Posttranslational modification
Overview
 
Posttranslational modification (PTM) is the chemical
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....

 modification of a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 after its translation. It is one of the later steps in protein biosynthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...

, and thus gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

, for many proteins.

A protein (also called a polypeptide) is a chain of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s. 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 group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...

s (such as acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...

, phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

, various lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

s and carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

s), changing the chemical nature of an amino acid (e.g.
Encyclopedia
Posttranslational modification (PTM) is the chemical
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....

 modification of a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 after its translation. It is one of the later steps in protein biosynthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...

, and thus gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

, for many proteins.

A protein (also called a polypeptide) is a chain of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s. 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 group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...

s (such as acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...

, phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

, various lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

s and carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

s), changing the chemical nature of an amino acid (e.g. citrullination
Citrullination
Citrullination or deimination is the term used for the post-translational modification of the amino acid arginine in a protein into the amino acid citrulline. This reaction, shown below, is performed by enzymes called peptidylarginine deiminases...

), or making structural changes (e.g. formation of disulfide bridges).

Also, enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s may remove amino acids from the amino end
N-terminal end
The N-terminus refers to the start of a protein or polypeptide terminated by an amino acid with a free amine group . The convention for writing peptide sequences is to put the N-terminus on the left and write the sequence from N- to C-terminus...

 of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 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
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...

 because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

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

Post-translational modification of proteins is detected by mass spectrometry
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...

 or Eastern blotting
Eastern blotting
Eastern blotting is a biochemical technique used to analyze protein post translational modifications such as lipids and glycoconjugates. It is most often used to detect carbohydrate epitopes. Thus, Eastern blotting can be considered an extension of the biochemical technique of Western blotting...

.

PTMs involving addition of functional groups

PTMs involving addition of hydrophobic groups for membrane localization

  • myristoylation
    Myristoylation
    Myristoylation is an irreversible, co-translational protein modification found in animals, plants, fungi, protozoans and viruses. In this protein modification, a myristoyl group is covalently attached via an amide bond to the alpha-amino group of an N-terminal amino acid of a nascent polypeptide...

    , attachment of myristate, a C14 saturated acid
  • palmitoylation
    Palmitoylation
    S-Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine residues of membrane proteins. The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their...

    , attachment of palmitate, a C16 saturated acid
  • isoprenylation or prenylation
    Prenylation
    Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...

    , the addition of an isoprenoid group (e.g. farnesol
    Farnesol
    Farnesol is a natural organic compound which is an acyclic sesquiterpene alcohol found as a colorless liquid. It is insoluble in water, but miscible with oils...

     and geranylgeraniol
    Geranylgeraniol
    Geranylgeraniol is a diterpene alcohol which plays a role a several important biological processes. It is an intermediate in the biosynthesis of other diterpenes and of vitamins E and K. It also used in the post-translational modification known as geranylgeranylation...

    )
    • farnesylation
    • geranylgeranylation
      Geranylgeranylation
      Geranylgeranylation is a form of prenylation, which is a post-translational modification of proteins that involves the attachment of one or two 20-carbon lipophilic geranylgeranyl isoprene units from geranylgeranyl diphosphate to one or two cysteine residue at the C-terminus of specific proteins...

  • 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
    FMN
    FMN may refer to several things:* Flavin mononucleotide.* Forsvarsministeriet, the Danish Ministry of Defence.* Four Corners Regional Airport outside Farmington, New Mexico, its IATA airport code.* Fluid Music....

     or FAD
    FAD
    In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate...

    ) may be covalently attached
  • heme C
    Heme c
    Heme C differs from heme B in that the two vinyl side chains of heme B are replaced by covalent, thioether linkages to the apoprotein...

     attachment via thioether
    Thioether
    A thioether is a functional group in organosulfur chemistry with the connectivity C-S-C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors. A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen...

     bonds with cysteins
  • phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety from coenzyme A
    Coenzyme A
    Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...

    , as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis
  • retinylidene Schiff base
    Schiff base
    A Schiff base, named after Hugo Schiff, is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, not hydrogen....

     formation

PTMs involving unique modifications of translation factors

  • diphthamide
    Diphthamide
    Diphthamide is a modified histidine amino acid found in eukaryotic elongation factor 2 .It is usually found at position H715 in mammalian eEF2 . This residue is modified by the protein encoded by the OVCA1 gene . DPH1 knockout mice are inviable while heterozygotes develop diverse types of...

     formation (on a histidine found in eEF2
    EEF2
    Elongation factor 2 is a protein that in humans is encoded by the EEF2 gene.This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the nascent protein chain from...

    )
  • ethanolamine phosphoglycerol attachment (on glutamte found in eEF1α)
  • hypusine
    Hypusine
    Hypusine is an unusual amino acid found in all eukaryotes and in some archaea, but not in bacteria. The only known protein containing hypusine is eukaryotic translation initiation factor 5A and a similar protein found in archaebacteria. In humans, two isoforms of eIF-5A have been described:...

     formation (on conserved lysine of eIF5A
    EIF5A
    Eukaryotic translation initiation factor 5A-1 is a protein that in humans is encoded by the EIF5A gene.It is the only known protein to contain the unusual amino acid hypusine [N - -lysine], which is formed from the polyamine spermidine by two catalytic steps.-Further reading:...

     (eukaryotic) and aIF5A (archeal))

PTMs involving addition of smaller chemical groups

  • acylation
    Acylation
    In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....

    , e.g. O-acylation (esters), N-acylation (amides), S-acylation (thioesters)
    • acetylation
      Acetylation
      Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...

      , the addition of an acetyl
      Acetyl
      In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...

       group, either at the N-terminus  of the protein or at lysine
      Lysine
      Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

       residues. See also histone
      Histone
      In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...

       acetylation
      . The reverse is called deacetylation.
    • formylation
      Formylation
      Formylation is a type of posttranslational modification in which a formyl group is added to the N-terminus of a protein....

  • alkylation
    Alkylation
    Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

    , the addition of an alkyl group, e.g. methyl, ethyl
    Ethyl group
    In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5....

    • methylation
      Methylation
      In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...

       the addition of a methyl group, usually at lysine
      Lysine
      Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

       or arginine
      Arginine
      Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...

       residues. The reverse is called demethylation
      Demethylation
      Demethylation is the chemical process resulting in the removal a of methyl group from a molecule.A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms....

      .
  • amide
    Amide
    In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...

     bond formation
    • amidation at C-terminus
    • amino acid
      Amino acid
      Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

       addition
      • arginylation, a tRNA-mediation addition
      • polyglutamylation
        Polyglutamylation
        Polyglutamylation is a form of reversible posttranslational modification of glutamate residues seen for example in alpha and beta tubulins, nucleosome assembly proteins NAP1 and NAP2. The γ-carboxy group of glutamate may form peptide-like bond with the amino group of a free glutamate whose...

        , covalent linkage of glutamic acid
        Glutamic acid
        Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

         residues to the N-terminus of tubulin and some other proteins. (See tubulin polyglutamylase)
      • polyglycylation
        Polyglycylation
        Polyglycylation is a form of posttranslational modification of glutamate residues of the carboxyl-terminal region tubulin in certain microtubules originally discovered in Paramecium, and later shown in mammalian neurons as well....

        , covalent linkage of one to more than 40 glycine
        Glycine
        Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

         residues to the tubulin
        Tubulin
        Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...

         C-terminal tail
  • gamma-carboxylation dependent on Vitamin K
    Vitamin K
    Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...

  • glycosylation
    Glycosylation
    Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

    , the addition of a glycosyl
    Glycosyl
    A glycosyl group is a univalent free radical or substituent structure obtained by removing the hemiacetal hydroxyl group from the cyclic form of a monosaccharide and, by extension, of a lower oligosaccharide....

     group to either asparagine
    Asparagine
    Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...

    , hydroxylysine
    Hydroxylysine
    5-Hydroxylysine is an amino acid with the molecular formula C6H14N2O3. It was first discovered in 1921 by Donald Van Slyke. It is a hydroxy derivative of lysine. It is most widely known as a component of collagen....

    , serine
    Serine
    Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

    , or threonine
    Threonine
    Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

    , resulting in a glycoprotein
    Glycoprotein
    Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

    . Distinct from glycation
    Glycation
    Glycation is the result of the bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme. All blood sugars are reducing molecules. Glycation may occur either inside the body or outside the body...

    , which is regarded as a nonenzymatic attachment of sugars.
    • polysialylation, addition of polysialic acid
      Polysialic acid
      Polysialic acid is an unusual posttranslational modification that occurs on neural cell adhesion molecules . Polysialic acid is considerably anionic. This strong negative charge gives this modification the ability to change the protein's surface charge and binding ability. In the synapse,...

      , PSA, to NCAM
    • ADP-ribosylation
      ADP-ribosylation
      ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.-ADP-ribosylation enzymes:...

  • hydroxylation
  • iodination (e.g. of thyroglobulin
    Thyroglobulin
    Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

    )
  • oxidation
  • phosphate ester (O-linked) or phosphoramidate
    Phosphoramidate
    A phosphoramidate is a phosphate that has an NR2 instead of an OH group. The structure of phosphoramidic acid , 2PONH2, is present in PubChem....

     (N-linked) formation
    • phosphorylation
      Phosphorylation
      Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

      , the addition of a phosphate
      Phosphate
      A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

       group, usually to serine
      Serine
      Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

      , threonine
      Threonine
      Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

      , and tyrosine
      Tyrosine
      Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

       (O-linked), or histidine
      Histidine
      Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

       (N-linked)
    • adenylylation, the addition of an adenylyl moiety, usually to tyrosine
      Tyrosine
      Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

       (O-linked), or histidine
      Histidine
      Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

       and lysine
      Lysine
      Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

       (N-linked)
  • pyroglutamate formation
  • S-glutathionylation
  • S-nitrosylation
  • sulfation
    Tyrosine sulfation
    Tyrosine sulfation is a posttranslational modification where a sulfate group is added to a tyrosine residue of a protein molecule. Secreted proteins and extracellular parts of membrane proteins that pass through the Golgi apparatus may be sulfated...

    , the addition of a sulfate group to a tyrosine
    Tyrosine
    Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

    .
  • selenoylation (co-translational incorporation of selenium
    Selenium
    Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...

     in selenoproteins)

PTMs involving non-enzymatic additions in vivo

  • glycation
    Glycation
    Glycation is the result of the bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme. All blood sugars are reducing molecules. Glycation may occur either inside the body or outside the body...

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

PTMs involving non-enzymatic additions in vitro

  • biotinylation
    Biotinylation
    In biochemistry, biotinylation is the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to perturb the natural function of the molecule due to the small size of biotin...

    , acylation of conserved lysine
    Lysine
    Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

     residues with a biotin appendage
  • pegylation
    PEGylation
    PEGylation is the process of covalent attachment of polyethylene glycol polymer chains to another molecule, normally a drug or therapeutic protein. PEGylation is routinely achieved by incubation of a reactive derivative of PEG with the target macromolecule...


PTMs involving addition of other proteins or peptides

  • ISGylation, the covalent linkage to the ISG15 protein (Interferon-Stimulated Gene 15)
  • SUMOylation, the covalent linkage to the SUMO protein
    SUMO protein
    Small Ubiquitin-like Modifier or SUMO proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function...

     (Small Ubiquitin-related MOdifier)
  • ubiquitin
    Ubiquitin
    Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

    ation, the covalent linkage to the protein ubiquitin.
  • Neddylation
    Neddylation
    Neddylation is the process by which the ubiquitin like protein Nedd8 is conjugated to its target proteins. This process is analogous to ubiquitination, although relies on its own E1 and E2 enzymes...

    , the covalent linkage to Nedd

PTMs involving changing the chemical nature of amino acids

  • citrullination
    Citrullination
    Citrullination or deimination is the term used for the post-translational modification of the amino acid arginine in a protein into the amino acid citrulline. This reaction, shown below, is performed by enzymes called peptidylarginine deiminases...

    , or deimination, the conversion of arginine
    Arginine
    Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...

     to citrulline
    Citrulline
    The organic compound citrulline is an α-amino acid. Its name is derived from citrullus, the Latin word for watermelon, from which it was first isolated in 1930.It has the idealized formula H2NCNH3CHCO2H...

  • deamidation
    Deamidation
    Deamidation is a chemical reaction in which an amide functional group is removed from an organic compound. In biochemistry, the reaction is important in the degradation of proteins because it damages the amide-containing side chains of the amino acids asparagine and glutamine.In the biochemical...

    , the conversion of glutamine
    Glutamine
    Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...

     to glutamic acid
    Glutamic acid
    Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

     or asparagine
    Asparagine
    Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...

     to aspartic acid
    Aspartic acid
    Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...

  • eliminylation, the conversion to an alkene
    Alkene
    In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...

     by beta-elimination
    Elimination reaction
    An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism...

     of phosphothreonine and phosphoserine
    Phosphoserine
    Phosphoserine is an ester of serine and phosphoric acid. Phosphoserine is a component of many proteins as the result of posttranslational modifications. The phosphorylation of the alcohol functional group in serine to produce phosphoserine is catalyzed by various types of kinases....

    , or dehydration
    Dehydration reaction
    In chemistry and the biological sciences, a dehydration reaction is usually defined as a chemical reaction that involves the loss of water from the reacting molecule. Dehydration reactions are a subset of elimination reactions...

     of threonine
    Threonine
    Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

     and serine
    Serine
    Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

    , as well as by decarboxylation
    Decarboxylation
    Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...

     of cysteine
    Cysteine
    Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

  • carbamylation, the conversion of lysine
    Lysine
    Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

     to homocitrulline

PTMs involving structural changes

  • disulfide bridges, the covalent linkage of two cysteine
    Cysteine
    Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

     amino acids
  • proteolytic cleavage, cleavage of a protein at a peptide bond
  • racemization
    Racemization
    In chemistry, racemization refers to the converting of an enantiomerically pure mixture into a mixture where more than one of the enantiomers are present...

     of proline
    Proline
    Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...

     by prolyl isomerase
    Prolyl isomerase
    Prolyl isomerase is an enzyme found in both prokaryotes and eukaryotes that interconverts the cis and trans isomers of peptide bonds with the amino acid proline. Proline has an unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its...


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. These statistics can be found at http://selene.princeton.edu/PTMCuration/.

Case examples

  • Cleavage and formation of disulfide bridges during the production of insulin
    Insulin
    Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

  • PTM of histone
    Histone
    In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...

    s as regulation of transcription
    Transcription (genetics)
    Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

    : RNA polymerase control by chromatin structure
  • PTM of RNA polymerase II
    RNA polymerase II
    RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...

    as regulation of transcription
  • Cleavage of polypeptide chains as crucial for lectin specificity

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK