AOXC_RAT
ID AOXC_RAT Reviewed; 1334 AA.
AC Q5QE80;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Aldehyde oxidase 3;
DE EC=1.2.3.1;
DE AltName: Full=Aldehyde oxidase homolog 1;
DE AltName: Full=Azaheterocycle hydroxylase 3;
DE EC=1.17.3.-;
GN Name=Aox3; Synonyms=Aoh1;
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 FUNCTION IN SUPEROXIDE PRODUCTION, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, HOMODIMER, AND COFACTOR.
RX PubMed=17353002; DOI=10.1016/j.abb.2006.12.032;
RA Kundu T.K., Hille R., Velayutham M., Zweier J.L.;
RT "Characterization of superoxide production from aldehyde oxidase: an
RT important source of oxidants in biological tissues.";
RL Arch. Biochem. Biophys. 460:113-121(2007).
RN [3]
RP FUNCTION IN NITRIC OXIDE PRODUCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP ACTIVITY REGULATION.
RX PubMed=19801639; DOI=10.1074/jbc.m109.019125;
RA Li H., Kundu T.K., Zweier J.L.;
RT "Characterization of the magnitude and mechanism of aldehyde oxidase-
RT mediated nitric oxide production from nitrite.";
RL J. Biol. Chem. 284:33850-33858(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [5]
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: Oxidase with broad substrate specificity, oxidizing aromatic
CC azaheterocycles, such as N1-methylnicotinamide and phthalazine, as well
CC as aldehydes, such as benzaldehyde, retinal and pyridoxal. Plays a key
CC role in the metabolism of xenobiotics and drugs containing aromatic
CC azaheterocyclic substituents. Is probably involved in the regulation of
CC reactive oxygen species homeostasis. Is a prominent source of
CC superoxide generation via the one-electron reduction of molecular
CC oxygen. Also catalyzes nitric oxide (NO) production; under anaerobic
CC conditions, reduces nitrite to NO with NADH or aldehyde as electron
CC donor, but under aerobic conditions, NADH is the preferred substrate.
CC These reactions may be catalyzed by several isozymes.
CC {ECO:0000269|PubMed:17353002, ECO:0000269|PubMed:19801639}.
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:0000269|PubMed:17353002};
CC Note=Binds 2 [2Fe-2S] clusters per subunit.
CC {ECO:0000269|PubMed:17353002};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:17353002};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:17353002};
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:0000269|PubMed:17353002}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17353002}.
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 -!- CAUTION: The experimental design does not allow to distinguish AOX1
CC from AOX3 in rat liver as the effector of the superoxide and nitric
CC oxide production (PubMed:17353002 and 19801639). {ECO:0000305}.
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DR EMBL; AY665586; AAV68253.1; -; mRNA.
DR RefSeq; NP_001008527.1; NM_001008527.1.
DR AlphaFoldDB; Q5QE80; -.
DR SMR; Q5QE80; -.
DR iPTMnet; Q5QE80; -.
DR PhosphoSitePlus; Q5QE80; -.
DR PRIDE; Q5QE80; -.
DR GeneID; 493909; -.
DR KEGG; rno:493909; -.
DR UCSC; RGD:1359328; rat.
DR CTD; 71724; -.
DR RGD; 1359328; Aox3.
DR OrthoDB; 48717at2759; -.
DR PhylomeDB; Q5QE80; -.
DR BRENDA; 1.2.3.1; 5301.
DR PRO; PR:Q5QE80; -.
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 1: Evidence at protein level;
KW 2Fe-2S; Cytoplasm; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding;
KW Molybdenum; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..1334
FT /note="Aldehyde oxidase 3"
FT /id="PRO_0000425248"
FT DOMAIN 8..95
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 236..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:G3X982"
FT BINDING 47
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 52
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 55
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 77
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 116
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 117
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 120
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 152
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 154
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 264..271
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
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:G3X982"
FT BINDING 367
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 411
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 801
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 1042
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT BINDING 1198
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:G3X982"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 1334 AA; 146751 MW; 5F801F0315F170DC CRC64;
MSRSKESDEL IFFVNGKKVI ERNADPEVNL LFYLRKIIQL TGTKYGCGGG DCGACTVMIS
RYNPISKKIS HFSAAACLVP ICSLHGAAVT TVEGIGSTKT RIHPVQERIA KGHGTQCGFC
TPGMVMSIYT LLRNHPEPST EQIMETLGGN LCRCTGYRPI VESARSFSPN SACCPMNEKW
KCCLDEGKNE PERKNSVCTK LYEKEEFQPL DPTQELIFPP ELMRMAEDSP NTVLTFRGER
TTWIAPGTLN DLLELKMEYP SAPLVIGNTC LGLDMKFKDV SYPIIISPAR ILELFVVTNT
NEGLTLGAGL SLTQVKNILS DVVSRLPKER TQTYRALLKH LRTLAGQQIR NVASLGGHII
SRLPTSDLNP IFGVGNCKLN VASTEGTQQI PLNDHFLAGV PEAILKPEQV LISVFVPLSR
KWEFVSAFRQ APRQQNAFAI VNAGMRVAFK EDTNTITDLS ILYGGIGATV VSAKSCQQLI
GRCWDEEMLD DAGRMIREEV SLLTAAPGGM VEYRKTLAIS FLFKFYLDVL KQLKRRNPHR
CPDISQKLLQ VLEDFPLTMP HGTQSFKDVD SQQPLQDQSG RPIMHQSGIK HATGEAVFCD
DMSVLAGELF LAVVTSSKPH ARIISLDASE ALASPGVVDV ITAQDVPGDN GREEESLYAQ
DEVICVGQIV CAVAADSYAR AKQATKKVKI VYEDMEPMIV TVQDALQHES FIGPEKKLEQ
GNVQLAFQSA DQILEGEVHL GGQEHFYMET QSVRVIPKGE DMEMDIYVSS QDAAFTQEMV
ARTLGIPKNR ITCHVKRVGG GFGGKTSKPG LLASVAAVAA QKTGRPIRFI LERGDDMLIT
GGRHPLLGKY RVGFMNNGKI KAADIQLYIN GGCTPDDSEL VIEYALLKLE NAYKIPNLRV
RGRVCKTNLP SNTAFRGFGF PQGAFVTGTW VSAVAAKCHL PPEKVRELNM YKTIDRTIHK
QEFDPTNLIK CWETCMENSS YYSRKKAVDE FNQQSFWKKR GIAIIPMKFS VGFPKTFYHQ
AAALVQIYTD GSVLVAHGGV ELGQGINTKM IQVASRELKI PMSYIHLDEM NTMTVPNTIT
TGGSTGADVN GRAVQNACQI LMKRLEPIIS QNPNGDWEEW INEAFIQSIS LSATGYFRGY
QADMDWEKGE GDIYPYFVFG AACSEVEIDC LTGAHKNIRT DIVMDGSFSI NPAVDIGQIE
GAFVQGLGLY TLEELKYSPE GVLYTRGPHQ YKIASVSDIP EEFHVSLLTP TQNPKAIYSS
KGLGEAGMFL GSSVFFAIAA AVAAARKERG LPLILAINSP ATAEVIRMAC EDQFTNLVPK
TDSKCCKPWS IPVA
