DUOX2_PIG
ID DUOX2_PIG Reviewed; 1545 AA.
AC Q8HZK2; Q9TT98;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Dual oxidase 2;
DE EC=1.11.1.-;
DE EC=1.6.3.1;
DE AltName: Full=NADH/NADPH thyroid oxidase p138-tox;
DE Flags: Precursor;
GN Name=DUOX2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, AND INDUCTION.
RC TISSUE=Thyroid;
RX PubMed=12639906; DOI=10.1210/en.2002-220981;
RA Morand S., Chaaraoui M., Kaniewski J., Deme D., Ohayon R.,
RA Noel-Hudson M.-S., Virion A., Dupuy C.;
RT "Effect of iodide on nicotinamide adenine dinucleotide phosphate oxidase
RT activity and Duox2 protein expression in isolated porcine thyroid
RT follicles.";
RL Endocrinology 144:1241-1248(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 339-1545, INDUCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Thyroid;
RX PubMed=10601291; DOI=10.1074/jbc.274.52.37265;
RA Dupuy C., Ohayon R., Valent A., Noel-Hudson M.-S., Deme D., Virion A.;
RT "Purification of a novel flavoprotein involved in the thyroid NADPH
RT oxidase. Cloning of the porcine and human cDNAs.";
RL J. Biol. Chem. 274:37265-37269(1999).
RN [3]
RP INDUCTION.
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15591162; DOI=10.1152/ajpgi.00198.2004;
RA Ameziane-El-Hassani R., Benfares N., Caillou B., Talbot M., Sabourin J.-C.,
RA Belotte V., Morand S., Gnidehou S., Agnandji D., Ohayon R., Kaniewski J.,
RA Noel-Hudson M.-S., Bidart J.-M., Schlumberger M., Virion A., Dupuy C.;
RT "Dual oxidase2 is expressed all along the digestive tract.";
RL Am. J. Physiol. 288:G933-G942(2005).
RN [5]
RP CATALYTIC ACTIVITY.
RX PubMed=15972824; DOI=10.1074/jbc.m500516200;
RA Ameziane-El-Hassani R., Morand S., Boucher J.L., Frapart Y.-M.,
RA Apostolou D., Agnandji D., Gnidehou S., Ohayon R., Noel-Hudson M.-S.,
RA Francon J., Lalaoui K., Virion A., Dupuy C.;
RT "Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity.";
RL J. Biol. Chem. 280:30046-30054(2005).
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 Evidence={ECO:0000269|PubMed:15972824};
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 Evidence={ECO:0000269|PubMed:15972824};
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:0000269|PubMed:15591162}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15591162}. 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 -!- TISSUE SPECIFICITY: Expressed in thyroid, and the digestive tract
CC especially in stomach, cecum and sigmoidal colon (at protein level).
CC Expressed in thyroid. {ECO:0000269|PubMed:10601291,
CC ECO:0000269|PubMed:15591162}.
CC -!- INDUCTION: By forskolin and down-regulated by iodide (at protein
CC level). By insulin. {ECO:0000269|PubMed:10601291,
CC ECO:0000269|PubMed:12538618, ECO:0000269|PubMed:12639906}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12639906}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the peroxidase
CC family. {ECO:0000305}.
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DR EMBL; AF547267; AAN39339.2; -; mRNA.
DR EMBL; AF181973; AAF20056.1; -; mRNA.
DR RefSeq; NP_999164.2; NM_213999.2.
DR AlphaFoldDB; Q8HZK2; -.
DR SMR; Q8HZK2; -.
DR STRING; 9823.ENSSSCP00000005038; -.
DR PeroxiBase; 3340; SscDuOx02.
DR PaxDb; Q8HZK2; -.
DR GeneID; 397060; -.
DR KEGG; ssc:397060; -.
DR CTD; 50506; -.
DR eggNOG; KOG0039; Eukaryota.
DR InParanoid; Q8HZK2; -.
DR OrthoDB; 27424at2759; -.
DR BRENDA; 1.6.3.1; 6170.
DR UniPathway; UPA00194; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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: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; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
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: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:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0050665; P:hydrogen peroxide biosynthetic process; IEA:InterPro.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051591; P:response to cAMP; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central.
DR GO; GO:0006590; P:thyroid hormone generation; IEA:UniProtKB-UniPathway.
DR CDD; cd09820; dual_peroxidase_like; 1.
DR CDD; cd00051; EFh; 2.
DR Gene3D; 1.10.640.10; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR034818; DUOX2.
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; PTHR11972:SF67; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00036; EF-hand_1; 1.
DR Pfam; PF13202; EF-hand_5; 1.
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 SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF48113; SSF48113; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 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 1: Evidence at protein level;
KW Calcium; Cell junction; Cell membrane; Disulfide bond; FAD; Flavoprotein;
KW Glycoprotein; Hydrogen peroxide; Membrane; Metal-binding; NADP;
KW Oxidoreductase; Peroxidase; Reference proteome; Repeat; Signal;
KW Thyroid hormones biosynthesis; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1545
FT /note="Dual oxidase 2"
FT /id="PRO_0000223350"
FT TOPO_DOM 26..601
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 602..622
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 623..1037
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1038..1058
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1059..1074
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1075..1097
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1098..1125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1126..1148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1149..1182
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1183..1203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1204..1220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1221..1241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1242
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1243..1263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1264..1545
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 1081..1263
FT /note="Ferric oxidoreductase"
FT DOMAIN 1264..1370
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..1242
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 312
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 358
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 549
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 124..1159
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 CONFLICT 1531
FT /note="N -> S (in Ref. 2; AAF20056)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1545 AA; 175284 MW; 29A6B1A0C69552DD CRC64;
MLCIRPEALV LLGALLTVPL DPVGGQDALS LTWEVQRYDG WFNNLRQHEH GAAGSPLRRL
VPANYADGVY QALGEPLLPN PRQLSHTTMR GPAGLRSIRN RTVLGVFFGY HVLSDLVSIE
KPGCPAEFLN IHIPPGDPVF DPHKSGDVVL PFQRSRWDPN TGQSPSNPRD LTNEVTGWLD
GSAIYGSSHS WSDELRSFSG GQLASGPDPA FPRQAQDPLF MWTPPDPATG QRGPQGLYAF
GAEQGNREPF LQALGLLWFR YHNLCAQKLA REHPLWGDEE LFQHARKRVI ATYQSITMYE
WLPSFLQQTP PNYTEYRPFL DPSISPEFLA ASEQFFSTMV PPGVYMRNAS CHFQMVLNES
YGSFPALRVC NSYWIRENPN LNSAEAVNQL LLGMASQISE LEDWIVVEDL RDYWPGPGKF
SRTDYVASSI QRGRDMGLPS YTQALQALGL NTPKNWSDFN PNVDPQVLEA TAALYNQDLS
RLELFSGGLL ESYGDPGPLF STIVLDQFVR LRDGDRYWFE NTKNGLFSKE EIAEIRSTTL
RDVLVAVTNV SSSALQPNVF IWNEDSPCPQ PQQLTTEDLP HCVPLTVIQY FEGSGPGFGI
TIVALCCLPL MSLLISGVVA YFRSRERKKL QKRGKESVKK EADKDGVSAM EWPGPKERSY
PVSIQLLPDR HLQVLDRHLS VLRTIQLRPR HRVNLILSNN LGRRTLLLKI PKEYDLVLLF
NSEDERGAFV QHLQGFCASC ALGLDIDEMG ESELFRKAVT KQQRGRILEI FFRHLFAQVL
DIDQADAGAL PLDSSQKVRE ALTCELSRAE FAESLGLKPQ DMFVESMFSL ADKDGNGYLS
FREFLDVLVV FMKGSPEDKS RLMFTMYDLD GNGFLSKDEF FTMIRSFIEI SNNCLSKAQL
TEVVESMFRE AGFQDKQELT WEDFHFMLRD HDSELRHTQL CVKGGGGGVG VIFKPDISSR
VSFIIRTPEE RSSPQGVRLP ASEASELGGP VLKKRFGKKA VVPPPRLYTE ALQEKKQRGF
LAQKLQQYKR FVENYRRHIV CVAIFSAICA GLFVERAYYY AFVSPPSGIA ETTFVGIILS
RGTAASVSFM FSYILLTMCR NLITFLRETF LNHYVPFDAA VDFHRWIAMA ALVLAILHSV
GHVVNVYIFS VSPLSLLACV FPSVFVNDGS KLPQKFYWWF FQTIPGMTGV LLLVVLAIMY
VFASPYFRRR SFRGFWLTHH FYILLYVLLI IHGSFALIQL PRFHIFFLVP ALIYVGDKLV
SLSRKKVEIS VVKAELLPSG VTHLQFQRPQ GFEYKSGQWV RIACLGLGTN EYHPFTLTSA
PHEDTLSLHI RAVGPWTTRL REIYSHPMGD GYARYPKLYL DGPFGEGHQE WHKFEVSVLV
GGGIGVTPFA SILKDLVFKS SLGSQMLCKK IYFIWVTRTQ RQFEWLADII REVEENDHRD
LVSVHIYITQ LAEKFDLRTT MLYICERHFQ KVLNRSLFTG LRSITHFGRP PFEPFFNSLQ
EVHPQVRKIG VFSCGPPGMT KNVEKTCQLI NRQDQTHFVH HYENF
