AOXA_HUMAN
ID AOXA_HUMAN Reviewed; 1338 AA.
AC Q06278; O14765; Q53RR8; Q53TV3; Q9BYF0; Q9UPG6;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Aldehyde oxidase {ECO:0000312|HGNC:HGNC:553};
DE EC=1.2.3.1 {ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:26322824};
DE AltName: Full=Aldehyde oxidase 1;
DE AltName: Full=Azaheterocycle hydroxylase {ECO:0000305|PubMed:7786031, ECO:0000305|PubMed:9224775};
DE EC=1.17.3.- {ECO:0000269|PubMed:7786031, ECO:0000269|PubMed:9224775};
GN Name=AOX1 {ECO:0000312|HGNC:HGNC:553}; Synonyms=AO;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=8248161; DOI=10.1073/pnas.90.22.10690;
RA Wright R.M., Vaitaitis G.M., Wilson C.M., Repine T.B., Terada L.S.,
RA Repine J.E.;
RT "cDNA cloning, characterization, and tissue-specific expression of human
RT xanthine dehydrogenase/xanthine oxidase.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10690-10694(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Wright R.M., Weigel L.K., Varella-Garcia M., Vaitaitis G., Repine J.E.;
RT "Molecular cloning, refined chromosomal mapping, and structural analysis of
RT the human gene encoding aldehyde oxidase (AOX1), a candidate for the ALS2
RT gene.";
RL Redox Rep. 3:135-144(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=11302742; DOI=10.1006/bbrc.2001.4719;
RA Ichida K., Matsumura T., Sakuma R., Hosoya T., Nishino T.;
RT "Mutation of human molybdenum cofactor sulfurase gene is responsible to
RT classical xanthinuria type II.";
RL Biochem. Biophys. Res. Commun. 282:1194-1200(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION AS AZAHETEROCYCLE OXIDASE, AND SUBSTRATE SPECIFICITY.
RX PubMed=7786031; DOI=10.1006/abbi.1995.1320;
RA Beedham C., Critchley D.J., Rance D.J.;
RT "Substrate specificity of human liver aldehyde oxidase toward substituted
RT quinazolines and phthalazines: a comparison with hepatic enzyme from guinea
RT pig, rabbit, and baboon.";
RL Arch. Biochem. Biophys. 319:481-490(1995).
RN [8]
RP FUNCTION AS AZAHETEROCYCLE OXIDASE, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9224775;
RA Rashidi M.R., Smith J.A., Clarke S.E., Beedham C.;
RT "In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde
RT oxidase from human, guinea pig, rabbit, and rat liver.";
RL Drug Metab. Dispos. 25:805-813(1997).
RN [9]
RP INDUCTION.
RX PubMed=17022944; DOI=10.1016/j.bbrc.2006.09.101;
RA Neumeier M., Weigert J., Schaeffler A., Weiss T.S., Schmidl C.,
RA Buettner R., Bollheimer C., Aslanidis C., Schoelmerich J., Buechler C.;
RT "Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is down-
RT regulated by adiponectin and fenofibric acid in hepatocytes in vitro.";
RL Biochem. Biophys. Res. Commun. 350:731-735(2006).
RN [10]
RP REVIEW, NOMENCLATURE, AND TISSUE SPECIFICITY.
RX PubMed=18066686; DOI=10.1007/s00018-007-7398-y;
RA Garattini E., Fratelli M., Terao M.;
RT "Mammalian aldehyde oxidases: genetics, evolution and biochemistry.";
RL Cell. Mol. Life Sci. 65:1019-1048(2008).
RN [11]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=18671973; DOI=10.1016/j.febslet.2008.07.034;
RA Weigert J., Neumeier M., Bauer S., Mages W., Schnitzbauer A.A., Obed A.,
RA Groeschl B., Hartmann A., Schaeffler A., Aslanidis C., Schoelmerich J.,
RA Buechler C.;
RT "Small-interference RNA-mediated knock-down of aldehyde oxidase 1 in 3T3-L1
RT cells impairs adipogenesis and adiponectin release.";
RL FEBS Lett. 582:2965-2972(2008).
RN [12]
RP FUNCTION AS DRUG-METABOLIZING ENZYME, SUBSTRATE SPECIFICITY, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=20444863; DOI=10.1124/dmd.110.033555;
RA Zientek M., Jiang Y., Youdim K., Obach R.S.;
RT "In vitro-in vivo correlation for intrinsic clearance for drugs metabolized
RT by human aldehyde oxidase.";
RL Drug Metab. Dispos. 38:1322-1327(2010).
RN [13]
RP FUNCTION AS DRUG-METABOLIZING ENZYME, ACTIVITY REGULATION, SUBSTRATE
RP SPECIFICITY, AND TISSUE SPECIFICITY.
RX PubMed=22031625; DOI=10.1124/dmd.111.042861;
RA Hutzler J.M., Yang Y.S., Albaugh D., Fullenwider C.L., Schmenk J.,
RA Fisher M.B.;
RT "Characterization of aldehyde oxidase enzyme activity in cryopreserved
RT human hepatocytes.";
RL Drug Metab. Dispos. 40:267-275(2012).
RN [14]
RP FUNCTION AS DRUG-METABOLIZING ENZYME, ACTIVITY REGULATION, SUBSTRATE
RP SPECIFICITY, AND TISSUE SPECIFICITY.
RX PubMed=22522748; DOI=10.1124/dmd.112.045195;
RA Strelevitz T.J., Orozco C.C., Obach R.S.;
RT "Hydralazine as a selective probe inactivator of aldehyde oxidase in human
RT hepatocytes: estimation of the contribution of aldehyde oxidase to
RT metabolic clearance.";
RL Drug Metab. Dispos. 40:1441-1448(2012).
RN [15]
RP REVIEW.
RX PubMed=22335465; DOI=10.1517/17425255.2012.663352;
RA Garattini E., Terao M.;
RT "The role of aldehyde oxidase in drug metabolism.";
RL Expert Opin. Drug Metab. Toxicol. 8:487-503(2012).
RN [16]
RP FUNCTION AS AZAHETEROCYCLE OXIDASE, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22996261; DOI=10.1124/dmd.112.048546;
RA Barr J.T., Jones J.P.;
RT "Evidence for substrate-dependent inhibition profiles for human liver
RT aldehyde oxidase.";
RL Drug Metab. Dispos. 41:24-29(2013).
RN [17]
RP FUNCTION AS DRUG-METABOLIZING ENZYME, SUBSTRATE SPECIFICITY, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23857892; DOI=10.1124/dmd.113.053082;
RA Fu C., Di L., Han X., Soderstrom C., Snyder M., Troutman M.D., Obach R.S.,
RA Zhang H.;
RT "Aldehyde oxidase 1 (AOX1) in human liver cytosols: quantitative
RT characterization of AOX1 expression level and activity relationship.";
RL Drug Metab. Dispos. 41:1797-1804(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1068, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH FAD; IRON-SULFUR
RP (2FE-2S); MOLYBDOPTERIN; AN INHIBITOR AND SUBSTRATE, SUBUNIT, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, FUNCTION, AND COFACTOR.
RX PubMed=26322824; DOI=10.1038/nchembio.1895;
RA Coelho C., Foti A., Hartmann T., Santos-Silva T., Leimkuhler S.,
RA Romao M.J.;
RT "Structural insights into xenobiotic and inhibitor binding to human
RT aldehyde oxidase.";
RL Nat. Chem. Biol. 11:779-783(2015).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (3.39 ANGSTROMS) OF VARIANT LEU-1271 IN COMPLEX WITH
RP FAD; IRON-SULFUR (2FE-2S) AND MOLYBDOPTERIN, CHARACTERIZATION OF VARIANT
RP LEU-1271, FUNCTION, SUBUNIT, COFACTOR, MUTAGENESIS OF CYS-44 AND GLY-1269,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=26842593; DOI=10.1124/dmd.115.068395;
RA Foti A., Hartmann T., Coelho C., Santos-Silva T., Romao M.J.,
RA Leimkuhler S.;
RT "Optimization of the Expression of Human Aldehyde Oxidase for
RT Investigations of Single-Nucleotide Polymorphisms.";
RL Drug Metab. Dispos. 44:1277-1285(2016).
RN [21]
RP VARIANTS CYS-802; HIS-921; SER-1135; LEU-1271 AND ARG-1297,
RP CHARACTERIZATION OF VARIANTS CYS-802; HIS-921; SER-1135 AND ARG-1297,
RP FUNCTION AS OXIDASE, HOMODIMER, COFACTOR, SUBSTRATE SPECIFICITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22279051; DOI=10.1124/dmd.111.043828;
RA Hartmann T., Terao M., Garattini E., Teutloff C., Alfaro J.F., Jones J.P.,
RA Leimkuehler S.;
RT "The impact of single nucleotide polymorphisms on human aldehyde oxidase.";
RL Drug Metab. Dispos. 40:856-864(2012).
CC -!- FUNCTION: Oxidase with broad substrate specificity, oxidizing aromatic
CC azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium
CC and phthalazine, as well as aldehydes, such as benzaldehyde, retinal,
CC pyridoxal, and vanillin. Plays a key role in the metabolism of
CC xenobiotics and drugs containing aromatic azaheterocyclic substituents.
CC Participates in the bioactivation of prodrugs such as famciclovir,
CC catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir,
CC which is a potent antiviral agent. Is probably involved in the
CC regulation of reactive oxygen species homeostasis. May be a prominent
CC source of superoxide generation via the one-electron reduction of
CC molecular oxygen. May also catalyze nitric oxide (NO) production via
CC the reduction of nitrite to NO with NADH or aldehyde as electron donor.
CC May play a role in adipogenesis. {ECO:0000269|PubMed:20444863,
CC ECO:0000269|PubMed:22031625, ECO:0000269|PubMed:22279051,
CC ECO:0000269|PubMed:22522748, ECO:0000269|PubMed:22996261,
CC ECO:0000269|PubMed:23857892, ECO:0000269|PubMed:26322824,
CC ECO:0000269|PubMed:7786031, ECO:0000269|PubMed:9224775}.
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; Evidence={ECO:0000269|PubMed:22996261,
CC ECO:0000269|PubMed:26322824};
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:O54754};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:26322824,
CC ECO:0000269|PubMed:26842593};
CC Note=Binds 2 [2Fe-2S] clusters per subunit.
CC {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:26322824};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:26322824};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:22279051,
CC ECO:0000269|PubMed:26322824};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:26322824,
CC ECO:0000269|PubMed:26842593};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:26322824};
CC -!- ACTIVITY REGULATION: Is very potently inhibited by raloxifene
CC (PubMed:26842593). Also inhibited by estradiol, ethinyl estradiol,
CC hydralazine, menadione, isovanillin and thioridazine. Not inhibited by
CC allopurinol, a xanthine dehydrogenase potent inhibitor
CC (PubMed:22031625, PubMed:22522748, PubMed:22996261, PubMed:9224775,
CC PubMed:26322824). {ECO:0000269|PubMed:22031625,
CC ECO:0000269|PubMed:22522748, ECO:0000269|PubMed:22996261,
CC ECO:0000269|PubMed:26322824, ECO:0000269|PubMed:26842593,
CC ECO:0000269|PubMed:9224775}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.6 uM for benzaldehyde (in the presence of 2,6-dichlorophenol
CC indophenol as electron acceptor) {ECO:0000269|PubMed:26842593};
CC KM=45.18 uM for benzaldehyde (in the presence of ferricyanide as
CC electron acceptor) {ECO:0000269|PubMed:26842593};
CC KM=1.3 uM for phthalazine (at 25 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:22279051};
CC KM=8.96 uM for phthalazine (in the presence of 2,6-dichlorophenol
CC indophenol as electron acceptor) {ECO:0000269|PubMed:26842593};
CC KM=125.7 uM for phthalazine (in the presence of ferricyanide as
CC electron acceptor) {ECO:0000269|PubMed:26842593};
CC KM=0.78 uM for phenanthridine (in the pres 2,6-dichlorophenol
CC indophenol as electron acceptor) {ECO:0000269|PubMed:26842593};
CC KM=25.5 uM for phenanthridine (in the presence of ferricyanide as
CC electron acceptor) {ECO:0000269|PubMed:26842593};
CC KM=26.53 uM for phenanthridine (in the presence of molecular oxygen
CC as electron acceptor) {ECO:0000269|PubMed:26842593};
CC KM=3.9 uM for phenanthridine (at 25 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:22279051};
CC KM=5.2 uM for chloroquinazolinone (at 25 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:22279051};
CC KM=0.42 mM for 6-deoxypenciclovir (at 37 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9224775};
CC KM=0.15 mM for famciclovir (at 37 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9224775};
CC KM=6.3 uM for N-[(2-dimethylamino)ethyl]acridine-4-carboxamide (at 37
CC degrees Celsius and pH 7.4) {ECO:0000269|PubMed:22996261};
CC Vmax=16 nmol/min/mg enzyme with 6-deoxypenciclovir as substrate
CC {ECO:0000269|PubMed:9224775};
CC Vmax=61 nmol/min/mg enzyme with famciclovir as substrate
CC {ECO:0000269|PubMed:9224775};
CC Vmax=2.3 nmol/min/mg enzyme with N-[(2-dimethylamino)ethyl]acridine-
CC 4-carboxamide as substrate {ECO:0000269|PubMed:22996261};
CC Note=kcat is 6.4 min(-1) for benzaldehyde oxidation, 5.6 min(-1) for
CC phthalazine oxidation, 12.2 min(-1) for phenanthridine oxidation and
CC 5.6 min(-1) for chloroquinazolinone oxidation.
CC {ECO:0000269|PubMed:22279051};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:26322824,
CC ECO:0000269|PubMed:26842593}.
CC -!- INTERACTION:
CC Q06278; Q06278: AOX1; NbExp=2; IntAct=EBI-3926368, EBI-3926368;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18671973,
CC ECO:0000269|PubMed:20444863, ECO:0000269|PubMed:23857892}.
CC -!- TISSUE SPECIFICITY: Abundant in liver, expressed in adipose tissue and
CC at lower levels in lung, skeletal muscle, pancreas. In contrast to
CC mice, no significant gender difference in AOX1 expression level (at
CC protein level). {ECO:0000269|PubMed:18066686,
CC ECO:0000269|PubMed:18671973, ECO:0000269|PubMed:20444863,
CC ECO:0000269|PubMed:22031625, ECO:0000269|PubMed:22522748,
CC ECO:0000269|PubMed:23857892, ECO:0000269|PubMed:8248161}.
CC -!- DEVELOPMENTAL STAGE: Not detected in preadipocytes but strongly induced
CC in mature adipocytes. {ECO:0000269|PubMed:18671973}.
CC -!- INDUCTION: In liver, is down-regulated by adiponectin and by the PPARA
CC agonist, fenofibric acid. {ECO:0000269|PubMed:17022944}.
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:22335465). {ECO:0000305|PubMed:22335465}.
CC -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a xanthine dehydrogenase.
CC {ECO:0000305|PubMed:8248161}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA96650.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB83966.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L11005; AAA96650.1; ALT_FRAME; mRNA.
DR EMBL; AF017060; AAB83966.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AF009441; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009442; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009443; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009444; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009445; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009446; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009447; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009448; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009449; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009450; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009451; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009452; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009453; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009454; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009455; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009456; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009457; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009458; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009459; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009460; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009461; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009462; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009463; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009464; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009465; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009466; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009467; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009468; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009469; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009470; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009471; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009472; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009473; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF009474; AAB83966.1; JOINED; Genomic_DNA.
DR EMBL; AF010260; AAB83968.1; -; Genomic_DNA.
DR EMBL; AB046692; BAB40305.1; -; mRNA.
DR EMBL; AC007163; AAX93285.1; -; Genomic_DNA.
DR EMBL; AC080164; AAY24265.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70209.1; -; Genomic_DNA.
DR EMBL; BC117179; AAI17180.1; -; mRNA.
DR EMBL; BC117181; AAI17182.1; -; mRNA.
DR CCDS; CCDS33360.1; -.
DR PIR; A49634; A49634.
DR RefSeq; NP_001150.3; NM_001159.3.
DR PDB; 4UHW; X-ray; 2.60 A; A=1-1338.
DR PDB; 4UHX; X-ray; 2.70 A; A=1-1338.
DR PDB; 5EPG; X-ray; 3.39 A; A=1-1338.
DR PDB; 6Q6Q; X-ray; 3.10 A; A=1-1338.
DR PDB; 7OPN; X-ray; 2.60 A; A/B=1-1338.
DR PDB; 7ORC; X-ray; 2.70 A; A/B=1-1338.
DR PDBsum; 4UHW; -.
DR PDBsum; 4UHX; -.
DR PDBsum; 5EPG; -.
DR PDBsum; 6Q6Q; -.
DR PDBsum; 7OPN; -.
DR PDBsum; 7ORC; -.
DR AlphaFoldDB; Q06278; -.
DR SMR; Q06278; -.
DR BioGRID; 106813; 10.
DR DIP; DIP-61698N; -.
DR IntAct; Q06278; 5.
DR STRING; 9606.ENSP00000363832; -.
DR BindingDB; Q06278; -.
DR ChEMBL; CHEMBL3257; -.
DR DrugBank; DB00437; Allopurinol.
DR DrugBank; DB00513; Aminocaproic acid.
DR DrugBank; DB00484; Brimonidine.
DR DrugBank; DB11791; Capmatinib.
DR DrugBank; DB00924; Cyclobenzaprine.
DR DrugBank; DB03516; Eniluracil.
DR DrugBank; DB00426; Famciclovir.
DR DrugBank; DB12466; Favipiravir.
DR DrugBank; DB09054; Idelalisib.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB01033; Mercaptopurine.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB08840; N-methylnicotinamide.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00339; Pyrazinamide.
DR DrugBank; DB00481; Raloxifene.
DR DrugBank; DB04827; Urethane.
DR DrugBank; DB00962; Zaleplon.
DR DrugBank; DB00246; Ziprasidone.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; Q06278; -.
DR iPTMnet; Q06278; -.
DR PhosphoSitePlus; Q06278; -.
DR BioMuta; AOX1; -.
DR DMDM; 215273968; -.
DR EPD; Q06278; -.
DR jPOST; Q06278; -.
DR MassIVE; Q06278; -.
DR MaxQB; Q06278; -.
DR PaxDb; Q06278; -.
DR PeptideAtlas; Q06278; -.
DR PRIDE; Q06278; -.
DR ProteomicsDB; 58430; -.
DR Antibodypedia; 34105; 242 antibodies from 28 providers.
DR DNASU; 316; -.
DR Ensembl; ENST00000374700.7; ENSP00000363832.2; ENSG00000138356.14.
DR GeneID; 316; -.
DR KEGG; hsa:316; -.
DR MANE-Select; ENST00000374700.7; ENSP00000363832.2; NM_001159.4; NP_001150.3.
DR UCSC; uc002uvx.4; human.
DR CTD; 316; -.
DR DisGeNET; 316; -.
DR GeneCards; AOX1; -.
DR HGNC; HGNC:553; AOX1.
DR HPA; ENSG00000138356; Group enriched (adrenal gland, liver).
DR MIM; 602841; gene.
DR neXtProt; NX_Q06278; -.
DR OpenTargets; ENSG00000138356; -.
DR PharmGKB; PA24842; -.
DR VEuPathDB; HostDB:ENSG00000138356; -.
DR eggNOG; KOG0430; Eukaryota.
DR GeneTree; ENSGT00950000183114; -.
DR HOGENOM; CLU_001681_1_2_1; -.
DR InParanoid; Q06278; -.
DR OMA; PQAMFIA; -.
DR OrthoDB; 48717at2759; -.
DR PhylomeDB; Q06278; -.
DR TreeFam; TF353036; -.
DR BioCyc; MetaCyc:ENSG00000138356-MON; -.
DR BRENDA; 1.2.3.1; 2681.
DR PathwayCommons; Q06278; -.
DR Reactome; R-HSA-964975; Vitamins B6 activation to pyridoxal phosphate.
DR SABIO-RK; Q06278; -.
DR SignaLink; Q06278; -.
DR BioGRID-ORCS; 316; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; AOX1; human.
DR GeneWiki; Aldehyde_oxidase_1; -.
DR GenomeRNAi; 316; -.
DR Pharos; Q06278; Tchem.
DR PRO; PR:Q06278; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q06278; protein.
DR Bgee; ENSG00000138356; Expressed in right adrenal gland cortex and 160 other tissues.
DR ExpressionAtlas; Q06278; baseline and differential.
DR Genevisible; Q06278; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0004031; F:aldehyde oxidase activity; IDA:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0043546; F:molybdopterin cofactor binding; IDA: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; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA: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 InterPro; IPR022407; OxRdtase_Mopterin_BS.
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.
DR PROSITE; PS00559; MOLYBDOPTERIN_EUK; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; 3D-structure; Cytoplasm; FAD; Flavoprotein; Iron; Iron-sulfur;
KW Lipid metabolism; Metal-binding; Molybdenum; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..1338
FT /note="Aldehyde oxidase"
FT /id="PRO_0000166104"
FT DOMAIN 5..92
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 1270
FT /note="Proton acceptor; for azaheterocycle hydroxylase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:O54754"
FT BINDING 44
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0007744|PDB:4UHW"
FT BINDING 49
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 52
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 74
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 113
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0007744|PDB:4UHW, ECO:0007744|PDB:4UHX"
FT BINDING 114
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 117
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 149
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 151
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 151
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 264..271
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 345
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0007744|PDB:4UHW, ECO:0007744|PDB:4UHX"
FT BINDING 354
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 358
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:5EPG"
FT BINDING 367
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 411
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 806..807
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 1047
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 1088..1091
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 1203
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0000269|PubMed:26842593, ECO:0007744|PDB:4UHW,
FT ECO:0007744|PDB:4UHX, ECO:0007744|PDB:5EPG"
FT BINDING 1268
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000269|PubMed:26322824,
FT ECO:0007744|PDB:4UHX"
FT MOD_RES 1068
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 314
FT /note="Q -> R (in dbSNP:rs58185012)"
FT /id="VAR_061136"
FT VARIANT 802
FT /note="R -> C (decreases homodimerization but nearly no
FT effect on kinetic parameters; dbSNP:rs41309768)"
FT /evidence="ECO:0000269|PubMed:22279051"
FT /id="VAR_047517"
FT VARIANT 921
FT /note="R -> H (increases homodimerization; abolishes
FT enzymatic activity on phenanthridine; decreases turnover
FT number with benzaldehyde, phtalazine and
FT chloroquinazolinone as substrate, while nearly no effect on
FT the KM; dbSNP:rs56199635)"
FT /evidence="ECO:0000269|PubMed:22279051"
FT /id="VAR_070256"
FT VARIANT 1135
FT /note="N -> S (increases homodimerization and turnover
FT number with phenanthridine as substrate; nearly no effect
FT on kinetic parameters with benzaldehyde, phtalazine and
FT chloroquinazolinone as substrate; dbSNP:rs55754655)"
FT /evidence="ECO:0000269|PubMed:22279051"
FT /id="VAR_070257"
FT VARIANT 1271
FT /note="S -> L (no effect on dimerization; no effect on
FT oxidase activity; dbSNP:rs141786030)"
FT /evidence="ECO:0000269|PubMed:22279051,
FT ECO:0000269|PubMed:26842593"
FT /id="VAR_070258"
FT VARIANT 1297
FT /note="H -> R (increases homodimerization and turnover
FT number with phenanthridine as substrate; nearly no effect
FT on kinetic parameters with benzaldehyde, phtalazine and
FT chloroquinazolinone as substrate; dbSNP:rs3731722)"
FT /evidence="ECO:0000269|PubMed:22279051"
FT /id="VAR_047518"
FT MUTAGEN 44
FT /note="C->W: Disrupts protein stability."
FT /evidence="ECO:0000269|PubMed:26842593"
FT MUTAGEN 1269
FT /note="G->R: No effect on dimerization. Loss of oxidase
FT activity."
FT /evidence="ECO:0000269|PubMed:26842593"
FT CONFLICT 41
FT /note="K -> P (in Ref. 1; AAA96650 and 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="T -> P (in Ref. 1; AAA96650 and 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="T -> H (in Ref. 1; AAA96650 and 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="E -> D (in Ref. 1; AAA96650 and 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="E -> D (in Ref. 1; AAA96650)"
FT /evidence="ECO:0000305"
FT CONFLICT 418
FT /note="Y -> I (in Ref. 1; AAA96650 and 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="V -> L (in Ref. 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 627
FT /note="I -> N (in Ref. 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 929
FT /note="A -> V (in Ref. 1; AAA96650 and 2; AAB83966)"
FT /evidence="ECO:0000305"
FT CONFLICT 1019
FT /note="G -> A (in Ref. 1; AAA96650 and 2; AAB83966)"
FT /evidence="ECO:0000305"
FT STRAND 6..11
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 14..20
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:4UHX"
FT HELIX 101..108
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 118..131
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 155..162
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:7OPN"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:4UHX"
FT HELIX 220..226
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 234..237
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 242..245
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 249..258
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 271..277
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 283..286
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 301..307
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 312..325
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 328..330
FT /evidence="ECO:0007829|PDB:7OPN"
FT HELIX 332..343
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 347..352
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 355..361
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 369..374
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 378..382
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 387..391
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 394..397
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 401..403
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 410..417
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 423..430
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 432..437
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 440..448
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 458..469
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 474..480
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:7OPN"
FT HELIX 487..498
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 512..537
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 539..541
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 547..549
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 550..552
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 562..566
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 572..574
FT /evidence="ECO:0007829|PDB:4UHX"
FT HELIX 589..593
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 600..602
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 610..616
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 620..628
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 630..633
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 638..642
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 644..646
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 648..650
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 651..663
FT /evidence="ECO:0007829|PDB:7OPN"
FT STRAND 666..668
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 674..682
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 683..690
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 694..699
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 709..711
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 721..726
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 728..731
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 732..734
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 736..745
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 756..762
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 769..773
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 778..789
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 793..795
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 796..801
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 812..828
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 832..835
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 838..844
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 851..859
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 865..878
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 884..893
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 894..897
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 901..911
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 921..924
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 925..943
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 947..954
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 958..961
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 967..969
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 971..984
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 986..999
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1001..1016
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1019..1021
FT /evidence="ECO:0007829|PDB:7OPN"
FT HELIX 1022..1024
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1026..1032
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1038..1043
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1047..1049
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1051..1062
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1067..1069
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 1077..1079
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1088..1090
FT /evidence="ECO:0007829|PDB:6Q6Q"
FT HELIX 1091..1115
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1118..1120
FT /evidence="ECO:0007829|PDB:6Q6Q"
FT HELIX 1122..1131
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1137..1142
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1148..1150
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 1151..1154
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1155..1157
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1160..1174
FT /evidence="ECO:0007829|PDB:4UHW"
FT TURN 1175..1177
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1180..1190
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1197..1215
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1232..1234
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1241..1243
FT /evidence="ECO:0007829|PDB:4UHW"
FT STRAND 1246..1252
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1262..1264
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1271..1276
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1277..1293
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1308..1314
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1318..1322
FT /evidence="ECO:0007829|PDB:4UHW"
FT HELIX 1328..1330
FT /evidence="ECO:0007829|PDB:4UHW"
SQ SEQUENCE 1338 AA; 147918 MW; 2AB5E543F18C9261 CRC64;
MDRASELLFY VNGRKVIEKN VDPETMLLPY LRKKLRLTGT KYGCGGGGCG ACTVMISRYN
PITKRIRHHP ANACLIPICS LYGAAVTTVE GIGSTHTRIH PVQERIAKCH GTQCGFCTPG
MVMSIYTLLR NHPEPTLDQL TDALGGNLCR CTGYRPIIDA CKTFCKTSGC CQSKENGVCC
LDQGINGLPE FEEGSKTSPK LFAEEEFLPL DPTQELIFPP ELMIMAEKQS QRTRVFGSER
MMWFSPVTLK ELLEFKFKYP QAPVIMGNTS VGPEVKFKGV FHPVIISPDR IEELSVVNHA
YNGLTLGAGL SLAQVKDILA DVVQKLPEEK TQMYHALLKH LGTLAGSQIR NMASLGGHII
SRHPDSDLNP ILAVGNCTLN LLSKEGKRQI PLNEQFLSKC PNADLKPQEI LVSVNIPYSR
KWEFVSAFRQ AQRQENALAI VNSGMRVFFG EGDGIIRELC ISYGGVGPAT ICAKNSCQKL
IGRHWNEQML DIACRLILNE VSLLGSAPGG KVEFKRTLII SFLFKFYLEV SQILKKMDPV
HYPSLADKYE SALEDLHSKH HCSTLKYQNI GPKQHPEDPI GHPIMHLSGV KHATGEAIYC
DDMPLVDQEL FLTFVTSSRA HAKIVSIDLS EALSMPGVVD IMTAEHLSDV NSFCFFTEAE
KFLATDKVFC VGQLVCAVLA DSEVQAKRAA KRVKIVYQDL EPLILTIEES IQHNSSFKPE
RKLEYGNVDE AFKVVDQILE GEIHMGGQEH FYMETQSMLV VPKGEDQEMD VYVSTQFPKY
IQDIVASTLK LPANKVMCHV RRVGGAFGGK VLKTGIIAAV TAFAANKHGR AVRCVLERGE
DMLITGGRHP YLGKYKAGFM NDGRILALDM EHYSNAGASL DESLFVIEMG LLKMDNAYKF
PNLRCRGWAC RTNLPSNTAF RGFGFPQAAL ITESCITEVA AKCGLSPEKV RIINMYKEID
QTPYKQEINA KNLIQCWREC MAMSSYSLRK VAVEKFNAEN YWKKKGLAMV PLKFPVGLGS
RAAGQAAALV HIYLDGSVLV THGGIEMGQG VHTKMIQVVS RELRMPMSNV HLRGTSTETV
PNANISGGSV VADLNGLAVK DACQTLLKRL EPIISKNPKG TWKDWAQTAF DESINLSAVG
YFRGYESDMN WEKGEGQPFE YFVYGAACSE VEIDCLTGDH KNIRTDIVMD VGCSINPAID
IGQIEGAFIQ GMGLYTIEEL NYSPQGILHT RGPDQYKIPA ICDMPTELHI ALLPPSQNSN
TLYSSKGLGE SGVFLGCSVF FAIHDAVSAA RQERGLHGPL TLNSPLTPEK IRMACEDKFT
KMIPRDEPGS YVPWNVPI
