DUOX2

Protein identityUniProt · HPA

UniProt accession

Q9NRD8

Gene

DUOX2

Ensembl

ENSG00000140279

Chromosome

15

Canonical length

1548 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted membrane proteins, Transporters

OverviewNCBI Gene

The protein encoded by this gene is a glycoprotein and a member of the NADPH oxidase family. The synthesis of thyroid hormone is catalyzed by a protein complex located at the apical membrane of thyroid follicular cells. This complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes this encoded protein and DUOX1. This protein is known as dual oxidase because it has both a peroxidase homology domain and a gp91phox domain. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1548 residues, UniProt reviewed canonical sequence.

>Q9NRD8|DUOX2
     1  MLRARPEALM LLGALLTGSL GPSGNQDALS LPWEVQRYDG WFNNLRHHER GAVGCRLQRR
    61  VPANYADGVY QALEEPQLPN PRRLSNAATR GIAGLPSLHN RTVLGVFFGY HVLSDVVSVE
   121  TPGCPAEFLN IRIPPGDPVF DPDQRGDVVL PFQRSRWDPE TGRSPSNPRD LANQVTGWLD
   181  GSAIYGSSHS WSDALRSFSG GQLASGPDPA FPRDSQNPLL MWAAPDPATG QNGPRGLYAF
   241  GAERGNREPF LQALGLLWFR YHNLWAQRLA RQHPDWEDEE LFQHARKRVI ATYQNIAVYE
   301  WLPSFLQKTL PEYTGYRPFL DPSISPEFVV ASEQFFSTMV PPGVYMRNAS CHFRKVLNKG
   361  FQSSQALRVC NNYWIRENPN LNSTQEVNEL LLGMASQISE LEDNIVVEDL RDYWPGPGKF
   421  SRTDYVASSI QRGRDMGLPS YSQALLAFGL DIPRNWSDLN PNVDPQVLEA TAALYNQDLS
   481  QLELLLGGLL ESHGDPGPLF SAIVLDQFVR LRDGDRYWFE NTRNGLFSKK EIEDIRNTTL
   541  RDVLVAVINI DPSALQPNVF VWHKGAPCPQ PKQLTTDGLP QCAPLTVLDF FEGSSPGFAI
   601  TIIALCCLPL VSLLLSGVVA YFRGREHKKL QKKLKESVKK EAAKDGVPAM EWPGPKERSS
   661  PIIIQLLSDR CLQVLNRHLT VLRVVQLQPL QQVNLILSNN RGCRTLLLKI PKEYDLVLLF
   721  SSEEERGAFV QQLWDFCVRW ALGLHVAEMS EKELFRKAVT KQQRERILEI FFRHLFAQVL
   781  DINQADAGTL PLDSSQKVRE ALTCELSRAE FAESLGLKPQ DMFVESMFSL ADKDGNGYLS
   841  FREFLDILVV FMKGSPEDKS RLMFTMYDLD ENGFLSKDEF FTMMRSFIEI SNNCLSKAQL
   901  AEVVESMFRE SGFQDKEELT WEDFHFMLRD HDSELRFTQL CVKGGGGGGN GIRDIFKQNI
   961  SCRVSFITRT PGERSHPQGL GPPAPEAPEL GGPGLKKRFG KKAAVPTPRL YTEALQEKMQ
  1021  RGFLAQKLQQ YKRFVENYRR HIVCVAIFSA ICVGVFADRA YYYGFASPPS DIAQTTLVGI
  1081  ILSRGTAASV SFMFSYILLT MCRNLITFLR ETFLNRYVPF DAAVDFHRWI AMAAVVLAIL
  1141  HSAGHAVNVY IFSVSPLSLL ACIFPNVFVN DGSKLPQKFY WWFFQTVPGM TGVLLLLVLA
  1201  IMYVFASHHF RRRSFRGFWL THHLYILLYA LLIIHGSYAL IQLPTFHIYF LVPAIIYGGD
  1261  KLVSLSRKKV EISVVKAELL PSGVTYLQFQ RPQGFEYKSG QWVRIACLAL GTTEYHPFTL
  1321  TSAPHEDTLS LHIRAVGPWT TRLREIYSSP KGNGCAGYPK LYLDGPFGEG HQEWHKFEVS
  1381  VLVGGGIGVT PFASILKDLV FKSSLGSQML CKKIYFIWVT RTQRQFEWLA DIIQEVEEND
  1441  HQDLVSVHIY VTQLAEKFDL RTTMLYICER HFQKVLNRSL FTGLRSITHF GRPPFEPFFN
  1501  SLQEVHPQVR KIGVFSCGPP GMTKNVEKAC QLVNRQDRAH FMHHYENF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DUOX2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

6

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

273 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DUOX2.

Disease | AllUniProt

Conditions DUOX2 is implicated in, by any mechanism.

• Thyroid dyshormonogenesis 6 (TDH6) MIM:607200

Disease | GeneticClinVar

240 pathogenic / likely-pathogenic of 2,351 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Thyroid dyshormonogenesis 6
• DUOX2-related disorder
• Familial thyroid dyshormonogenesis
• Inborn genetic diseases
• Congenital hypothyroidism

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.27

gnomAD pLI

0

gnomAD missense Z

-1.17

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cuticle development
• cytokine-mediated signaling pathway
• defense response
• hormone biosynthetic process
• hydrogen peroxide biosynthetic process
• hydrogen peroxide catabolic process
• positive regulation of cell motility
• positive regulation of wound healing
• response to cAMP
• response to oxidative stress
• response to virus
• superoxide anion generation
• thyroid hormone generation

Molecular functions

• calcium ion binding
• heme binding
• NAD(P)H oxidase H2O2-forming activity
• peroxidase activity
• superoxide-generating NAD(P)H oxidase activity

Cellular components

• anchoring junction
• apical part of cell
• apical plasma membrane
• cell leading edge
• cell surface
• cytosol
• endoplasmic reticulum
• extracellular exosome
• NADPH oxidase complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EF-hand domain
• Haem peroxidase superfamily
• EF-hand domain pair
• FAD-binding 8
• Ferric reductase, NAD binding domain
• Ferric reductase transmembrane component-like domain
• FAD-binding domain, ferredoxin reductase-type
• Riboflavin synthase-like beta-barrel
• EF-Hand 1, calcium-binding site
• Haem peroxidase, animal-type
• Dual oxidase, peroxidase domain
• Haem peroxidase domain superfamily, animal type
• Ferredoxin-NADP reductase (FNR), nucleotide-binding domain
• Respiratory burst oxidase/Ferric reductase
• EF hand domain
• Ferric reductase like transmembrane component
• Animal haem peroxidase
• FAD-binding domain
• Ferric reductase NAD binding domain
• EF-hand domain pair

KeywordsUniProt

• Calcium
• Cell junction
• Cell membrane
• Congenital hypothyroidism
• Disulfide bond
• FAD
• Flavoprotein
• Glycoprotein
• Hydrogen peroxide
• Membrane
• Metal-binding
• NADP
• Oxidoreductase
• Peroxidase
• Repeat
• Signal
• Thyroid hormones biosynthesis
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of DUOX2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CYBA
• TPO
• TXNDC11