[1]	NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, AND INDUCTION. TISSUE=Thyroid; DOI=10.1210/en.2002-220981; PubMed=12639906 [NCBI, ExPASy, EBI, Israel, Japan] Morand S., Chaaraoui M., Kaniewski J., Deme D., Ohayon R., Noel-Hudson M.-S., Virion A., Dupuy C.; "Effect of iodide on nicotinamide adenine dinucleotide phosphate oxidase activity and Duox2 protein expression in isolated porcine thyroid follicles."; Endocrinology 144:1241-1248(2003).
[2]	NUCLEOTIDE SEQUENCE [MRNA] OF 339-1545, INDUCTION, AND TISSUE SPECIFICITY. TISSUE=Thyroid; DOI=10.1074/jbc.274.52.37265; PubMed=10601291 [NCBI, ExPASy, EBI, Israel, Japan] Dupuy C., Ohayon R., Valent A., Noel-Hudson M.-S., Deme D., Virion A.; "Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cDNAs."; J. Biol. Chem. 274:37265-37269(1999).
[3]	INDUCTION. DOI=10.1210/en.2002-220824; PubMed=12538618 [NCBI, ExPASy, EBI, Israel, Japan] Morand S., Dos Santos O.F., Ohayon R., Kaniewski J., Noel-Hudson M.-S., Virion A., Dupuy C.; "Identification of a truncated dual oxidase 2 (DUOX2) messenger ribonucleic acid (mRNA) in two rat thyroid cell lines. Insulin and forskolin regulation of DUOX2 mRNA levels in FRTL-5 cells and porcine thyrocytes."; Endocrinology 144:567-574(2003).
[4]	SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. DOI=10.1152/ajpgi.00198.2004; PubMed=15591162 [NCBI, ExPASy, EBI, Israel, Japan] Ameziane-El-Hassani R., Benfares N., Caillou B., Talbot M., Sabourin J.-C., Belotte V., Morand S., Gnidehou S., Agnandji D., Ohayon R., Kaniewski J., Noel-Hudson M.-S., Bidart J.-M., Schlumberger M., Virion A., Dupuy C.; "Dual oxidase2 is expressed all along the digestive tract."; Am. J. Physiol. 288:G933-G942(2005).
[5]	CATALYTIC ACTIVITY. DOI=10.1074/jbc.M500516200; PubMed=15972824 [NCBI, ExPASy, EBI, Israel, Japan] Ameziane-El-Hassani R., Morand S., Boucher J.L., Frapart Y.-M., Apostolou D., Agnandji D., Gnidehou S., Ohayon R., Noel-Hudson M.-S., Francon J., Lalaoui K., Virion A., Dupuy C.; "Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity."; J. Biol. Chem. 280:30046-30054(2005).

Comments

FUNCTION: 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.
CATALYTIC ACTIVITY: NAD(P)H + O₂ = NAD(P)⁺ + H₂O₂.
ENZYME REGULATION: The NADPH oxidase activity is calcium-dependent. Peroxidase activity is inhibited by aminobenzohydrazide (By similarity).
PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis .
SUBUNIT: Interacts with TXNDC11, TPO and CYBA (By similarity).
SUBCELLULAR LOCATION: Apical cell membrane; Multi-pass membrane protein. Note=Localizes to the apical membrane of epithelial cells.
TISSUE SPECIFICITY: Expressed in thyroid, and the digestive tract especially in stomach, cecum and sigmoidal colon (at protein level). Expressed in thyroid.
INDUCTION: By forskolin and down-regulated by iodide (at protein level). By insulin.
PTM: N-glycosylated.
SIMILARITY: In the N-terminal section; belongs to the peroxidase family.
SIMILARITY: Contains 3 EF-hand domains.
SIMILARITY: Contains 1 FAD-binding FR-type domain.
SIMILARITY: Contains 1 ferric oxidoreductase domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF547267; AAN39339.2; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF181973; AAF20056.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_999164.2; -.

UniGene

Ssc.33

3D structure databases

HSSP

P06495; 1NYA. [HSSP ENTRY / PDB]

ModBase

Q8HZK2.

Protein family/group databases

PeroxiBase

3340; SscDuOx02.

Ontologies

GO:0016324;	Cellular component: apical plasma membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0016021;	Cellular component: integral to membrane (inferred from electronic annotation from InterPro).
GO:0005509;	Molecular function: calcium ion binding (inferred from electronic annotation from InterPro).
GO:0009055;	Molecular function: electron carrier activity (inferred from electronic annotation from InterPro).
GO:0050660;	Molecular function: FAD binding (inferred from electronic annotation from InterPro).
GO:0020037;	Molecular function: heme binding (inferred from electronic annotation from InterPro).
GO:0005506;	Molecular function: iron ion binding (inferred from electronic annotation from InterPro).
GO:0016174;	Molecular function: NAD(P)H oxidase activity (inferred from electronic annotation from EC).
GO:0004601;	Molecular function: peroxidase activity (inferred from electronic annotation from InterPro).
GO:0042335;	Biological process: cuticle development (inferred from sequence or structural similarity from UniProtKB).
GO:0019221;	Biological process: cytokine-mediated signaling pathway (inferred from sequence or structural similarity from UniProtKB).
GO:0042446;	Biological process: hormone biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0042744;	Biological process: hydrogen peroxide catabolic process (inferred from electronic annotation from UniProtKB-KW).
GO:0055114;	Biological process: oxidation reduction (traceable author statement from UniProtKB).
GO:0051591;	Biological process: response to cAMP (inferred from sequence or structural similarity from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR011992; EF-Hand_type.
IPR002048; EF_hand_Ca_bd.
IPR013112; FAD_bd_8.
IPR013130; Fe3_reduct_TM_N.
IPR013121; Fe_red_NAD_bd_6.
IPR002007; Haem_peroxidase_animal.
IPR001221; Phe_hydroxylase.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.238.10; EF-Hand_type; 1.
G3DSA:1.10.640.10; Haem_peroxidase_animal; 1.

Pfam

PF03098; An_peroxidase; 1.
PF00036; efhand; 2.
PF08022; FAD_binding_8; 1.
PF01794; Ferric_reduct; 1.
PF08030; NAD_binding_6; 1.
Pfam graphical view of domain structure.

PRINTS

PR00457; ANPEROXIDASE.
PR00410; PHEHYDRXLASE.

ProDom

PD000012; EF-hand; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00054; EFh; 2.
SMART graphical view of domain structure.

PROSITE

PS00018; EF_HAND_1; 2.
PS50222; EF_HAND_2; 3.
PS51384; FAD_FR; 1.
PS50292; PEROXIDASE_3; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

GeneID

397060; -.

KEGG

ssc:397060; -.

Phylogenomic databases

HOVERGEN

Q8HZK2; -.

Other

ProtoNet

Q8HZK2.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Calcium; Cell membrane; FAD; Glycoprotein; Hydrogen peroxide; Membrane; NADP; Oxidoreductase; Peroxidase; Repeat; Signal; Thyroid hormones biosynthesis; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 25`	`25`	`Potential.`
`CHAIN`	`26 1545`	`1520`	`Dual oxidase 2.`	`PRO_0000223350`
`TOPO_DOM`	`26 601`	`576`	`Extracellular (Potential).`
`TRANSMEM`	`602 622`	`21`	`Potential.`
`TOPO_DOM`	`623 1037`	`415`	`Cytoplasmic (Potential).`
`TRANSMEM`	`1038 1058`	`21`	`Potential.`
`TOPO_DOM`	`1059 1074`	`16`	`Extracellular (Potential).`
`TRANSMEM`	`1075 1097`	`23`	`Potential.`
`TOPO_DOM`	`1098 1145`	`48`	`Cytoplasmic (Potential).`
`TRANSMEM`	`1146 1166`	`21`	`Potential.`
`TOPO_DOM`	`1167 1182`	`16`	`Extracellular (Potential).`
`TRANSMEM`	`1183 1203`	`21`	`Potential.`
`TOPO_DOM`	`1204 1220`	`17`	`Cytoplasmic (Potential).`
`TRANSMEM`	`1221 1241`	`21`	`Potential.`
`TOPO_DOM`	`1242 1242`	`1`	`Extracellular (Potential).`
`TRANSMEM`	`1243 1263`	`21`	`Potential.`
`TOPO_DOM`	`1264 1545`	`282`	`Cytoplasmic (Potential).`
`DOMAIN`	`819 854`	`36`	`EF-hand 1.`
`DOMAIN`	`855 890`	`36`	`EF-hand 2.`
`DOMAIN`	`899 934`	`36`	`EF-hand 3.`
`DOMAIN`	`1081 1263`	`183`	`Ferric oxidoreductase.`
`DOMAIN`	`1264 1370`	`107`	`FAD-binding FR-type.`
`CA_BIND`	`832 843`	`12`	`1 (Potential).`
`CA_BIND`	`868 879`	`12`	`2 (Potential).`
`REGION`	`30 596`	`567`	`Peroxidase-like; mediates peroxidase activity (By similarity).`
`REGION`	`960 1242`	`283`	`Interaction with TXNDC11 (By similarity).`
`CARBOHYD`	`100 100`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`312 312`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`348 348`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`358 358`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`455 455`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`549 549`		`N-linked (GlcNAc...) (Potential).`
`CONFLICT`	`1531 1531`		`N -> S (in Ref. 2; AAF20056).`

Sequence information

Length: 1545 AA [This is the length of the unprocessed precursor]

Molecular weight: 175284 Da [This is the MW of the unprocessed precursor]

CRC64: 29A6B1A0C69552DD [This is a checksum on the sequence]

        10         20         30         40         50         60 
MLCIRPEALV LLGALLTVPL DPVGGQDALS LTWEVQRYDG WFNNLRQHEH GAAGSPLRRL 

        70         80         90        100        110        120 
VPANYADGVY QALGEPLLPN PRQLSHTTMR GPAGLRSIRN RTVLGVFFGY HVLSDLVSIE 

       130        140        150        160        170        180 
KPGCPAEFLN IHIPPGDPVF DPHKSGDVVL PFQRSRWDPN TGQSPSNPRD LTNEVTGWLD 

       190        200        210        220        230        240 
GSAIYGSSHS WSDELRSFSG GQLASGPDPA FPRQAQDPLF MWTPPDPATG QRGPQGLYAF 

       250        260        270        280        290        300 
GAEQGNREPF LQALGLLWFR YHNLCAQKLA REHPLWGDEE LFQHARKRVI ATYQSITMYE 

       310        320        330        340        350        360 
WLPSFLQQTP PNYTEYRPFL DPSISPEFLA ASEQFFSTMV PPGVYMRNAS CHFQMVLNES 

       370        380        390        400        410        420 
YGSFPALRVC NSYWIRENPN LNSAEAVNQL LLGMASQISE LEDWIVVEDL RDYWPGPGKF 

       430        440        450        460        470        480 
SRTDYVASSI QRGRDMGLPS YTQALQALGL NTPKNWSDFN PNVDPQVLEA TAALYNQDLS 

       490        500        510        520        530        540 
RLELFSGGLL ESYGDPGPLF STIVLDQFVR LRDGDRYWFE NTKNGLFSKE EIAEIRSTTL 

       550        560        570        580        590        600 
RDVLVAVTNV SSSALQPNVF IWNEDSPCPQ PQQLTTEDLP HCVPLTVIQY FEGSGPGFGI 

       610        620        630        640        650        660 
TIVALCCLPL MSLLISGVVA YFRSRERKKL QKRGKESVKK EADKDGVSAM EWPGPKERSY 

       670        680        690        700        710        720 
PVSIQLLPDR HLQVLDRHLS VLRTIQLRPR HRVNLILSNN LGRRTLLLKI PKEYDLVLLF 

       730        740        750        760        770        780 
NSEDERGAFV QHLQGFCASC ALGLDIDEMG ESELFRKAVT KQQRGRILEI FFRHLFAQVL 

       790        800        810        820        830        840 
DIDQADAGAL PLDSSQKVRE ALTCELSRAE FAESLGLKPQ DMFVESMFSL ADKDGNGYLS 

       850        860        870        880        890        900 
FREFLDVLVV FMKGSPEDKS RLMFTMYDLD GNGFLSKDEF FTMIRSFIEI SNNCLSKAQL 

       910        920        930        940        950        960 
TEVVESMFRE AGFQDKQELT WEDFHFMLRD HDSELRHTQL CVKGGGGGVG VIFKPDISSR 

       970        980        990       1000       1010       1020 
VSFIIRTPEE RSSPQGVRLP ASEASELGGP VLKKRFGKKA VVPPPRLYTE ALQEKKQRGF 

      1030       1040       1050       1060       1070       1080 
LAQKLQQYKR FVENYRRHIV CVAIFSAICA GLFVERAYYY AFVSPPSGIA ETTFVGIILS 

      1090       1100       1110       1120       1130       1140 
RGTAASVSFM FSYILLTMCR NLITFLRETF LNHYVPFDAA VDFHRWIAMA ALVLAILHSV 

      1150       1160       1170       1180       1190       1200 
GHVVNVYIFS VSPLSLLACV FPSVFVNDGS KLPQKFYWWF FQTIPGMTGV LLLVVLAIMY 

      1210       1220       1230       1240       1250       1260 
VFASPYFRRR SFRGFWLTHH FYILLYVLLI IHGSFALIQL PRFHIFFLVP ALIYVGDKLV 

      1270       1280       1290       1300       1310       1320 
SLSRKKVEIS VVKAELLPSG VTHLQFQRPQ GFEYKSGQWV RIACLGLGTN EYHPFTLTSA 

      1330       1340       1350       1360       1370       1380 
PHEDTLSLHI RAVGPWTTRL REIYSHPMGD GYARYPKLYL DGPFGEGHQE WHKFEVSVLV 

      1390       1400       1410       1420       1430       1440 
GGGIGVTPFA SILKDLVFKS SLGSQMLCKK IYFIWVTRTQ RQFEWLADII REVEENDHRD 

      1450       1460       1470       1480       1490       1500 
LVSVHIYITQ LAEKFDLRTT MLYICERHFQ KVLNRSLFTG LRSITHFGRP PFEPFFNSLQ 

      1510       1520       1530       1540 
EVHPQVRKIG VFSCGPPGMT KNVEKTCQLI NRQDQTHFVH HYENF

Q8HZK2 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools