the SUMO protein (small ubiquitin-related modifier)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}}.
• neddylation, the covalent linkage to the Nedd protein
• ISGylation, the covalent linkage to the ISG15 protein (interferon-stimulated gene 15){{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 }}
• pupylation, the covalent linkage to the prokaryotic ubiquitin-like protein

• citrullination, or deimination, the conversion of arginine to citrulline{{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 }}
• 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{{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 }}

• disulfide bridges, the covalent linkage of two cysteine amino acids
• lysine-cysteine bridges, the covalent linkage of 1 lysine and 1 or 2 cystine residues via an oxygen atom (NOS and SONOS bridges){{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 }}
• 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 inteins analogous to mRNA processing

In 2011, statistics of each post-translational modification experimentally and putatively detected have been compiled using proteome-wide information from the Swiss-Prot database.{{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 }} The 10 most common experimentally found modifications were as follows:{{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}}

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

File:Image for Wiki 2.jpg

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.

• [http://www.phosphosite.org/ PhosphoSitePlus]{{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 }} – A database of comprehensive information and tools for the study of mammalian protein post-translational modification
• ProteomeScout{{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 }} – A database of proteins and post-translational modifications experimentally
• Human Protein Reference Database – A database for different modifications and understand different proteins, their class, and function/process related to disease causing proteins
• PROSITE{{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 }} – A database of Consensus patterns for many types of PTM's including sites
• RESID{{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 }} – A database consisting of a collection of annotations and structures for PTMs.
• [https://research.bioinformatics.udel.edu/iptmnet/ iPTMnet] {{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}}– A database that integrates PTM information from several knowledgbases and text mining results.
• dbPTM – 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
• [https://www.oglcnac.mcw.edu/ The O-GlcNAc Database]{{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 }}{{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 }} - A curated database for protein O-GlcNAcylation and referencing more than 14 000 protein entries and 10 000 O-GlcNAc sites.

List of software for visualization of proteins and their PTMs

• PyMOL{{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 }} – introduce a set of common PTM's into protein models
• AWESOME{{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 }} – Interactive tool to see the role of single nucleotide polymorphisms to PTM's
• Chimera{{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 }} – Interactive Database to visualize molecules

{{more citations needed section|date=January 2016}}

• 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{{cite web|url=http://www.proteopedia.org/wiki/index.php/1tp8|title=1tp8 - Proteopedia, life in 3D|website=www.proteopedia.org}}
• Influence of Ni(II) in the Acetylation of Histones H4 Protein {{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}}

• Protein targeting
• Post-translational regulation

{{reflist|30em}}

• [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]

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