DUOX2_HUMAN
ID DUOX2_HUMAN Reviewed; 1548 AA.
AC Q9NRD8; A8MQ13; D2XI64; Q9NR02; Q9UHF9;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Dual oxidase 2;
DE EC=1.11.1.-;
DE EC=1.6.3.1;
DE AltName: Full=Large NOX 2;
DE AltName: Full=Long NOX 2;
DE AltName: Full=NADH/NADPH thyroid oxidase p138-tox;
DE AltName: Full=NADPH oxidase/peroxidase DUOX2;
DE AltName: Full=NADPH thyroid oxidase 2;
DE AltName: Full=Thyroid oxidase 2;
DE AltName: Full=p138 thyroid oxidase;
DE Flags: Precursor;
GN Name=DUOX2; Synonyms=LNOX2, THOX2;
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], INDUCTION, TISSUE SPECIFICITY, AND VARIANT
RP LEU-1067.
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], VARIANTS LEU-138 AND LEU-1067, DEVELOPMENTAL
RP STAGE, AND TISSUE SPECIFICITY.
RC TISSUE=Pancreas, and Thyroid;
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 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 339-1548, AND VARIANT LEU-1067.
RC TISSUE=Thyroid;
RX PubMed=10601291; DOI=10.1074/jbc.274.52.37265;
RA Dupuy C., Ohayon R., Valent A., Noel-Hudson M.-S., Deme D., Virion A.;
RT "Purification of a novel flavoprotein involved in the thyroid NADPH
RT oxidase. Cloning of the porcine and human cDNAs.";
RL J. Biol. Chem. 274:37265-37269(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1509-1548, VARIANT TDH6 SER-1518, AND
RP CHARACTERIZATION OF VARIANT TDH6 SER-1518.
RX PubMed=20187165; DOI=10.1002/humu.21227;
RA Hoste C., Rigutto S., Van Vliet G., Miot F., De Deken X.;
RT "Compound heterozygosity for a novel hemizygous missense mutation and a
RT partial deletion affecting the catalytic core of the H2O2-generating enzyme
RT DUOX2 associated with transient congenital hypothyroidism.";
RL Hum. Mutat. 31:E1304-E1319(2010).
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 INVOLVEMENT IN TDH6.
RX PubMed=12110737; DOI=10.1056/nejmoa012752;
RA Moreno J.C., Bikker H., Kempers M.J.E., van Trotsenburg A.S., Baas F.,
RA de Vijlder J.J.M., Vulsma T., Ris-Stalpers C.;
RT "Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and
RT congenital hypothyroidism.";
RL N. Engl. J. Med. 347:95-102(2002).
RN [8]
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 [9]
RP 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 [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15591162; DOI=10.1152/ajpgi.00198.2004;
RA Ameziane-El-Hassani R., Benfares N., Caillou B., Talbot M., Sabourin J.-C.,
RA Belotte V., Morand S., Gnidehou S., Agnandji D., Ohayon R., Kaniewski J.,
RA Noel-Hudson M.-S., Bidart J.-M., Schlumberger M., Virion A., Dupuy C.;
RT "Dual oxidase2 is expressed all along the digestive tract.";
RL Am. J. Physiol. 288:G933-G942(2005).
RN [11]
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 [12]
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).
RN [13]
RP VARIANT TDH6 TRP-376.
RX PubMed=16134168; DOI=10.1002/humu.9372;
RA Vigone M.C., Fugazzola L., Zamproni I., Passoni A., Di Candia S.,
RA Chiumello G., Persani L., Weber G.;
RT "Persistent mild hypothyroidism associated with novel sequence variants of
RT the DUOX2 gene in two siblings.";
RL Hum. Mutat. 26:395-395(2005).
RN [14]
RP VARIANT TDH6 HIS-36.
RX PubMed=16322276; DOI=10.1373/clinchem.2005.058321;
RA Varela V., Rivolta C.M., Esperante S.A., Gruneiro-Papendieck L., Chiesa A.,
RA Targovnik H.M.;
RT "Three mutations (p.Q36H, p.G418fsX482, and g.IVS19-2A-->C) in the dual
RT oxidase 2 gene responsible for congenital goiter and iodide organification
RT defect.";
RL Clin. Chem. 52:182-191(2006).
RN [15]
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=25761904; DOI=10.1089/ars.2015.6265;
RA Carre A., Louzada R.A., Fortunato R.S., Ameziane-El-Hassani R., Morand S.,
RA Ogryzko V., de Carvalho D.P., Grasberger H., Leto T.L., Dupuy C.;
RT "When an intramolecular disulfide bridge governs the interaction of DUOX2
RT with its partner DUOXA2.";
RL Antioxid. Redox Signal. 23:724-733(2015).
RN [16]
RP POSSIBLE INVOLVEMENT IN INFLAMMATORY BOWEL DISEASE, VARIANTS CYS-1211 AND
RP CYS-1492, AND SUBCELLULAR LOCATION.
RX PubMed=26301257; DOI=10.1016/j.jcmgh.2015.06.005;
RA Hayes P., Dhillon S., O'Neill K., Thoeni C., Hui K.Y., Elkadri A.,
RA Guo C.H., Kovacic L., Aviello G., Alvarez L.A., Griffiths A.M.,
RA Snapper S.B., Brant S.R., Doroshow J.H., Silverberg M.S., Peter I.,
RA McGovern D.P., Cho J., Brumell J.H., Uhlig H.H., Bourke B., Muise A.A.,
RA Knaus U.G.;
RT "Defects in NADPH oxidase genes NOX1 and DUOX2 in very early onset
RT inflammatory bowel disease.";
RL Cell. Mol. Gastroenterol. Hepatol. 1:489-502(2015).
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: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: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:15972824};
CC -!- ACTIVITY REGULATION: Peroxidase activity is inhibited by
CC aminobenzohydrazide (By similarity). The NADPH oxidase activity is
CC calcium-dependent. {ECO:0000250, ECO:0000269|PubMed:15972824}.
CC -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis.
CC -!- SUBUNIT: Heterodimer with DUOXA2; disulfide-linked. Interacts with
CC TXNDC11, TPO and CYBA. {ECO:0000269|PubMed:15561711,
CC ECO:0000269|PubMed:25761904}.
CC -!- INTERACTION:
CC Q9NRD8; Q1HG44: DUOXA2; NbExp=5; IntAct=EBI-12740885, EBI-25589731;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15591162, ECO:0000269|PubMed:26301257}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15591162}. Cell junction
CC {ECO:0000269|PubMed:26301257}. Note=Localizes to the apical membrane of
CC epithelial cells. Localizes on internal membrane structures under
CC resting conditions, translocates to the plasma membrane and cell-cell
CC junctions upon challenge with enteric pathogens, such as Escherichia
CC coli. {ECO:0000269|PubMed:26301257}.
CC -!- TISSUE SPECIFICITY: Expressed in colon, small intestine, duodenum and
CC tracheal surface epithelial cells (at protein level). Expressed in
CC thyrocytes. Also detected in kidney, liver, lung, pancreas, prostate,
CC salivary glands, rectum and testis. {ECO:0000269|PubMed:10806195,
CC ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:12824283,
CC ECO:0000269|PubMed:15210697, ECO:0000269|PubMed:15591162}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed in fetal tissues.
CC {ECO:0000269|PubMed:11514595}.
CC -!- INDUCTION: By forskolin, thyrotropin and the Th1-specific cytokine
CC IFNG/IFN-gamma. {ECO:0000269|PubMed:10806195}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11822874}.
CC -!- DISEASE: Thyroid dyshormonogenesis 6 (TDH6) [MIM:607200]: A disorder
CC due to a defective conversion of accumulated iodide to organically
CC bound iodine. The iodide organification defect can be partial or
CC complete. {ECO:0000269|PubMed:12110737, ECO:0000269|PubMed:16134168,
CC ECO:0000269|PubMed:16322276, ECO:0000269|PubMed:20187165}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Defects in DUOX2 may play a role in the pathogenesis of
CC very early onset inflammatory bowel disease (VEOIBD), a chronic,
CC relapsing inflammation of the gastrointestinal tract with a complex
CC etiology diagnosed before 6 years of age. VEOIBD is subdivided into
CC Crohn disease and ulcerative colitis phenotypes. Crohn disease may
CC affect any part of the gastrointestinal tract from the mouth to the
CC anus, but the phenotype of children with onset of Crohn disease
CC occurring younger than the age of 10 is predominantly colonic, with a
CC lower risk of ileal disease. Bowel inflammation is transmural and
CC discontinuous; it may contain granulomas or be associated with
CC intestinal or perianal fistulas. In contrast, in ulcerative colitis,
CC the inflammation is continuous and limited to rectal and colonic
CC mucosal layers; fistulas and granulomas are not observed. Both diseases
CC include extraintestinal inflammation of the skin, eyes, or joints.
CC {ECO:0000269|PubMed:26301257}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the peroxidase
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Undiagnosed Disease Network; Note=DUOX2;
CC URL="https://undiagnosed.hms.harvard.edu/updates/genes-of-interest/duox2-gene/";
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DR EMBL; AF230496; AAF73922.1; -; mRNA.
DR EMBL; AF267981; AAF78954.1; -; mRNA.
DR EMBL; AC091117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF181972; AAF20055.1; -; mRNA.
DR EMBL; GU174495; ADB22378.1; -; Genomic_DNA.
DR CCDS; CCDS10117.1; -.
DR RefSeq; NP_054799.4; NM_014080.4.
DR AlphaFoldDB; Q9NRD8; -.
DR SMR; Q9NRD8; -.
DR BioGRID; 119077; 3.
DR IntAct; Q9NRD8; 2.
DR STRING; 9606.ENSP00000475084; -.
DR GuidetoPHARMACOLOGY; 2999; -.
DR PeroxiBase; 3338; HsDuOx02.
DR TCDB; 5.B.1.1.7; the phagocyte (gp91(phox)) nadph oxidase family.
DR GlyGen; Q9NRD8; 5 sites.
DR iPTMnet; Q9NRD8; -.
DR PhosphoSitePlus; Q9NRD8; -.
DR BioMuta; DUOX2; -.
DR DMDM; 296434485; -.
DR EPD; Q9NRD8; -.
DR jPOST; Q9NRD8; -.
DR MassIVE; Q9NRD8; -.
DR PaxDb; Q9NRD8; -.
DR PeptideAtlas; Q9NRD8; -.
DR PRIDE; Q9NRD8; -.
DR ProteomicsDB; 82340; -.
DR Antibodypedia; 24313; 175 antibodies from 22 providers.
DR DNASU; 50506; -.
DR Ensembl; ENST00000603300.1; ENSP00000475084.1; ENSG00000140279.13.
DR GeneID; 50506; -.
DR KEGG; hsa:50506; -.
DR UCSC; uc010bea.4; human.
DR CTD; 50506; -.
DR DisGeNET; 50506; -.
DR GeneCards; DUOX2; -.
DR HGNC; HGNC:13273; DUOX2.
DR HPA; ENSG00000140279; Tissue enhanced (gallbladder, thyroid gland, urinary bladder).
DR MalaCards; DUOX2; -.
DR MIM; 606759; gene.
DR MIM; 607200; phenotype.
DR neXtProt; NX_Q9NRD8; -.
DR OpenTargets; ENSG00000140279; -.
DR Orphanet; 95716; Familial thyroid dyshormonogenesis.
DR Orphanet; 226316; Genetic transient congenital hypothyroidism.
DR PharmGKB; PA27517; -.
DR VEuPathDB; HostDB:ENSG00000140279; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000160291; -.
DR InParanoid; Q9NRD8; -.
DR PhylomeDB; Q9NRD8; -.
DR TreeFam; TF105424; -.
DR BRENDA; 1.6.3.1; 2681.
DR PathwayCommons; Q9NRD8; -.
DR Reactome; R-HSA-209968; Thyroxine biosynthesis.
DR SABIO-RK; Q9NRD8; -.
DR SignaLink; Q9NRD8; -.
DR SIGNOR; Q9NRD8; -.
DR UniPathway; UPA00194; -.
DR BioGRID-ORCS; 50506; 11 hits in 1070 CRISPR screens.
DR ChiTaRS; DUOX2; human.
DR GeneWiki; Dual_oxidase_2; -.
DR GenomeRNAi; 50506; -.
DR Pharos; Q9NRD8; Tchem.
DR PRO; PR:Q9NRD8; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9NRD8; protein.
DR Bgee; ENSG00000140279; Expressed in gall bladder and 129 other tissues.
DR ExpressionAtlas; Q9NRD8; baseline and differential.
DR Genevisible; Q9NRD8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031252; C:cell leading edge; IGI:UniProtKB.
DR GO; GO:0009986; C:cell surface; IGI:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA: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; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IDA:UniProtKB.
DR GO; GO:0106293; F:NADH oxidase H202-forming activity; IEA:RHEA.
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; ISS: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:0009615; P:response to virus; IDA:UniProtKB.
DR GO; GO:0042554; P:superoxide anion generation; IGI:UniProtKB.
DR GO; GO:0006590; P:thyroid hormone generation; TAS:Reactome.
DR CDD; cd09820; dual_peroxidase_like; 1.
DR CDD; cd00051; EFh; 2.
DR Gene3D; 1.10.640.10; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR034818; DUOX2.
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:SF67; PTHR11972:SF67; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00036; EF-hand_1; 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 SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF48113; SSF48113; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 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.
PE 1: Evidence at protein level;
KW Calcium; Cell junction; Cell membrane; Congenital hypothyroidism;
KW Disease variant; Disulfide bond; FAD; Flavoprotein; Glycoprotein;
KW Hydrogen peroxide; Membrane; Metal-binding; NADP; Oxidoreductase;
KW Peroxidase; Reference proteome; Repeat; Signal;
KW Thyroid hormones biosynthesis; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1548
FT /note="Dual oxidase 2"
FT /id="PRO_0000223349"
FT TOPO_DOM 26..601
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 602..622
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 623..1041
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1042..1062
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1063..1076
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1077..1097
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1098..1128
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1129..1151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1152..1185
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1186..1206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1207..1223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1224..1244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1245..1265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1266..1548
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 819..854
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 855..890
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 899..934
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 1084..1266
FT /note="Ferric oxidoreductase"
FT DOMAIN 1267..1373
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 30..596
FT /note="Peroxidase-like; mediates peroxidase activity"
FT /evidence="ECO:0000250"
FT REGION 960..1245
FT /note="Interaction with TXNDC11"
FT /evidence="ECO:0000250"
FT REGION 971..991
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 836
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 838
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 843
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
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 870
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 872
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 879
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 537
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 124..1162
FT /evidence="ECO:0000269|PubMed:25761904"
FT DISULFID 568
FT /note="Interchain (with C-167 in DUOXA2)"
FT /evidence="ECO:0000269|PubMed:25761904"
FT DISULFID 582
FT /note="Interchain (with C-233 in DUOXA2)"
FT /evidence="ECO:0000269|PubMed:25761904"
FT VARIANT 36
FT /note="Q -> H (in TDH6)"
FT /evidence="ECO:0000269|PubMed:16322276"
FT /id="VAR_025323"
FT VARIANT 138
FT /note="P -> L (in dbSNP:rs2001616)"
FT /evidence="ECO:0000269|PubMed:11514595"
FT /id="VAR_025324"
FT VARIANT 376
FT /note="R -> W (in TDH6; dbSNP:rs119472029)"
FT /evidence="ECO:0000269|PubMed:16134168"
FT /id="VAR_025325"
FT VARIANT 678
FT /note="H -> R (in dbSNP:rs57659670)"
FT /id="VAR_061177"
FT VARIANT 1067
FT /note="S -> L (in dbSNP:rs269868)"
FT /evidence="ECO:0000269|PubMed:10601291,
FT ECO:0000269|PubMed:10806195, ECO:0000269|PubMed:11514595"
FT /id="VAR_047075"
FT VARIANT 1211
FT /note="R -> C (found in a patient with very early onset
FT inflammatory bowel disease; unknown pathological
FT significance; no effect on subcellular location;
FT significantly reduced ROS generation, which may decrease
FT resistance to infection by enteric pathogens, such as
FT Escherichia coli; dbSNP:rs374410986)"
FT /evidence="ECO:0000269|PubMed:26301257"
FT /id="VAR_075549"
FT VARIANT 1492
FT /note="R -> C (found in a patient with very early onset
FT inflammatory bowel disease; unknown pathological
FT significance; no effect on subcellular location;
FT significantly reduced ROS generation, which may decrease
FT resistance to infection by enteric pathogens, such as
FT Escherichia coli; dbSNP:rs747720952)"
FT /evidence="ECO:0000269|PubMed:26301257"
FT /id="VAR_075550"
FT VARIANT 1518
FT /note="G -> S (in TDH6; the enzyme is non-functional;
FT expressed at the cell surface of cells albeit at low level;
FT dbSNP:rs368512412)"
FT /evidence="ECO:0000269|PubMed:20187165"
FT /id="VAR_064619"
FT CONFLICT 25
FT /note="N -> S (in Ref. 1; AAF73922 and 2; AAF78954)"
FT /evidence="ECO:0000305"
FT CONFLICT 984
FT /note="A -> V (in Ref. 2; AAF78954)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1548 AA; 175364 MW; 7BAA2350EC0A2A7E CRC64;
MLRARPEALM LLGALLTGSL GPSGNQDALS LPWEVQRYDG WFNNLRHHER GAVGCRLQRR
VPANYADGVY QALEEPQLPN PRRLSNAATR GIAGLPSLHN RTVLGVFFGY HVLSDVVSVE
TPGCPAEFLN IRIPPGDPVF DPDQRGDVVL PFQRSRWDPE TGRSPSNPRD LANQVTGWLD
GSAIYGSSHS WSDALRSFSG GQLASGPDPA FPRDSQNPLL MWAAPDPATG QNGPRGLYAF
GAERGNREPF LQALGLLWFR YHNLWAQRLA RQHPDWEDEE LFQHARKRVI ATYQNIAVYE
WLPSFLQKTL PEYTGYRPFL DPSISPEFVV ASEQFFSTMV PPGVYMRNAS CHFRKVLNKG
FQSSQALRVC NNYWIRENPN LNSTQEVNEL LLGMASQISE LEDNIVVEDL RDYWPGPGKF
SRTDYVASSI QRGRDMGLPS YSQALLAFGL DIPRNWSDLN PNVDPQVLEA TAALYNQDLS
QLELLLGGLL ESHGDPGPLF SAIVLDQFVR LRDGDRYWFE NTRNGLFSKK EIEDIRNTTL
RDVLVAVINI DPSALQPNVF VWHKGAPCPQ PKQLTTDGLP QCAPLTVLDF FEGSSPGFAI
TIIALCCLPL VSLLLSGVVA YFRGREHKKL QKKLKESVKK EAAKDGVPAM EWPGPKERSS
PIIIQLLSDR CLQVLNRHLT VLRVVQLQPL QQVNLILSNN RGCRTLLLKI PKEYDLVLLF
SSEEERGAFV QQLWDFCVRW ALGLHVAEMS EKELFRKAVT KQQRERILEI FFRHLFAQVL
DINQADAGTL PLDSSQKVRE ALTCELSRAE FAESLGLKPQ DMFVESMFSL ADKDGNGYLS
FREFLDILVV FMKGSPEDKS RLMFTMYDLD ENGFLSKDEF FTMMRSFIEI SNNCLSKAQL
AEVVESMFRE SGFQDKEELT WEDFHFMLRD HDSELRFTQL CVKGGGGGGN GIRDIFKQNI
SCRVSFITRT PGERSHPQGL GPPAPEAPEL GGPGLKKRFG KKAAVPTPRL YTEALQEKMQ
RGFLAQKLQQ YKRFVENYRR HIVCVAIFSA ICVGVFADRA YYYGFASPPS DIAQTTLVGI
ILSRGTAASV SFMFSYILLT MCRNLITFLR ETFLNRYVPF DAAVDFHRWI AMAAVVLAIL
HSAGHAVNVY IFSVSPLSLL ACIFPNVFVN DGSKLPQKFY WWFFQTVPGM TGVLLLLVLA
IMYVFASHHF RRRSFRGFWL THHLYILLYA LLIIHGSYAL IQLPTFHIYF LVPAIIYGGD
KLVSLSRKKV EISVVKAELL PSGVTYLQFQ RPQGFEYKSG QWVRIACLAL GTTEYHPFTL
TSAPHEDTLS LHIRAVGPWT TRLREIYSSP KGNGCAGYPK LYLDGPFGEG HQEWHKFEVS
VLVGGGIGVT PFASILKDLV FKSSLGSQML CKKIYFIWVT RTQRQFEWLA DIIQEVEEND
HQDLVSVHIY VTQLAEKFDL RTTMLYICER HFQKVLNRSL FTGLRSITHF GRPPFEPFFN
SLQEVHPQVR KIGVFSCGPP GMTKNVEKAC QLVNRQDRAH FMHHYENF
