DUOX1_CANLF
ID DUOX1_CANLF Reviewed; 1551 AA.
AC Q9MZF4;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Dual oxidase 1;
DE EC=1.11.1.-;
DE EC=1.6.3.1;
DE AltName: Full=NADPH thyroid oxidase 1;
DE Short=Thyroid oxidase 1;
DE Flags: Precursor;
GN Name=DUOX1; Synonyms=THOX1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
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 SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
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 [3]
RP INTERACTION WITH TXNDC11.
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).
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 -!- 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:11822874};
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:11822874};
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:11822874}.
CC -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis.
CC -!- SUBUNIT: Interacts with TPO and CYBA (By similarity). Interacts with
CC TXNDC11. {ECO:0000250, ECO:0000269|PubMed:15561711}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}. Note=Localizes to the apical membrane
CC of epithelial cells. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in thyrocytes (at protein level).
CC Specifically expressed in thyroid. {ECO:0000269|PubMed:10806195}.
CC -!- INDUCTION: By forskolin (at protein level). By thyrotropin.
CC {ECO:0000269|PubMed:10806195}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11822874}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the peroxidase
CC family. {ECO:0000305}.
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DR EMBL; AF230497; AAF73923.1; -; mRNA.
DR RefSeq; NP_001003122.1; NM_001003122.2.
DR RefSeq; XP_005638229.1; XM_005638172.1.
DR RefSeq; XP_005638230.1; XM_005638173.1.
DR RefSeq; XP_013964813.1; XM_014109338.1.
DR AlphaFoldDB; Q9MZF4; -.
DR SMR; Q9MZF4; -.
DR IntAct; Q9MZF4; 1.
DR STRING; 9612.ENSCAFP00000020209; -.
DR PeroxiBase; 3336; CfaDuOx01.
DR PaxDb; Q9MZF4; -.
DR Ensembl; ENSCAFT00845054476; ENSCAFP00845042818; ENSCAFG00845030684.
DR GeneID; 403720; -.
DR KEGG; cfa:403720; -.
DR CTD; 53905; -.
DR VEuPathDB; HostDB:ENSCAFG00845030684; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000161792; -.
DR HOGENOM; CLU_004482_1_0_1; -.
DR InParanoid; Q9MZF4; -.
DR OMA; AREVIYT; -.
DR OrthoDB; 27424at2759; -.
DR TreeFam; TF105424; -.
DR Reactome; R-CFA-209968; Thyroxine biosynthesis.
DR UniPathway; UPA00194; -.
DR Proteomes; UP000002254; Chromosome 30.
DR Bgee; ENSCAFG00000013715; Expressed in nose and 32 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; NAS:UniProtKB.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS: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; NAS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS: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; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:2000147; P:positive regulation of cell motility; IEA:Ensembl.
DR GO; GO:0090303; P:positive regulation of wound healing; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; ISS: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; IEA:UniProtKB-UniPathway.
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; IPR029595; DUOX1/Duox.
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; PTHR11972:SF75; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00036; EF-hand_1; 2.
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 membrane; FAD; Flavoprotein; Glycoprotein; Hydrogen peroxide;
KW Membrane; Metal-binding; NADP; Oxidoreductase; Peroxidase;
KW Reference proteome; Repeat; Signal; Thyroid hormones biosynthesis;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1551
FT /note="Dual oxidase 1"
FT /id="PRO_0000223347"
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..1151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1152..1172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1173..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 /evidence="ECO:0000250"
FT REGION 197..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 956..1248
FT /note="Interaction with TXNDC11"
FT /evidence="ECO:0000269|PubMed:15561711"
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"
SQ SEQUENCE 1551 AA; 176716 MW; 94F7E93F34C9F1EE CRC64;
MGFCLALTWT FLVGSWTSMG AQKPISWEVQ RFDGWYNNLM EHKWGSKGSR LQRLVPASYA
DGVYQPLGEP HLPNPRDLSN AAMRGPAGQA SLRNRTVLGV FFGYHVLSDL VSVETPGCPA
EFLNIRIPPG DPVFDPNGRG DVVLPFQRSR WDPESGQSPS NPRDLTNAVT GWLDGSAIYG
SSHSWSDALR SFSGGQLASG PDPAFPRNAQ PPLLMWSAPD PASGQRGPGG LYAFGAERGN
RDPFLQALGL LWFRYHNLCA QRLARQHPHW GDEELFQHAR KRVIATYQNI ALYEWLPSFL
QQAPVKYAGY NPFLDPSISP EFLVASEQFF STMVPPGIYM RNASCHFQEV INRNSSISRA
LRVCNSYWSR KHPNLRRAED VDALLLGMAS QIAEREDHVV VEDVLDFWPG SLKFSRTDHV
AGCLQRGRDL GLPSYTKARA ALGLPPITRW QDINPALSQN NHTVLEATAA LYNQDLSQLE
LLPGGLLESH GDPGPLFSAI VLNQFVRLRD GDRYWFENTR NGLFSEEEIA EIRNTSLRDV
LVAVTNMNPS TLQPNVFFWH MGDPCPQPRQ LSTQGLPACA PSTMQDYFEG SGFGFGVTIG
TLCCFPLVSL LSAWIVARLR KKNFKKLQGQ DRKSVMSEKL VGGMEALEWQ GHKEPCRPVL
VHLQPGQICV VDGRLSVLRT IQLRPPQQVN LILSGNRGRR ALLLKIPKEY DLVLLFNLEE
ERQVLVENLR GALKESGLKF QEWELREQEL MRTAVTRQQR SHLLETFFRH LFSQVLDIDQ
ADAGTLPLDS SQKVQEALTC ELSRAEFAES LGLKPQDMFV ESMFSLADKD GNGYLSFREF
LDILVVFMKG SPEEKSRLMF RMYDFDGNGL ISKDEFIRML RSFIEISNNC LSKAQLTEVV
ESMFRESGFQ DKEELTWEDF HFMLRDHDSE LRFTQLCVRG VEVPEVIKDL CRRASYISQE
KICPSPRVSA RCPHSNTEVE WTPQRLQCPV DTDPPQEIRR RFGKKVTSFQ PLLFTEAQRE
KFQRSRRHQT LQQFKRFIEN YRRHIGCVAV FYAITGGLFL ERAYYYAFGA HHMGITDTTR
VGIILSRGTA ASISFMFSYI LLTMCRNLIT FLRETFLNRY VPFDAAVDFH RLIASTAIVL
TVLHSAGHVV NVYLFSISPL SVLSCLFPGL FHNDGSEFPQ KYYWWFFQTV PGLTGVMLLL
VLAIMYVFAS HHFRRHSFRG FWLTHHLYIL LYVLLIIHGS FGLIQLPRFH IFFLVPALIY
VGDKLVSLSR KKVEISVVKA ELLPSGVTHL QFQRPQGFEY KSGQWVQIAC LALGTTEYHP
FTLTSAPHED TLSLHIRAAG PWTTRLREIY SPPTGDGCAK YPKLYLDGPF GEGHQEWHKF
EVSVLVGGGI GVTPFASILK DLVFKSSVSC QVFCKKIYFI WVTRTQRQFE WLADIIREVE
ENDCQDLVSV HIYITQLAEK FDLRTTMLYI CERHFQKVLN RSLFTGLRSI THFGRPPFEP
FFKSLQEVHP QVRKIGVFSC GPPGMTKNVE KACQLINRQD RTHFSHHYEN F
