ID AOC2_HUMAN Reviewed; 756 AA. AC O75106; A5PKW2; O00120; O75105; Q4TTW5; Q9UNY0; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2006, sequence version 2. DT 13-FEB-2019, entry version 161. DE RecName: Full=Retina-specific copper amine oxidase; DE Short=RAO; DE EC=1.4.3.21 {ECO:0000250|UniProtKB:P19801}; DE AltName: Full=Amine oxidase [copper-containing]; DE AltName: Full=Semicarbazide-sensitive amine oxidase; DE Short=SSAO; DE Flags: Precursor; GN Name=AOC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Retina; RX PubMed=9119395; DOI=10.1006/geno.1996.4570; RA Imamura Y., Kubota R., Wang Y., Asakawa S., Kudoh J., Mashima Y., RA Oguchi Y., Shimizu N.; RT "Human retina-specific amine oxidase (RAO): cDNA cloning, tissue RT expression, and chromosomal mapping."; RL Genomics 40:277-283(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING. RX PubMed=9722954; DOI=10.1006/geno.1998.5357; RA Imamura Y., Noda S., Mashima Y., Kudoh J., Oguchi Y., Shimizu N.; RT "Human retina-specific amine oxidase: genomic structure of the gene RT (AOC2), alternatively spliced variant, and mRNA expression in RT retina."; RL Genomics 51:293-298(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RA Zhang X., McIntire W.S.; RT "Human copper-containing amine oxidases."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-5; CYS-22; RP LEU-141; GLN-273 AND ASP-427. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP TISSUE SPECIFICITY. RX PubMed=12755418; DOI=10.1007/s000110300061; RA Heniquez A., Meissonnier G., Visentin V., Prevot D., Carpene C.; RT "High expression of semicarbazide-sensitive amine oxidase genes AOC2 RT and AOC3, but not the diamine oxidase gene AOC1 in human adipocytes."; RL Inflamm. Res. 52:S74-S75(2003). RN [9] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=17400359; DOI=10.1016/j.biochi.2007.02.013; RA Bour S., Daviaud D., Gres S., Lefort C., Prevot D., Zorzano A., RA Wabitsch M., Saulnier-Blache J.-S., Valet P., Carpene C.; RT "Adipogenesis-related increase of semicarbazide-sensitive amine RT oxidase and monoamine oxidase in human adipocytes."; RL Biochimie 89:916-925(2007). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=19588076; DOI=10.1007/s00018-009-0076-5; RA Kaitaniemi S., Elovaara H., Groen K., Kidron H., Liukkonen J., RA Salminen T., Salmi M., Jalkanen S., Elima K.; RT "The unique substrate specificity of human AOC2, a semicarbazide- RT sensitive amine oxidase."; RL Cell. Mol. Life Sci. 66:2743-2757(2009). CC -!- FUNCTION: Has a monoamine oxidase activity with substrate CC specificity for 2-phenylethylamine and tryptamine. May play a role CC in adipogenesis. May be a critical modulator of signal CC transmission in retina. {ECO:0000269|PubMed:17400359, CC ECO:0000269|PubMed:19588076}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an aliphatic amine + H2O + O2 = an aldehyde + H2O2 + CC NH4(+); Xref=Rhea:RHEA:16153, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17478, CC ChEBI:CHEBI:28938, ChEBI:CHEBI:58001; EC=1.4.3.21; CC Evidence={ECO:0000250|UniProtKB:P19801}; CC -!- COFACTOR: CC Name=Cu cation; Xref=ChEBI:CHEBI:23378; CC Evidence={ECO:0000250|UniProtKB:P19801}; CC Note=Binds 1 copper ion per subunit. CC {ECO:0000250|UniProtKB:P19801}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:P19801}; CC Note=Binds 2 calcium ions per subunit. CC {ECO:0000250|UniProtKB:P19801}; CC -!- COFACTOR: CC Name=L-topaquinone; Xref=ChEBI:CHEBI:79027; CC Evidence={ECO:0000250|UniProtKB:P19801}; CC Note=Contains 1 topaquinone per subunit. CC {ECO:0000250|UniProtKB:P19801}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.056 mM for tryptamine {ECO:0000269|PubMed:19588076}; CC KM=0.077 mM for 2-phenylethylamine CC {ECO:0000269|PubMed:19588076}; CC KM=0.167 mM for benzylamine {ECO:0000269|PubMed:19588076}; CC KM=0.178 mM for p-tyramine {ECO:0000269|PubMed:19588076}; CC KM=1.7 mM for methylamine {ECO:0000269|PubMed:19588076}; CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Forms a CC heterodimer with AOC3, in vitro. {ECO:0000250|UniProtKB:P19801, CC ECO:0000269|PubMed:19588076}. CC -!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane CC {ECO:0000269|PubMed:19588076}; Peripheral membrane protein CC {ECO:0000269|PubMed:19588076}. Note=Present on the surface of the CC cells. {ECO:0000269|PubMed:19588076}. CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm CC {ECO:0000269|PubMed:19588076}. Note=Either not translocated to the CC plasma membrane or below detection level. CC {ECO:0000269|PubMed:19588076}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=Long; CC IsoId=O75106-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=O75106-2; Sequence=VSP_006549; CC -!- TISSUE SPECIFICITY: Expressed in many tissues with much higher CC expression in retina. Isoform 1 and isoform 2 are expressed in CC adipose tissue, whereas isoform 1 only seems to be present in CC thymus, and isoform 2 only in testis. CC {ECO:0000269|PubMed:12755418, ECO:0000269|PubMed:17400359, CC ECO:0000269|PubMed:19588076}. CC -!- INDUCTION: Up-regulated during in vitro adipocyte differentiation. CC {ECO:0000269|PubMed:17400359}. CC -!- PTM: Topaquinone (TPQ) is generated by copper-dependent CC autoxidation of a specific tyrosyl residue. CC {ECO:0000250|UniProtKB:P12807}. CC -!- SIMILARITY: Belongs to the copper/topaquinone oxidase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/aoc2/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; D88213; BAA19001.1; -; mRNA. DR EMBL; AB012943; BAA32590.1; -; Genomic_DNA. DR EMBL; AB012943; BAA32589.1; -; Genomic_DNA. DR EMBL; AF081363; AAD39345.1; -; mRNA. DR EMBL; DQ060035; AAY43129.1; -; Genomic_DNA. DR EMBL; AC016889; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471152; EAW60895.1; -; Genomic_DNA. DR EMBL; BC142641; AAI42642.1; -; mRNA. DR CCDS; CCDS11443.1; -. [O75106-1] DR CCDS; CCDS45690.1; -. [O75106-2] DR RefSeq; NP_001149.2; NM_001158.4. [O75106-2] DR RefSeq; NP_033720.2; NM_009590.3. [O75106-1] DR UniGene; Hs.143102; -. DR ProteinModelPortal; O75106; -. DR SMR; O75106; -. DR BioGrid; 106811; 6. DR IntAct; O75106; 2. DR STRING; 9606.ENSP00000253799; -. DR BindingDB; O75106; -. DR ChEMBL; CHEMBL4112; -. DR GlyConnect; 1714; -. DR iPTMnet; O75106; -. DR PhosphoSitePlus; O75106; -. DR BioMuta; AOC2; -. DR jPOST; O75106; -. DR PaxDb; O75106; -. DR PeptideAtlas; O75106; -. DR PRIDE; O75106; -. DR ProteomicsDB; 49761; -. DR ProteomicsDB; 49762; -. [O75106-2] DR Ensembl; ENST00000253799; ENSP00000253799; ENSG00000131480. [O75106-1] DR Ensembl; ENST00000452774; ENSP00000406134; ENSG00000131480. [O75106-2] DR GeneID; 314; -. DR KEGG; hsa:314; -. DR UCSC; uc002ibt.5; human. [O75106-1] DR CTD; 314; -. DR DisGeNET; 314; -. DR EuPathDB; HostDB:ENSG00000131480.8; -. DR GeneCards; AOC2; -. DR HGNC; HGNC:549; AOC2. DR HPA; HPA057779; -. DR MIM; 602268; gene. DR neXtProt; NX_O75106; -. DR OpenTargets; ENSG00000131480; -. DR PharmGKB; PA24839; -. DR eggNOG; KOG1186; Eukaryota. DR eggNOG; COG3733; LUCA. DR GeneTree; ENSGT00940000153738; -. DR HOGENOM; HOG000233919; -. DR HOVERGEN; HBG004164; -. DR InParanoid; O75106; -. DR KO; K00276; -. DR OMA; NANWARY; -. DR OrthoDB; 1320015at2759; -. DR PhylomeDB; O75106; -. DR TreeFam; TF314750; -. DR BRENDA; 1.4.3.21; 2681. DR Reactome; R-HSA-211945; Phase I - Functionalization of compounds. DR SABIO-RK; O75106; -. DR GenomeRNAi; 314; -. DR PRO; PR:O75106; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; ENSG00000131480; Expressed in 97 organ(s), highest expression level in blood. DR Genevisible; O75106; HS. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0052595; F:aliphatic-amine oxidase activity; IEA:UniProtKB-EC. DR GO; GO:0052594; F:aminoacetone:oxygen oxidoreductase(deaminating) activity; IEA:UniProtKB-EC. DR GO; GO:0005507; F:copper ion binding; IBA:GO_Central. DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB. DR GO; GO:0052596; F:phenethylamine:oxygen oxidoreductase (deaminating) activity; IEA:UniProtKB-EC. DR GO; GO:0008131; F:primary amine oxidase activity; IBA:GO_Central. DR GO; GO:0048038; F:quinone binding; IEA:InterPro. DR GO; GO:0052593; F:tryptamine:oxygen oxidoreductase (deaminating) activity; IEA:UniProtKB-EC. DR GO; GO:0009308; P:amine metabolic process; IBA:GO_Central. DR GO; GO:0006584; P:catecholamine metabolic process; IEA:UniProtKB-KW. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. DR Gene3D; 2.70.98.20; -; 1. DR InterPro; IPR032952; AOC2. DR InterPro; IPR000269; Cu_amine_oxidase. DR InterPro; IPR015798; Cu_amine_oxidase_C. DR InterPro; IPR036460; Cu_amine_oxidase_C_sf. DR InterPro; IPR016182; Cu_amine_oxidase_N-reg. DR InterPro; IPR015800; Cu_amine_oxidase_N2. DR InterPro; IPR015802; Cu_amine_oxidase_N3. DR PANTHER; PTHR10638; PTHR10638; 1. DR PANTHER; PTHR10638:SF4; PTHR10638:SF4; 1. DR Pfam; PF01179; Cu_amine_oxid; 1. DR Pfam; PF02727; Cu_amine_oxidN2; 1. DR Pfam; PF02728; Cu_amine_oxidN3; 1. DR PRINTS; PR00766; CUDAOXIDASE. DR SUPFAM; SSF49998; SSF49998; 1. DR SUPFAM; SSF54416; SSF54416; 2. DR PROSITE; PS01164; COPPER_AMINE_OXID_1; 1. DR PROSITE; PS01165; COPPER_AMINE_OXID_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Catecholamine metabolism; KW Cell membrane; Complete proteome; Copper; Cytoplasm; Disulfide bond; KW Glycoprotein; Membrane; Metal-binding; Oxidoreductase; Polymorphism; KW Reference proteome; Signal; TPQ. FT SIGNAL 1 32 {ECO:0000255}. FT CHAIN 33 756 Retina-specific copper amine oxidase. FT /FTId=PRO_0000035671. FT REGION 378 388 Substrate binding. FT {ECO:0000250|UniProtKB:P19801}. FT REGION 462 467 Substrate binding. FT {ECO:0000250|UniProtKB:P19801}. FT REGION 574 581 Heparin-binding. {ECO:0000250}. FT ACT_SITE 380 380 Proton acceptor. FT {ECO:0000250|UniProtKB:P19801}. FT ACT_SITE 465 465 Schiff-base intermediate with substrate; FT via topaquinone. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 516 516 Copper; via tele nitrogen. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 518 518 Copper; via tele nitrogen. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 525 525 Calcium 1. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 526 526 Calcium 1; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 527 527 Calcium 1. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 568 568 Calcium 2. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 659 659 Calcium 2; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 661 661 Calcium 2. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 663 663 Calcium 2. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 669 669 Calcium 1. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 670 670 Calcium 1; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19801}. FT METAL 680 680 Copper; via pros nitrogen. FT {ECO:0000250|UniProtKB:P19801}. FT MOD_RES 465 465 2',4',5'-topaquinone. FT {ECO:0000250|UniProtKB:P12807}. FT CARBOHYD 133 133 N-linked (GlcNAc...) asparagine. FT {ECO:0000250|UniProtKB:P19801}. FT CARBOHYD 198 198 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 226 226 N-linked (GlcNAc...) asparagine. FT {ECO:0000250|UniProtKB:Q16853}. FT CARBOHYD 588 588 N-linked (GlcNAc...) (complex) FT asparagine. FT {ECO:0000250|UniProtKB:Q16853}. FT CARBOHYD 662 662 N-linked (GlcNAc...) asparagine. FT {ECO:0000250|UniProtKB:Q16853}. FT DISULFID 398 424 {ECO:0000250|UniProtKB:P19801}. FT DISULFID 730 737 {ECO:0000250|UniProtKB:Q16853}. FT DISULFID 744 744 Interchain. FT {ECO:0000250|UniProtKB:P19801}. FT VAR_SEQ 599 625 Missing (in isoform 2). FT {ECO:0000303|PubMed:9119395}. FT /FTId=VSP_006549. FT VARIANT 5 5 I -> V (in dbSNP:rs34230945). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025022. FT VARIANT 22 22 Y -> C (in dbSNP:rs34435306). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025023. FT VARIANT 141 141 P -> L (in dbSNP:rs35833794). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025024. FT VARIANT 273 273 R -> Q (in dbSNP:rs35508987). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025025. FT VARIANT 427 427 E -> D (in dbSNP:rs34351794). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025026. FT CONFLICT 181 181 E -> D (in Ref. 1 and 2). {ECO:0000305}. FT CONFLICT 215 218 GDRA -> RERT (in Ref. 1 and 2). FT {ECO:0000305}. FT CONFLICT 221 222 MA -> IG (in Ref. 1). {ECO:0000305}. FT CONFLICT 610 610 H -> Q (in Ref. 1 and 2). {ECO:0000305}. SQ SEQUENCE 756 AA; 83673 MW; 10263D8D56D3BD25 CRC64; MHLKIVLAFL ALSLITIFAL AYVLLTSPGG SSQPPHCPSV SHRAQPWPHP GQSQLFADLS REELTAVMRF LTQRLGPGLV DAAQAQPSDN CIFSVELQLP PKAAALAHLD RGSPPPAREA LAIVLFGGQP QPNVSELVVG PLPHPSYMRD VTVERHGGPL PYHRRPVLRA EFTQMWRHLK EVELPKAPIF LSSTFNYNGS TLAAVHATPR GLRSGDRATW MALYHNISGV GLFLHPVGLE LLLDHRALDP AHWTVQQVFY LGHYYADLGQ LEREFKSGRL EVVRVPLPPP NGASSLRSRN SPGPLPPLQF SPQGSQYSVQ GNLVVSSLWS FTFGHGVFSG LRIFDVRFQG ERIAYEVSVQ ECVSIYGADS PKTMLTRYLD SSFGLGRNSR GLVRGVDCPY QATMVDIHIL VGKGAVQLLP GAVCVFEEAQ GLPLRRHHNY LQNHFYGGLA SSALVVRSVS SVGNYDYIWD FVLYPNGALE GRVHATGYIN TAFLKGGEEG LLFGNRVGER VLGTVHTHAF HFKLDLDVAG LKNWVVAEDV VFKPVAAPWN PEHWLQRPQL TRQVLGKEDL TAFSLGSPLP RYLYLASNQT NAWGHQRGYR IQIHSPLGIH IPLESDMERA LSWGRYQLVV TQRKEEESQS SSIYHQNDIW TPTVTFADFI NNETLLGEDL VAWVTASFLH IPHAEDIPNT VTLGNRVGFL LRPYNFFDED PSIFSPGSVY FEKGQDAGLC SINPVACLPD LAACVPDLPP FSYHGF //