Reviewed, UniProtKB/Swiss-Prot Q9ES45 (DUOX2_RAT)

Names and origin

Protein names

Recommended name:
    Dual oxidase 2
    EC=1.6.3.1
    EC=1.11.1.-
Alternative name(s):
    NADH/NADPH thyroid oxidase THOX2
    Large NOX 2
    Long NOX 2
    Thyroid oxidase 2

Gene names

Name:	Duox2
Synonyms:	Lnox2, Thox2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1517 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (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 structure	Interacts with TXNDC11, TPO and CYBA By similarity.
Subcellular location	Apical cell membrane; Multi-pass membrane protein By similarity. Note: Localizes to the apical membrane of epithelial cells By similarity.
Tissue specificity	Expressed in colon, duodenum, rectum and thyroid. Ref.1 Ref.3
Induction	By forskolin, thyrotropin and insulin. Down-regulated by the antithyroid drug methimazole. Ref.1 Ref.2
Post-translational modification	N-glycosylated By similarity.
Sequence similarities	In the N-terminal section; belongs to the peroxidase family. Contains 3 EF-hand domains. Contains 1 FAD-binding FR-type domain. Contains 1 ferric oxidoreductase domain.

Ontologies

Keywords
Biological process	Hydrogen peroxide Thyroid hormones biosynthesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane
Ligand	Calcium FAD NADP
Molecular function	Oxidoreductase Peroxidase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	cuticle development Inferred from sequence or structural similarity. Source: UniProtKB cytokine-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW hydrogen peroxide catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to cAMP Inferred from sequence or structural similarity. Source: UniProtKB thyroid hormone generation Ref.2 Traceable author statement. Source: RGD
Cellular component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro NAD(P)H oxidase activity Inferred from electronic annotation. Source: EC calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro peroxidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9ES45-1)

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.

Isoform 2 (identifier: Q9ES45-2)

Also known as: short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1061: Missing.

Note: There is no evidence for the expression of the corresponding protein in vitro.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 1517	1492	Dual oxidase 2		PRO_0000223351
Regions
	Topological domain	26 – 599	574	Extracellular Potential
	Transmembrane	600 – 620	21	Potential
	Topological domain	621 – 1010	390	Cytoplasmic Potential
	Transmembrane	1011 – 1031	21	Potential
	Topological domain	1032 – 1046	15	Extracellular Potential
	Transmembrane	1047 – 1067	21	Potential
	Topological domain	1068 – 1100	33	Cytoplasmic Potential
	Transmembrane	1101 – 1121	21	Potential
	Topological domain	1122 – 1154	33	Extracellular Potential
	Transmembrane	1155 – 1175	21	Potential
	Topological domain	1176 – 1185	10	Cytoplasmic Potential
	Transmembrane	1186 – 1206	21	Potential
	Topological domain	1207	1	Extracellular Potential
	Transmembrane	1208 – 1228	21	Potential
	Topological domain	1229 – 1517	289	Cytoplasmic Potential
	Domain	819 – 854	36	EF-hand 1
	Domain	855 – 890	36	EF-hand 2
	Domain	899 – 934	36	EF-hand 3
	Domain	1053 – 1235	183	Ferric oxidoreductase
	Domain	1236 – 1342	107	FAD-binding FR-type
	Calcium binding	832 – 843	12	1 Potential
	Calcium binding	868 – 879	12	2 Potential
	Region	30 – 596	567	Peroxidase-like; mediates peroxidase activity By similarity
	Region	960 – 1214	255	Interaction with TXNDC11 By similarity
Amino acid modifications
	Glycosylation	100	1	N-linked (GlcNAc...) Potential
	Glycosylation	348	1	N-linked (GlcNAc...) Potential
	Glycosylation	455	1	N-linked (GlcNAc...) Potential
	Glycosylation	537	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 1061	1061	Missing in isoform 2.		VSP_017264
Experimental info
	Sequence conflict	1243	1	V → A in AAN39340. Ref.2
	Sequence conflict	1246	1	V → A in AAN39340. Ref.2
	Sequence conflict	1409	1	G → D in AAN39340. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 07FBA427DEA299D1	FASTA	1,517	171,558
	10 20 30 40 50 60 MLPTSLKTLV LLGALLTGPL GPAGGQDAPS LPREVQRYDG WFNNLKYHQR GAAGSQLRRL 70 80 90 100 110 120 VPANYADGVY QALQEPLLPN ARLLSDAVSK GKAGLPSAHN RTVLGLFFGY HVLSDLVSVE 130 140 150 160 170 180 TPGCPAEFLN IYIPRGDPVF DPDKRGNVVL PFQRSRWDRS TGQSPSNPRD LTNQVTGWLD 190 200 210 220 230 240 GSAIYGSSHS WSDTLRSFSG GQLASGPDPA FPRNSQNSLL MWMAPDPATG QGGPQGLYAF 250 260 270 280 290 300 GAQRGNREPF LQALGLLWFR YHNLCAKRLA QEHPHWGDEE LFQHARKRVI ATYQNIALYQ 310 320 330 340 350 360 WLPSFLQKTP PEYSGYRPFM DPSISPEFVA ASEQFLSTMV PPGVYMRNSS CHFREFPKEG 370 380 390 400 410 420 SSSSPALRVC NNYWIRENPS LKTAQDVDQL LLGMASQISE LEDRIVIEDL RDYWPGPDRY 430 440 450 460 470 480 SRTDYVASSI QSGRDMGLPS YSQALQALGL EPPKNWSALN PKVDPQVLEA TAALYNQDLS 490 500 510 520 530 540 RLELFLGGLL ESHGDPGPLF SNIILDQFVR LRDGDRYWFE NTRNGLFSKE EIAEIRNTTL 550 560 570 580 590 600 RDVLVAVSNV DPSALQPNVF FWQEGAPCPQ PQQLTTEGLP QCVPVTVIDY FEGSGAGYGV 610 620 630 640 650 660 TLLAVCCFPV VSLIIAWVVA RFRNRERKML LKKGKESLKK QTASDGVPAM EWPGPKESSY 670 680 690 700 710 720 PVTVQLLPDR SLKVLDKRLT VLRTIQLQPT QQVNLILSSS HGRRTLLLKI PKEYDLVLMF 730 740 750 760 770 780 NSEEDRDAFV QLLQDLCVCS TPGLRIAEMD EKELLRKAVT KQQRAGILEI FFRQLFAQVL 790 800 810 820 830 840 DINQADAGTL PLDSSQQVRE ALTCELSRAE FADSLGLKPQ DMFVESMFSL ADKDGNGYIS 850 860 870 880 890 900 FREFLDILVV FMKGSPQDKS RLMFTMYDLD GNGFLSKEEF FTMMRSFIEI SNNCLSKDQL 910 920 930 940 950 960 AEVVESMFRE SGFQDKEELT WEDFHFMLRD HDSDLRFTQL CVKGGAGGTG DIFKQSNACR 970 980 990 1000 1010 1020 VSFLTRTPGN RVMAPSPRLY TEALQEKMQR GFLAQKLKQF KRFVENYRRH IVCVTIFSAI 1030 1040 1050 1060 1070 1080 CAGLFADRAY YYGFASPPTD IEETTYVGII LSRGTAASIS FMFSYILLTM CRNLITFLRE 1090 1100 1110 1120 1130 1140 TFLNRYIPFD AAVDFHRWIA MAAVVLAVVH SLGHAVNVYI FSVSPLSLMT CVFPSVFVND 1150 1160 1170 1180 1190 1200 GSKLPPKYYW WFFETVPGMT GVLLLLVLAI MYVFASHHFR RHSFRGFWLT HHLYVVLYAL 1210 1220 1230 1240 1250 1260 IIIHGSYALI QLPSFHIYFL VPAIIYVGDK LVSLSRKKVE ISVVKVELLP SGVTYLQFQR 1270 1280 1290 1300 1310 1320 PKTFEYKSGQ WVRIACLSLG TNEYHPFTLT SAPHEDTLSL HIRAVGPWTT RLREIYSPPV 1330 1340 1350 1360 1370 1380 GGTSARYPKL YLDGPFGEGH QEWHKFEVSV LVGGGIGVTP FASILKDLVF KSSMGTQMLC 1390 1400 1410 1420 1430 1440 KKIYFIWVTR TQRQFEWLAD IIREVEENGS RDLVSVHIYI TQLAEKFDLR TTMLYICERH 1450 1460 1470 1480 1490 1500 FQKVLNRSLF TGLRSVTHFG RPPFELFLDS LQEVHPQVHK IGVFSCGPPG MTKNVEKACQ 1510 LINRQDRAHF VHHYENF
	Isoform 2 (short). Checksum: B39E79E45F2DF3FE	FASTA	456	52,576
	10 20 30 40 50 60 MFSYILLTMC RNLITFLRET FLNRYIPFDA AVDFHRWIAM AAVVLAVVHS LGHAVNVYIF 70 80 90 100 110 120 SVSPLSLMTC VFPSVFVNDG SKLPPKYYWW FFETVPGMTG VLLLLVLAIM YVFASHHFRR 130 140 150 160 170 180 HSFRGFWLTH HLYVVLYALI IIHGSYALIQ LPSFHIYFLV PAIIYVGDKL VSLSRKKVEI 190 200 210 220 230 240 SVVKVELLPS GVTYLQFQRP KTFEYKSGQW VRIACLSLGT NEYHPFTLTS APHEDTLSLH 250 260 270 280 290 300 IRAVGPWTTR LREIYSPPVG GTSARYPKLY LDGPFGEGHQ EWHKFEVSVL VGGGIGVTPF 310 320 330 340 350 360 ASILKDLVFK SSMGTQMLCK KIYFIWVTRT QRQFEWLADI IREVEENGSR DLVSVHIYIT 370 380 390 400 410 420 QLAEKFDLRT TMLYICERHF QKVLNRSLFT GLRSVTHFGR PPFELFLDSL QEVHPQVHKI 430 440 450 GVFSCGPPGM TKNVEKACQL INRQDRAHFV HHYENF

References

[1]	"Thyroid oxidase (THOX2) gene expression in the rat thyroid cell line FRTL-5." Dupuy C., Pomerance M., Ohayon R., Noel-Hudson M.-S., Deme D., Chaaraoui M., Francon J., Virion A. Biochem. Biophys. Res. Commun. 277:287-292(2000) [PubMed: 11032719] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION. Tissue: Thyroid.
[2]	"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." Morand S., Dos Santos O.F., Ohayon R., Kaniewski J., Noel-Hudson M.-S., Virion A., Dupuy C. Endocrinology 144:567-574(2003) [PubMed: 12538618] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION. Strain: Fischer.
[3]	"Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense." Geiszt M., Witta J., Baffi J., Lekstrom K., Leto T.L. FASEB J. 17:1502-1504(2003) [PubMed: 12824283] [Abstract] Cited for: TISSUE SPECIFICITY.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF237962 mRNA. Translation: AAG21895.1. AF547268 mRNA. Translation: AAN39340.1. Different initiation.
IPI	IPI00191453. IPI00734574.
RefSeq	NP_077055.1.
UniGene	Rn.55542
3D structure databases
ModBase	Search...
Protein family/group databases
PeroxiBase	3971. RnoDuOx02-b. 3972. RnoDuOx02-a.
Genome annotation databases
Ensembl	ENSRNOG00000017395. Rattus norvegicus. [Contig view]
GeneID	79107.
KEGG	rno:79107.
Organism-specific databases
RGD	628761. Duox2.
Phylogenomic databases
HOVERGEN	Q9ES45.
Enzyme and pathway databases
BRENDA	1.6.3.1. 248.
Gene expression databases
ArrayExpress	Q9ES45.
GermOnline	ENSRNOG00000017395. Rattus norvegicus.
Family and domain databases
InterPro	IPR011992. EF-Hand_type. IPR018248. EF_hand. IPR018247. EF_HAND_1. IPR018249. EF_HAND_2. IPR002048. EF_hand_Ca_bd. IPR013112. FAD_bd_8. IPR017927. Fd_Rdtase_FAD-bd. IPR013130. Fe3_reduct_TM_N. IPR013121. Fe_red_NAD_bd_6. IPR002007. Haem_peroxidase_animal. IPR019791. Haem_peroxidase_animal_sg. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit. G3DSA:1.10.640.10. Haem_peroxidase_animal. 1 hit.
Pfam	PF03098. An_peroxidase. 1 hit. PF00036. efhand. 2 hits. PF08022. FAD_binding_8. 1 hit. PF01794. Ferric_reduct. 1 hit. PF08030. NAD_binding_6. 1 hit. [Graphical view]
PRINTS	PR00457. ANPEROXIDASE.
ProDom	PD000012. EF-hand. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00054. EFh. 2 hits. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 2 hits. PS50222. EF_HAND_2. 3 hits. PS51384. FAD_FR. 1 hit. PS50292. PEROXIDASE_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	614498.

Entry information

Entry name

DUOX2_RAT

Accession

Primary (citable) accession number: Q9ES45
Secondary accession number(s): Q811Y4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2006
Last sequence update:	March 1, 2001
Last modified:	June 16, 2009
This is version 52 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)