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Protein

Dual oxidase 2

Gene

DUOX2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain.1 Publication

Catalytic activityi

NAD(P)H + O2 = NAD(P)+ + H2O2.1 Publication

Enzyme regulationi

Peroxidase activity is inhibited by aminobenzohydrazide (By similarity). The NADPH oxidase activity is calcium-dependent.By similarity1 Publication

Pathwayi: thyroid hormone biosynthesis

This protein is involved in the pathway thyroid hormone biosynthesis, which is part of Hormone biosynthesis.
View all proteins of this organism that are known to be involved in the pathway thyroid hormone biosynthesis and in Hormone biosynthesis.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi832 – 8431PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi868 – 8792PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • heme binding Source: InterPro
  • NAD(P)H oxidase activity Source: UniProtKB
  • peroxidase activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase, Peroxidase
Biological processHydrogen peroxide, Thyroid hormones biosynthesis
LigandCalcium, FAD, Flavoprotein, Metal-binding, NADP

Enzyme and pathway databases

BRENDAi1.6.3.1 2681
ReactomeiR-HSA-209968 Thyroxine biosynthesis
SABIO-RKiQ9NRD8
UniPathwayiUPA00194

Protein family/group databases

PeroxiBasei3338 HsDuOx02
TCDBi5.B.1.1.7 the phagocyte (gp91(phox)) nadph oxidase family

Names & Taxonomyi

Protein namesi
Recommended name:
Dual oxidase 2 (EC:1.11.1.-, EC:1.6.3.1)
Alternative name(s):
Large NOX 2
Long NOX 2
NADH/NADPH thyroid oxidase p138-tox
NADPH oxidase/peroxidase DUOX2
NADPH thyroid oxidase 2
Thyroid oxidase 2
p138 thyroid oxidase
Gene namesi
Name:DUOX2
Synonyms:LNOX2, THOX2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000140279.12
HGNCiHGNC:13273 DUOX2
MIMi606759 gene
neXtProtiNX_Q9NRD8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 601ExtracellularSequence analysisAdd BLAST576
Transmembranei602 – 622HelicalSequence analysisAdd BLAST21
Topological domaini623 – 1041CytoplasmicSequence analysisAdd BLAST419
Transmembranei1042 – 1062HelicalSequence analysisAdd BLAST21
Topological domaini1063 – 1076ExtracellularSequence analysisAdd BLAST14
Transmembranei1077 – 1097HelicalSequence analysisAdd BLAST21
Topological domaini1098 – 1128CytoplasmicSequence analysisAdd BLAST31
Transmembranei1129 – 1151HelicalSequence analysisAdd BLAST23
Topological domaini1152 – 1185ExtracellularSequence analysisAdd BLAST34
Transmembranei1186 – 1206HelicalSequence analysisAdd BLAST21
Topological domaini1207 – 1223CytoplasmicSequence analysisAdd BLAST17
Transmembranei1224 – 1244HelicalSequence analysisAdd BLAST21
Transmembranei1245 – 1265HelicalSequence analysisAdd BLAST21
Topological domaini1266 – 1548CytoplasmicSequence analysisAdd BLAST283

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Thyroid dyshormonogenesis 6 (TDH6)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder due to a defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete.
See also OMIM:607200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02532336Q → H in TDH6. 1 Publication1
Natural variantiVAR_025325376R → W in TDH6. 1 PublicationCorresponds to variant dbSNP:rs119472029EnsemblClinVar.1
Natural variantiVAR_0646191518G → S in TDH6; the enzyme is non-functional; expressed at the cell surface of cells albeit at low level. 1 PublicationCorresponds to variant dbSNP:rs368512412Ensembl.1
Defects in DUOX2 may play a role in the pathogenesis of very early onset inflammatory bowel disease (VEOIBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology diagnosed before 6 years of age. VEOIBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but the phenotype of children with onset of Crohn disease occurring younger than the age of 10 is predominantly colonic, with a lower risk of ileal disease. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.1 Publication

Keywords - Diseasei

Congenital hypothyroidism, Disease mutation

Organism-specific databases

DisGeNETi50506
MalaCardsiDUOX2
MIMi607200 phenotype
OpenTargetsiENSG00000140279
Orphaneti95716 Familial thyroid dyshormonogenesis
226316 Genetic transient congenital hypothyroidism
PharmGKBiPA27517

Polymorphism and mutation databases

BioMutaiDUOX2
DMDMi296434485

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000022334926 – 1548Dual oxidase 2Add BLAST1523

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi100N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi124 ↔ 11621 Publication
Glycosylationi348N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi382N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi455N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi537N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi568Interchain (with C-167 in DUOXA2)1 Publication
Disulfide bondi582Interchain (with C-233 in DUOXA2)1 Publication

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NRD8
PeptideAtlasiQ9NRD8
PRIDEiQ9NRD8

PTM databases

iPTMnetiQ9NRD8
PhosphoSitePlusiQ9NRD8

Expressioni

Tissue specificityi

Expressed in colon, small intestine, duodenum and tracheal surface epithelial cells (at protein level). Expressed in thyrocytes. Also detected in kidney, liver, lung, pancreas, prostate, salivary glands, rectum and testis.5 Publications

Developmental stagei

Widely expressed in fetal tissues.1 Publication

Inductioni

By forskolin, thyrotropin and the Th1-specific cytokine IFNG/IFN-gamma.1 Publication

Gene expression databases

BgeeiENSG00000140279
CleanExiHS_DUOX2
ExpressionAtlasiQ9NRD8 baseline and differential
GenevisibleiQ9NRD8 HS

Interactioni

Subunit structurei

Heterodimer with DUOXA2; disulfide-linked. Interacts with TXNDC11, TPO and CYBA.2 Publications

Protein-protein interaction databases

IntActiQ9NRD8, 1 interactor
STRINGi9606.ENSP00000373691

Structurei

3D structure databases

ProteinModelPortaliQ9NRD8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini819 – 854EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini855 – 890EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini899 – 934EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini1084 – 1266Ferric oxidoreductaseAdd BLAST183
Domaini1267 – 1373FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST107

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 596Peroxidase-like; mediates peroxidase activityBy similarityAdd BLAST567
Regioni960 – 1245Interaction with TXNDC11By similarityAdd BLAST286

Sequence similaritiesi

In the N-terminal section; belongs to the peroxidase family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0039 Eukaryota
ENOG410XNZY LUCA
GeneTreeiENSGT00550000074350
HOGENOMiHOG000231774
HOVERGENiHBG080428
InParanoidiQ9NRD8
KOiK13411
OrthoDBiEOG091G00PO
PhylomeDBiQ9NRD8
TreeFamiTF105424

Family and domain databases

CDDicd09820 dual_peroxidase_like, 1 hit
cd00051 EFh, 2 hits
Gene3Di1.10.640.10, 1 hit
InterProiView protein in InterPro
IPR034818 DUOX2
IPR034821 DUOX_peroxidase
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR013112 FAD-bd_8
IPR017927 Fd_Rdtase_FAD-bd
IPR013130 Fe3_Rdtase_TM_dom
IPR013121 Fe_red_NAD-bd_6
IPR010255 Haem_peroxidase
IPR019791 Haem_peroxidase_animal
IPR037120 Haem_peroxidase_sf
IPR017938 Riboflavin_synthase-like_b-brl
PANTHERiPTHR11972:SF67 PTHR11972:SF67, 1 hit
PfamiView protein in Pfam
PF03098 An_peroxidase, 1 hit
PF00036 EF-hand_1, 1 hit
PF08022 FAD_binding_8, 1 hit
PF01794 Ferric_reduct, 1 hit
PF08030 NAD_binding_6, 1 hit
PRINTSiPR00457 ANPEROXIDASE
SMARTiView protein in SMART
SM00054 EFh, 2 hits
SUPFAMiSSF47473 SSF47473, 1 hit
SSF48113 SSF48113, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 3 hits
PS51384 FAD_FR, 1 hit
PS50292 PEROXIDASE_3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9NRD8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRARPEALM LLGALLTGSL GPSGNQDALS LPWEVQRYDG WFNNLRHHER
60 70 80 90 100
GAVGCRLQRR VPANYADGVY QALEEPQLPN PRRLSNAATR GIAGLPSLHN
110 120 130 140 150
RTVLGVFFGY HVLSDVVSVE TPGCPAEFLN IRIPPGDPVF DPDQRGDVVL
160 170 180 190 200
PFQRSRWDPE TGRSPSNPRD LANQVTGWLD GSAIYGSSHS WSDALRSFSG
210 220 230 240 250
GQLASGPDPA FPRDSQNPLL MWAAPDPATG QNGPRGLYAF GAERGNREPF
260 270 280 290 300
LQALGLLWFR YHNLWAQRLA RQHPDWEDEE LFQHARKRVI ATYQNIAVYE
310 320 330 340 350
WLPSFLQKTL PEYTGYRPFL DPSISPEFVV ASEQFFSTMV PPGVYMRNAS
360 370 380 390 400
CHFRKVLNKG FQSSQALRVC NNYWIRENPN LNSTQEVNEL LLGMASQISE
410 420 430 440 450
LEDNIVVEDL RDYWPGPGKF SRTDYVASSI QRGRDMGLPS YSQALLAFGL
460 470 480 490 500
DIPRNWSDLN PNVDPQVLEA TAALYNQDLS QLELLLGGLL ESHGDPGPLF
510 520 530 540 550
SAIVLDQFVR LRDGDRYWFE NTRNGLFSKK EIEDIRNTTL RDVLVAVINI
560 570 580 590 600
DPSALQPNVF VWHKGAPCPQ PKQLTTDGLP QCAPLTVLDF FEGSSPGFAI
610 620 630 640 650
TIIALCCLPL VSLLLSGVVA YFRGREHKKL QKKLKESVKK EAAKDGVPAM
660 670 680 690 700
EWPGPKERSS PIIIQLLSDR CLQVLNRHLT VLRVVQLQPL QQVNLILSNN
710 720 730 740 750
RGCRTLLLKI PKEYDLVLLF SSEEERGAFV QQLWDFCVRW ALGLHVAEMS
760 770 780 790 800
EKELFRKAVT KQQRERILEI FFRHLFAQVL DINQADAGTL PLDSSQKVRE
810 820 830 840 850
ALTCELSRAE FAESLGLKPQ DMFVESMFSL ADKDGNGYLS FREFLDILVV
860 870 880 890 900
FMKGSPEDKS RLMFTMYDLD ENGFLSKDEF FTMMRSFIEI SNNCLSKAQL
910 920 930 940 950
AEVVESMFRE SGFQDKEELT WEDFHFMLRD HDSELRFTQL CVKGGGGGGN
960 970 980 990 1000
GIRDIFKQNI SCRVSFITRT PGERSHPQGL GPPAPEAPEL GGPGLKKRFG
1010 1020 1030 1040 1050
KKAAVPTPRL YTEALQEKMQ RGFLAQKLQQ YKRFVENYRR HIVCVAIFSA
1060 1070 1080 1090 1100
ICVGVFADRA YYYGFASPPS DIAQTTLVGI ILSRGTAASV SFMFSYILLT
1110 1120 1130 1140 1150
MCRNLITFLR ETFLNRYVPF DAAVDFHRWI AMAAVVLAIL HSAGHAVNVY
1160 1170 1180 1190 1200
IFSVSPLSLL ACIFPNVFVN DGSKLPQKFY WWFFQTVPGM TGVLLLLVLA
1210 1220 1230 1240 1250
IMYVFASHHF RRRSFRGFWL THHLYILLYA LLIIHGSYAL IQLPTFHIYF
1260 1270 1280 1290 1300
LVPAIIYGGD KLVSLSRKKV EISVVKAELL PSGVTYLQFQ RPQGFEYKSG
1310 1320 1330 1340 1350
QWVRIACLAL GTTEYHPFTL TSAPHEDTLS LHIRAVGPWT TRLREIYSSP
1360 1370 1380 1390 1400
KGNGCAGYPK LYLDGPFGEG HQEWHKFEVS VLVGGGIGVT PFASILKDLV
1410 1420 1430 1440 1450
FKSSLGSQML CKKIYFIWVT RTQRQFEWLA DIIQEVEEND HQDLVSVHIY
1460 1470 1480 1490 1500
VTQLAEKFDL RTTMLYICER HFQKVLNRSL FTGLRSITHF GRPPFEPFFN
1510 1520 1530 1540
SLQEVHPQVR KIGVFSCGPP GMTKNVEKAC QLVNRQDRAH FMHHYENF
Length:1,548
Mass (Da):175,364
Last modified:May 18, 2010 - v2
Checksum:i7BAA2350EC0A2A7E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25N → S in AAF73922 (PubMed:10806195).Curated1
Sequence conflicti25N → S in AAF78954 (PubMed:11514595).Curated1
Sequence conflicti984A → V in AAF78954 (PubMed:11514595).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02532336Q → H in TDH6. 1 Publication1
Natural variantiVAR_025324138P → L1 PublicationCorresponds to variant dbSNP:rs2001616EnsemblClinVar.1
Natural variantiVAR_025325376R → W in TDH6. 1 PublicationCorresponds to variant dbSNP:rs119472029EnsemblClinVar.1
Natural variantiVAR_061177678H → R. Corresponds to variant dbSNP:rs57659670EnsemblClinVar.1
Natural variantiVAR_0470751067S → L3 PublicationsCorresponds to variant dbSNP:rs269868EnsemblClinVar.1
Natural variantiVAR_0755491211R → C Found in a patient with very early onset inflammatory bowel disease; unknown pathological significance; no effect on subcellular location; significantly reduced ROS generation, which may decrease resistance to infection by enteric pathogens, such as Escherichia coli. 1 PublicationCorresponds to variant dbSNP:rs747720952Ensembl.1
Natural variantiVAR_0755501492R → C Found in a patient with very early onset inflammatory bowel disease; unknown pathological significance; no effect on subcellular location; significantly reduced ROS generation, which may decrease resistance to infection by enteric pathogens, such as Escherichia coli. 1 PublicationCorresponds to variant dbSNP:rs374410986Ensembl.1
Natural variantiVAR_0646191518G → S in TDH6; the enzyme is non-functional; expressed at the cell surface of cells albeit at low level. 1 PublicationCorresponds to variant dbSNP:rs368512412Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF230496 mRNA Translation: AAF73922.1
AF267981 mRNA Translation: AAF78954.1
AC091117 Genomic DNA No translation available.
AF181972 mRNA Translation: AAF20055.1
GU174495 Genomic DNA Translation: ADB22378.1
CCDSiCCDS10117.1
RefSeqiNP_054799.4, NM_014080.4
UniGeneiHs.71377

Genome annotation databases

EnsembliENST00000603300; ENSP00000475084; ENSG00000140279
GeneIDi50506
KEGGihsa:50506
UCSCiuc010bea.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDUOX2_HUMAN
AccessioniPrimary (citable) accession number: Q9NRD8
Secondary accession number(s): A8MQ13
, D2XI64, Q9NR02, Q9UHF9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: May 18, 2010
Last modified: March 28, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

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