AOXD_CAVPO
ID AOXD_CAVPO Reviewed; 1341 AA.
AC H9TB18;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 2.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Aldehyde oxidase 4;
DE EC=1.2.3.1;
DE AltName: Full=Aldehyde oxidase homolog 2;
DE AltName: Full=Azaheterocycle hydroxylase 4;
DE EC=1.17.3.-;
DE AltName: Full=Retinal oxidase;
GN Name=AOX4;
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: Aldehyde oxidase able to catalyze the oxidation of
CC retinaldehyde into retinoate. Acts as a negative modulator of the
CC epidermal trophism. May be able to oxidize a wide variety of aldehydes
CC into their corresponding carboxylates and to hydroxylate
CC azaheterocycles (By similarity). {ECO:0000250}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O2 + retinal = H(+) + H2O2 + retinoate;
CC Xref=Rhea:RHEA:56736, ChEBI:CHEBI:15035, ChEBI:CHEBI:15036,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240;
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:G3X982};
CC Note=Binds 2 [2Fe-2S] clusters per subunit.
CC {ECO:0000250|UniProtKB:G3X982};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:G3X982};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:G3X982};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000250|UniProtKB:G3X982};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000250|UniProtKB:G3X982};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:G3X982}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in liver, testis, kidney, brain, Harderian
CC gland and olfactory 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}.
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DR EMBL; JQ280310; AFG18182.1; -; mRNA.
DR EMBL; AAKN02051282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAKN02051283; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001265709.1; NM_001278780.1.
DR AlphaFoldDB; H9TB18; -.
DR SMR; H9TB18; -.
DR STRING; 10141.ENSCPOP00000016070; -.
DR Ensembl; ENSCPOT00000021726; ENSCPOP00000016070; ENSCPOG00000033032.
DR GeneID; 100714172; -.
DR KEGG; cpoc:100714172; -.
DR CTD; 71872; -.
DR eggNOG; KOG0430; Eukaryota.
DR GeneTree; ENSGT00950000183114; -.
DR OrthoDB; 48717at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000033032; Expressed in uterine cervix and 2 other tissues.
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:0051287; F:NAD binding; IEA:InterPro.
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; IPR014313; Aldehyde_oxidase.
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 TIGRFAMs; TIGR02969; mam_aldehyde_ox; 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..1341
FT /note="Aldehyde oxidase 4"
FT /id="PRO_0000425249"
FT DOMAIN 8..95
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 239..424
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1268
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 267..274
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 348
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 357
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 361
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 370
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 414
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 805..806
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 805
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 1046
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 1087..1090
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1202
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1266
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT CONFLICT 39
FT /note="H -> Q (in Ref. 1; AFG18182)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="E -> V (in Ref. 1; AFG18182)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="R -> G (in Ref. 1; AFG18182)"
FT /evidence="ECO:0000305"
FT CONFLICT 504
FT /note="L -> F (in Ref. 1; AFG18182)"
FT /evidence="ECO:0000305"
FT CONFLICT 624
FT /note="H -> R (in Ref. 1; AFG18182)"
FT /evidence="ECO:0000305"
FT CONFLICT 935
FT /note="M -> V (in Ref. 1; AFG18182)"
FT /evidence="ECO:0000305"
FT CONFLICT 1008
FT /note="M -> V (in Ref. 1; AFG18182)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1341 AA; 147634 MW; D7CABAC957858F9D CRC64;
MPSLSGSDEL IFFVNGKKVV VKKPDPEVTL LFYLRRELHL TGTKFACGEG GCGACTVMVS
RYSASSKQIR HYPVTACLVP ICSLHGAAVT TVEGVGSIRT RVHPVQERLA KCHGTQCGFC
SPGMVMSIYT LLRNHPDPTP EQVTEALGGN LCRCTGYRPI VESGKTFCAN PTVCQVKRPG
RCCLEQEEEE AGSVHTREKM CTKLYDKDEF QPLDPSQEPI FPPELIRMAE DPNKRRLTFQ
GERTTWLAPA TLPDLLELRA EFPQAPLIMG NTTVGPDIKF KGEFHPVFVS PLELPELCVL
NSEGDGVTVG SGHSLAQLSD ALQSIVSQQP SERTETCRAL LNHLRTLAGV QIRSMATLGG
HVATRATVSD LNPILAAGKT TIHLVSKEGE RQIPLDGAFL EGSPRAGLRP GEIVLSVFIP
YSSQWQFVSG LRQAQRQENA MAIVNAGMSV RLEDGSSTIR DLQVFYGGIG PTVLSASRTC
GQLVGRQWDD QMLGEACRGI LDELRLPPGA KGGQVEFRHT LMLSLLFKFY LRVQRALSKL
DPQKFPDIPE EYTSALEEFP IGTPQGTQIF RCVDPHQPPQ DPVGHPVMHQ AGLKHATGEA
AFVDDLPLVS QELFLAVVTS TRAHAKIISI DTGEALALPG VVAVITAEDV PGENNHQGEI
FYAQREVVCV GQIVCTVAAD TYAHAREAAQ KVKVEYEDIE PRIITIEQAL EHSSFLSPER
KIEQGNVEQA FKHVDQVIEG EVHVEGQEHF YMETQTILAV PRAEDKEMVL HLGTQFPTHV
QEFVATALNV PRNRIACHMR RAGGAFGGKV TKPALLGAVA AVAAKKTGRP IRFVLERGDD
MLITAGRHPL LGRYKVGFMK SGLIKAVDLE FYINGGCTPD ESQLVIEYVV LKSENAYYIP
NFRCRGRACK TNLPSNTAFR GFGFPQATVV VEAYMTAVAS HCDLLPEEVR EMNMYKRPSQ
TAYRQRFDPE PLRRCWKDCL EHSSFHARKR AAEDFNRQSR WKKRGLAMIP MKYTIGVPVA
YYHQAAALVH IYLDGSVLLT HGGCELGQGL HTKMMQVASR ELGIPTSYIH LSETSTVTVP
NAVFTAGSMG TDINGKAVQN ACQTLMARLQ PVIRRNPKGK WEEWIKKAFE ESISLSATGY
FRGFQTNMDW DKERGDAFPY YVYGAACAEV DVDCLSGAHK LLRADIFMDA AFSINPAVDI
GQIEGAFVQG MGLYTTEELK YSPKGKLRSQ GTNDYKIPTV TEIPEEFHVT LVHSRNPVAI
YSSKGLGEAG MFLGSSVISA IWDAVAAARK ERKGAESVPE TLAVRSPATP EWIRMACVDQ
FTDMIPRDDP STFTPWSICV S
