O75106 (AOC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Retina-specific copper amine oxidase
Short name=RAO
EC=1.4.3.21

Alternative name(s):
Amine oxidase [copper-containing]
Semicarbazide-sensitive amine oxidase
Short name=SSAO

Gene names

Name:

AOC2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	756 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has a monoamine oxidase activity with substrate specificity for 2-phenylethylamine and tryptamine. May play a role in adipogenesis. May be a critical modulator of signal transmission in retina. Ref.9 Ref.10
Catalytic activity	RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2.
Cofactor	Binds 1 copper ion per subunit By similarity. Binds 2 calcium ions per subunit By similarity. Contains 1 topaquinone per subunit By similarity.
Subunit structure	Forms heterodimer with AOC3, in vitro. Ref.10
Subcellular location	Isoform 1: Cell membrane; Peripheral membrane protein. Note: Present on the surface of the cells. Ref.10 Isoform 2: Cytoplasm. Note: Either not translocated to the plasma membrane or below detection level. Ref.10
Tissue specificity	Expressed in many tissues with much higher expression in retina. Isoform 1 and isoform 2 are expressed in adipose tissue, whereas isoform 1 only seems to be present in thymus, and isoform 2 only in testis. Ref.8 Ref.9 Ref.10
Induction	Up-regulated during in vitro adipocyte differentiation. Ref.9
Post-translational modification	Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue.
Sequence similarities	Belongs to the copper/topaquinone oxidase family.
Biophysicochemical properties	Kinetic parameters: KM=0.056 mM for tryptamine Ref.10 KM=0.077 mM for 2-phenylethylamine KM=0.167 mM for benzylamine KM=0.178 mM for p-tyramine KM=1.7 mM for methylamine

Ontologies

Keywords
Biological process	Catecholamine metabolism
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Calcium Copper Metal-binding
Molecular function	Oxidoreductase
PTM	Glycoprotein TPQ
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	catecholamine metabolic process Inferred from electronic annotation. Source: UniProtKB-KW visual perception Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aliphatic-amine oxidase activity Inferred from electronic annotation. Source: EC aminoacetone:oxygen oxidoreductase(deaminating) activity Inferred from electronic annotation. Source: EC copper ion binding Inferred from electronic annotation. Source: InterPro electron carrier activity Traceable author statement Ref.1. Source: UniProtKB phenethylamine:oxygen oxidoreductase (deaminating) activity Inferred from electronic annotation. Source: EC primary amine oxidase activity Inferred from electronic annotation. Source: EC quinone binding Inferred from electronic annotation. Source: InterPro tryptamine:oxygen oxidoreductase (deaminating) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: O75106-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O75106-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     599-625: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Potential
	Chain	33 – 756	724	Retina-specific copper amine oxidase		PRO_0000035671
Sites
	Active site	380	1	Proton acceptor By similarity
	Active site	465	1	Schiff-base intermediate with substrate; via topaquinone By similarity
	Metal binding	516	1	Copper By similarity
	Metal binding	518	1	Copper By similarity
	Metal binding	525	1	Calcium 1 By similarity
	Metal binding	526	1	Calcium 1; via carbonyl oxygen By similarity
	Metal binding	527	1	Calcium 1 By similarity
	Metal binding	568	1	Calcium 2 By similarity
	Metal binding	634	1	Calcium 2 By similarity
	Metal binding	659	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	661	1	Calcium 2 By similarity
	Metal binding	663	1	Calcium 2 By similarity
	Metal binding	669	1	Calcium 1 By similarity
	Metal binding	670	1	Calcium 1; via carbonyl oxygen By similarity
	Metal binding	680	1	Copper By similarity
Amino acid modifications
	Modified residue	465	1	2',4',5'-topaquinone By similarity
	Glycosylation	133	1	N-linked (GlcNAc...) Potential
	Glycosylation	198	1	N-linked (GlcNAc...) Potential
	Glycosylation	226	1	N-linked (GlcNAc...) Potential
	Glycosylation	588	1	N-linked (GlcNAc...) Potential
	Glycosylation	662	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	599 – 625	27	Missing in isoform 2.		VSP_006549
	Natural variant	5	1	I → V. Ref.4 Corresponds to variant rs34230945 [ dbSNP | Ensembl ].		VAR_025022
	Natural variant	22	1	Y → C. Ref.4 Corresponds to variant rs34435306 [ dbSNP | Ensembl ].		VAR_025023
	Natural variant	141	1	P → L. Ref.4 Corresponds to variant rs35833794 [ dbSNP | Ensembl ].		VAR_025024
	Natural variant	273	1	R → Q. Ref.4 Corresponds to variant rs35508987 [ dbSNP | Ensembl ].		VAR_025025
	Natural variant	427	1	E → D. Ref.4 Corresponds to variant rs34351794 [ dbSNP | Ensembl ].		VAR_025026
Experimental info
	Sequence conflict	181	1	E → D Ref.1
	Sequence conflict	181	1	E → D Ref.2
	Sequence conflict	215 – 218	4	GDRA → RERT Ref.1
	Sequence conflict	215 – 218	4	GDRA → RERT Ref.2
	Sequence conflict	221 – 222	2	MA → IG Ref.1
	Sequence conflict	610	1	H → Q Ref.1
	Sequence conflict	610	1	H → Q Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified January 24, 2006. Version 2. Checksum: 10263D8D56D3BD25	FASTA	756	83,673
	10 20 30 40 50 60 MHLKIVLAFL ALSLITIFAL AYVLLTSPGG SSQPPHCPSV SHRAQPWPHP GQSQLFADLS 70 80 90 100 110 120 REELTAVMRF LTQRLGPGLV DAAQAQPSDN CIFSVELQLP PKAAALAHLD RGSPPPAREA 130 140 150 160 170 180 LAIVLFGGQP QPNVSELVVG PLPHPSYMRD VTVERHGGPL PYHRRPVLRA EFTQMWRHLK 190 200 210 220 230 240 EVELPKAPIF LSSTFNYNGS TLAAVHATPR GLRSGDRATW MALYHNISGV GLFLHPVGLE 250 260 270 280 290 300 LLLDHRALDP AHWTVQQVFY LGHYYADLGQ LEREFKSGRL EVVRVPLPPP NGASSLRSRN 310 320 330 340 350 360 SPGPLPPLQF SPQGSQYSVQ GNLVVSSLWS FTFGHGVFSG LRIFDVRFQG ERIAYEVSVQ 370 380 390 400 410 420 ECVSIYGADS PKTMLTRYLD SSFGLGRNSR GLVRGVDCPY QATMVDIHIL VGKGAVQLLP 430 440 450 460 470 480 GAVCVFEEAQ GLPLRRHHNY LQNHFYGGLA SSALVVRSVS SVGNYDYIWD FVLYPNGALE 490 500 510 520 530 540 GRVHATGYIN TAFLKGGEEG LLFGNRVGER VLGTVHTHAF HFKLDLDVAG LKNWVVAEDV 550 560 570 580 590 600 VFKPVAAPWN PEHWLQRPQL TRQVLGKEDL TAFSLGSPLP RYLYLASNQT NAWGHQRGYR 610 620 630 640 650 660 IQIHSPLGIH IPLESDMERA LSWGRYQLVV TQRKEEESQS SSIYHQNDIW TPTVTFADFI 670 680 690 700 710 720 NNETLLGEDL VAWVTASFLH IPHAEDIPNT VTLGNRVGFL LRPYNFFDED PSIFSPGSVY 730 740 750 FEKGQDAGLC SINPVACLPD LAACVPDLPP FSYHGF
	Isoform 2 (Short) [UniParc]. Checksum: 5F28CCC8EE353415	FASTA	729	80,516
	10 20 30 40 50 60 MHLKIVLAFL ALSLITIFAL AYVLLTSPGG SSQPPHCPSV SHRAQPWPHP GQSQLFADLS 70 80 90 100 110 120 REELTAVMRF LTQRLGPGLV DAAQAQPSDN CIFSVELQLP PKAAALAHLD RGSPPPAREA 130 140 150 160 170 180 LAIVLFGGQP QPNVSELVVG PLPHPSYMRD VTVERHGGPL PYHRRPVLRA EFTQMWRHLK 190 200 210 220 230 240 EVELPKAPIF LSSTFNYNGS TLAAVHATPR GLRSGDRATW MALYHNISGV GLFLHPVGLE 250 260 270 280 290 300 LLLDHRALDP AHWTVQQVFY LGHYYADLGQ LEREFKSGRL EVVRVPLPPP NGASSLRSRN 310 320 330 340 350 360 SPGPLPPLQF SPQGSQYSVQ GNLVVSSLWS FTFGHGVFSG LRIFDVRFQG ERIAYEVSVQ 370 380 390 400 410 420 ECVSIYGADS PKTMLTRYLD SSFGLGRNSR GLVRGVDCPY QATMVDIHIL VGKGAVQLLP 430 440 450 460 470 480 GAVCVFEEAQ GLPLRRHHNY LQNHFYGGLA SSALVVRSVS SVGNYDYIWD FVLYPNGALE 490 500 510 520 530 540 GRVHATGYIN TAFLKGGEEG LLFGNRVGER VLGTVHTHAF HFKLDLDVAG LKNWVVAEDV 550 560 570 580 590 600 VFKPVAAPWN PEHWLQRPQL TRQVLGKEDL TAFSLGSPLP RYLYLASNQT NAWGHQRGYQ 610 620 630 640 650 660 LVVTQRKEEE SQSSSIYHQN DIWTPTVTFA DFINNETLLG EDLVAWVTAS FLHIPHAEDI 670 680 690 700 710 720 PNTVTLGNRV GFLLRPYNFF DEDPSIFSPG SVYFEKGQDA GLCSINPVAC LPDLAACVPD LPPFSYHGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human retina-specific amine oxidase (RAO): cDNA cloning, tissue expression, and chromosomal mapping." Imamura Y., Kubota R., Wang Y., Asakawa S., Kudoh J., Mashima Y., Oguchi Y., Shimizu N. Genomics 40:277-283(1997) [PubMed: 9119395] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Retina.
[2]	"Human retina-specific amine oxidase: genomic structure of the gene (AOC2), alternatively spliced variant, and mRNA expression in retina." Imamura Y., Noda S., Mashima Y., Kudoh J., Oguchi Y., Shimizu N. Genomics 51:293-298(1998) [PubMed: 9722954] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[3]	"Human copper-containing amine oxidases." Zhang X., McIntire W.S. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Retina.
[4]	NIEHS SNPs program Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-5; CYS-22; LEU-141; GLN-273 AND ASP-427.
[5]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1).
[8]	"High expression of semicarbazide-sensitive amine oxidase genes AOC2 and AOC3, but not the diamine oxidase gene AOC1 in human adipocytes." Heniquez A., Meissonnier G., Visentin V., Prevot D., Carpene C. Inflamm. Res. 52:S74-S75(2003) [PubMed: 12755418] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Adipogenesis-related increase of semicarbazide-sensitive amine oxidase and monoamine oxidase in human adipocytes." Bour S., Daviaud D., Gres S., Lefort C., Prevot D., Zorzano A., Wabitsch M., Saulnier-Blache J.-S., Valet P., Carpene C. Biochimie 89:916-925(2007) [PubMed: 17400359] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[10]	"The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase." Kaitaniemi S., Elovaara H., Groen K., Kidron H., Liukkonen J., Salminen T., Salmi M., Jalkanen S., Elima K. Cell. Mol. Life Sci. 66:2743-2757(2009) [PubMed: 19588076] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	D88213 mRNA. Translation: BAA19001.1. AB012943 Genomic DNA. Translation: BAA32590.1. AB012943 Genomic DNA. Translation: BAA32589.1. AF081363 mRNA. Translation: AAD39345.1. DQ060035 Genomic DNA. Translation: AAY43129.1. AC016889 Genomic DNA. No translation available. CH471152 Genomic DNA. Translation: EAW60895.1. BC142641 mRNA. Translation: AAI42642.1.
IPI	IPI00024357. IPI00293889.
RefSeq	NP_001149.2. NM_001158.3. NP_033720.2. NM_009590.2.
UniGene	Hs.143102.
3D structure databases
ProteinModelPortal	O75106.
SMR	O75106. Positions 51-756.
ModBase	Search...
Protein-protein interaction databases
STRING	O75106.
Proteomic databases
PRIDE	O75106.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000253799; ENSP00000253799; ENSG00000131480.
GeneID	314.
KEGG	hsa:314.
NMPDR	fig|9606.3.peg.13800.
UCSC	uc002ibt.1. human. uc002ibu.1. human.
Organism-specific databases
CTD	314.
GeneCards	GC17P040996.
H-InvDB	HIX0039050.
HGNC	HGNC:549. AOC2.
MIM	602268. gene.
neXtProt	NX_O75106.
PharmGKB	PA24839.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13438.
GeneTree	ENSGT00510000046461.
HOGENOM	HBG356524.
HOVERGEN	HBG004164.
InParanoid	O75106.
OMA	QFSPQGS.
PhylomeDB	O75106.
Gene expression databases
ArrayExpress	O75106.
Bgee	O75106.
CleanEx	HS_AOC2.
Genevestigator	O75106.
GermOnline	ENSG00000131480. Homo sapiens.
Family and domain databases
InterPro	IPR000269. Cu_amine_oxidase. IPR015798. Cu_amine_oxidase_C. IPR016182. Cu_amine_oxidase_N-reg. IPR015800. Cu_amine_oxidase_N2. IPR015801. Cu_amine_oxidase_N2/3. IPR015802. Cu_amine_oxidase_N3. [Graphical view]
Gene3D	G3DSA:3.10.450.40. CuNH_oxidase. 2 hits. G3DSA:2.70.98.20. Lyase_8_central. 1 hit.
KO	K00276.
PANTHER	PTHR10638. CuNH_oxidase. 1 hit.
Pfam	PF01179. Cu_amine_oxid. 1 hit. PF02727. Cu_amine_oxidN2. 1 hit. PF02728. Cu_amine_oxidN3. 1 hit. [Graphical view]
PRINTS	PR00766. CUDAOXIDASE.
SUPFAM	SSF54416. Cu_amine_oxidase_N-reg. 2 hits. SSF49998. CuNH_oxidase. 1 hit.
PROSITE	PS01164. COPPER_AMINE_OXID_1. 1 hit. PS01165. COPPER_AMINE_OXID_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	1277.
SOURCE	Search...

Entry information

Entry name

AOC2_HUMAN

Accession

Primary (citable) accession number: O75106
Secondary accession number(s): A5PKW2 , O00120, O75105, Q4TTW5, Q9UNY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 24, 2006
Last modified:	January 25, 2012
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.