ID X6RAN8_HUMAN Unreviewed; 1548 AA.
AC X6RAN8;
DT 11-JUN-2014, integrated into UniProtKB/TrEMBL.
DT 11-JUN-2014, sequence version 1.
DT 27-MAR-2024, entry version 72.
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=DUOX2 {ECO:0000313|Ensembl:ENSP00000373691.7};
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 {ECO:0000313|Ensembl:ENSP00000373691.7, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0000313|Ensembl:ENSP00000373691.7, ECO:0000313|Proteomes:UP000005640}
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., Stewart S.,
RA Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R.,
RA 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 [2] {ECO:0000313|Ensembl:ENSP00000373691.7}
RP IDENTIFICATION.
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 EMBL; AC091117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005254478.1; XM_005254421.2.
DR SMR; X6RAN8; -.
DR MassIVE; X6RAN8; -.
DR PeptideAtlas; X6RAN8; -.
DR Antibodypedia; 24313; 187 antibodies from 22 providers.
DR Ensembl; ENST00000389039.11; ENSP00000373691.7; ENSG00000140279.13.
DR MANE-Select; ENST00000389039.11; ENSP00000373691.7; NM_001363711.2; NP_001350640.1.
DR UCSC; uc001zun.4; human.
DR HGNC; HGNC:13273; DUOX2.
DR VEuPathDB; HostDB:ENSG00000140279; -.
DR GeneTree; ENSGT00940000160291; -.
DR HOGENOM; CLU_004482_1_0_1; -.
DR OMA; YLRHIMC; -.
DR OrthoDB; 367877at2759; -.
DR UniPathway; UPA00194; -.
DR BioGRID-ORCS; 50506; 13 hits in 1149 CRISPR screens.
DR ChiTaRS; DUOX2; human.
DR GenomeRNAi; 50506; -.
DR Proteomes; UP000005640; Chromosome 15.
DR Bgee; ENSG00000140279; Expressed in gall bladder and 130 other cell types or tissues.
DR ExpressionAtlas; X6RAN8; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
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:0048855; P:adenohypophysis morphogenesis; IEA:Ensembl.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
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:SF67; DUAL OXIDASE 2; 1.
DR PANTHER; PTHR11972; NADPH OXIDASE; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00036; EF-hand_1; 1.
DR Pfam; PF13833; EF-hand_8; 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.
PE 1: Evidence at protein level;
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|MaxQB:X6RAN8,
KW ECO:0007829|PeptideAtlas:X6RAN8};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640};
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..25
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 26..1548
FT /note="NAD(P)H oxidase (H2O2-forming)"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5004976498"
FT TRANSMEM 598..622
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 1038..1057
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 1077..1099
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 1149..1168
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 1180..1205
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 1217..1234
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 819..854
FT /note="EF-hand"
FT /evidence="ECO:0000259|PROSITE:PS50222"
FT DOMAIN 855..890
FT /note="EF-hand"
FT /evidence="ECO:0000259|PROSITE:PS50222"
FT DOMAIN 1267..1373
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000259|PROSITE:PS51384"
FT REGION 971..991
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1548 AA; 175337 MW; 34572350947EE0C1 CRC64;
MLRARPEALM LLGALLTGSL GPSGSQDALS 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
//
