Reviewed, UniProtKB/Swiss-Prot P21397 (AOFA_HUMAN)

Names and origin

Protein names

Recommended name:
    Amine oxidase [flavin-containing] A
    EC=1.4.3.4
Alternative name(s):
    Monoamine oxidase type A
      Short name=MAO-A

Gene names

Name:

MAOA

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	527 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Catalytic activity	RCH2NHR' + H2O + O2 = RCHO + R'NH2 + H2O2.
Cofactor	FAD. Ref.12 Ref.14
Subunit structure	Monomer, homo- or heterodimer (containing two subunits of similar size). Each subunit contains a covalently bound flavin. Enzymatically active as monomer. Ref.12
Subcellular location	Mitochondrion outer membrane; Single-pass type IV membrane protein; Cytoplasmic side.
Tissue specificity	Heart, liver, duodenum, blood vessels and kidney.
Involvement in disease	Defects in MAOA are the cause of Brunner syndrome (BRUNS) [MIM:300615]. Brunner syndrome is a form of X-linked non-dysmorphic mild mental retardation. Male patients are affected by a syndrome of borderline mental retardation and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior.
Sequence similarities	Belongs to the flavin monoamine oxidase family.
Mass spectrometry	Molecular mass is 60512±6 Da from positions 1 - 527. Determined by ESI. Ref.10

Ontologies

Keywords
Biological process	Catecholamine metabolism Neurotransmitter degradation
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Polymorphism
Disease	Mental retardation
Domain	Transmembrane
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	behavior Ref.13 Traceable author statement. Source: ProtInc neurotransmitter catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW internal side of plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial outer membrane Ref.13 Inferred from Experiment. Source: Reactome
Molecular function	amine oxidase activity Ref.13 Inferred from Experiment. Source: Reactome electron carrier activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NDRG1	Q92597	1	EBI-1190845,EBI-716486

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 527

527

Amine oxidase [flavin-containing] A

PRO_0000099850

Regions

Topological domain

1 – 497

497

Cytoplasmic Ref.14

Transmembrane

498 – 518

21

Anchor for type IV membrane protein

Topological domain

519 – 527

9

Mitochondrial intermembrane Ref.14

Region

520 – 522

3

Interaction with membrane phospholipid headgroups Probable

Sites

Site

335

1

Important for substrate specificity By similarity

Site

374

1

Important for catalytic activity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.10

Modified residue

406

1

S-8alpha-FAD cysteine

Natural variations

Natural variant

15

1

D → E in a breast cancer sample; somatic mutation. Ref.15

VAR_036545

Natural variant

314

1

F → V: dbSNP rs1799835.

VAR_014795

Natural variant

520

1

K → R: dbSNP rs1800466.

VAR_014796

Experimental info

Mutagenesis

165

1

C → S: No loss of activity. Ref.11

Mutagenesis

266

1

C → S: No loss of activity. Ref.11

Mutagenesis

306

1

C → S: No loss of activity. Ref.11

Mutagenesis

321

1

C → S: No loss of activity. Ref.11

Mutagenesis

323

1

C → S: No loss of activity. Ref.11

Mutagenesis

374

1

C → S: Complete loss of activity. Ref.11

Mutagenesis

398

1

C → S: No loss of activity. Ref.11

Mutagenesis

406

1

C → S: Complete loss of activity. Ref.11

Sequence conflict

111

1

Missing Ref.4

Sequence conflict

138

1

I → R Ref.4

Sequence conflict

397

1

W → M AA sequence Ref.8

Secondary structure

1

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527

Helix Strand Turn

Details...

Beta strand

15 – 19

5

Helix

23 – 34

12

Beta strand

39 – 42

4

Beta strand

44 – 49

6

Beta strand

54 – 57

4

Turn

58 – 60

3

Beta strand

61 – 66

6

Helix

75 – 83

9

Beta strand

88 – 90

3

Beta strand

94 – 101

8

Beta strand

104 – 108

5

Beta strand

110 – 112

3

Helix

118 – 136

19

Helix

143 – 145

3

Helix

149 – 154

6

Helix

157 – 164

8

Helix

168 – 182

15

Turn

186 – 188

3

Helix

191 – 199

9

Turn

200 – 202

3

Helix

204 – 208

5

Beta strand

216 – 219

4

Helix

224 – 234

11

Helix

235 – 237

3

Beta strand

238 – 241

4

Beta strand

244 – 248

5

Beta strand

250 – 258

9

Beta strand

263 – 271

9

Helix

275 – 278

4

Beta strand

281 – 285

5

Helix

289 – 296

8

Beta strand

303 – 309

7

Helix

314 – 317

4

Beta strand

320 – 327

8

Beta strand

334 – 338

5

Beta strand

348 – 354

7

Helix

355 – 361

7

Helix

366 – 381

16

Helix

384 – 387

4

Beta strand

390 – 396

7

Helix

397 – 399

3

Turn

401 – 403

3

Beta strand

405 – 407

3

Helix

415 – 419

5

Helix

420 – 422

3

Beta strand

430 – 432

3

Helix

435 – 437

3

Beta strand

439 – 441

3

Helix

445 – 462

18

Helix

468 – 470

3

Beta strand

479 – 481

3

Helix

490 – 494

5

Helix

498 – 520

23

Sequences

	Sequence		Length	Mass (Da)
	P21397-1 [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 4270E346928AE832	FASTA	527	59,682
	10 20 30 40 50 60 MENQEKASIA GHMFDVVVIG GGISGLSAAK LLTEYGVSVL VLEARDRVGG RTYTIRNEHV 70 80 90 100 110 120 DYVDVGGAYV GPTQNRILRL SKELGIETYK VNVSERLVQY VKGKTYPFRG AFPPVWNPIA 130 140 150 160 170 180 YLDYNNLWRT IDNMGKEIPT DAPWEAQHAD KWDKMTMKEL IDKICWTKTA RRFAYLFVNI 190 200 210 220 230 240 NVTSEPHEVS ALWFLWYVKQ CGGTTRIFSV TNGGQERKFV GGSGQVSERI MDLLGDQVKL 250 260 270 280 290 300 NHPVTHVDQS SDNIIIETLN HEHYECKYVI NAIPPTLTAK IHFRPELPAE RNQLIQRLPM 310 320 330 340 350 360 GAVIKCMMYY KEAFWKKKDY CGCMIIEDED APISITLDDT KPDGSLPAIM GFILARKADR 370 380 390 400 410 420 LAKLHKEIRK KKICELYAKV LGSQEALHPV HYEEKNWCEE QYSGGCYTAY FPPGIMTQYG 430 440 450 460 470 480 RVIRQPVGRI FFAGTETATK WSGYMEGAVE AGERAAREVL NGLGKVTEKD IWVQEPESKD 490 500 510 520 VPAVEITHTF WERNLPSVSG LLKIIGFSTS VTALGFVLYK YKLLPRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structural features of human monoamine oxidase A elucidated from cDNA and peptide sequences." Hsu Y.-P.P., Weyler W., Chen S., Sims K.B., Rinehart W.B., Utterback M.C., Powell J.F., Breakefield X.O. J. Neurochem. 51:1321-1324(1988) [PubMed: 3418353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties." Bach A.W.J., Lan N.C., Johnson D.L., Abell C.W., Bembenek M.E., Kwan S.W., Seeburg P.H., Shih J.C. Proc. Natl. Acad. Sci. U.S.A. 85:4934-4938(1988) [PubMed: 3387449] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Structure of the human gene for monoamine oxidase type A." Chen Z.-Y., Hotamisligil G.S., Huang J.-K., Wen L., Ezzeddine D., Aydin-Muderrisoglu N., Powell J.F., Huang R.H., Breakefield X.O., Craig I., Hsu Y.-P.P. Nucleic Acids Res. 19:4537-4541(1991) [PubMed: 1886775] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[5]	"Promoter organization and activity of human monoamine oxidase (MAO) A and B genes." Zhu Q.S., Grimsby J.S., Chen K., Shih J.C. J. Neurosci. 12:4437-4446(1992) [PubMed: 1432104] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
[6]	"The promoter of the human monoamine oxidase A gene." Denney R.M. Prog. Brain Res. 106:57-66(1995) [PubMed: 8584674] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
[7]	"A new look at the promoter of the human monoamine oxidase A gene: mapping transcription initiation sites and capacity to drive luciferase expression." Denney R.M., Sharma A., Dave S.K., Waguespack A. J. Neurochem. 63:843-856(1994) [PubMed: 7519662] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
[8]	"Partial amino acid sequence analysis of human placenta monoamine oxidase A and bovine liver monoamine oxidase B." Chen S.-Y., Weyler W. Biochem. Biophys. Res. Commun. 156:445-450(1988) [PubMed: 3178846] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-45; 62-78; 109-129; 268-288; 298-315; 318-332; 336-352; 372-412; 430-440 AND 458-493. Tissue: Placenta.
[9]	"Monoamine oxidase A from human placenta and monoamine oxidase B from bovine liver both have one FAD per subunit." Weyler W. Biochem. J. 260:725-729(1989) [PubMed: 2764901] [Abstract] Cited for: DETERMINATION OF PROTEIN-FAD RATIO. Tissue: Placenta.
[10]	"High-level expression of human liver monoamine oxidase A in Pichia pastoris: comparison with the enzyme expressed in Saccharomyces cerevisiae." Li M., Hubalek F., Newton-Vinson P., Edmondson D.E. Protein Expr. Purif. 24:152-162(2002) [PubMed: 11812236] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, ACETYLATION AT MET-1, MASS SPECTROMETRY.
[11]	"Site-directed mutagenesis of monoamine oxidase A and B: role of cysteines." Wu H.F., Chen K., Shih J.C. Mol. Pharmacol. 43:888-893(1993) [PubMed: 8316221] [Abstract] Cited for: MUTAGENESIS OF CYS-165; CYS-266; CYS-306; CYS-321; CYS-323; CYS-374; CYS-398 AND CYS-406.
[12]	"Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B." De Colibus L., Li M., Binda C., Lustig A., Edmondson D.E., Mattevi A. Proc. Natl. Acad. Sci. U.S.A. 102:12684-12689(2005) [PubMed: 16129825] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), COFACTOR, SUBUNIT.
[13]	"Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A." Brunner H.G., Nelen M., Breakefield X.O., Ropers H.-H., van Oost B.A. Science 262:578-580(1993) [PubMed: 8211186] [Abstract] Cited for: INVOLVEMENT IN BRUNNER SYNDROME.
[14]	"Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors." Son S.-Y., Ma J., Kondou Y., Yoshimura M., Yamashita E., Tsukihara T. Proc. Natl. Acad. Sci. U.S.A. 105:5739-5744(2008) [PubMed: 18391214] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF 12-524 IN COMPLEX WITH FAD AND THE INHIBITOR HARMINE, COFACTOR, TOPOLOGY.
[15]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-15.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Monoamine oxidase entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M68840 mRNA. Translation: AAA59548.1.
M68857 , M68843, M68844, M68845, M68846, M68847, M68848, M68849, M68850, M68851, M68852, M68853, M68854, M68855, M68856 Genomic DNA. Translation: AAA59547.1.
M69226 mRNA. Translation: AAA59549.1.
X60806 Genomic DNA. No translation available.
X60807 Genomic DNA. No translation available.
X60808 Genomic DNA. No translation available.
X60809 Genomic DNA. No translation available.
X60810 Genomic DNA. No translation available.
X60811 Genomic DNA. No translation available.
X60812 Genomic DNA. No translation available.
X60813 Genomic DNA. No translation available.
X60814 Genomic DNA. No translation available.
X60815 Genomic DNA. No translation available.
X60816 Genomic DNA. No translation available.
X60817 Genomic DNA. No translation available.
X60818 Genomic DNA. No translation available.
X60819 Genomic DNA. No translation available.
BC008064 mRNA. Translation: AAH08064.1.
M89636 Genomic DNA. Translation: AAB46385.1.
S81371 Genomic DNA. Translation: AAD14361.1.
S72704 Genomic DNA. Translation: AAD14113.1.

IPI

IPI00008483.

PIR

A36175.

RefSeq

NP_000231.1.

UniGene

Hs.183109

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H8Q	model	-	A	14-468	[»]
2BXR	X-ray	3.00	A/B	1-527	[»]
2BXS	X-ray	3.15	A/B	1-527	[»]
2Z5X	X-ray	2.20	A	12-524	[»]
2Z5Y	X-ray	2.17	A	12-524	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P21397. 1 interaction.

STRING

P21397.

PTM databases

PhosphoSite

P21397.

Proteomic databases

PeptideAtlas

P21397.

PRIDE

P21397.

Genome annotation databases

Ensembl

ENST00000338702; ENSP00000340684; ENSG00000189221; Homo sapiens. [Genome view]

GeneID

4128.

KEGG

hsa:4128.

UCSC

uc004dfy.1. human.

Organism-specific databases

CTD

4128.

GeneCards

GC0XP043400.

H-InvDB

HIX0021483.

HGNC

HGNC:6833. MAOA.

HPA

CAB009437.

MIM

300615. phenotype.
309850. gene+phenotype.

Orphanet

3065. Intellectual deficit, X-linked - monoamine oxidase A metabolism anomaly.
3057. Monoamine oxidase-A deficiency.

PharmGKB

PA236.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P21397.

HOVERGEN

P21397.

OMA

YLFVNIN.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000094598-MON.

BRENDA

1.4.3.4. 247.

Reactome

REACT_13433. Biological oxidations.
REACT_13685. Synaptic Transmission.
REACT_649. Phase 1 functionalization.

Gene expression databases

ArrayExpress

P21397.

Bgee

P21397.

CleanEx

HS_MAOA.

Genevestigator

P21397.

GermOnline

ENSG00000189221. Homo sapiens.

Family and domain databases

InterPro

IPR001613. Amineoxid_fl.
IPR002937. Amino_oxidase.
[Graphical view]

Pfam

PF01593. Amino_oxidase. 1 hit.
[Graphical view]

PRINTS

PR00757. AMINEOXDASEF.

ProtoNet

Search...

Other Resources

DrugBank

DB00918. Almotriptan.
DB00190. Carbidopa.
DB01068. Clonazepam.
DB00988. Dopamine.
DB00176. Fluvoxamine.
DB01381. Ginkgo biloba.
DB00458. Imipramine.
DB01247. Isocarboxazid.
DB01235. Levodopa.
DB00601. Linezolid.
DB00186. Lorazepam.
DB01171. Moclobemide.
DB00184. Nicotine.
DB00368. Norepinephrine.
DB00780. Phenelzine.
DB00830. Phenmetrazine.
DB00191. Phentermine.
DB00388. Phenylephrine.
DB00397. Phenylpropanolamine.
DB00852. Pseudoephedrine.
DB01367. Rasagiline.
DB00140. Riboflavin.
DB00953. Rizatriptan.
DB01037. Selegiline.
DB00669. Sumatriptan.
DB00624. Testosterone.
DB00752. Tranylcypromine.
DB00315. Zolmitriptan.

NextBio

16206.

SOURCE

Search...

Entry information

Entry name

AOFA_HUMAN

Accession

Primary (citable) accession number: P21397
Secondary accession number(s): Q16426

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	November 3, 2009
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.