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Protein

Dual oxidase 1

Gene

DUOX1

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.2 Publications

Catalytic activityi

NAD(P)H + O2 = NAD(P)+ + H2O2.2 Publications

Enzyme regulationi

The NADPH oxidase activity is calcium-dependent. Peroxidase activity is inhibited by aminobenzohydrazide.2 Publications

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 bindingi828 – 8391PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi864 – 8752PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

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

GO - Biological processi

  • cuticle development Source: UniProtKB
  • cytokine-mediated signaling pathway Source: UniProtKB
  • hormone biosynthetic process Source: UniProtKB-KW
  • hydrogen peroxide biosynthetic process Source: UniProtKB
  • hydrogen peroxide catabolic process Source: UniProtKB-KW
  • oxidation-reduction process Source: UniProtKB
  • response to cAMP Source: UniProtKB
  • response to oxidative stress Source: InterPro
  • superoxide anion generation Source: UniProtKB
  • thyroid hormone generation Source: Reactome

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-RKiQ9NRD9
SIGNORiQ9NRD9
UniPathwayiUPA00194

Protein family/group databases

PeroxiBasei3339 HsDuOx01
TCDBi5.B.1.1.6 the phagocyte (gp91(phox)) nadph oxidase family

Names & Taxonomyi

Protein namesi
Recommended name:
Dual oxidase 1 (EC:1.11.1.-, EC:1.6.3.1)
Alternative name(s):
Large NOX 1
Long NOX 1
NADPH thyroid oxidase 1
Thyroid oxidase 1
Gene namesi
Name:DUOX1
Synonyms:DUOX, LNOX1, THOX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000137857.17
HGNCiHGNC:3062 DUOX1
MIMi606758 gene
neXtProtiNX_Q9NRD9

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 domaini22 – 596ExtracellularSequence analysisAdd BLAST575
Transmembranei597 – 617HelicalSequence analysisAdd BLAST21
Topological domaini618 – 1044CytoplasmicSequence analysisAdd BLAST427
Transmembranei1045 – 1065HelicalSequence analysisAdd BLAST21
Topological domaini1066 – 1080ExtracellularSequence analysisAdd BLAST15
Transmembranei1081 – 1101HelicalSequence analysisAdd BLAST21
Topological domaini1102 – 1148CytoplasmicSequence analysisAdd BLAST47
Transmembranei1149 – 1171HelicalSequence analysisAdd BLAST23
Topological domaini1172 – 1188ExtracellularSequence analysisAdd BLAST17
Transmembranei1189 – 1209HelicalSequence analysisAdd BLAST21
Topological domaini1210 – 1226CytoplasmicSequence analysisAdd BLAST17
Transmembranei1227 – 1247HelicalSequence analysisAdd BLAST21
Topological domaini1248ExtracellularSequence analysis1
Transmembranei1249 – 1269HelicalSequence analysisAdd BLAST21
Topological domaini1270 – 1551CytoplasmicSequence analysisAdd BLAST282

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi53905
OpenTargetsiENSG00000137857
PharmGKBiPA27516

Polymorphism and mutation databases

BioMutaiDUOX1
DMDMi74719102

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000022334422 – 1551Dual oxidase 1Add BLAST1530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi94N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi342N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi354N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi461N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi534N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ9NRD9
MaxQBiQ9NRD9
PaxDbiQ9NRD9
PeptideAtlasiQ9NRD9
PRIDEiQ9NRD9
ProteomicsDBi82341
82342 [Q9NRD9-2]

PTM databases

iPTMnetiQ9NRD9
PhosphoSitePlusiQ9NRD9

Expressioni

Tissue specificityi

Expressed in thyrocytes and tracheal surface epithelial cells (at protein level). Expressed in thyroid, trachea, bronchium, and to a lower extent, in placenta, testis, prostate, pancreas and heart.4 Publications

Developmental stagei

Widely expressed in fetal tissues.1 Publication

Inductioni

By forskolin (at protein level). By thyrotropin and the Th2-specific cytokines IL-4 and IL-13.2 Publications

Gene expression databases

BgeeiENSG00000137857
CleanExiHS_DUOX1
ExpressionAtlasiQ9NRD9 baseline and differential
GenevisibleiQ9NRD9 HS

Organism-specific databases

HPAiHPA023544

Interactioni

Subunit structurei

Interacts with TXNDC11, TPO and CYBA.1 Publication

Protein-protein interaction databases

BioGridi119815, 1 interactor
IntActiQ9NRD9, 2 interactors
STRINGi9606.ENSP00000317997

Structurei

3D structure databases

ProteinModelPortaliQ9NRD9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini815 – 850EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini851 – 886EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini895 – 930EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini1087 – 1269Ferric oxidoreductaseAdd BLAST183
Domaini1270 – 1376FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST107

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni26 – 593Peroxidase-like; mediates peroxidase activityAdd BLAST568
Regioni956 – 1248Interaction with TXNDC11By similarityAdd BLAST293

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
InParanoidiQ9NRD9
KOiK13411
OMAiTHFSHHY
OrthoDBiEOG091G00PO
PhylomeDBiQ9NRD9
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
IPR029595 DUOX1/Duox
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:SF75 PTHR11972:SF75, 1 hit
PfamiView protein in Pfam
PF03098 An_peroxidase, 1 hit
PF00036 EF-hand_1, 2 hits
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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRD9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGFCLALAWT LLVGAWTPLG AQNPISWEVQ RFDGWYNNLM EHRWGSKGSR
60 70 80 90 100
LQRLVPASYA DGVYQPLGEP HLPNPRDLSN TISRGPAGLA SLRNRTVLGV
110 120 130 140 150
FFGYHVLSDL VSVETPGCPA EFLNIRIPPG DPMFDPDQRG DVVLPFQRSR
160 170 180 190 200
WDPETGRSPS NPRDPANQVT GWLDGSAIYG SSHSWSDALR SFSRGQLASG
210 220 230 240 250
PDPAFPRDSQ NPLLMWAAPD PATGQNGPRG LYAFGAERGN REPFLQALGL
260 270 280 290 300
LWFRYHNLWA QRLARQHPDW EDEELFQHAR KRVIATYQNI AVYEWLPSFL
310 320 330 340 350
QKTLPEYTGY RPFLDPSISS EFVAASEQFL STMVPPGVYM RNASCHFQGV
360 370 380 390 400
INRNSSVSRA LRVCNSYWSR EHPSLQSAED VDALLLGMAS QIAEREDHVL
410 420 430 440 450
VEDVRDFWPG PLKFSRTDHL ASCLQRGRDL GLPSYTKARA ALGLSPITRW
460 470 480 490 500
QDINPALSRS NDTVLEATAA LYNQDLSWLE LLPGGLLESH RDPGPLFSTI
510 520 530 540 550
VLEQFVRLRD GDRYWFENTR NGLFSKKEIE EIRNTTLQDV LVAVINIDPS
560 570 580 590 600
ALQPNVFVWH KGDPCPQPRQ LSTEGLPACA PSVVRDYFEG SGFGFGVTIG
610 620 630 640 650
TLCCFPLVSL LSAWIVARLR MRNFKRLQGQ DRQSIVSEKL VGGMEALEWQ
660 670 680 690 700
GHKEPCRPVL VYLQPGQIRV VDGRLTVLRT IQLQPPQKVN FVLSSNRGRR
710 720 730 740 750
TLLLKIPKEY DLVLLFNLEE ERQALVENLR GALKESGLSI QEWELREQEL
760 770 780 790 800
MRAAVTREQR RHLLETFFRH LFSQVLDINQ ADAGTLPLDS SQKVREALTC
810 820 830 840 850
ELSRAEFAES LGLKPQDMFV ESMFSLADKD GNGYLSFREF LDILVVFMKG
860 870 880 890 900
SPEEKSRLMF RMYDFDGNGL ISKDEFIRML RSFIEISNNC LSKAQLAEVV
910 920 930 940 950
ESMFRESGFQ DKEELTWEDF HFMLRDHNSE LRFTQLCVKG VEVPEVIKDL
960 970 980 990 1000
CRRASYISQD MICPSPRVSA RCSRSDIETE LTPQRLQCPM DTDPPQEIRR
1010 1020 1030 1040 1050
RFGKKVTSFQ PLLFTEAHRE KFQRSCLHQT VQQFKRFIEN YRRHIGCVAV
1060 1070 1080 1090 1100
FYAIAGGLFL ERAYYYAFAA HHTGITDTTR VGIILSRGTA ASISFMFSYI
1110 1120 1130 1140 1150
LLTMCRNLIT FLRETFLNRY VPFDAAVDFH RLIASTAIVL TVLHSVGHVV
1160 1170 1180 1190 1200
NVYLFSISPL SVLSCLFPGL FHDDGSELPQ KYYWWFFQTV PGLTGVVLLL
1210 1220 1230 1240 1250
ILAIMYVFAS HHFRRRSFRG FWLTHHLYIL LYVLLIIHGS FALIQLPRFH
1260 1270 1280 1290 1300
IFFLVPAIIY GGDKLVSLSR KKVEISVVKA ELLPSGVTHL RFQRPQGFEY
1310 1320 1330 1340 1350
KSGQWVRIAC LALGTTEYHP FTLTSAPHED TLSLHIRAAG PWTTRLREIY
1360 1370 1380 1390 1400
SAPTGDRCAR YPKLYLDGPF GEGHQEWHKF EVSVLVGGGI GVTPFASILK
1410 1420 1430 1440 1450
DLVFKSSVSC QVFCKKIYFI WVTRTQRQFE WLADIIREVE ENDHQDLVSV
1460 1470 1480 1490 1500
HIYITQLAEK FDLRTTMLYI CERHFQKVLN RSLFTGLRSI THFGRPPFEP
1510 1520 1530 1540 1550
FFNSLQEVHP QVRKIGVFSC GPPGMTKNVE KACQLINRQD RTHFSHHYEN

F
Length:1,551
Mass (Da):177,235
Last modified:October 1, 2000 - v1
Checksum:i37CF124A579446B0
GO
Isoform 2 (identifier: Q9NRD9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-354: Missing.
     355-405: SSVSRALRVC...EDHVLVEDVR → MWMHCCWAWP...GRGSAGLPEP

Note: No experimental confirmation available.
Show »
Length:1,197
Mass (Da):137,604
Checksum:i44391BD31C81E18F
GO

Sequence cautioni

The sequence AK128591 differs from that shown. Reason: Erroneous termination at position 967. Translated as Arg.Curated
The sequence BAD18816 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti413K → E in AK128591 (PubMed:14702039).Curated1
Sequence conflicti1388G → R in BAD18816 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049104962I → T. Corresponds to variant dbSNP:rs16939743Ensembl.1
Natural variantiVAR_0253211026C → R1 PublicationCorresponds to variant dbSNP:rs16939752Ensembl.1
Natural variantiVAR_0253221178L → F1 PublicationCorresponds to variant dbSNP:rs2458236Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0172621 – 354Missing in isoform 2. 1 PublicationAdd BLAST354
Alternative sequenceiVSP_017263355 – 405SSVSR…VEDVR → MWMHCCWAWPPRSQSERTMC WLKMCGVSLRLSLQVVNSWP LGRGSAGLPEP in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF230495 mRNA Translation: AAF73921.1
AF213465 mRNA Translation: AAF71295.1
AK128591 mRNA No translation available.
AK172859 mRNA Translation: BAD18816.1 Different initiation.
AC051619 Genomic DNA No translation available.
BC114628 mRNA Translation: AAI14629.1
CCDSiCCDS32221.1 [Q9NRD9-1]
RefSeqiNP_059130.2, NM_017434.4 [Q9NRD9-1]
NP_787954.1, NM_175940.2 [Q9NRD9-1]
XP_011519984.1, XM_011521682.1 [Q9NRD9-2]
UniGeneiHs.272813

Genome annotation databases

EnsembliENST00000321429; ENSP00000317997; ENSG00000137857 [Q9NRD9-1]
ENST00000389037; ENSP00000373689; ENSG00000137857 [Q9NRD9-1]
ENST00000561166; ENSP00000454065; ENSG00000137857 [Q9NRD9-2]
GeneIDi53905
KEGGihsa:53905
UCSCiuc001zus.3 human [Q9NRD9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDUOX1_HUMAN
AccessioniPrimary (citable) accession number: Q9NRD9
Secondary accession number(s): A6NH28
, Q14C94, Q6ZMB3, Q6ZR09, Q9NZC1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: October 1, 2000
Last modified: June 20, 2018
This is version 148 of the entry and version 1 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

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