ID   A2AQ92_MOUSE            Unreviewed;      1551 AA.
AC   A2AQ92;
DT   20-FEB-2007, integrated into UniProtKB/TrEMBL.
DT   20-FEB-2007, sequence version 1.
DT   27-MAR-2024, entry version 146.
DE   RecName: Full=NAD(P)H oxidase (H2O2-forming) {ECO:0000256|ARBA:ARBA00012698};
DE            EC=1.6.3.1 {ECO:0000256|ARBA:ARBA00012698};
GN   Name=Duox1 {ECO:0000313|Ensembl:ENSMUSP00000097060.4,
GN   ECO:0000313|MGI:MGI:2139422};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090 {ECO:0000313|Ensembl:ENSMUSP00000097060.4, ECO:0000313|Proteomes:UP000000589};
RN   [1] {ECO:0000313|Ensembl:ENSMUSP00000097060.4, ECO:0000313|Proteomes:UP000000589}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J {ECO:0000313|Ensembl:ENSMUSP00000097060.4,
RC   ECO:0000313|Proteomes:UP000000589};
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2] {ECO:0007829|PDB:6WXR, ECO:0007829|PDB:6WXU}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) OF 20-1551, AND DISULFIDE
RP   BONDS.
RX   PubMed=32929281; DOI=10.1038/s41594-020-0501-x;
RA   Sun J.;
RT   "Structures of mouse DUOX1-DUOXA1 provide mechanistic insights into enzyme
RT   activation and regulation.";
RL   Nat. Struct. Mol. Biol. 27:1086-1093(2020).
RN   [3] {ECO:0000313|Ensembl:ENSMUSP00000097060.4}
RP   IDENTIFICATION.
RC   STRAIN=C57BL/6J {ECO:0000313|Ensembl:ENSMUSP00000097060.4};
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
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:0000256|ARBA:ARBA00003796}.
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:0000256|ARBA:ARBA00000518};
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:0000256|ARBA:ARBA00000547};
CC   -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis.
CC       {ECO:0000256|ARBA:ARBA00005197}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000256|ARBA:ARBA00004424}; Multi-pass membrane protein
CC       {ECO:0000256|ARBA:ARBA00004424}. Cell membrane
CC       {ECO:0000256|ARBA:ARBA00004651}; Multi-pass membrane protein
CC       {ECO:0000256|ARBA:ARBA00004651}. Membrane
CC       {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein
CC       {ECO:0000256|ARBA:ARBA00004141}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the peroxidase
CC       family. {ECO:0000256|ARBA:ARBA00005644}.
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DR   RefSeq; NP_001092767.1; NM_001099297.1.
DR   RefSeq; XP_006500550.1; XM_006500487.2.
DR   PDB; 6WXR; EM; 3.20 A; A=20-1551.
DR   PDB; 6WXU; EM; 2.70 A; A/C=20-1551.
DR   PDB; 6WXV; EM; 3.30 A; A=20-1551.
DR   AlphaFoldDB; A2AQ92; -.
DR   SMR; A2AQ92; -.
DR   STRING; 10090.ENSMUSP00000097060; -.
DR   iPTMnet; A2AQ92; -.
DR   PhosphoSitePlus; A2AQ92; -.
DR   PaxDb; 10090-ENSMUSP00000097060; -.
DR   ProteomicsDB; 345233; -.
DR   Antibodypedia; 11716; 149 antibodies from 28 providers.
DR   DNASU; 99439; -.
DR   Ensembl; ENSMUST00000099461.4; ENSMUSP00000097060.4; ENSMUSG00000033268.9.
DR   GeneID; 99439; -.
DR   KEGG; mmu:99439; -.
DR   UCSC; uc008map.1; mouse.
DR   AGR; MGI:2139422; -.
DR   CTD; 53905; -.
DR   MGI; MGI:2139422; Duox1.
DR   VEuPathDB; HostDB:ENSMUSG00000033268; -.
DR   eggNOG; KOG0039; Eukaryota.
DR   GeneTree; ENSGT00940000161792; -.
DR   HOGENOM; CLU_004482_1_0_1; -.
DR   InParanoid; A2AQ92; -.
DR   OMA; VTSEIIM; -.
DR   OrthoDB; 367877at2759; -.
DR   PhylomeDB; A2AQ92; -.
DR   TreeFam; TF105424; -.
DR   Reactome; R-MMU-209968; Thyroxine biosynthesis.
DR   UniPathway; UPA00194; -.
DR   BioGRID-ORCS; 99439; 2 hits in 77 CRISPR screens.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; A2AQ92; Protein.
DR   Bgee; ENSMUSG00000033268; Expressed in esophagus and 32 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0031252; C:cell leading edge; ISO:MGI.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
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; IEA:UniProtKB-EC.
DR   GO; GO:0004601; F:peroxidase activity; IEA:InterPro.
DR   GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IBA:GO_Central.
DR   GO; GO:0042335; P:cuticle development; ISO:MGI.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR   GO; GO:2000147; P:positive regulation of cell motility; ISO:MGI.
DR   GO; GO:0090303; P:positive regulation of wound healing; ISO:MGI.
DR   GO; GO:0072593; P:reactive oxygen species metabolic process; IGI:MGI.
DR   GO; GO:0051591; P:response to cAMP; ISO:MGI.
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; IEA:UniProtKB-UniPathway.
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; 2.
DR   PROSITE; PS51384; FAD_FR; 1.
DR   PROSITE; PS50292; PEROXIDASE_3; 1.
DR   Genevisible; A2AQ92; MM.
PE   1: Evidence at protein level;
KW   3D-structure {ECO:0007829|PDB:6WXR, ECO:0007829|PDB:6WXU};
KW   Calcium {ECO:0000256|ARBA:ARBA00022837};
KW   Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW   FAD {ECO:0000256|ARBA:ARBA00022827};
KW   Flavoprotein {ECO:0000256|ARBA:ARBA00022630};
KW   Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW   Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   NADP {ECO:0000256|ARBA:ARBA00022857};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW   Proteomics identification {ECO:0007829|ProteomicsDB:A2AQ92};
KW   Reference proteome {ECO:0000313|Proteomes:UP000000589};
KW   Repeat {ECO:0000256|ARBA:ARBA00022737}; Signal {ECO:0000256|SAM:SignalP};
KW   Thyroid hormones biosynthesis {ECO:0000256|ARBA:ARBA00022534};
KW   Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius};
KW   Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW   ECO:0000256|SAM:Phobius}.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT   CHAIN           22..1551
FT                   /note="NAD(P)H oxidase (H2O2-forming)"
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT                   /id="PRO_5002642730"
FT   TRANSMEM        593..617
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        1045..1068
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        1088..1109
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        1152..1171
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        1183..1209
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   TRANSMEM        1221..1243
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|SAM:Phobius"
FT   DOMAIN          815..850
FT                   /note="EF-hand"
FT                   /evidence="ECO:0000259|PROSITE:PS50222"
FT   DOMAIN          851..886
FT                   /note="EF-hand"
FT                   /evidence="ECO:0000259|PROSITE:PS50222"
FT   DOMAIN          1270..1376
FT                   /note="FAD-binding FR-type"
FT                   /evidence="ECO:0000259|PROSITE:PS51384"
FT   REGION          147..171
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        148..171
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        118..1165
FT                   /evidence="ECO:0007829|PDB:6WXR, ECO:0007829|PDB:6WXU"
FT   DISULFID        345..565
FT                   /evidence="ECO:0007829|PDB:6WXR, ECO:0007829|PDB:6WXU"
FT   DISULFID        364..579
FT                   /evidence="ECO:0007829|PDB:6WXR, ECO:0007829|PDB:6WXU"
SQ   SEQUENCE   1551 AA;  177132 MW;  8B9729E2F23CAF1E CRC64;
     MGFHLALAWI LLVGTLASLG AQNSISWEVQ RFDGWYNNLM EHRWGSKGSR LQRLVPASYA
     DGVYQPLKEP YLPNPRHLSN RVMRGSAGQP SLRNRTVLGV FFGYHVLSDL VSVETPGCPA
     EFLNIYIPHG DPVFDPDKRG NVVLPFQRSR WDRNTGQSPS NPRDQSNQVT GWLDGSAIYG
     SSHSWSDTLR SFSGGQLASG PDPAFPSDSQ SSLLMWMAPD PSTGQGGPRG VYAFGAQRGN
     REPFLQALGL LWFRYHNLCA RKLAQEHPHW GDEELFQHAR KRVIATYQNI AMYEWLPSFL
     KQTPPEYPGY RPFLDPSISP EFVVASEQFL STMVPSGVYM RNASCHFQGI PSHNSSVSGA
     LRVCNSYWSR EHPKLQRAED VDALLLGMAS QIAEREDHVV VEDMQDFWPG PLKFSRTDYL
     ASCLQRGRDL GLPSYTKARE ALGLSPISHW QDINPALSRS NGTVLEATAA LYNQDLSRLE
     LLPGGLLESH GDPGPLFSTI VLDQFVRLRD GDRYWFENTR NGLFSKEEIA EIRNTSLRDI
     LVAVTNVDPS ALQPNVFFWL AGDPCPQPSQ LSAKGLPACA PLFIRDYFEG SGFGFGLTIG
     TLCCFPLVSL LSAWIVARLR KRNFKRLQRQ DRQSIMSEKL VGGVEALEWQ GRNEPCRPVL
     VHLQPGQIRV VDGRLTVLRT IQLRPPQQVN LILSSNRGRR TLLLKIPKEY DLVLLFNMEE
     ERQALVENVR GALKENGLSF QEWELREQEL MRAAVTRQQR GHLLETFFRH LFSQVLDINQ
     ADAGTLPLDS STKVREALTC ELSRAEFADS LGLKPQDMFV ESMFSLADKD GNGYLSFREF
     LDILVVFMKG SPEEKSRLMF RMYDFDGNGL ISKDEFIRML RSFIEISNNC LSKAQLAEVV
     ESMFRESGFQ DKEELTWEDF HFMLRDHDSD LRFTQLCVKG VEVPEVIKNL CRRASYISQE
     KICPSPRMSA HCARNNMKTA SSPQRLQCPM DTDPPQEIRR RFGKKVTSFQ PLLFTEAHRE
     KFQRSRRHQT VQQFKRFIEN YRRHIGCVAV FYTITGALFL ERAYYYAFAA HHSGITDTTR
     VGIILSRGTA ASISFMFSYI LLTMCRNLIT FLRETFLNRY IPFDAAVDFH RLIASTAIIL
     TVLHSAGHVV NVYLFSISPL SVLSCLFPGL FHDDGSEFPQ KYYWWFFQTV PGLTGVLLLL
     ALAIMYVFAS HHFRRRSFRG FWLTHHLYIF LYILLIIHGS FALIQMPRFH IFFLVPAIIY
     VGDKLVSLSR KKVEISVVKA ELLPSGVTHL RFQRPQGFEY KSGQWVRIAC LALGTTEYHP
     FTLTSAPHED TLSLHIRAAG PWTTRLREIY SPPTGDTCAR YPKLYLDGPF GEGHQEWHKF
     EVSVLVGGGI GVTPFASILK DLVFKSSVSC QVFCKKIYFI WVTRTQRQFE WLADIIREVE
     ENDRQDLVSV HIYITQLAEK FDLRTTMLYI CERHFQKVLN RSLFTGLRSI THFGRPPFEP
     FFNSLQEVHP QVRKIGVFSC GPPGMTKNVE KACQLINRQD RTHFSHHYEN F
//