Post-translational modification - wikipedia Post-translational modification 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. Post-translational modification ( PTM ) refers to the covalent and generally enzymatic modification of proteins following protein biosynthesis. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the mature protein product. PTMs are important components in cell signaling, as for example when prohormones are converted to hormones. Post-translational modifications can occur on the amino acid side chains or at the protein 's C - or N - termini. They can extend the chemical repertoire of the 20 standard amino acids by modifying an existing functional group or introducing a new one such as phosphate. Phosphorylation is a very common mechanism for regulating the activity of enzymes and is the most common post-translational modification. Many eukaryotic 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 bonds, as in processing a propeptide to a mature form or removing the initiator methionine residue. The formation of disulfide bonds from cysteine residues may also be referred to as a post-translational modification. 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. Specific amino acid modifications can be used as biomarkers indicating oxidative damage. 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 carboxylates 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 glycans. Rarer modifications can occur at oxidized methionines and at some methylenes in side chains. Post-translational modification of proteins can be experimentally detected by a variety of techniques, including mass spectrometry, Eastern blotting, and Western blotting. Additional methods are provided in the external links sections. Contents 1 PTMs involving addition of functional groups 1.1 Addition by an enzyme in vivo 1.1. 1 Hydrophobic groups for membrane localization 1.1. 2 Cofactors for enhanced enzymatic activity 1.1. 3 Modifications of translation factors 1.1. 4 Smaller chemical groups 1.2 Non-enzymatic additions in vivo 1.3 Non-enzymatic additions in vitro 2 Other proteins or peptides 3 Chemical modification of amino acids 4 Structural changes 5 Statistics 5.1 Common PTMs by frequency 5.2 Common PTMs by residue 6 Case examples 7 Addiction 8 See also 9 References 10 External links Ptms involving addition of functional groups Addition by an enzyme in vivo Hydrophobic groups for membrane localization myristoylation ( a type of acylation ), attachment of myristate, a C saturated acid palmitoylation ( a type of acylation ), attachment of palmitate, a C 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 Cofactors for enhanced enzymatic activity lipoylation ( a type of acylation ), attachment of a lipoate ( C ) functional group flavin moiety ( FMN or 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 Modifications of translation factors diphthamide formation ( on a histidine found in eEF2 ) ethanolamine phosphoglycerol attachment ( on glutamate found in eEF1α ) 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. EFP is an 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. See also histone acetylation. 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. 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. ( 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 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 : 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 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. Nonenzymatic additions in vivo 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. 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. Nonenzymatic 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. 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. Other proteins or peptides ISGylation, the covalent linkage to the ISG15 protein ( Interferon - Stimulated Gene 15 ) SUMOylation, the covalent linkage to the SUMO protein ( Small Ubiquitin - related MOdifier ) ubiquitination, the covalent linkage to the protein ubiquitin. Neddylation, the covalent linkage to Nedd Pupylation, the covalent linkage to the Prokaryotic ubiquitin - like protein Chemical modification 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 Structural changes disulfide bridges, the covalent linkage of two cysteine amino acids 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 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. The 10 most common experimentally found modifications were as follows : Frequency Modification 58383 Phosphorylation 6751 Acetylation 5526 N - linked glycosylation 2844 Amidation 1619 Hydroxylation 1523 Methylation 1133 O - linked glycosylation 878 Ubiquitylation 826 Pyrrolidone Carboxylic Acid 504 Sulfation More details can be found at http://selene.princeton.edu/PTMCuration/. 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. Amino Acid Abbrev. Modification Alanine Ala N - acetylation ( N - terminus ) Arginine Arg deimination to citrulline, methylation Asparagine Asn deamidation to Asp or iso ( Asp ), N - linked glycosylation Aspartic acid Asp isomerization to isoaspartic acid Cysteine Cys disulfide - bond formation, oxidation to sulfenic, sulfinic or sulfonic acid, palmitoylation, N - acetylation ( N - terminus ), S - nitrosylation Glutamine Gln cyclization to Pyroglutamic acid ( N - terminus ), deamidation to Glutamic acid or isopeptide bond formation to a lysine by a transglutaminase Glutamic acid Glu cyclization to Pyroglutamic acid ( N - terminus ), gamma - carboxylation Glycine Gly N - Myristoylation ( N - terminus ), N - acetylation ( N - terminus ) Histidine His Phosphorylation Isoleucine Ile Leucine Leu Lysine Lys acetylation, Ubiquitination, SUMOylation, methylation, hydroxylation Methionine Met N - acetylation ( N - terminus ), oxidation to sulfoxide or sulfone Phenylalanine Phe Proline Pro hydroxylation Serine Ser Phosphorylation, O - linked glycosylation, N - acetylation ( N - terminus ) Threonine Thr Phosphorylation, O - linked glycosylation, N - acetylation ( N - terminus ) Tryptophan Trp mono - or di - oxidation, formation of Kynurenine Tyrosine Tyr sulfation, phosphorylation Valine Val N - acetylation ( N - terminus ) Case examples This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. ( 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 Addiction A major feature of addiction is its persistence. The addictive phenotype can be lifelong, with drug craving and relapse occurring even after decades of abstinence. Post-translational modifications consisting of epigenetic alterations of histone protein tails in specific regions of the brain appear to be crucial to the molecular basis of addictions. Once particular post-translational epigenetic modifications occur, they appear to be long lasting `` molecular scars '' that may account for the persistence of addictions. Cigarette smokers ( about 21 % of the US population in 2013 ) ) are usually addicted to nicotine. After 7 days of nicotine treatment of mice, the post-translational modifications consisting of acetylation of both histone H3 and histone H4 was increased at the FosB promoter in the nucleus accumbens of the brain, causing a 61 % increase in FosB expression. This also increases expression of the splice variant Delta FosB. In the nucleus accumbens of the brain, Delta FosB functions as a `` sustained molecular switch '' and `` master control protein '' in the development of an addiction. Similarly, after 15 days of nicotine treatment of rats, the post-translational modification consisting of 3-fold increased acetylation of histone H4 occurs at the promoter of the dopamine D1 receptor ( DRD1 ) gene in the prefrontal cortex ( PFC ) of the rats. This caused increased dopamine release in the PFC reward - related brain region, and such increased dopamine release is recognized as an important factor for addiction. About 7 % of the US population is addicted to alcohol. In rats exposed to alcohol for up to 5 days, there was an increase in the post-translational modification of histone 3 lysine 9 acetylation in the pronociceptin promoter in the brain amygdala complex. This acetylation is an activating mark for pronociceptin. The nociceptin / nociceptin opioid receptor system is involved in the reinforcing or conditioning effects of alcohol. Cocaine addiction occurs in about 0.5 % of the US population. Repeated cocaine administration in mice induces post-translational modifications including hyperacetylation of histone 3 ( H3 ) or histone 4 ( H4 ) at 1,696 genes in one brain reward region ( the nucleus accumbens ) and deacetylation at 206 genes. At least 45 genes, shown in previous studies to be upregulated in the nucleus accumbens of mice after chronic cocaine exposure, were found to be associated with post-translational hyperacetylation of histone H3 or histone H4. Many of these individual genes are directly related to aspects of addiction associated with cocaine exposure. In 2013, 22.7 million persons aged 12 or older in the United States needed treatment for an illicit drug or alcohol use problem ( 8.6 percent of persons aged 12 or older ). See also Protein targeting Post-translational regulation References Jump up ^ Pratt, Donald Voet ; Judith G. Voet ; Charlotte W. ( 2006 ). Fundamentals of biochemistry : life at the molecular level ( 2. ed. ). Hoboken, NJ : Wiley. ISBN 0 - 471 - 21495 - 7. Jump up ^ Khoury, GA ; Baliban, RC ; Floudas, CA ( 13 September 2011 ). `` Proteome - wide post-translational modification statistics : frequency analysis and curation of the swiss - prot database ''. Scientific Reports. 1. 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Jump up ^ https://www.drugsandalcohol.ie/12728/1/NIDA_Cocaine.pdf 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 Overview and description of commonly used post-translational modification detection techniques Proteins Processes Protein biosynthesis Post-translational modification Protein folding Protein targeting Proteome Protein methods Structures Protein structure Protein structural domains Proteasome Types List of types of proteins List of proteins Membrane protein Globular protein Globulin Edestin Albumin Fibrous protein Proteins : key methods of study Experimental Protein purification Green fluorescent protein Western blot Protein immunostaining Protein sequencing Gel electrophoresis / Protein electrophoresis Protein immunoprecipitation Peptide mass fingerprinting / Protein mass spectrometry Dual - polarization interferometry Microscale thermophoresis Chromatin immunoprecipitation Surface plasmon resonance Isothermal titration calorimetry X-ray crystallography Protein NMR Cryo - electron microscopy Freeze - fracture electron microscopy Bioinformatics Protein structure prediction Protein -- protein docking Protein structural alignment Protein ontology Protein -- protein interaction prediction Assay Enzyme assay Protein assay Secretion assay Display techniques Bacterial display mRNA display Phage display Ribosome display Yeast display Super-resolution microscopy Photoactivated localization microscopy Vertico SMI Protein primary structure and posttranslational modifications General Peptide bond Protein biosynthesis Proteolysis Racemization N-O acyl shift N terminus Acetylation Carbamylation Formylation Glycation Methylation Myristoylation ( Gly ) C terminus Amidation Glycosyl phosphatidylinositol ( GPI ) O - methylation Detyrosination Single specific AAs Serine / Threonine Phosphorylation Dephosphorylation Glycosylation Methylidene - imidazolone ( MIO ) formation Tyrosine Phosphorylation Dephosphorylation Sulfation Porphyrin ring linkage Adenylylation Flavin linkage Topaquinone ( TPQ ) formation Detyrosination Cysteine Palmitoylation Prenylation Aspartate Succinimide formation Glutamate Carboxylation Methylation Polyglutamylation Polyglycylation Asparagine Deamidation Glycosylation Glutamine Transglutamination Lysine Methylation Acetylation Acylation Adenylylation Hydroxylation Ubiquitination Sumoylation ADP - ribosylation Deamination Oxidative deamination to aldehyde O - glycosylation Imine formation Glycation Carbamylation Succinylation Arginine Citrullination Methylation ADP - ribosylation Proline Hydroxylation Histidine Diphthamide formation Adenylylation Tryptophan C - mannosylation Crosslinks between two AAs Cysteine - Cysteine Disulfide bond Methionine - Hydroxylysine Sulfilimine bond Lysine - Tyrosylquinone Lysine tyrosylquinone ( LTQ ) formation Tryptophan - Tryptophylquinone Tryptophan tryptophylquinone ( TTQ ) formation Three consecutive AAs ( chromophore formation ) Serine -- Tyrosine -- Glycine p - Hydroxybenzylidene - imidazolinone formation Histidine -- Tyrosine -- Glycine 4 - ( p - hydroxybenzylidene ) - 5 - imidazolinone formation Crosslinks between four AAs Allysine - Allysine - Allysine - Lysine Desmosine Posttranslational modification Chaperones / protein folding Heat shock proteins / Chaperonins Hsp10 / GroES Hsp27 Hsp47 HSP60 / GroEL Hsp40 / DnaJ A1 A2 A3 B1 B2 B11 B4 B6 B9 C1 C3 C5 C6 C7 C10 C11 C13 C14 C19 Hsp70 1A 1B 1L 4L 5 6 7 8 9 12A 14 Hsp90 α α β ER TRAP1 Other Alpha crystallin Clusterin Survival of motor neuron SMN1 SMN2 Protein targeting Signal peptide Mitochondrial targeting signal Ubiquitin E1 Ubiquitin - activating enzyme UBA1 UBA2 UBA3 UBA5 UBA6 UBA7 ATG7 NAE1 SAE1 E2 Ubiquitin - conjugating enzyme D1 D2 D3 E1 E2 E3 G1 G2 J1 J2 L1 L2 L3 L4 L6 O Q1 Q2 R1 ( CDC34 ) R2 V1 V2 Z E3 Ubiquitin ligase VHL Cullin CBL MDM2 FANCL UBR1 Deubiquitinating enzyme : Ataxin 3 USP6 CYLD ATG3 BIRC6 UFC1 Other Ubiquitin - like modifiers SUMO protein ISG15 URM1 NEDD8 FAT10 ATG8 ATG12 FUB1 MUB UFM1 UBL5 Prokaryotic ubiquitin - like protein Gene expression Introduction to genetics Genetic code Central dogma DNA → RNA → Protein Special transfers RNA → RNA RNA → DNA Protein → Protein Transcription Types Bacterial Eukaryotic Key elements Transcription factor RNA polymerase Promoter Post-transcription Precursor mRNA ( pre-mRNA / hnRNA ) 5 ' capping Splicing Polyadenylation Histone acetylation and deacetylation Translation Types Prokaryotic Eukaryotic Key elements Ribosome Transfer RNA ( tRNA ) Ribosome - nascent chain complex ( RNC ) Post-translational modification ( functional groups peptides structural changes ) Regulation Epigenetic imprinting Transcriptional Gene regulatory network cis - regulatory element lac operon Post-transcriptional sequestration ( P - bodies ) alternative splicing microRNA Translational Post-translational reversible irreversible Influential people François Jacob Jacques Monod Molecular and cellular biology portal Retrieved from `` https://en.wikipedia.org/w/index.php?title=Post-translational_modification&oldid=853045446 '' Categories : Gene expression Protein structure Protein biosynthesis Posttranslational modification Cell biology Hidden categories : CS1 maint : Multiple names : authors list Webarchive template wayback links Articles needing additional references from January 2016 All articles needing additional references Talk Contents About Wikipedia Català Čeština Dansk Deutsch Español فارسی Français Galego Italiano Magyar Bahasa Melayu Nederlands 日本 語 Polski Português Русский Српски / srpski Srpskohrvatski / српскохрватски Türkçe Українська 中文 12 more Edit links This page was last edited on 2 August 2018, at 02 : 18 ( UTC ). 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Question: where do post translational modifications occur in the cell
Answer: on the amino acid side chains or at the protein's C- or N- termini