AOXD_RAT
ID AOXD_RAT Reviewed; 1334 AA.
AC Q5QE79;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 131.
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; Synonyms=Aoh2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CD Charles River;
RX PubMed=15383531; DOI=10.1074/jbc.m408734200;
RA Kurosaki M., Terao M., Barzago M.M., Bastone A., Bernardinello D.,
RA Salmona M., Garattini E.;
RT "The aldehyde oxidase gene cluster in mice and rats. Aldehyde oxidase
RT homologue 3, a novel member of the molybdo-flavoenzyme family with
RT selective expression in the olfactory mucosa.";
RL J. Biol. Chem. 279:50482-50498(2004).
RN [2]
RP IDENTIFICATION OF 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).
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|UniProtKB:Q3TYQ9}.
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 Evidence={ECO:0000250|UniProtKB:Q3TYQ9};
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; Evidence={ECO:0000250|UniProtKB:Q3TYQ9};
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|UniProtKB:Q3TYQ9}.
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; AY665587; AAV68254.1; -; mRNA.
DR RefSeq; NP_001008523.1; NM_001008523.1.
DR AlphaFoldDB; Q5QE79; -.
DR SMR; Q5QE79; -.
DR STRING; 10116.ENSRNOP00000035377; -.
DR PhosphoSitePlus; Q5QE79; -.
DR PaxDb; Q5QE79; -.
DR PRIDE; Q5QE79; -.
DR GeneID; 316424; -.
DR KEGG; rno:316424; -.
DR CTD; 71872; -.
DR RGD; 1311975; Aox4.
DR eggNOG; KOG0430; Eukaryota.
DR OrthoDB; 48717at2759; -.
DR BRENDA; 1.2.3.1; 5301.
DR PRO; PR:Q5QE79; -.
DR Proteomes; UP000002494; Unplaced.
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:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
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..1334
FT /note="Aldehyde oxidase 4"
FT /id="PRO_0000425251"
FT DOMAIN 6..93
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 235..421
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1265
FT /note="Proton acceptor; for azaheterocycle hydroxylase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:O54754"
FT BINDING 45
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 50
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 53
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 75
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 114
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 115
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 118
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 150
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 152
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 263..270
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 345
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 354
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 358
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 367
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 411
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 802..803
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 802
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 1043
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 1084..1087
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1199
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1263
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
SQ SEQUENCE 1334 AA; 147841 MW; B87151E36E3C47E4 CRC64;
MPSSSDELIF FVNGKKVIEK NPVPEMNLLF YVRKVLHLTG TKYSCGGGGC GACTVMISRY
NPESKKIYHY PATACLVPVC SLHGAAVTTV EGVGSIKRRI HPVQERLAKC HGTQCGFCSP
GMVMSIYTLL RNHPEPTPDQ ITEALGGNLC RCTGYRPIVE SGKTFSPESS VCQMKGSGKC
CMDLDEGCSE STKERMCTKL YNEDEFQPLD PSQEPIFPPE LIRMAEDPHK RRLTFQGERT
IWIMPVTLNG LLELKASYPE APLVMGNTAV GPGMKFNNEF HPVFISPLGL PELNLVDTAN
SGGVTIGARH SLAQMKDILH SLTLEQPKEK TKTHQALLKH LRTLAGPQIR NMATLGGHVV
SRPDFSDLNP ILAAGNATIN VISKEGQRQI PLNGPFLERL PEASLKPEEV ALSVFIPYSG
QWQYVSGLRL AQRQENAFAI VNAGMSVEFE EGTNTIKDLQ MLFGSVAPTV VSASQTCKQL
IGRQWDDQML SDACQLVLEE IRIPPDAEGG MVEYRRTLII SLLFKFYLKV RRWLSEMDPQ
KFPDIPEKFV SALDDLPIET PQGIQMFQCV DPNQPEQDPV GHPIMHQSGI KHATGEAKFV
DDMPRINQEL CLTVVTSTRA HAKITSIDVS EALAYPGVVD VITAEDVPGD NNHSGEIFYA
QNEVICVGQI ICTVAADTYI HAKEAAKRVK ITYDDIEPAI ITIEQALEHN SFLSSEKKIE
QGNVDYAFKH VDHIIEGEIH VEGQEHFYME TQTILAIPQT EDKEMVLHVG TQFPTHVQEY
VSAALKVPRN RIACQMKRTG GAFGGKVTKP ALLGAVCAVA AHKTGRPIRF ILDRSNDMLI
TAGRHPLLGK YKIGFMNNGK IKAADVEYYT NGGCTPDESE MVIEFIVLKS ENAYHIPNFR
CRGRACKTNL PSNTAFRGFG FPQATVVVEA YIAAVASKCN LLPEEIREIN MYKQISKTAY
KQTFNPEPLR RCWKECLQKS SFFARKQAAE EFNKNNYWKK KGLAVVPMKF SVAVPMAFYN
QAAALVHIFL DGSVLLTHGG CELGQGLHTK MIQVASRELN IPKSYVHLVE TSTVTVPNAV
FTAGSMGADI NGKAVQNACQ TLLDRLQPII KKNPKGKWEE WVKKAFEESI SLSATGYFKG
YQTNMDWEKE EGDPYPYYVY GAACSEVEVD CLTGAHKLLR TDIFMDAAFS INPALDIGQV
EGAFIQGMGF YTIEELKYSP KGVLYSRGPD DYKIPTVTEI PEEFYVTMVR SRNPIAIYSS
KGLGEAGMFL GSSVLFAIYD AVTTARKERG LSDIFPLNSP ATPEVIRMAC KDQFTDMIPR
DDPSTFTPWS IHVS
