Here, we describe a stress-related protein, YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine-5¡ä-monophosphate to a protein tyrosine/histidine residue, an unusual modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+ binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function.

Reference
Pubmed: Yang Y, Yue Y, Song N, Li C, Yuan Z, Wang Y, Ma Y, Li H, Zhang F, Wang W, Jia H, Li P, Li X, Wang Q, Ding Z, Dong H, Gu L, Li B. The YdiU Domain Modulates Bacterial Stress Signaling through Mn2+-Dependent UMPylation. Cell Rep. 2020 Sep 22;32(12):108161. doi: 10.1016/j.celrep.2020.108161.

    Ubiquitination (also known as ubiquitylation) is an enzymatic, post-translational modification (PTM) process in which a ubiquitin protein is attached to a substrate protein. This process most commonly binds the last amino acid of ubiquitin (glycine 76) to a lysine residue on the substrate. An isopeptide bond is formed between the carboxylic acid group of the ubiquitin's glycine and the epsilon amino group of the substrate's lysine. Cases are known in which the amine group of a protein's N-terminus is used for ubiquitination, rather than a lysine residue. In a few rare cases nonlysine residues have been identified as ubiquitination targets, such as cysteine, threonine and serine. The end result of this process is the addition of one ubiquitin molecule (monoubiquitination) or a chain of ubiquitin molecules (polyubiquitination) to the substrate protein.

Reference
Wiki: Ubiquitination

    Tyrosine phosphorylation is the addition of a phosphate (PO43?) group to the amino acid tyrosine on a protein. It is one of the main types of protein phosphorylation. This transfer is made possible through enzymes called tyrosine kinases. Tyrosine phosphorylation is a key step in signal transduction and the regulation of enzymatic activity.

Reference
Wiki: Tyrosine phosphorylation

    In particular, dimethylation and trimethylation of lysine side chains in proteins increase both hydrophobicity and steric bulk and can affect protein¨Cprotein interactions if they are in an interacting surface.

Reference
Wiki: Trimethylation

    Protein phosphorylation is a post-translational modification of proteins in which a serine, a threonine or a tyrosine residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. Regulation of proteins by phosphorylation is one of the most common modes of regulation of protein function, and is often termed "phosphoregulation". In almost all cases of phosphoregulation, the protein switches between a phosphorylated and an unphosphorylated form, and one of these two is an active form, while the other one is an inactive form. A serine/threonine protein kinase is a kinase enzyme that phosphorylates the OH group of serine or threonine (which have similar sidechains). At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK). Serine/Threonine Kinase receptors play a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell differentiation, and embryonic development.

Reference
Wiki: Threonine phosphorylation

    SUMO proteins are similar to ubiquitin, and SUMOylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. In contrast to ubiquitin, SUMO is not used to tag proteins for degradation. Mature SUMO is produced when the last four amino acids of the C-terminus have been cleaved off to allow formation of an isopeptide bond between the C-terminal glycine residue of SUMO and an acceptor lysine on the target protein.

Reference
Wiki: SUMOylation

    Hydrogen sulfide (H2S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H2S acts. Ion channels and neuronal receptors are key target proteins for S-sulfhydration and this can influence a range of neuronal functions. Voltage-gated K+ channels, including Kv2.1, are fundamental components of neuronal excitability.

Reference
Pubmed: Dallas ML, Al-Owais MM, Hettiarachchi NT, Vandiver MS, Jarosz-Griffiths HH, Scragg JL, Boyle JP, Steele D, Peers C. Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1. Sci Rep. 2021 Apr 14;11(1):8194. doi: 10.1038/s41598-021-87646-5.

    Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the installation of a sulfate-like group on a substrate leads to substantial changes.

Reference
Wiki: Sulfation

    In biochemistry, succinylation is a posttranslational modification where a succinyl group (?CO?CH2?CH2?CO2H) is added to a lysine residue of a protein molecule. This modification is found in many proteins, including histones. The potential role of succinylation is under investigation, but as addition of succinyl group changes lysine's charge from +1 to ?1 (at physiological pH) and introduces a relatively large structural moiety (100 Da), bigger than acetylation (42 Da) or methylation (14 Da), it is expected to lead to more significant changes in protein structure and function. By analogy to acetylation, it has been suggested that succinyl-CoA is the cofactor of enzyme-mediated lysine succinylation.

Reference
Wiki: Succinylation

    Serotonylation is a receptor independent signaling mechanism by which serotonin activates intracellular processes by creating long lasting covalent bonds upon proteins. It occurs through the modification of proteins by the attachment of serotonin on their glutamine residues. This happens through the enzyme transglutaminase and the creation of glutamyl-amide bonds. This process occurs following serotonin transportation into the cell rather on plasma membranes as with the brief interactions that serotonin has when it activates 5-HT receptors.

Reference
Wiki: Serotonylation

    Protein phosphorylation is a reversible post-translational modification of proteins in which an amino acid residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. Phosphorylation alters the structural conformation of a protein, causing it to become activated, deactivated, or otherwise modifying its function.[1] Approximately 13,000 human proteins have sites that are phosphorylated.

Reference
Wiki: Serine phosphorylation

    S-palmitoylation is generally done by proteins with the DHHC domain. Exceptions exist in non-enzymatic reactions. Acyl-protein thioesterase (APT) catalyses the reverse reaction. Other acyl groups such as stearate (C18:0) or oleate (C18:1) are also frequently accepted, more so in plant and viral proteins, making S-acylation a more useful name.

Reference
Wiki: S-palmitoylation

    In biochemistry, S-nitrosylation is the covalent attachment of a nitric oxide group (?NO) to a cysteine thiol within a protein to form an S-nitrosothiol (SNO). S-Nitrosylation has diverse regulatory roles in bacteria, yeast and plants and in all mammalian cells. It thus operates as a fundamental mechanism for cellular signaling across phylogeny and accounts for the large part of NO bioactivity.

Reference
Wiki: S-Nitrosylation

    Proteins that contain cysteine (Cys) residues normally contain either intrachain or interchain or both intrachain and interchain disulfide bonds. Such Cys residues of proteins are commonly called as paired Cys residues. Some proteins contain free Cys residues that may be due to structural constraints of disulfide bond formation. The free Cys residues of proteins are often referred as unpaired Cys residues. The unpaired Cys residues often form disulfide bonds with free Cys molecules, and such a process is called cysteinylation. In some proteins, trisulfide bond formation between two internal Cys residues of proteins with one free Cys molecule is observed.

Reference
Wiley Online Library: S-Cysteinylation

    S-acylation is the process of chemically linking a molecule to another molecule via a thioester bond. Protein S-acylation is a sub-type of S-acylation where the first of those molecules is a protein, and connected to the second through a cysteine amino acid. A prominent type of protein S-acylation is palmitoylation, which promotes lipid membrane association of the protein, for instance to the plasma membrane, Golgi apparatus or inner nuclear membrane.

Reference
Wiki: S-acylation

    Propionylation is a post-translational modification of proteins, in which a propionyl-group is added to a lysine amino acid of a protein. Propionylation participates in crucial biological processes, including metabolic processes and cellular stress response. Lysine propionylation was first identified on histone proteins, and since has also been identified on other proteins. Histone propionylation is a mark of active chromatin. The substrate for protein propionylation is propionyl-CoA. Propionyl-CoA in the cell is metabolised by the enzyme propionyl-CoA carboxylase. Accumulation of propionyl-CoA leads to increased protein propionylation. In patients with propionic acidemia, a rare autosomal recessive metabolic disorder, propionyl-CoA levels elevated and increased propionylation, which might contribute to the pathology in these patients.

Reference
Wiki: Propionylation

    Polyubiquitination is the formation of a ubiquitin chain on a single lysine residue on the substrate protein. Following addition of a single ubiquitin moiety to a protein substrate, further ubiquitin molecules can be added to the first, yielding a polyubiquitin chain. These chains are made by linking the glycine residue of a ubiquitin molecule to a lysine of ubiquitin bound to a substrate. Ubiquitin has seven lysine residues and an N-terminus that may serve as points of ubiquitination; they are K6, K11, K27, K29, K33, K48, and K63. Lysine 48-linked chains were the first identified and are the best-characterised type of ubiquitin chain. K63 chains have also been well-characterised, whereas the function of other lysine chains, mixed chains, branched chains, N-terminal linear chains, and heterologous chains (mixtures of ubiquitin and other ubiquitin-like proteins) remains more unclear.

Reference
Wiki: Polyubiquitination

    Poly(ADP-ribose)polymerases (PARPs) are found mostly in eukaryotes and catalyze the transfer of multiple ADP-ribose molecules to target proteins. As with mono(ADP-ribosyl)ation, the source of ADP-ribose is NAD+. PARPs use a catalytic triad of His-Tyr-Glu to facilitate binding of NAD+ and positioning of the end of the existing poly(ADP-ribose) chain on the target protein; the Glu facilitates catalysis and formation of a (1''¡ú2') O-glycosidic linkage between two ribose molecules. There are several other enzymes that recognize poly(ADP-ribose) chains, hydrolyse them or form branches; over 800 proteins have been annotated to contain the loosely defined poly(ADP-ribose) binding motif; therefore, in addition to this modification altering target protein conformation and structure, it may also be used as a tag to recruit other proteins or for regulation of the target protein.

Reference
Wiki: Poly(ADP-ribosyl)ation

    In biochemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology. Protein phosphorylation often activates (or deactivates) many enzymes.

Reference
Wiki: Phosphorylation

    Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (S-palmitoylation) and less frequently to serine and threonine (O-palmitoylation) residues of proteins, which are typically membrane proteins. The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their membrane association. Palmitoylation also appears to play a significant role in subcellular trafficking of proteins between membrane compartments, as well as in modulating protein¨Cprotein interactions. In contrast to prenylation and myristoylation, palmitoylation is usually reversible (because the bond between palmitic acid and protein is often a thioester bond). The reverse reaction in mammalian cells is catalyzed by acyl-protein thioesterases (APTs) in the cytosol and palmitoyl protein thioesterases in lysosomes. Because palmitoylation is a dynamic, post-translational process, it is believed to be employed by the cell to alter the subcellular localization, protein¨Cprotein interactions, or binding capacities of a protein.

Reference
Wiki: Palmitoylation

    Redox (reduction¨Coxidation or oxidation¨Creduction) is a type of chemical reaction in which the oxidation states of a reactant change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a decrease in the oxidation state.

Reference
Wiki: Oxidation

    Octanoylation is a rare process in nature and several of the octanoyltransferases known to date are involved in fatty acid metabolism. LipB (EC 2.3.1.181) participates in the synthesis of lipoic acid, a highly conserved organosulfur cofactor derived from octanoic acid, which is essential in aerobic bacteria and eukaryotes49.

Reference
Pubmed: Maranha A, Moynihan PJ, Miranda V, Correia Louren?o E, Nunes-Costa D, Fraga JS, Jos¨¦ Barbosa Pereira P, Macedo-Ribeiro S, Ventura MR, Clarke AJ, Empadinhas N. Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides. Sci Rep. 2015 Sep 1;5:13610. doi: 10.1038/srep13610.

    O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm.Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility.Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia,Neisseria gonorrhoeae and Acinetobacter baumannii.

Reference
Wiki: O-linked glycosylation

    Neddylation (also NEDDylation) is the process by which the ubiquitin-like protein NEDD8 is conjugated to its target proteins. This process is analogous to ubiquitination, although it relies on its own E1 and E2 enzymes. No NEDD8-specific E3 has yet been identified and it is possible that the Neddylation system relies on E3 ligases with dual specificity.

Reference
Wiki: Neddylation

    Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases (NMTs), which are ubiquitous enzymes in eukaryotes. Specifically, attachment of a myristoyl group is vital for proteins participating in various biological functions, including signal transduction, cellular localization, and oncogenesis. Recent studies have revealed unexpected mechanisms indicating that protein N-myristoylation is involved in host defense against microbial and viral infections.

Reference
Pubmed: Wang B, Dai T, Sun W, Wei Y, Ren J, Zhang L, Zhang M, Zhou F. Protein N-myristoylation: functions and mechanisms in control of innate immunity. Cell Mol Immunol. 2021 Apr;18(4):878-888. doi: 10.1038/s41423-021-00663-2.

    N-linked glycosylation, is the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom (the amide nitrogen of an asparagine (Asn) residue of a protein), in a process called N-glycosylation, studied in biochemistry. The resulting protein is called an N-linked glycan, or simply an N-glycan.

Reference
Wiki: N-linked glycosylation

    Monoubiquitination is the addition of one ubiquitin molecule to one substrate protein residue. Multi-monoubiquitination is the addition of one ubiquitin molecule to multiple substrate residues. The monoubiquitination of a protein can have different effects to the polyubiquitination of the same protein. The addition of a single ubiquitin molecule is thought to be required prior to the formation of polyubiquitin chains. Monoubiquitination affects cellular processes such as membrane trafficking, endocytosis and viral budding.

Reference
Wiki: Monoubiquitination

    During the transportation from the cytosol, then the nucleus, and then to incorporate new chromatin at the replication fork, histones receive more modifications like monomethylation of lysine 9.

Reference
Wiki: Monomethylation

    Mono(ADP-ribosyl)transferases commonly catalyze the addition of ADP-ribose to arginine side chains using a highly conserved R-S-EXE motif of the enzyme. The reaction proceeds by breaking the bond between nicotinamide and ribose to form an oxonium ion. Next, the arginine side chain of the target protein then acts a nucleophile, attacking the electrophilic carbon adjacent to the oxonium ion. In order for this step to occur, the arginine nucleophile is deprotonated by a glutamate residue on the catalyzing enzyme[disputed ¨C discuss]. Another conserved glutamate residue forms a hydrogen bond with one of the hydroxyl groups on the ribose chain to further facilitate this nucleophilic attack. As a result of the cleavage reaction, nicotinamide is released. The modification can be reversed by (ADP-ribosyl)hydrolases, which cleave the N-glycosidic bond between arginine and ribose to release ADP-ribose and unmodified protein; NAD+ is not restored by the reverse reaction.

Reference
Wiki: Mono(ADP-ribosyl)ation

    Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and biology. In biological systems, methylation is catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA processing. In vitro methylation of tissue samples is also a way to reduce some histological staining artifacts. The reverse of methylation is demethylation.

Reference
Wiki: Methylation

    Protein malonylation, a reversible post-translational modification of lysine residues, is associated with various biological functions, such as cellular regulation and pathogenesis. In proteomics, to improve our understanding of the mechanisms of malonylation at the molecular level, the identification of malonylation sites via an efficient methodology is essential. However, experimental identification of malonylated substrates via mass spectrometry is time-consuming, labor-intensive, and expensive.

Reference
Pubmed: Chung CR, Chang YP, Hsu YL, Chen S, Wu LC, Horng JT, Lee TY. Incorporating hybrid models into lysine malonylation sites prediction on mammalian and plant proteins. Sci Rep. 2020 Jun 29;10(1):10541. doi: 10.1038/s41598-020-67384-w.

    Protein lysine methylation, is a PTM involving the transfer of one, two or three methyl groups to the epsilon - amine of a lysine side chain. Lysine methylation represents a complex and often elusive PTM that has nonetheless the potential to alter the function of the modified protein. lysine methylation has been observed in both nuclear and cytoplasmic proteins and is now considered a prevalent modification in eukaryotes, prokaryotes and archaea. Two groups of enzymes, both using S - adenosyl - L - methionine (SAM) as a methyl donor, catalyze the addition of a methyl group to the epsilon - amine group of a lysine side chain. The first type of protein lysine methyltransferase regroups the enzymes containing a catalytic SET domain and the second class of PKMTs, the seven beta - strand methyltransferases (class I methyltransferases), belongs to an extended superfamily of methyltransferases found throughout eukaryotes, prokaryotes and archaea.

Reference
Wiki: Lysine methylation

    Histone lactylation is the addition of a lactyl group to lysine residues in histone proteins, derived from the metabolite lactate.

Reference
Pubmed: Izzo LT, Wellen KE. Histone lactylation links metabolism and gene regulation. Nature. 2019 Oct;574(7779):492-493. doi: 10.1038/d41586-019-03122-1.

    Here, we report that INH and its metabolites induce a post-translational modification (PTM) of histones, lysine isonicotinylation (Kinic), also called 4-picolinylation, in cells and mice. INH promotes the biosynthesis of isonicotinyl-CoA (Inic-CoA), a co-factor of intracellular isonicotinylation.

Reference
Pubmed: Jiang Y, Li Y, Liu C, Zhang L, Lv D, Weng Y, Cheng Z, Chen X, Zhan J, Zhang H. Isonicotinylation is a histone mark induced by the anti-tuberculosis first-line drug isoniazid. Nat Commun. 2021 Sep 20;12(1):5548. doi: 10.1038/s41467-021-25867-y.

    Here we show that disruption of SPPL3 caused CD19 hyperglycosylation which impairs the binding of anti-CD19 antibodies and impairs CAR T cell activation, thus enabling resistance to CAR therapy. We identify that hyperglycosylation of an asparagine residue proximal to the CAR binding epitope is directly responsible for enabling resistance.

Reference
Pubmed: Heard A, Landmann JH, Hansen AR, Papadopolou A, Hsu YS, Selli ME, Warrington JM, Lattin J, Chang J, Ha H, Haug-Kroeper M, Doray B, Gill S, Ruella M, Hayer KE, Weitzman MD, Green AM, Fluhrer R, Singh N. Antigen glycosylation regulates efficacy of CAR T cells targeting CD19. Nat Commun. 2022 Jun 11;13(1):3367. doi: 10.1038/s41467-022-31035-7.

    Protein hydroxylation is a post-translational modification catalyzed by 2-oxoglutarate-dependent dioxygenases. The hydroxylation modification can take place on various amino acids, including but not limited to proline, lysine, asparagine, aspartate and histidine.

Reference
Pubmed: Zurlo G, Guo J, Takada M, Wei W, Zhang Q. New Insights into Protein Hydroxylation and Its Important Role in Human Diseases. Biochim Biophys Acta. 2016 Dec;1866(2):208-220. doi: 10.1016/j.bbcan.2016.09.004.

    Glycosylphosphatidylinositol or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide variety of biological processes. GPI is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker (glucosamine and mannose glycosidically bound to the inositol residue) and via an ethanolamine phosphate (EtNP) bridge to the C-terminal amino acid of a mature protein. The two fatty acids within the hydrophobic phosphatidyl-inositol group anchor the protein to the cell membrane.

Reference
Wiki: GPI-anchor

    Glycosylation is the reaction in which a carbohydrate (or 'glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not always in chemistry), glycosylation usually refers to an enzyme-catalysed reaction, whereas glycation (also 'non-enzymatic glycation' and 'non-enzymatic glycosylation') may refer to a non-enzymatic reaction.

Reference
Wiki: Glycosylation

    Glycation (non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging. Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus. In contrast with glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to protein or lipid. Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein.

Reference
Wiki: Glycation

    S-Glutathionylation is the posttranslational modification of protein cysteine residues by the addition of glutathione, the most abundant and important low-molecular-mass thiol within most cell types.

Reference
Wiki: Glutathionylation

    Post-translational modifications (PTMs) dynamically regulate cellular processes. Lysine undergoes a range of acylations, including malonylation, succinylation (SucK) and glutarylation (GluK). These PTMs increase the size of the lysine side chain and reverse its charge from +1 to ?1 under physiological conditions, probably impacting protein structure and function. To understand the functional roles of these PTMs, homogeneously modified proteins are required for biochemical studies.

Reference
Pubmed: Weyh M, Jokisch ML, Nguyen TA, Fottner M, Lang K. Deciphering functional roles of protein succinylation and glutarylation using genetic code expansion. Nat Chem. 2024 Mar 26. doi: 10.1038/s41557-024-01500-5.

    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(s) at the C-terminus of specific proteins. Prenylation (including geranylgeranylation) is thought to function, at least in part, as a membrane anchor for proteins.

Reference
Wiki: Geranylgeranylation

    Carboxyglutamic acid (or the conjugate base, carboxyglutamate), is an uncommon amino acid introduced into proteins by a post-translational carboxylation of glutamic acid residues. This modification is found, for example, in clotting factors and other proteins of the coagulation cascade. This modification introduces an affinity for calcium ions. In the blood coagulation cascade, vitamin K is required to introduce ¦Ã-carboxylation of clotting factors II, VII, IX, X and protein Z.

Reference
Wiki: Gamma-carboxylation

    An isopeptide bond is a type of amide bond formed between a carboxyl group of one amino acid and an amino group of another. An isopeptide bond is the linkage between the side chain amino or carboxyl group of one amino acid to the ¦Á-carboxyl, ¦Á-amino group, or the side chain of another amino acid. In a typical peptide bond, also known as eupeptide bond, the amide bond always forms between the ¦Á-carboxyl group of one amino acid and the ¦Á-amino group of the second amino acid. Isopeptide bonds are rarer than regular peptide bonds. Isopeptide bonds lead to branching in the primary sequence of a protein. Proteins formed from normal peptide bonds typically have a linear primary sequence.

Reference
Wiki: Formation of an isopeptide bond

    Prenylation (also known as isoprenylation or lipidation) is the addition of hydrophobic molecules to a protein or a biomolecule. It is usually assumed that prenyl groups (3-methylbut-2-en-1-yl) facilitate attachment to cell membranes, similar to lipid anchors like the GPI anchor, though direct evidence of this has not been observed. Prenyl groups (also called isoprenyl groups, having one hydrogen atom more than isoprene) have been shown to be important for protein¨Cprotein binding through specialized prenyl-binding domains.Farnesylation is a type of prenylation, a post-translational modification of proteins by which an isoprenyl group is added to a cysteine residue. It is an important process to mediate protein¨Cprotein interactions and protein¨Cmembrane interactions.

Reference
Wiki: Farnesylation

    In particular, dimethylation and trimethylation of lysine side chains in proteins increase both hydrophobicity and steric bulk and can affect protein¨Cprotein interactions if they are in an interacting surface.

Reference
Wiki: Dimethylation

    Deubiquitinating enzymes (deubiquitinases; DUBs) oppose the role of ubiquitylation by removing ubiquitin from substrate proteins. They are cysteine proteases that cleave the amide bond between the two proteins. They are highly specific, as are the E3 ligases that attach the ubiquitin, with only a few substrates per enzyme. They can cleave both isopeptide (between ubiquitin and lysine) and peptide bonds (between ubiquitin and the N-terminus). In addition to removing ubiquitin from substrate proteins, DUBs have many other roles within the cell. Ubiquitin is either expressed as multiple copies joined in a chain (polyubiquitin) or attached to ribosomal subunits. DUBs cleave these proteins to produce active ubiquitin. They also recycle ubiquitin that has been bound to small nucleophilic molecules during the ubiquitylation process. Monoubiquitin is formed by DUBs that cleave ubiquitin from free polyubiquitin chains that have been previously removed from proteins.

Reference
Wiki: Deubiquitination

    In biochemistry, succinylation is a posttranslational modification where a succinyl group (?CO?CH2?CH2?CO2H) is added to a lysine residue of a protein molecule. This modification is found in many proteins, including histones. The potential role of succinylation is under investigation, but as addition of succinyl group changes lysine's charge from +1 to ?1 (at physiological pH) and introduces a relatively large structural moiety (100 Da), bigger than acetylation (42 Da) or methylation (14 Da), it is expected to lead to more significant changes in protein structure and function. By analogy to acetylation, it has been suggested that succinyl-CoA is the cofactor of enzyme-mediated lysine succinylation.

Reference
Wiki: Desuccinylation

    In biochemistry, dephosphorylation is the removal of a phosphate (PO43?) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deactivate enzymes by detaching or attaching phosphoric esters and anhydrides. A notable occurrence of dephosphorylation is the conversion of ATP to ADP and inorganic phosphate. Dephosphorylation employs a type of hydrolytic enzyme, or hydrolase, which cleaves ester bonds. The prominent hydrolase subclass used in dephosphorylation is phosphatase, which removes phosphate groups by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl (-OH) group. The reversible phosphorylation-dephosphorylation reaction occurs in every physiological process, making proper function of protein phosphatases necessary for organism viability. Because protein dephosphorylation is a key process involved in cell signalling, protein phosphatases are implicated in conditions such as cardiac disease, diabetes, and Alzheimer's disease.

Reference
Wiki: Dephosphorylation

    PARylation is a transient posttranslational modification and is quickly degraded by dePARylation enzymes, such as poly(ADP-ribose) glycohydrolase (PARG) . PARG specifically hydrolyzes the glycosidic bonds between ADP-ribose units in PAR chains and is the major dePARylation enzyme that accounts for ~90% of dePARylation activity . Notably, similar to PARPs, PARG also facilitates both DNA double-strand break (DSB) and single-strand break (SSB) repair . Following DNA damage, a number of DNA damage response factors recognize PARylation and are recruited by PARylation to the proximity of DNA lesions . However, PARylation has to be digested so that DNA damage machinery directly recognizes DNA lesions and repairs lesions . Otherwise, the repair machineries will be trapped by PARylation at the vicinity of DNA lesions. Thus, dePARylation is an immediate downstream step of PARylation in DNA repair, and suppression of dePARylation will affect PARylation-dependent DNA repair. It indicates that targeting dePARylation, similar to targeting PARPs, may selectively kill tumor cells with DNA repair defects.

Reference
Pubmed: Chen SH, Yu X. Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies. Sci Adv. 2019 Apr 10;5(4):eaav4340. doi: 10.1126/sciadv.aav4340.

    Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (S-palmitoylation) and less frequently to serine and threonine (O-palmitoylation) residues of proteins, which are typically membrane proteins. The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their membrane association. Palmitoylation also appears to play a significant role in subcellular trafficking of proteins between membrane compartments, as well as in modulating protein¨Cprotein interactions. In contrast to prenylation and myristoylation, palmitoylation is usually reversible (because the bond between palmitic acid and protein is often a thioester bond). The reverse reaction in mammalian cells is catalyzed by acyl-protein thioesterases (APTs) in the cytosol and palmitoyl protein thioesterases in lysosomes. Because palmitoylation is a dynamic, post-translational process, it is believed to be employed by the cell to alter the subcellular localization, protein¨Cprotein interactions, or binding capacities of a protein.

Reference
Wiki: Depalmitoylation

    Neddylation (also NEDDylation) is the process by which the ubiquitin-like protein NEDD8 is conjugated to its target proteins. This process is analogous to ubiquitination, although it relies on its own E1 and E2 enzymes. No NEDD8-specific E3 has yet been identified and it is possible that the Neddylation system relies on E3 ligases with dual specificity.

Reference
Wiki: Deneddylation

    Demethylation is the chemical process resulting in the removal of a methyl group (CH3) 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. The counterpart of demethylation is methylation.

Reference
Wiki: Demethylation

    Glycosylphosphatidylinositol or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide variety of biological processes. GPI is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker (glucosamine and mannose glycosidically bound to the inositol residue) and via an ethanolamine phosphate (EtNP) bridge to the C-terminal amino acid of a mature protein. The two fatty acids within the hydrophobic phosphatidyl-inositol group anchor the protein to the cell membrane.

Reference
Wiki: DeGPI-anchor

    There are different enzymes to remove the glycans from the proteins or remove some part of the sugar chain. ¦Á2-3,6,8,9-Neuraminidase (from Arthrobacter ureafaciens): cleaves all non-reducing terminal branched and unbranched sialic acids. ¦Â1,4-Galactosidase (from Streptococcus pneumoniae): releases only ¦Â1,4-linked, nonreducing terminal galactose from complex carbohydrates and glycoproteins. ¦Â-N-Acetylglucosaminidase (from Streptococcus pneumoniae): cleaves all non-reducing terminal ¦Â-linked N-acetylglucosamine residues from complex carbohydrates and glycoproteins. endo-¦Á-N-Acetylgalactosaminidase (O-glycosidase from Streptococcus pneumoniae): removes O-glycosylation. This enzyme cleaves serine- or threonine-linked unsubstituted Gal¦Â1,3GalNAc PNGase F: cleaves asparagine-linked oligosaccharides unless ¦Á1,3-core fucosylated.

Reference
Wiki: Deglycosylation

    Glycation (non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging. Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus. In contrast with glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to protein or lipid. Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein.

Reference
Wiki: Deglycation

    Post-translational modifications (PTMs) dynamically regulate cellular processes. Lysine undergoes a range of acylations, including malonylation, succinylation (SucK) and glutarylation (GluK). These PTMs increase the size of the lysine side chain and reverse its charge from +1 to ?1 under physiological conditions, probably impacting protein structure and function. To understand the functional roles of these PTMs, homogeneously modified proteins are required for biochemical studies.

Reference
Pubmed: Weyh M, Jokisch ML, Nguyen TA, Fottner M, Lang K. Deciphering functional roles of protein succinylation and glutarylation using genetic code expansion. Nat Chem. 2024 Mar 26. doi: 10.1038/s41557-024-01500-5.

    Lysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon¨Ccarbon ¦Ð-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation.

Reference
Pubmed: Jiang G, Li C, Lu M, Lu K, Li H. Protein lysine crotonylation: past, present, perspective. Cell Death Dis. 2021 Jul 14;12(7):703. doi: 10.1038/s41419-021-03987-z.

    Deamidation is a chemical reaction in which an amide functional group in the side chain of the amino acids asparagine or glutamine is removed or converted to another functional group. Typically, asparagine is converted to aspartic acid or isoaspartic acid. Glutamine is converted to glutamic acid or pyroglutamic acid (5-oxoproline). In a protein or peptide, these reactions are important because they may alter its structure, stability or function and may lead to protein degradation. The net chemical change is the addition of a water group and removal of an ammonia group, which corresponds to a +1 (0.98402) Da mass increase. Although deamidation occurs on glutamine, glycosylated asparagine and other amides, these are negligible under typical proteolysis conditions.

Reference
Wiki: Deamidation

    In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed acetate esters or simply acetates. Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound.

Reference
Wiki: Deacetylation

    Lysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon¨Ccarbon ¦Ð-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation.

Reference
Pubmed: Jiang G, Li C, Lu M, Lu K, Li H. Protein lysine crotonylation: past, present, perspective. Cell Death Dis. 2021 Jul 14;12(7):703. doi: 10.1038/s41419-021-03987-z.

    Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. Citrulline is not one of the 20 standard amino acids encoded by DNA in the genetic code. Instead, it is the result of a post-translational modification. Citrullination is distinct from the formation of the free amino acid citrulline as part of the urea cycle or as a byproduct of enzymes of the nitric oxide synthase family.

Reference
Wiki: Citrullination

    Furthermore, chemical modification of RNA such as carboxymethylation is possible when traces of DEPC or its byproducts are present, resulting in impaired recovery of intact RNA even after buffer exchange (after precipitation).

Reference
Wiki: Carboxymethylation

    C-linked glycosylation is essential for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. The tryptophan C-mannosyltransferase (CMT) enzymes that install the modification attach a mannose to the first tryptophan of WxxW/C sequons in nascent polypeptide chains by an unknown mechanism.

Reference
Pubmed: Bloch JS, John A, Mao R, Mukherjee S, Boilevin J, Irobalieva RN, Darbre T, Scott NE, Reymond JL, Kossiakoff AA, Goddard-Borger ED, Locher KP. Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. Nat Chem Biol. 2023 May;19(5):575-584. doi: 10.1038/s41589-022-01219-9.

    Lysine butyrylation (Kbu) is a novel PTM that is found in histone and nonhistone proteins8. Kbu has been identified in fungi, plants and animals9,10,11, but a global landscape of nonhistone protein Kbu modification in humans is lacking. More importantly, the writer and eraser responsible for Kbu deposition and removal in humans, respectively, have not been reported.

Reference
Pubmed: He Y, Zheng CC, Yang J, Li SJ, Xu TY, Wei X, Chen WY, Jiang ZL, Xu JJ, Zhang GG, Cheng C, Chen KS, Shi XY, Qin DJ, Liu JB, Li B. Lysine butyrylation of HSP90 regulated by KAT8 and HDAC11 confers chemoresistance. Cell Discov. 2023 Jul 18;9(1):74. doi: 10.1038/s41421-023-00570-y.

    Analysis of monoglycosylceramides can be done by high-resolution thin-layer chromatography, high-performance liquid chromatography (HPLC), and mass spectrometry. Reversed-phase HPLC is now the standard method for separation of molecular species, often after benzoylation, enabling lipids to be detected by UV spectrophotometry.

Reference
Wiki: Benzoylation

    The autoubiquitination activity of BCA2, RING-H2 mutant, BZF mutant, and various lysine mutants of BCA2 were investigated. Our results indicate that the BCA2 protein is strongly ubiquitinated and no ubiquitination is detected with the BCA2 RING-H2 mutant, indicating that the RING domain is essential for autoubiquitination.

Reference
Pubmed: Amemiya Y, Azmi P, Seth A. Autoubiquitination of BCA2 RING E3 ligase regulates its own stability and affects cell migration. Mol Cancer Res. 2008 Sep;6(9):1385-96. doi: 10.1158/1541-7786.MCR-08-0094.

    Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself. In eukaryotes, this process occurs by the addition of a phosphate group to serine, threonine or tyrosine residues within protein kinases, normally to regulate the catalytic activity. Autophosphorylation may occur when a kinases' own active site catalyzes the phosphorylation reaction (cis autophosphorylation), or when another kinase of the same type provides the active site that carries out the chemistry (trans autophosphorylation). The latter often occurs when kinase molecules dimerize. In general, the phosphate groups introduced are gamma phosphates from nucleoside triphosphates, most commonly ATP.

Reference
Wiki: Autophosphorylation

    The Metnase SET domain is not only responsible for dimethylation of H3K36 but also crucial for automethylation at K485 within the catalytic pocket.

Reference
Pubmed: Kim HS, Kim SK, Hromas R, Lee SH. The SET Domain Is Essential for Metnase Functions in Replication Restart and the 5' End of SS-Overhang Cleavage. PLoS One. 2015 Oct 5;10(10):e0139418. doi: 10.1371/journal.pone.0139418.

    Arginine methylation is a prevalent post-translational modification found on both nuclear and cytoplasmic proteins. The methylation of arginine residues is catalyzed by the protein arginine Nmethyltransferase (PRMT) family of enzymes. Proteins that are arginine methylated are involved in a number of different cellular processes, including transcriptional regulation, RNA metabolism and DNA damage repair (Bedford and Richard, 2005). Most PRMTs methylate glycine- and arginine-rich patches (GAR motifs) within their substrates.

Reference
Wiki: Arginine methylation

    In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed acetate esters or simply acetates. Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound.

Reference
Wiki: Acetylation

    Recent studies, and evolutionary advances seen within prokaryotes, show that CobB is an enzyme that removes a chemical modification called Khib ( de-2-hydroxyisobutyrylation) from lysine, an amino acid found in proteins. Khib is a type of histone mark that affects how DNA is packaged and expressed. CobB can also remove another modification called Kac (acetylation) from lysine. CobB binds to Khib using a special peptide probe and can change the activity of proteins involved in glycolysis, a process that breaks down sugar for energy. Researchers found that 99 endogenous substrates were targeted by CobB for de-2-hydroxyisobutyrylation. Researchers have demonstrated that CobB affects the growth of bacteria by altering the function of enolase (ENO), a key enzyme in glycolysis. It does so by removing K343hib and K326ac of ENO simultaneously. Come to find out CobB is the first enzyme known to remove Khib from proteins. This may change soon as research continues to explore more of CobB as well as the advancements within technology.

Reference
Wiki: 2-Hydroxyisobutyrylation