Monoamine oxidase A

2Z5Y, 2BXR, 2BXS, 2Z5X412817161ENSG00000189221ENSMUSG00000025037P21397Q64133NM_001270458NM_000240NM_173740NP_000231NP_001257387NP_776101Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAOA gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. A mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed.2bxr: HUMAN MONOAMINE OXIDASE A IN COMPLEX WITH CLORGYLINE, CRYSTAL FORM A2bxs: HUMAN MONOAMINE OXIDASE A IN COMPLEX WITH CLORGYLINE, CRYSTAL FORM B Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAOA gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. A mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed. Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAOA gene. The promoter of MAOA contains conserved binding sites for Sp1, GATA2, and TBP. This gene is adjacent to a related gene (MAOB) on the opposite strand of the X chromosome. In humans, there is a 30-base repeat sequence repeated several different numbers of times in the promoter region of MAO-A. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant. Studies have found differences in the frequency distribution of variants of the MAOA gene between ethnic groups: of the participants, 59% of Black men, 54% of Chinese men, 56% of Maori men, and 34% of Caucasian men carried the 3R allele, while 5.5% of Black men, 0.1% of Caucasian men, and 0.00067% of Asian men carried the 2R allele. The epigenetic modification of MAOA gene expression through methylation likely plays an important role in women. A study from 2010 found epigenetic methylation of MAOA in men to be very low and with little variability compared to women, while having higher heritability in men than women. The gene encodes a monomeric protein which shares a 70% amino acid sequence identity, as well as conserved chain folds and flavin adenine dinucleotide (FAD)-binding site structures, with MAO-B. However, MAO-A has a monopartite cavity of approximately 550 angstroms, compared to the 290-angstrom bipartite cavity in MAO-B. Nonetheless, both proteins adopt dimeric forms when membrane-bound. The C-terminal domain of MAO-A forms helical tails which are responsible for attaching the protein to the outer mitochondrial membrane (OMM). MAO-A contains loop structures at the entrance of its active site. MAO-A is a key regulator for normal brain function. It is a flavoenzyme which degrades amine neurotransmitters, such as dopamine, norepinephrine, and serotonin, via oxidative deamination. It is highly expressed in neural and cardiac cells and localizes to the outer mitochondrial membrane. Its expression is regulated by the transcription factors SP1, GATA2, and TBP via the CAMP pathway in response to stress such as ischemia and inflammation. MAO-A produces an amine oxidase, which is a class of enzyme known to affect carcinogenesis. Clorgyline, an MAO-A enzyme inhibitor, prevents apoptosis in melanoma cells, in vitro. Cholangiocarcinoma suppresses MAO-A expression, and those patients with higher MAO-A expression had less adjacent organ invasion and better prognosis and survival. MAOA activity is linked to apoptosis and cardiac damage during cardiac injury following ischemic-reperfusion.