Target type: biologicalprocess
The removal of a methyl group, from a protein amino acid. A methyl group is derived from methane by the removal of a hydrogen atom. [GOC:mah]
Protein demethylation is a crucial biological process that involves the removal of methyl groups from proteins. This process is catalyzed by enzymes called demethylases, which play vital roles in regulating various cellular functions, including gene expression, signal transduction, and protein stability.
Demethylation is a dynamic and reversible process that is tightly regulated by a complex interplay of factors, including the specific type of demethylase involved, the location of the methyl group on the protein, and the cellular context.
There are two main types of demethylases: histone demethylases and non-histone demethylases. Histone demethylases specifically target methyl groups on histone proteins, which are responsible for packaging and organizing DNA within the nucleus. These enzymes play a critical role in regulating gene expression by altering the accessibility of DNA to transcription factors.
Non-histone demethylases, on the other hand, remove methyl groups from a wide range of non-histone proteins. These enzymes are involved in diverse cellular processes, including cell signaling, metabolism, and protein stability.
The mechanism of protein demethylation involves the following steps:
1. **Recognition and Binding:** Demethylases bind to their target proteins, specifically recognizing the methylated lysine or arginine residues.
2. **Oxidation:** Demethylases utilize an oxidative reaction to remove the methyl group from the target residue. This typically involves the transfer of an oxygen atom from a cofactor, such as alpha-ketoglutarate, to the methyl group.
3. **Hydrolysis:** The oxidized methyl group is then hydrolyzed, resulting in the release of formaldehyde and the demethylated protein.
Protein demethylation plays a crucial role in various cellular processes, including:
* **Gene Expression Regulation:** Demethylation of histones can alter chromatin structure, making DNA more accessible to transcription factors and promoting gene expression.
* **Signal Transduction:** Demethylation of signaling proteins can modulate their activity, influencing downstream pathways and cellular responses.
* **Protein Stability:** Demethylation can affect protein stability by altering their interactions with other molecules or their susceptibility to degradation.
Dysregulation of protein demethylation has been implicated in a variety of diseases, including cancer, neurodevelopmental disorders, and immune disorders. Therefore, understanding the intricate mechanisms of protein demethylation is crucial for developing novel therapeutic strategies for these diseases.'
"
| Protein | Definition | Taxonomy |
|---|---|---|
| Lysine-specific demethylase 7A | A lysine-specific demethylase 7A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6ZMT4] | Homo sapiens (human) |
| Lysine-specific demethylase 2B | A lysine-specific demethylase 2B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8NHM5] | Homo sapiens (human) |
| Histone lysine demethylase PHF8 | A histone lysine demethylase PHF8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UPP1] | Homo sapiens (human) |
| Lysine-specific demethylase 2A | A lysine-specific demethylase 2A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y2K7] | Homo sapiens (human) |
| Protein phosphatase methylesterase 1 | A protein phosphatase methylesterase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y570] | Homo sapiens (human) |
| Lysine-specific demethylase PHF2 | A lysine-specific demethylase PHF2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O75151] | Homo sapiens (human) |
| Lysine-specific histone demethylase 1A | A lysine-specific histone demethylase 1A that is encoded in the genome of human. [PRO:DNx, UniProtKB:O60341] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
| berberine | alkaloid antibiotic; berberine alkaloid; botanical anti-fungal agent; organic heteropentacyclic compound | antilipemic drug; antineoplastic agent; antioxidant; EC 1.1.1.141 [15-hydroxyprostaglandin dehydrogenase (NAD(+))] inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.13.11.52 (indoleamine 2,3-dioxygenase) inhibitor; EC 1.21.3.3 (reticuline oxidase) inhibitor; EC 2.1.1.116 [3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase] inhibitor; EC 2.1.1.122 [(S)-tetrahydroprotoberberine N-methyltransferase] inhibitor; EC 2.7.11.10 (IkappaB kinase) inhibitor; EC 3.1.1.4 (phospholipase A2) inhibitor; EC 3.1.1.7 (acetylcholinesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor; EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; geroprotector; hypoglycemic agent; metabolite; potassium channel blocker | |
| deferiprone | deferiprone : A member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia. Deferiprone: A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA. | 4-pyridones | iron chelator; protective agent |
| phenelzine | Phenelzine: One of the MONOAMINE OXIDASE INHIBITORS used to treat DEPRESSION; PHOBIC DISORDERS; and PANIC. | primary amine | |
| raloxifene | raloxifene : A member of the class of 1-benzothiophenes that is 1-benzothiophene in which the hydrogens at positions 2, 3, and 6 have been replaced by p-hydroxyphenyl, p-[2-(piperidin-1-yl)ethoxy]benzoyl, and hydroxy groups, respectively. | 1-benzothiophenes; aromatic ketone; N-oxyethylpiperidine; phenols | bone density conservation agent; estrogen antagonist; estrogen receptor modulator |
| vorinostat | vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL). Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME. | dicarboxylic acid diamide; hydroxamic acid | antineoplastic agent; apoptosis inducer; EC 3.5.1.98 (histone deacetylase) inhibitor |
| succinylacetone | 4,6-dioxoheptanoic acid : A dioxo monocarboxylic acid that is heptanoic acid in which oxo groups replace the hydrogens at positions 4 and 6. It is an abnormal metabolite of the tyrosine metabolic pathway and a marker for type 1 tyrosinaemia. succinylacetone: inhibitor of heme biosynthesis | beta-diketone; dioxo monocarboxylic acid | human metabolite |
| 2-phenylcyclopropan-1-amine | 2-phenylcyclopropan-1-amine : A member of the class of cyclopropanes carrying amino and phenyl substituents at positions 1 and 2 respectively. | benzenes; cyclopropanes; primary amine | |
| 2,4-pyridinedicarboxylic acid | lutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4. | pyridinedicarboxylic acid | |
| hesperidin | hesperidin : A disaccharide derivative that consists of hesperetin substituted by a 6-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. Hesperidin: A flavanone glycoside found in CITRUS fruit peels. | 3'-hydroxyflavanones; 4'-methoxyflavanones; dihydroxyflavanone; disaccharide derivative; flavanone glycoside; monomethoxyflavanone; rutinoside | mutagen |
| daminozide | daminozide: induces tumors | straight-chain fatty acid | |
| palmatine | burasaine: structure in first source | berberine alkaloid; organic heterotetracyclic compound | plant metabolite |
| tranylcypromine | (1R,2S)-tranylcypromine : A 2-phenylcyclopropan-1-amine that is the (1R,2S)-enantiomer of tranylcypromine. tranylcypromine : A racemate comprising equal amounts of (1R,2S)- and (1S,2R)-2-phenylcyclopropan-1-amine. An irreversible monoamine oxidase inhibitor that is used as an antidepressant (INN tranylcypromine). Tranylcypromine: A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311) | 2-phenylcyclopropan-1-amine | |
| (1S,2R)-tranylcypromine | (1S,2R)-tranylcypromine : A 2-phenylcyclopropan-1-amine that is the (1S,2R)-enantiomer of tranylcypromine. | 2-phenylcyclopropan-1-amine | |
| dehydrocorydalin | dehydrocorydalin: alkaloid from Corydalis bulbuso D.C. used in therapy of peptic ulcer; RN given refers to parent cpd | alkaloid | |
| baicalin | dihydroxyflavone; glucosiduronic acid; glycosyloxyflavone; monosaccharide derivative | antiatherosclerotic agent; antibacterial agent; anticoronaviral agent; antineoplastic agent; antioxidant; cardioprotective agent; EC 2.7.7.48 (RNA-directed RNA polymerase) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; ferroptosis inhibitor; neuroprotective agent; non-steroidal anti-inflammatory drug; plant metabolite; prodrug | |
| hesperetin | 3'-hydroxyflavanones; 4'-methoxyflavanones; monomethoxyflavanone; trihydroxyflavanone | antineoplastic agent; antioxidant; plant metabolite | |
| columbamine | berberine alkaloid; organic heterotetracyclic compound | ||
| jatrorrhizine | jatrorrhizine: isolated from bark of Enantia chlorantha (Annonaceae); structure given in first source | alkaloid | |
| higenamine | higenamine: structure; RN given refers to (+-)-isomer | norcoclaurine | |
| tanshinone | tanshinone: from root of Salvia miltiorrhiza Bunge; RN given refers to tanshinone I; cardioprotective agent and neuroprotective agent | abietane diterpenoid | anticoronaviral agent |
| cryptotanshinone | cryptotanshinone: from Salvia miltiorrhiza | abietane diterpenoid | anticoronaviral agent |
| epiberberine | epiberberine: isolated in plants of Coptis from China | ||
| erlotinib | aromatic ether; quinazolines; secondary amino compound; terminal acetylenic compound | antineoplastic agent; epidermal growth factor receptor antagonist; protein kinase inhibitor | |
| d-2-hydroxyglutarate | (R)-2-hydroxyglutaric acid : The (R)-enantiomer of 2-hydroxyglutaric acid. | 2-hydroxyglutaric acid | algal metabolite |
| alpha-hydroxyglutarate, (l)-isomer | 2-hydroxyglutaric acid | ||
| resveratrol | trans-resveratrol : A resveratrol in which the double bond has E configuration. | resveratrol | antioxidant; phytoalexin; plant metabolite; quorum sensing inhibitor; radical scavenger |
| 5-carboxy-8-hydroxyquinoline | 5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first source | quinolines | |
| curcumin | curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa. Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. | aromatic ether; beta-diketone; diarylheptanoid; enone; polyphenol | anti-inflammatory agent; antifungal agent; antineoplastic agent; biological pigment; contraceptive drug; dye; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.1.1.25 (shikimate dehydrogenase) inhibitor; EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor; EC 1.8.1.9 (thioredoxin reductase) inhibitor; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; flavouring agent; food colouring; geroprotector; hepatoprotective agent; immunomodulator; iron chelator; ligand; lipoxygenase inhibitor; metabolite; neuroprotective agent; nutraceutical; radical scavenger |
| capsaicin | ALGRX-4975: an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief capsaicinoid : A family of aromatic fatty amides produced as secondary metabolites by chilli peppers. | capsaicinoid | non-narcotic analgesic; TRPV1 agonist; voltage-gated sodium channel blocker |
| (1R,2S)-tranylcypromine hydrochloride | (1R,2S)-tranylcypromine hydrochloride : A hydrochloride obtained by combining (1R,2S)-tranylcypromine with one equivalent of hydrochloric acid. | hydrochloride | |
| N5-(2-chloro-6-phenoxybenzyl)-1H-1,2,4-triazole-3,5-diamine | aromatic ether | ||
| mdl 72527 | MDL 72527: RN given refers to di-HCl; RN for parent cpd not available 6/85; polyamine oxidase inhibitor | ||
| oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |
| wogonoside | wogonin 7-O-beta-D-glucuronide : The glycosyloxyflavone which is the 7-O-glucuronide of wogonin. wogonoside: from Scutellaria baicalensis; structure in first source | beta-D-glucosiduronic acid; glycosyloxyflavone; monohydroxyflavone; monomethoxyflavone; monosaccharide derivative | |
| quercetin | 7-hydroxyflavonol; pentahydroxyflavone | antibacterial agent; antineoplastic agent; antioxidant; Aurora kinase inhibitor; chelator; EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor; geroprotector; phytoestrogen; plant metabolite; protein kinase inhibitor; radical scavenger | |
| biochanin a | 4'-methoxyisoflavones; 7-hydroxyisoflavones | antineoplastic agent; EC 3.5.1.99 (fatty acid amide hydrolase) inhibitor; phytoestrogen; plant metabolite; tyrosine kinase inhibitor | |
| quercetin 3-o-glucopyranoside | quercetin 3-O-beta-D-glucopyranoside : A quercetin O-glucoside that is quercetin with a beta-D-glucosyl residue attached at position 3. Isolated from Lepisorus contortus, it exhibits antineoplastic activityand has been found to decrease the rate of polymerization and sickling of red blood cells quercetin 3-O-glucopyranoside: structure in first source | beta-D-glucoside; monosaccharide derivative; quercetin O-glucoside; tetrahydroxyflavone | antineoplastic agent; antioxidant; antipruritic drug; bone density conservation agent; geroprotector; histamine antagonist; osteogenesis regulator; plant metabolite |
| rutin | Hydroxyethylrutoside: Monohydroxyethyl derivative of rutin. Peripheral circulation stimulant used in treatment of venous disorders. | disaccharide derivative; quercetin O-glucoside; rutinoside; tetrahydroxyflavone | antioxidant; metabolite |
| baicalein | trihydroxyflavone | angiogenesis inhibitor; anti-inflammatory agent; antibacterial agent; anticoronaviral agent; antifungal agent; antineoplastic agent; antioxidant; apoptosis inducer; EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor; EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor; EC 4.1.1.17 (ornithine decarboxylase) inhibitor; ferroptosis inhibitor; geroprotector; hormone antagonist; plant metabolite; prostaglandin antagonist; radical scavenger | |
| diosmetin | 3'-hydroxyflavonoid; monomethoxyflavone; trihydroxyflavone | angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; antioxidant; apoptosis inducer; bone density conservation agent; cardioprotective agent; plant metabolite; tropomyosin-related kinase B receptor agonist; vasodilator agent | |
| diosmin | dihydroxyflavanone; disaccharide derivative; glycosyloxyflavone; monomethoxyflavone; rutinoside | anti-inflammatory agent; antioxidant | |
| mangostin | alpha-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3 and 6, a methoxy group at position 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antioxidant, antimicrobial and antitumour activities. mangostin: xanthone from rind of Garcinia mangostana Linn. fruit | aromatic ether; phenols; xanthones | antimicrobial agent; antineoplastic agent; antioxidant; plant metabolite |
| wogonin | wogonin : A dihydroxy- and monomethoxy-flavone in which the hydroxy groups are positioned at C-5 and C-7 and the methoxy group is at C-8. wogonin: structure in first source | dihydroxyflavone; monomethoxyflavone | angiogenesis inhibitor; antineoplastic agent; cyclooxygenase 2 inhibitor; plant metabolite |
| rosmarinic acid | (R)-rosmarinic acid : A stereoisomer of rosmarinic acid having (R)-configuration. rosmarinic acid : The 1-carboxy-2-(2,4-dihydroxyphenyl)ethyl ester of trans-caffeic acid. rosmarinic acid: RN given refers to parent cpd; promote OT project | rosmarinic acid | geroprotector; plant metabolite |
| afimoxifene | |||
| icaritin | icaritin: structure in first source | ||
| icariin | flavonols; glycosyloxyflavone | antioxidant; bone density conservation agent; EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor; phytoestrogen | |
| baohuoside i | baohuoside I: structure given in first source; isolated from the herb Epimedium davidii | glycosyloxyflavone | anti-inflammatory agent; antineoplastic agent; apoptosis inducer; plant metabolite |
| salvianolic acid B | salvianolic acid B : A member of the class of 1-benzofurans that is an antioxidant and free radical scavenging compound extracted from S. miltiorrhiza salvianolic acid B: isolated from Salvia miltiorrhiza | 1-benzofurans; catechols; dicarboxylic acid; enoate ester; polyphenol | anti-inflammatory agent; antidepressant; antineoplastic agent; antioxidant; apoptosis inducer; autophagy inhibitor; cardioprotective agent; hepatoprotective agent; hypoglycemic agent; neuroprotective agent; osteogenesis regulator; plant metabolite |
| Diosmetin 7-O-beta-D-glucopyranoside | flavonoids; glycoside | ||
| polymyxin b(1) | |||
| Dihydrotanshinone I | dihydrotanshinone I: extracted from Radix Salviae | abietane diterpenoid | anticoronaviral agent |
| N-(3-ethynylphenyl)-6,7-dimethoxy-4-quinazolinamine | quinazolines | ||
| amz 30 | |||
| 1-(4-methyl-1-piperazinyl)-2-[[(1R,2S)-2-(4-phenylmethoxyphenyl)cyclopropyl]amino]ethanone | amino acid amide | ||
| 3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acid | organonitrogen heterocyclic compound | ||
| gsk2879552 | GSK2879552 : A member of the class of piperidines that is piperidine substituted by (4-carboxyphenyl)methyl and {[(1R,2S)-2-phenylcyclopropyl]amino}methyl groups at positions 1 and 4, respectively. It is a potent and irreversible inhibitor of lysine specific demethylase 1 (LSD1, also known as KDM1A). It was under clinical investigation for the treatment of acute myeloid leukaemia and small cell lung carcinoma. GSK2879552: inhibits lysine demethylase 1; structure in first source | benzenes; benzoic acids; cyclopropanes; monocarboxylic acid; piperidines; secondary amino compound; tertiary amino compound | antineoplastic agent; EC 1.14.99.66 (lysine-specific histone demethylase 1A) inhibitor |
| osimertinib | osimertinib : A member of the class of aminopyrimidines that is 4-(1-methylindol-3-yl)pyrimidin-2-amine in which one of the amino hydrogens is replaced by a 2-methoxy-4-[2-(dimethylamino)ethyl](methyl)amino-5-acrylamidophenyl group. Used (as the mesylate salt) for treatment of EGFR T790M mutation positive non-small cell lung cancer. osimertinib: an EGFR tyrosine kinase inhibitor | acrylamides; aminopyrimidine; biaryl; indoles; monomethoxybenzene; secondary amino compound; secondary carboxamide; substituted aniline; tertiary amino compound | antineoplastic agent; epidermal growth factor receptor antagonist |