ID DUOX2_RAT Reviewed; 1517 AA.
AC Q9ES45; Q811Y4;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 08-NOV-2023, entry version 142.
DE RecName: Full=Dual oxidase 2;
DE EC=1.11.1.-;
DE EC=1.6.3.1;
DE AltName: Full=Large NOX 2;
DE AltName: Full=Long NOX 2;
DE AltName: Full=NADH/NADPH thyroid oxidase THOX2;
DE AltName: Full=Thyroid oxidase 2;
DE Flags: Precursor;
GN Name=Duox2; Synonyms=Lnox2, Thox2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Thyroid;
RX PubMed=11032719; DOI=10.1006/bbrc.2000.3671;
RA Dupuy C., Pomerance M., Ohayon R., Noel-Hudson M.-S., Deme D.,
RA Chaaraoui M., Francon J., Virion A.;
RT "Thyroid oxidase (THOX2) gene expression in the rat thyroid cell line FRTL-
RT 5.";
RL Biochem. Biophys. Res. Commun. 277:287-292(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INDUCTION.
RC STRAIN=Fischer;
RX PubMed=12538618; DOI=10.1210/en.2002-220824;
RA Morand S., Dos Santos O.F., Ohayon R., Kaniewski J., Noel-Hudson M.-S.,
RA Virion A., Dupuy C.;
RT "Identification of a truncated dual oxidase 2 (DUOX2) messenger ribonucleic
RT acid (mRNA) in two rat thyroid cell lines. Insulin and forskolin regulation
RT of DUOX2 mRNA levels in FRTL-5 cells and porcine thyrocytes.";
RL Endocrinology 144:567-574(2003).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=12824283; DOI=10.1096/fj.02-1104fje;
RA Geiszt M., Witta J., Baffi J., Lekstrom K., Leto T.L.;
RT "Dual oxidases represent novel hydrogen peroxide sources supporting mucosal
RT surface host defense.";
RL FASEB J. 17:1502-1504(2003).
CC -!- FUNCTION: Generates hydrogen peroxide which is required for the
CC activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a
CC role in thyroid hormones synthesis and lactoperoxidase-mediated
CC antimicrobial defense at the surface of mucosa. May have its own
CC peroxidase activity through its N-terminal peroxidase-like domain.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADH + O2 = H2O2 + NAD(+); Xref=Rhea:RHEA:11264,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.3.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 = H2O2 + NADP(+); Xref=Rhea:RHEA:11260,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.6.3.1;
CC -!- ACTIVITY REGULATION: The NADPH oxidase activity is calcium-dependent.
CC Peroxidase activity is inhibited by aminobenzohydrazide (By
CC similarity). {ECO:0000250}.
CC -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis.
CC -!- SUBUNIT: Heterodimer with DUOXA2; disulfide-linked. Interacts with
CC TXNDC11, TPO and CYBA. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9NRD8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NRD8}. Cell junction
CC {ECO:0000250|UniProtKB:Q9NRD8}. Note=Localizes to the apical membrane
CC of epithelial cells. Localizes on internal membrane structures under
CC resting conditions, translocates to the plasma membrane and cell-cell
CC junctions upon challenge with enteric pathogens.
CC {ECO:0000250|UniProtKB:Q9NRD8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9ES45-1; Sequence=Displayed;
CC Name=2; Synonyms=short;
CC IsoId=Q9ES45-2; Sequence=VSP_017264;
CC -!- TISSUE SPECIFICITY: Expressed in colon, duodenum, rectum and thyroid.
CC {ECO:0000269|PubMed:11032719, ECO:0000269|PubMed:12824283}.
CC -!- INDUCTION: By forskolin, thyrotropin and insulin. Down-regulated by the
CC antithyroid drug methimazole. {ECO:0000269|PubMed:11032719,
CC ECO:0000269|PubMed:12538618}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: There is no evidence for the expression of
CC the corresponding protein in vitro. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the peroxidase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN39340.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF237962; AAG21895.1; -; mRNA.
DR EMBL; AF547268; AAN39340.1; ALT_INIT; mRNA.
DR RefSeq; NP_077055.1; NM_024141.1.
DR AlphaFoldDB; Q9ES45; -.
DR SMR; Q9ES45; -.
DR STRING; 10116.ENSRNOP00000023939; -.
DR PeroxiBase; 3971; RnoDuOx02-B.
DR PeroxiBase; 3972; RnoDuOx02-A.
DR GlyCosmos; Q9ES45; 4 sites, No reported glycans.
DR GlyGen; Q9ES45; 4 sites.
DR iPTMnet; Q9ES45; -.
DR PhosphoSitePlus; Q9ES45; -.
DR PaxDb; 10116-ENSRNOP00000023939; -.
DR GeneID; 79107; -.
DR KEGG; rno:79107; -.
DR UCSC; RGD:628761; rat. [Q9ES45-1]
DR AGR; RGD:628761; -.
DR CTD; 50506; -.
DR RGD; 628761; Duox2.
DR eggNOG; KOG0039; Eukaryota.
DR InParanoid; Q9ES45; -.
DR OrthoDB; 367877at2759; -.
DR PhylomeDB; Q9ES45; -.
DR Reactome; R-RNO-209968; Thyroxine biosynthesis.
DR UniPathway; UPA00194; -.
DR PRO; PR:Q9ES45; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0045177; C:apical part of cell; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031252; C:cell leading edge; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; ISO:RGD.
DR GO; GO:0106293; F:NADH oxidase H202-forming activity; IEA:RHEA.
DR GO; GO:0106294; F:NADPH oxidase H202-forming activity; IEA:RHEA.
DR GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IBA:GO_Central.
DR GO; GO:0048855; P:adenohypophysis morphogenesis; ISO:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0042335; P:cuticle development; ISS:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0009566; P:fertilization; ISO:RGD.
DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042445; P:hormone metabolic process; ISO:RGD.
DR GO; GO:0050665; P:hydrogen peroxide biosynthetic process; ISO:RGD.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0048839; P:inner ear development; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:2000147; P:positive regulation of cell motility; ISO:RGD.
DR GO; GO:0090303; P:positive regulation of wound healing; ISO:RGD.
DR GO; GO:0051591; P:response to cAMP; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR GO; GO:0009615; P:response to virus; ISO:RGD.
DR GO; GO:0042554; P:superoxide anion generation; ISO:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0006590; P:thyroid hormone generation; TAS:RGD.
DR GO; GO:0042403; P:thyroid hormone metabolic process; ISO:RGD.
DR CDD; cd09820; dual_peroxidase_like; 1.
DR CDD; cd00051; EFh; 2.
DR CDD; cd06186; NOX_Duox_like_FAD_NADP; 1.
DR Gene3D; 1.10.238.10; EF-hand; 1.
DR Gene3D; 1.10.640.10; Haem peroxidase domain superfamily, animal type; 1.
DR Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1.
DR Gene3D; 2.40.30.10; Translation factors; 1.
DR InterPro; IPR034821; DUOX_peroxidase.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR013112; FAD-bd_8.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR InterPro; IPR013121; Fe_red_NAD-bd_6.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR11972:SF67; DUAL OXIDASE 2; 1.
DR PANTHER; PTHR11972; NADPH OXIDASE; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00036; EF-hand_1; 2.
DR Pfam; PF08022; FAD_binding_8; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR Pfam; PF08030; NAD_binding_6; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SFLD; SFLDS00052; Ferric_Reductase_Domain; 1.
DR SFLD; SFLDG01168; Ferric_reductase_subgroup_(FRE; 1.
DR SFLD; SFLDG01169; NADPH_oxidase_subgroup_(NOX); 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; EF-hand; 1.
DR SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1.
DR SUPFAM; SSF48113; Heme-dependent peroxidases; 1.
DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Cell junction; Cell membrane;
KW Disulfide bond; FAD; Flavoprotein; Glycoprotein; Hydrogen peroxide;
KW Membrane; Metal-binding; NADP; Oxidoreductase; Peroxidase;
KW Reference proteome; Repeat; Signal; Thyroid hormones biosynthesis;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1517
FT /note="Dual oxidase 2"
FT /id="PRO_0000223351"
FT TOPO_DOM 26..599
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 600..620
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 621..1010
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1011..1031
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1032..1046
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1047..1067
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1068..1100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1101..1121
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1122..1154
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1155..1175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1176..1185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1186..1206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1207
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1208..1228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1229..1517
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 819..854
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 855..890
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 899..934
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 1053..1235
FT /note="Ferric oxidoreductase"
FT DOMAIN 1236..1342
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 30..596
FT /note="Peroxidase-like; mediates peroxidase activity"
FT /evidence="ECO:0000250"
FT REGION 960..1214
FT /note="Interaction with TXNDC11"
FT /evidence="ECO:0000250"
FT BINDING 832
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 834
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 836
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 838
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 843
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 868
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 870
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 872
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 879
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 537
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 124..1131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 568
FT /note="Interchain (with C-167 in DUOXA2)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 582
FT /note="Interchain (with C-233 in DUOXA2)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..1061
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12538618"
FT /id="VSP_017264"
FT CONFLICT 1243
FT /note="V -> A (in Ref. 2; AAN39340)"
FT /evidence="ECO:0000305"
FT CONFLICT 1246
FT /note="V -> A (in Ref. 2; AAN39340)"
FT /evidence="ECO:0000305"
FT CONFLICT 1409
FT /note="G -> D (in Ref. 2; AAN39340)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1517 AA; 171558 MW; 07FBA427DEA299D1 CRC64;
MLPTSLKTLV LLGALLTGPL GPAGGQDAPS LPREVQRYDG WFNNLKYHQR GAAGSQLRRL
VPANYADGVY QALQEPLLPN ARLLSDAVSK GKAGLPSAHN RTVLGLFFGY HVLSDLVSVE
TPGCPAEFLN IYIPRGDPVF DPDKRGNVVL PFQRSRWDRS TGQSPSNPRD LTNQVTGWLD
GSAIYGSSHS WSDTLRSFSG GQLASGPDPA FPRNSQNSLL MWMAPDPATG QGGPQGLYAF
GAQRGNREPF LQALGLLWFR YHNLCAKRLA QEHPHWGDEE LFQHARKRVI ATYQNIALYQ
WLPSFLQKTP PEYSGYRPFM DPSISPEFVA ASEQFLSTMV PPGVYMRNSS CHFREFPKEG
SSSSPALRVC NNYWIRENPS LKTAQDVDQL LLGMASQISE LEDRIVIEDL RDYWPGPDRY
SRTDYVASSI QSGRDMGLPS YSQALQALGL EPPKNWSALN PKVDPQVLEA TAALYNQDLS
RLELFLGGLL ESHGDPGPLF SNIILDQFVR LRDGDRYWFE NTRNGLFSKE EIAEIRNTTL
RDVLVAVSNV DPSALQPNVF FWQEGAPCPQ PQQLTTEGLP QCVPVTVIDY FEGSGAGYGV
TLLAVCCFPV VSLIIAWVVA RFRNRERKML LKKGKESLKK QTASDGVPAM EWPGPKESSY
PVTVQLLPDR SLKVLDKRLT VLRTIQLQPT QQVNLILSSS HGRRTLLLKI PKEYDLVLMF
NSEEDRDAFV QLLQDLCVCS TPGLRIAEMD EKELLRKAVT KQQRAGILEI FFRQLFAQVL
DINQADAGTL PLDSSQQVRE ALTCELSRAE FADSLGLKPQ DMFVESMFSL ADKDGNGYIS
FREFLDILVV FMKGSPQDKS RLMFTMYDLD GNGFLSKEEF FTMMRSFIEI SNNCLSKDQL
AEVVESMFRE SGFQDKEELT WEDFHFMLRD HDSDLRFTQL CVKGGAGGTG DIFKQSNACR
VSFLTRTPGN RVMAPSPRLY TEALQEKMQR GFLAQKLKQF KRFVENYRRH IVCVTIFSAI
CAGLFADRAY YYGFASPPTD IEETTYVGII LSRGTAASIS FMFSYILLTM CRNLITFLRE
TFLNRYIPFD AAVDFHRWIA MAAVVLAVVH SLGHAVNVYI FSVSPLSLMT CVFPSVFVND
GSKLPPKYYW WFFETVPGMT GVLLLLVLAI MYVFASHHFR RHSFRGFWLT HHLYVVLYAL
IIIHGSYALI QLPSFHIYFL VPAIIYVGDK LVSLSRKKVE ISVVKVELLP SGVTYLQFQR
PKTFEYKSGQ WVRIACLSLG TNEYHPFTLT SAPHEDTLSL HIRAVGPWTT RLREIYSPPV
GGTSARYPKL YLDGPFGEGH QEWHKFEVSV LVGGGIGVTP FASILKDLVF KSSMGTQMLC
KKIYFIWVTR TQRQFEWLAD IIREVEENGS RDLVSVHIYI TQLAEKFDLR TTMLYICERH
FQKVLNRSLF TGLRSVTHFG RPPFELFLDS LQEVHPQVHK IGVFSCGPPG MTKNVEKACQ
LINRQDRAHF VHHYENF
//
