Target type: biologicalprocess
The addition of a methyl group to a protein amino acid. A methyl group is derived from methane by the removal of a hydrogen atom. [GOC:ai]
Protein methylation is a crucial post-translational modification where a methyl group (CH3) is added to a specific amino acid residue within a protein. This process is catalyzed by enzymes called methyltransferases, which utilize S-adenosyl methionine (SAM) as a methyl donor. The addition of a methyl group can alter the protein's structure, function, and interactions with other molecules.
The process of protein methylation can be broadly divided into three steps:
1. **Recognition and Binding:** The methyltransferase recognizes and binds to the specific target protein and its corresponding amino acid residue. This recognition is often mediated by specific interactions between the enzyme and the protein's amino acid sequence and structure.
2. **Methyl Group Transfer:** The methyltransferase transfers a methyl group from SAM to the target amino acid residue. This transfer involves a complex series of chemical reactions that involve the formation of a covalent bond between the methyl group and the amino acid.
3. **Product Release and Regeneration:** After the methylation reaction is complete, the methyltransferase releases the modified protein and SAM, which is now in its demethylated form (S-adenosyl homocysteine). SAM can be regenerated by a series of enzymatic reactions, allowing for continued methylation.
Protein methylation can occur on various amino acid residues, including lysine, arginine, histidine, and glutamate. The specific amino acid residue targeted for methylation can influence the protein's function.
**Lysine methylation:** Often found in histone proteins, lysine methylation plays a crucial role in gene regulation. It can activate or repress gene expression depending on the specific lysine residue and the number of methyl groups added.
**Arginine methylation:** Predominantly found in signaling proteins, arginine methylation can alter protein-protein interactions and signaling pathways.
**Histidine methylation:** Less common compared to lysine and arginine methylation, histidine methylation is involved in diverse cellular processes, including signal transduction and DNA repair.
**Glutamate methylation:** A relatively new discovery, glutamate methylation has been implicated in neuronal function and synaptic plasticity.
Protein methylation is a highly dynamic process, with specific methyltransferases and demethylases (enzymes that remove methyl groups) controlling the methylation state of proteins. This reversible nature allows for precise regulation of protein function and cellular processes.
Protein methylation is essential for a wide range of biological functions, including:
* **Gene regulation:** Controlling gene expression through modifications of histone proteins
* **Signal transduction:** Modulating signaling pathways by altering protein-protein interactions
* **Cellular development:** Regulating cell growth, differentiation, and apoptosis
* **Immune response:** Influencing immune cell function and activation
* **Disease pathogenesis:** Dysregulation of protein methylation is implicated in various diseases, such as cancer, neurological disorders, and autoimmune diseases.
Understanding the intricate mechanisms of protein methylation is crucial for elucidating the complexity of cellular processes and developing novel therapeutic strategies for various diseases.'
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Protein | Definition | Taxonomy |
---|---|---|
Protein arginine N-methyltransferase 3 | A protein arginine N-methyltransferase 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O60678] | Homo sapiens (human) |
Protein arginine N-methyltransferase 1 | A protein arginine N-methyltransferase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99873] | Homo sapiens (human) |
Protein-L-isoaspartate(D-aspartate) O-methyltransferase | A protein-L-isoaspartate(D-aspartate) O-methyltransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P22061] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
fluorescite | fluorescein (acid form) : A xanthene dye that is highly fluorescent and commonly used as a fluorescent tracer. | benzoic acids; cyclic ketone; hydroxy monocarboxylic acid; organic heterotricyclic compound; phenols; xanthene dye | fluorescent dye; radioopaque medium |
pentamidine | pentamidine : A diether consisting of pentane-1,5-diol in which both hydroxyl hydrogens have been replaced by 4-amidinophenyl groups. A trypanocidal drug that is used for treatment of cutaneous leishmaniasis and Chagas disease. Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. | aromatic ether; carboxamidine; diether | anti-inflammatory agent; antifungal agent; calmodulin antagonist; chemokine receptor 5 antagonist; EC 2.3.1.48 (histone acetyltransferase) inhibitor; NMDA receptor antagonist; S100 calcium-binding protein B inhibitor; trypanocidal drug; xenobiotic |
saccharin | saccharin : A 1,2-benzisothiazole having a keto-group at the 3-position and two oxo substituents at the 1-position. It is used as an artificial sweetening agent. Saccharin: Flavoring agent and non-nutritive sweetener. | 1,2-benzisothiazole; N-sulfonylcarboxamide | environmental contaminant; sweetening agent; xenobiotic |
suramin | suramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years. Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. | naphthalenesulfonic acid; phenylureas; secondary carboxamide | angiogenesis inhibitor; antinematodal drug; antineoplastic agent; apoptosis inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; GABA antagonist; GABA-gated chloride channel antagonist; purinergic receptor P2 antagonist; ryanodine receptor agonist; trypanocidal drug |
alizarin | dihydroxyanthraquinone | chromophore; dye; plant metabolite | |
7-amino-4-hydroxy-2-naphthalenesulfonic acid | 7-amino-4-hydroxy-2-naphthalenesulfonic acid : An aminonaphthalenesulfonic acid that is 2-naphthalenesulfonic acid substituted by an amino group at position 7 and a hydroxy group at position 4 respectively. 7-amino-4-hydroxy-2-naphthalenesulfonic acid: structure given in first source | aminonaphthalenesulfonic acid; naphthols | metabolite |
1-naphthol-8-amino-3,6-disulfonic acid | 1-naphthol-8-amino-3,6-disulfonic acid: dye and found in industrial waste | ||
methyl red | methyl red : An azo dye consisting of benzoic acid substituted at position 2 by a 4-[(dimethylamino)phenyl]diazenyl group. methyl red: RN given refers to parent cpd; structure | ||
s-adenosylmethionine | acylcarnitine: structure in first source S-adenosyl-L-methioninate : A sulfonium betaine that is a conjugate base of S-adenosyl-L-methionine obtained by the deprotonation of the carboxy group. | sulfonium betaine | human metabolite |
hexamidine | hexamidine : A polyether that is the bis(4-guanidinophenyl) ether of hexane-1,6-diol. | aromatic ether; guanidines; polyether | antimicrobial agent; antiseptic drug |
sinefungin | adenosines; non-proteinogenic alpha-amino acid | antifungal agent; antimicrobial agent | |
fluorone black | fluorone Black: structure | ||
c.i. direct red 23 | C.I. Direct Red 23: azo dye; structure in first source | ||
furamidine | furamidine: RN given refers to parent cpd; WR 199385 refers to di-HCl; pafuramidine is a prodrug of this | ||
s-adenosylhomocysteine | S-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine. S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions. | adenosines; amino acid zwitterion; homocysteine derivative; homocysteines; organic sulfide | cofactor; EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor; EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor; epitope; fundamental metabolite |
stilbamidine | stilbamidine: RN given refers to parent cpd | ||
mbx 1090 | |||
unc 0321 | 7-(2-(2-(dimethylamino)ethoxy)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine: a G9a antagonist; structure in first source | quinazolines | |
gsk343 | GSK343 : A member of the class of indazoles that is 1-isopropyl-1H-indazole-4-carboxamide in which the nitrogen of the carboxamide group is substituted by a (6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl group and in which the indazole ring is substituted at position 6 by a 2-(4-methylpiperazin-1-yl)pyridin-4-yl group. A highly potent and selective EZH2 inhibitor (IC50 = 4 nM). GSK343: an EZH2 methyltransferase inhibitor | aminopyridine; indazoles; N-alkylpiperazine; N-arylpiperazine; pyridone; secondary carboxamide | antineoplastic agent; apoptosis inducer; EC 2.1.1.43 (enhancer of zeste homolog 2) inhibitor |
6,7-dimethoxy-2-(pyrrolidin-1-yl)-n-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine | 6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine: a SETD8 inhibitor; structure in first source | ||
sgc707 |