ID   DUOX1_HUMAN             Reviewed;        1551 AA.
AC   Q9NRD9; A6NH28; Q14C94; Q6ZMB3; Q6ZR09; Q9NZC1;
DT   21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=Dual oxidase 1;
DE            EC=1.11.1.-;
DE            EC=1.6.3.1;
DE   AltName: Full=Large NOX 1;
DE   AltName: Full=Long NOX 1;
DE   AltName: Full=NADPH thyroid oxidase 1;
DE   AltName: Full=Thyroid oxidase 1;
DE   Flags: Precursor;
GN   Name=DUOX1; Synonyms=DUOX, LNOX1, THOX1;
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] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND INDUCTION.
RC   TISSUE=Thyroid;
RX   PubMed=10806195; DOI=10.1074/jbc.m000916200;
RA   De Deken X., Wang D., Many M.-C., Costagliola S., Libert F., Vassart G.,
RA   Dumont J.E., Miot F.;
RT   "Cloning of two human thyroid cDNAs encoding new members of the NADPH
RT   oxidase family.";
RL   J. Biol. Chem. 275:23227-23233(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PHE-1178, FUNCTION,
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, DEVELOPMENTAL STAGE, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Lung;
RX   PubMed=11514595; DOI=10.1083/jcb.200103132;
RA   Edens W.A., Sharling L., Cheng G., Shapira R., Kinkade J.M., Lee T.,
RA   Edens H.A., Tang X., Sullards C., Flaherty D.B., Benian G.M., Lambeth J.D.;
RT   "Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a
RT   multidomain oxidase/peroxidase with homology to the phagocyte oxidase
RT   subunit gp91phox.";
RL   J. Cell Biol. 154:879-891(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 1030-1551 (ISOFORMS 1/2), AND VARIANT ARG-1026.
RC   TISSUE=Lung, and Trachea;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16572171; DOI=10.1038/nature04601;
RA   Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA   Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA   FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA   Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA   Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA   DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA   Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA   Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA   Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA   O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA   Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA   Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT   "Analysis of the DNA sequence and duplication history of human chromosome
RT   15.";
RL   Nature 440:671-675(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [6]
RP   GLYCOSYLATION.
RX   PubMed=11822874; DOI=10.1006/excr.2001.5444;
RA   De Deken X., Wang D., Dumont J.E., Miot F.;
RT   "Characterization of ThOX proteins as components of the thyroid H(2)O(2)-
RT   generating system.";
RL   Exp. Cell Res. 273:187-196(2002).
RN   [7]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=12824283; DOI=10.1096/fj.02-1104fje;
RA   Geiszt M., Witta J., Baffi J., Lekstrom K., Leto T.L.;
RT   "Dual oxidases represent novel hydrogen peroxide sources supporting mucosal
RT   surface host defense.";
RL   FASEB J. 17:1502-1504(2003).
RN   [8]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=15210697; DOI=10.1074/jbc.m404983200;
RA   Schwarzer C., Machen T.E., Illek B., Fischer H.;
RT   "NADPH oxidase-dependent acid production in airway epithelial cells.";
RL   J. Biol. Chem. 279:36454-36461(2004).
RN   [9]
RP   INDUCTION.
RX   PubMed=16111680; DOI=10.1016/j.febslet.2005.08.002;
RA   Harper R.W., Xu C., Eiserich J.P., Chen Y., Kao C.-Y., Thai P., Setiadi H.,
RA   Wu R.;
RT   "Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and
RT   Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium.";
RL   FEBS Lett. 579:4911-4917(2005).
RN   [10]
RP   INTERACTION WITH TXNDC11; TPO AND CYBA.
RX   PubMed=15561711; DOI=10.1074/jbc.m407709200;
RA   Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E.,
RA   Miot F.;
RT   "Identification of a novel partner of duox: EFP1, a thioredoxin-related
RT   protein.";
RL   J. Biol. Chem. 280:3096-3103(2005).
RN   [11]
RP   CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=15972824; DOI=10.1074/jbc.m500516200;
RA   Ameziane-El-Hassani R., Morand S., Boucher J.L., Frapart Y.-M.,
RA   Apostolou D., Agnandji D., Gnidehou S., Ohayon R., Noel-Hudson M.-S.,
RA   Francon J., Lalaoui K., Virion A., Dupuy C.;
RT   "Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity.";
RL   J. Biol. Chem. 280:30046-30054(2005).
CC   -!- FUNCTION: Generates hydrogen peroxide which is required for the
CC       activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a
CC       role in thyroid hormones synthesis and lactoperoxidase-mediated
CC       antimicrobial defense at the surface of mucosa. May have its own
CC       peroxidase activity through its N-terminal peroxidase-like domain.
CC       {ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:12824283}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+) + NADH + O2 = H2O2 + NAD(+); Xref=Rhea:RHEA:11264,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.3.1;
CC         Evidence={ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:15972824};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+) + NADPH + O2 = H2O2 + NADP(+); Xref=Rhea:RHEA:11260,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.6.3.1;
CC         Evidence={ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:15972824};
CC   -!- ACTIVITY REGULATION: The NADPH oxidase activity is calcium-dependent.
CC       Peroxidase activity is inhibited by aminobenzohydrazide.
CC       {ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:15972824}.
CC   -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis.
CC   -!- SUBUNIT: Interacts with TXNDC11, TPO and CYBA.
CC       {ECO:0000269|PubMed:15561711}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:10806195, ECO:0000269|PubMed:15210697}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:10806195,
CC       ECO:0000269|PubMed:15210697}. Note=Localizes to the apical membrane of
CC       epithelial cells.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NRD9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NRD9-2; Sequence=VSP_017262, VSP_017263;
CC   -!- TISSUE SPECIFICITY: Expressed in thyrocytes and tracheal surface
CC       epithelial cells (at protein level). Expressed in thyroid, trachea,
CC       bronchium, and to a lower extent, in placenta, testis, prostate,
CC       pancreas and heart. {ECO:0000269|PubMed:10806195,
CC       ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:12824283,
CC       ECO:0000269|PubMed:15210697}.
CC   -!- DEVELOPMENTAL STAGE: Widely expressed in fetal tissues.
CC       {ECO:0000269|PubMed:11514595}.
CC   -!- INDUCTION: By forskolin (at protein level). By thyrotropin and the Th2-
CC       specific cytokines IL-4 and IL-13. {ECO:0000269|PubMed:10806195,
CC       ECO:0000269|PubMed:16111680}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11822874}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the peroxidase
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AK128591; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAD18816.1; Type=Erroneous initiation; Evidence={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; AF230495; AAF73921.1; -; mRNA.
DR   EMBL; AF213465; AAF71295.1; -; mRNA.
DR   EMBL; AK128591; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AK172859; BAD18816.1; ALT_INIT; mRNA.
DR   EMBL; AC051619; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC114628; AAI14629.1; -; mRNA.
DR   CCDS; CCDS32221.1; -. [Q9NRD9-1]
DR   RefSeq; NP_059130.2; NM_017434.4. [Q9NRD9-1]
DR   RefSeq; NP_787954.1; NM_175940.2. [Q9NRD9-1]
DR   RefSeq; XP_011519984.1; XM_011521682.1. [Q9NRD9-2]
DR   PDB; 7D3E; EM; 2.80 A; A/C=1-1551.
DR   PDB; 7D3F; EM; 2.30 A; A/C=1-1551.
DR   PDBsum; 7D3E; -.
DR   PDBsum; 7D3F; -.
DR   AlphaFoldDB; Q9NRD9; -.
DR   SMR; Q9NRD9; -.
DR   BioGRID; 119815; 12.
DR   ComplexPortal; CPX-8183; DUOX1-DUOXA1 dual oxidase complex.
DR   IntAct; Q9NRD9; 3.
DR   STRING; 9606.ENSP00000317997; -.
DR   PeroxiBase; 3339; HsDuOx01.
DR   TCDB; 5.B.1.1.6; the phagocyte (gp91(phox)) nadph oxidase family.
DR   GlyCosmos; Q9NRD9; 5 sites, No reported glycans.
DR   GlyGen; Q9NRD9; 6 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9NRD9; -.
DR   PhosphoSitePlus; Q9NRD9; -.
DR   BioMuta; DUOX1; -.
DR   DMDM; 74719102; -.
DR   EPD; Q9NRD9; -.
DR   jPOST; Q9NRD9; -.
DR   MassIVE; Q9NRD9; -.
DR   MaxQB; Q9NRD9; -.
DR   PaxDb; 9606-ENSP00000317997; -.
DR   PeptideAtlas; Q9NRD9; -.
DR   ProteomicsDB; 82341; -. [Q9NRD9-1]
DR   ProteomicsDB; 82342; -. [Q9NRD9-2]
DR   Antibodypedia; 11716; 149 antibodies from 28 providers.
DR   DNASU; 53905; -.
DR   Ensembl; ENST00000321429.8; ENSP00000317997.4; ENSG00000137857.18. [Q9NRD9-1]
DR   Ensembl; ENST00000389037.7; ENSP00000373689.3; ENSG00000137857.18. [Q9NRD9-1]
DR   Ensembl; ENST00000561166.1; ENSP00000454065.1; ENSG00000137857.18. [Q9NRD9-2]
DR   GeneID; 53905; -.
DR   KEGG; hsa:53905; -.
DR   MANE-Select; ENST00000389037.7; ENSP00000373689.3; NM_175940.3; NP_787954.1.
DR   UCSC; uc001zus.3; human. [Q9NRD9-1]
DR   AGR; HGNC:3062; -.
DR   CTD; 53905; -.
DR   DisGeNET; 53905; -.
DR   GeneCards; DUOX1; -.
DR   HGNC; HGNC:3062; DUOX1.
DR   HPA; ENSG00000137857; Tissue enhanced (esophagus, skin).
DR   MIM; 606758; gene.
DR   neXtProt; NX_Q9NRD9; -.
DR   OpenTargets; ENSG00000137857; -.
DR   PharmGKB; PA27516; -.
DR   VEuPathDB; HostDB:ENSG00000137857; -.
DR   eggNOG; KOG0039; Eukaryota.
DR   GeneTree; ENSGT00940000161792; -.
DR   HOGENOM; CLU_004482_1_0_1; -.
DR   InParanoid; Q9NRD9; -.
DR   OMA; VTSEIIM; -.
DR   OrthoDB; 367877at2759; -.
DR   PhylomeDB; Q9NRD9; -.
DR   TreeFam; TF105424; -.
DR   BRENDA; 1.6.3.1; 2681.
DR   PathwayCommons; Q9NRD9; -.
DR   Reactome; R-HSA-209968; Thyroxine biosynthesis.
DR   SABIO-RK; Q9NRD9; -.
DR   SignaLink; Q9NRD9; -.
DR   SIGNOR; Q9NRD9; -.
DR   UniPathway; UPA00194; -.
DR   BioGRID-ORCS; 53905; 10 hits in 1143 CRISPR screens.
DR   ChiTaRS; DUOX1; human.
DR   GeneWiki; Dual_oxidase_1; -.
DR   GenomeRNAi; 53905; -.
DR   Pharos; Q9NRD9; Tbio.
DR   PRO; PR:Q9NRD9; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q9NRD9; Protein.
DR   Bgee; ENSG00000137857; Expressed in tongue squamous epithelium and 138 other cell types or tissues.
DR   ExpressionAtlas; Q9NRD9; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; NAS:UniProtKB.
DR   GO; GO:0031252; C:cell leading edge; IGI:UniProtKB.
DR   GO; GO:0009986; C:cell surface; IGI:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; TAS:Reactome.
DR   GO; GO:0106293; F:NADH oxidase H202-forming activity; IEA:RHEA.
DR   GO; GO:0050661; F:NADP binding; NAS:UniProtKB.
DR   GO; GO:0106294; F:NADPH oxidase H202-forming activity; IEA:RHEA.
DR   GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IBA:GO_Central.
DR   GO; GO:0042335; P:cuticle development; IMP:UniProtKB.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB.
DR   GO; GO:0006952; P:defense response; IBA:GO_Central.
DR   GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0050665; P:hydrogen peroxide biosynthetic process; IGI:UniProtKB.
DR   GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR   GO; GO:2000147; P:positive regulation of cell motility; IGI:UniProtKB.
DR   GO; GO:0090303; P:positive regulation of wound healing; IGI:UniProtKB.
DR   GO; GO:0051591; P:response to cAMP; IDA:UniProtKB.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR   GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central.
DR   GO; GO:0006590; P:thyroid hormone generation; TAS:Reactome.
DR   CDD; cd09820; dual_peroxidase_like; 1.
DR   CDD; cd00051; EFh; 2.
DR   CDD; cd06186; NOX_Duox_like_FAD_NADP; 1.
DR   Gene3D; 1.10.238.10; EF-hand; 1.
DR   Gene3D; 1.10.640.10; Haem peroxidase domain superfamily, animal type; 1.
DR   Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1.
DR   Gene3D; 2.40.30.10; Translation factors; 1.
DR   InterPro; IPR034821; DUOX_peroxidase.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR   InterPro; IPR002048; EF_hand_dom.
DR   InterPro; IPR013112; FAD-bd_8.
DR   InterPro; IPR017927; FAD-bd_FR_type.
DR   InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR   InterPro; IPR013121; Fe_red_NAD-bd_6.
DR   InterPro; IPR039261; FNR_nucleotide-bd.
DR   InterPro; IPR019791; Haem_peroxidase_animal.
DR   InterPro; IPR010255; Haem_peroxidase_sf.
DR   InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR   InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR   PANTHER; PTHR11972:SF75; DUAL OXIDASE 1; 1.
DR   PANTHER; PTHR11972; NADPH OXIDASE; 1.
DR   Pfam; PF03098; An_peroxidase; 1.
DR   Pfam; PF00036; EF-hand_1; 1.
DR   Pfam; PF13499; EF-hand_7; 1.
DR   Pfam; PF08022; FAD_binding_8; 1.
DR   Pfam; PF01794; Ferric_reduct; 1.
DR   Pfam; PF08030; NAD_binding_6; 1.
DR   PRINTS; PR00457; ANPEROXIDASE.
DR   SFLD; SFLDS00052; Ferric_Reductase_Domain; 1.
DR   SFLD; SFLDG01168; Ferric_reductase_subgroup_(FRE; 1.
DR   SFLD; SFLDG01169; NADPH_oxidase_subgroup_(NOX); 1.
DR   SMART; SM00054; EFh; 2.
DR   SUPFAM; SSF47473; EF-hand; 1.
DR   SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1.
DR   SUPFAM; SSF48113; Heme-dependent peroxidases; 1.
DR   SUPFAM; SSF63380; Riboflavin synthase domain-like; 1.
DR   PROSITE; PS00018; EF_HAND_1; 2.
DR   PROSITE; PS50222; EF_HAND_2; 3.
DR   PROSITE; PS51384; FAD_FR; 1.
DR   PROSITE; PS50292; PEROXIDASE_3; 1.
DR   Genevisible; Q9NRD9; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Calcium; Cell membrane; FAD;
KW   Flavoprotein; Glycoprotein; Hydrogen peroxide; Membrane; Metal-binding;
KW   NADP; Oxidoreductase; Peroxidase; Reference proteome; Repeat; Signal;
KW   Thyroid hormones biosynthesis; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..1551
FT                   /note="Dual oxidase 1"
FT                   /id="PRO_0000223344"
FT   TOPO_DOM        22..596
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        597..617
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        618..1044
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1045..1065
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1066..1080
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1081..1101
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1102..1148
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1149..1171
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1172..1188
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1189..1209
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1210..1226
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1227..1247
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1248
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1249..1269
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1270..1551
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          815..850
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          851..886
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          895..930
FT                   /note="EF-hand 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          1087..1269
FT                   /note="Ferric oxidoreductase"
FT   DOMAIN          1270..1376
FT                   /note="FAD-binding FR-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT   REGION          26..593
FT                   /note="Peroxidase-like; mediates peroxidase activity"
FT   REGION          150..172
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          956..1248
FT                   /note="Interaction with TXNDC11"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        153..167
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         828
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         830
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         832
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         834
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         839
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         864
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         866
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         868
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         875
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   CARBOHYD        94
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        342
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        354
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        461
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        534
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..354
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_017262"
FT   VAR_SEQ         355..405
FT                   /note="SSVSRALRVCNSYWSREHPSLQSAEDVDALLLGMASQIAEREDHVLVEDVR
FT                   -> MWMHCCWAWPPRSQSERTMCWLKMCGVSLRLSLQVVNSWPLGRGSAGLPEP (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_017263"
FT   VARIANT         962
FT                   /note="I -> T (in dbSNP:rs16939743)"
FT                   /id="VAR_049104"
FT   VARIANT         1026
FT                   /note="C -> R (in dbSNP:rs16939752)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_025321"
FT   VARIANT         1178
FT                   /note="L -> F (in dbSNP:rs2458236)"
FT                   /evidence="ECO:0000269|PubMed:11514595"
FT                   /id="VAR_025322"
FT   CONFLICT        413
FT                   /note="K -> E (in Ref. 3; AK128591)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1388
FT                   /note="G -> R (in Ref. 3; BAD18816)"
FT                   /evidence="ECO:0000305"
FT   STRAND          38..40
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            42..45
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          60..64
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            69..71
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           75..83
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           97..110
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            132..134
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          155..158
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          171..175
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           176..179
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           183..189
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            221..223
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           228..230
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            237..240
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           243..266
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           272..293
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           295..300
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           320..331
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          336..338
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          357..363
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           378..390
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          396..398
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           402..405
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          411..417
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           419..429
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           435..441
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           450..452
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           455..459
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           464..471
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            472..474
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           476..478
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           481..488
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          490..492
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           495..510
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           519..521
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           526..534
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           537..545
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           549..551
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          563..565
FT                   /evidence="ECO:0007829|PDB:7D3E"
FT   HELIX           592..618
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          645..648
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          652..654
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          657..663
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          665..672
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          677..682
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          690..693
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          701..705
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          707..709
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          712..715
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           719..734
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          741..744
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           747..752
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           757..775
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           792..798
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           804..811
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           818..827
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          832..835
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           837..849
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           852..863
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          868..871
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           873..883
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           894..901
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           917..923
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            1025..1027
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1028..1068
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            1071..1074
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            1076..1078
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1081..1099
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1100..1104
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1106..1113
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1116..1119
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1123..1125
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1126..1157
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1160..1166
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            1168..1170
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1182..1187
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1190..1208
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1211..1216
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1219..1225
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1228..1238
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            1239..1241
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1243..1245
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1249..1269
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1273..1275
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1277..1283
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            1284..1286
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1287..1293
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1305..1310
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1311..1313
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1319..1323
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1329..1337
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1341..1349
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1364..1367
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1376..1379
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1380..1388
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1389..1392
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1393..1408
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1416..1424
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1430..1442
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1448..1454
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1458..1460
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1463..1473
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1478..1481
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   TURN            1483..1485
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1488..1494
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1498..1508
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1509..1511
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1513..1521
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   HELIX           1523..1538
FT                   /evidence="ECO:0007829|PDB:7D3F"
FT   STRAND          1539..1548
FT                   /evidence="ECO:0007829|PDB:7D3F"
SQ   SEQUENCE   1551 AA;  177235 MW;  37CF124A579446B0 CRC64;
     MGFCLALAWT LLVGAWTPLG AQNPISWEVQ RFDGWYNNLM EHRWGSKGSR LQRLVPASYA
     DGVYQPLGEP HLPNPRDLSN TISRGPAGLA SLRNRTVLGV FFGYHVLSDL VSVETPGCPA
     EFLNIRIPPG DPMFDPDQRG DVVLPFQRSR WDPETGRSPS NPRDPANQVT GWLDGSAIYG
     SSHSWSDALR SFSRGQLASG PDPAFPRDSQ NPLLMWAAPD PATGQNGPRG LYAFGAERGN
     REPFLQALGL LWFRYHNLWA QRLARQHPDW EDEELFQHAR KRVIATYQNI AVYEWLPSFL
     QKTLPEYTGY RPFLDPSISS EFVAASEQFL STMVPPGVYM RNASCHFQGV INRNSSVSRA
     LRVCNSYWSR EHPSLQSAED VDALLLGMAS QIAEREDHVL VEDVRDFWPG PLKFSRTDHL
     ASCLQRGRDL GLPSYTKARA ALGLSPITRW QDINPALSRS NDTVLEATAA LYNQDLSWLE
     LLPGGLLESH RDPGPLFSTI VLEQFVRLRD GDRYWFENTR NGLFSKKEIE EIRNTTLQDV
     LVAVINIDPS ALQPNVFVWH KGDPCPQPRQ LSTEGLPACA PSVVRDYFEG SGFGFGVTIG
     TLCCFPLVSL LSAWIVARLR MRNFKRLQGQ DRQSIVSEKL VGGMEALEWQ GHKEPCRPVL
     VYLQPGQIRV VDGRLTVLRT IQLQPPQKVN FVLSSNRGRR TLLLKIPKEY DLVLLFNLEE
     ERQALVENLR GALKESGLSI QEWELREQEL MRAAVTREQR RHLLETFFRH LFSQVLDINQ
     ADAGTLPLDS SQKVREALTC ELSRAEFAES LGLKPQDMFV ESMFSLADKD GNGYLSFREF
     LDILVVFMKG SPEEKSRLMF RMYDFDGNGL ISKDEFIRML RSFIEISNNC LSKAQLAEVV
     ESMFRESGFQ DKEELTWEDF HFMLRDHNSE LRFTQLCVKG VEVPEVIKDL CRRASYISQD
     MICPSPRVSA RCSRSDIETE LTPQRLQCPM DTDPPQEIRR RFGKKVTSFQ PLLFTEAHRE
     KFQRSCLHQT VQQFKRFIEN YRRHIGCVAV FYAIAGGLFL ERAYYYAFAA HHTGITDTTR
     VGIILSRGTA ASISFMFSYI LLTMCRNLIT FLRETFLNRY VPFDAAVDFH RLIASTAIVL
     TVLHSVGHVV NVYLFSISPL SVLSCLFPGL FHDDGSELPQ KYYWWFFQTV PGLTGVVLLL
     ILAIMYVFAS HHFRRRSFRG FWLTHHLYIL LYVLLIIHGS FALIQLPRFH IFFLVPAIIY
     GGDKLVSLSR KKVEISVVKA ELLPSGVTHL RFQRPQGFEY KSGQWVRIAC LALGTTEYHP
     FTLTSAPHED TLSLHIRAAG PWTTRLREIY SAPTGDRCAR YPKLYLDGPF GEGHQEWHKF
     EVSVLVGGGI GVTPFASILK DLVFKSSVSC QVFCKKIYFI WVTRTQRQFE WLADIIREVE
     ENDHQDLVSV HIYITQLAEK FDLRTTMLYI CERHFQKVLN RSLFTGLRSI THFGRPPFEP
     FFNSLQEVHP QVRKIGVFSC GPPGMTKNVE KACQLINRQD RTHFSHHYEN F
//