AOXB_CAVPO
ID AOXB_CAVPO Reviewed; 1335 AA.
AC H9TB19;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 2.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Aldehyde oxidase 2;
DE EC=1.2.3.1;
DE AltName: Full=Aldehyde oxidase homolog 3;
DE AltName: Full=Azaheterocycle hydroxylase 2;
DE EC=1.17.3.-;
GN Name=AOX2; Synonyms=AOH3, AOX3L1;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND IDENTIFICATION OF
RP PARALOGS.
RX PubMed=23263164; DOI=10.1007/s00018-012-1229-5;
RA Kurosaki M., Bolis M., Fratelli M., Barzago M.M., Pattini L., Perretta G.,
RA Terao M., Garattini E.;
RT "Structure and evolution of vertebrate aldehyde oxidases: from gene
RT duplication to gene suppression.";
RL Cell. Mol. Life Sci. 70:1807-1830(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2N;
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
CC -!- FUNCTION: Oxidase with broad substrate specificity, oxidizing aromatic
CC azaheterocycles, such as phthalazine, as well as aldehydes, such as
CC benzaldehyde and retinal. {ECO:0000250|UniProtKB:Q5SGK3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aldehyde + H2O + O2 = a carboxylate + H(+) + H2O2;
CC Xref=Rhea:RHEA:16829, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17478,
CC ChEBI:CHEBI:29067; EC=1.2.3.1;
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:O54754};
CC Note=Binds 2 [2Fe-2S] clusters per subunit.
CC {ECO:0000250|UniProtKB:O54754};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:O54754};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:O54754};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000250|UniProtKB:O54754};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000250|UniProtKB:O54754};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O54754}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q5SGK3}.
CC -!- TISSUE SPECIFICITY: Detected in kidney, Harderian gland and olfactory
CC mucosa. {ECO:0000269|PubMed:23263164}.
CC -!- MISCELLANEOUS: AOX genes evolved from a xanthine oxidoreductase
CC ancestral precursor via a series of gene duplication and
CC suppression/deletion events. Different animal species contain a
CC different complement of AOX genes encoding an equivalent number of AOX
CC isoenzymes. In mammals, the two extremes are represented by certain
CC rodents such as mice and rats, which are endowed with 4 AOX genes, and
CC by humans, whose genome is characterized by a single active gene
CC (PubMed:23263164). {ECO:0000305|PubMed:23263164}.
CC -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC {ECO:0000305}.
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; JQ280311; AFG18183.1; -; mRNA.
DR EMBL; AAKN02051282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAKN02051283; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001265693.1; NM_001278764.1.
DR AlphaFoldDB; H9TB19; -.
DR SMR; H9TB19; -.
DR PRIDE; H9TB19; -.
DR GeneID; 100719938; -.
DR KEGG; cpoc:100719938; -.
DR CTD; 213043; -.
DR OrthoDB; 48717at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0004031; F:aldehyde oxidase activity; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0043546; F:molybdopterin cofactor binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR CDD; cd00207; fer2; 1.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR002888; 2Fe-2S-bd.
DR InterPro; IPR036884; 2Fe-2S-bd_dom_sf.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR006058; 2Fe2S_fd_BS.
DR InterPro; IPR000674; Ald_Oxase/Xan_DH_a/b.
DR InterPro; IPR036856; Ald_Oxase/Xan_DH_a/b_sf.
DR InterPro; IPR016208; Ald_Oxase/xanthine_DH.
DR InterPro; IPR008274; AldOxase/xan_DH_Mopterin-bd.
DR InterPro; IPR037165; AldOxase/xan_DH_Mopterin-bd_sf.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR005107; CO_DH_flav_C.
DR InterPro; IPR036683; CO_DH_flav_C_dom_sf.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR002346; Mopterin_DH_FAD-bd.
DR PANTHER; PTHR11908; PTHR11908; 1.
DR Pfam; PF01315; Ald_Xan_dh_C; 1.
DR Pfam; PF02738; Ald_Xan_dh_C2; 1.
DR Pfam; PF03450; CO_deh_flav_C; 1.
DR Pfam; PF00941; FAD_binding_5; 1.
DR Pfam; PF00111; Fer2; 1.
DR Pfam; PF01799; Fer2_2; 1.
DR PIRSF; PIRSF000127; Xanthine_DH; 1.
DR SMART; SM01008; Ald_Xan_dh_C; 1.
DR SMART; SM01092; CO_deh_flav_C; 1.
DR SUPFAM; SSF47741; SSF47741; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR SUPFAM; SSF54665; SSF54665; 1.
DR SUPFAM; SSF55447; SSF55447; 1.
DR SUPFAM; SSF56003; SSF56003; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS00197; 2FE2S_FER_1; 1.
DR PROSITE; PS51085; 2FE2S_FER_2; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 2: Evidence at transcript level;
KW 2Fe-2S; Cytoplasm; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding;
KW Molybdenum; Oxidoreductase; Reference proteome.
FT CHAIN 1..1335
FT /note="Aldehyde oxidase 2"
FT /id="PRO_0000425243"
FT DOMAIN 8..95
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 242..427
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1287
FT /note="Proton acceptor; for azaheterocycle hydroxylase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:O54754"
FT BINDING 47
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 52
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 55
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 77
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 116
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 117
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 120
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 152
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 154
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 154
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 270..277
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 351
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 360
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 364
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 373
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 417
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 821..822
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1103..1106
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1218
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1285
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT CONFLICT 140
FT /note="E -> G (in Ref. 1; AFG18183)"
FT /evidence="ECO:0000305"
FT CONFLICT 854
FT /note="D -> N (in Ref. 1; AFG18183)"
FT /evidence="ECO:0000305"
FT CONFLICT 1074
FT /note="A -> V (in Ref. 1; AFG18183)"
FT /evidence="ECO:0000305"
FT CONFLICT 1177
FT /note="C -> Y (in Ref. 1; AFG18183)"
FT /evidence="ECO:0000305"
FT CONFLICT 1201
FT /note="D -> G (in Ref. 1; AFG18183)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1335 AA; 144924 MW; CC916D8865BFC555 CRC64;
MPHPPGSDVL VFFVNGRKVT ERDVDPEVTL LTYLRRNLGL TGTKSACGGG SCGTCTVMLS
RFDLASRKPR HIAVTACLVP LCSLHGAAVT TVEGVGSIRT RVHPVQERIA KSHGTQCGFC
TPGMVMSLYA LLRSHPQPSE EQLLEALAGN LCRCTGYRPI LESGRTFCLD SASCGQHGAR
QCCLDQPGDG TCPPGRNGPQ AHMCSELIPR TEFQPWDPTQ EPIFPPELMR MAESPVQPSL
TFRGDRVTWV SPGSLQELLA LRARHPEAPL VLGNTALGPA QRSQGRVHPL LISPARIPEL
STVTETSDGL TIGASCSLAQ LQDILAKSIS QLPVEKTQTL RALAKALRSV AGLQVRNLAS
LGGHVMSLHS YSDLNPILAV GQAALHLRSE GGARLISLDE HFLAGVVSAS LQPGEILESV
HIPHSQKWEF VFSFRQAQAP QNASPHVSAG MRVRFTEGTD TIEDLSIAYG GVGTTTVMAP
QACQRLLGRH WTEETLDEAC RLVLGEVTIP GAAPGGRVEF RRTLLVSFLF RFYLQVLQEL
KAHRFLKPPC TPRTLSDTWK YPQLPDQTLG ALEDVPIMVP RGVQMYERVD PQQPPQDPVG
RSIMHLSGLK HATGEAVFCD DLPRVDKELF MALVTSTRPH AKIVSVDPAE ALRLPGVVAI
VTAEDIPGTN GTEDDKLLAV DKVLCVGQVI CAVVAETDVQ ARQATGSVRV TYEDLEPVVL
SIQDAIGHSS FLCPEKKLEL GNTEEAFEDV DHILEGEVHV GGQEHFYMET QRVLVIPKVE
DQELDIYAST QDPAHMQKTV SSTLNVPLNR VTCHVKRVGG GFGGKQGRSA MLGAIAAVGA
IKTGRPVRLV LDRDEDMLIT GGRHPLFGKY KVGFMDSGRI KALDIQCYIN GGCVLDYSEL
VIEFLILKLE NAYKIRNLRF RGRACRTNLP SNTAFRGFGF PQGALVIESC ITAVAAKCGL
LPEKVREKNM YRTVDKTIYK QAFSPEPLHR CWAECLEQAD VPGRRALADA FNRQSPWRKR
GIAVVPMKFS VGFAATSYHQ AAALVHIYTD GSVLVTHGGN ELGQGIHTKM LQVASRELRV
PLCRLHIQET STATVPNTVT TAASVGADVN GRAVQNACQT LLKRLEPIMK KNPEGTWEAW
VEAAFEQRIS LSATGYFRGY KAFMDWEKGE GEPFPYCVFG AACSEVEIDC LTGAHRKLRT
DIVMDAGCSL NPALDIGQVE GAFLQGAGLY TTEELHYSPE GALLSGGPEE YKIPTAADVP
EKLNVTLLPS AQAQTGLTIY SSKGLGESGM FLGSSVFFAI QDAVAAARRD RGLAEDFTVP
REDPGTCKPW SISVA
