DUOX1_CAEEL
ID DUOX1_CAEEL Reviewed; 1497 AA.
AC O61213; Q9NH90;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Dual oxidase 1;
DE Short=DUOX1;
DE EC=1.11.1.-;
DE EC=1.6.3.1;
DE AltName: Full=Blistered cuticle protein 3;
DE AltName: Full=NADPH thyroid oxidase 1;
DE Flags: Precursor;
GN Name=bli-3 {ECO:0000312|WormBase:F56C11.1};
GN ORFNames=F56C11.1 {ECO:0000312|WormBase:F56C11.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=11514595; DOI=10.1083/jcb.200103132;
RA Edens W.A., Sharling L., Cheng G., Shapira R., Kinkade J.M., Lee T.,
RA Edens H.A., Tang X., Sullards C., Flaherty D.B., Benian G.M., Lambeth J.D.;
RT "Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a
RT multidomain oxidase/peroxidase with homology to the phagocyte oxidase
RT subunit gp91phox.";
RL J. Cell Biol. 154:879-891(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-66, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF GLY-246.
RX PubMed=18460651; DOI=10.1096/fj.08-108522;
RA Calvo A.C., Pey A.L., Ying M., Loer C.M., Martinez A.;
RT "Anabolic function of phenylalanine hydroxylase in Caenorhabditis
RT elegans.";
RL FASEB J. 22:3046-3058(2008).
RN [5]
RP FUNCTION.
RX PubMed=19406744; DOI=10.1074/jbc.m900831200;
RA Thein M.C., Winter A.D., Stepek G., McCormack G., Stapleton G.,
RA Johnstone I.L., Page A.P.;
RT "Combined extracellular matrix cross-linking activity of the peroxidase
RT MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability
RT in Caenorhabditis elegans.";
RL J. Biol. Chem. 284:17549-17563(2009).
RN [6]
RP FUNCTION, INTERACTION WITH DOXA-1 AND TSP-15, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF PRO-1311.
RX PubMed=23028364; DOI=10.1371/journal.pgen.1002957;
RA Moribe H., Konakawa R., Koga D., Ushiki T., Nakamura K., Mekada E.;
RT "Tetraspanin is required for generation of reactive oxygen species by the
RT dual oxidase system in Caenorhabditis elegans.";
RL PLoS Genet. 8:E1002957-E1002957(2012).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-246 AND ALA-1263.
RX PubMed=25480962; DOI=10.1534/g3.114.015982;
RA Xu Z., Luo J., Li Y., Ma L.;
RT "The BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for iodide
RT toxicity in Caenorhabditis elegans.";
RL G3 (Bethesda) 5:195-203(2015).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27974198; DOI=10.1016/j.celrep.2016.11.038;
RA Tang H., Pang S.;
RT "Proline Catabolism Modulates Innate Immunity in Caenorhabditis elegans.";
RL Cell Rep. 17:2837-2844(2016).
RN [9]
RP FUNCTION, INTERACTION WITH RHO-1, AND DISRUPTION PHENOTYPE.
RX PubMed=28085666; DOI=10.7554/elife.19493;
RA Ewald C.Y., Hourihan J.M., Bland M.S., Obieglo C., Katic I.,
RA Moronetti Mazzeo L.E., Alcedo J., Blackwell T.K., Hynes N.E.;
RT "NADPH oxidase-mediated redox signaling promotes oxidative stress
RT resistance and longevity through memo-1 in C. elegans.";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Plays a role in cuticle biogenesis (PubMed:11514595,
CC PubMed:19406744, PubMed:23028364, PubMed:25480962, PubMed:18460651). In
CC complex with doxa-1 and tsp-15, produces reactive oxygen species (ROS),
CC which are probably used by mlt-7 for tyrosine cross-linking, thus
CC stabilizing cuticular extracellular matrix (PubMed:11514595,
CC PubMed:19406744, PubMed:23028364). May regulate the production of ROS
CC by playing a role in modulating proline catabolism (PubMed:27974198).
CC Required in combination with mlt-7 for correct formation of cross-links
CC in cuticle collagens (PubMed:19406744). Association with the GTPase
CC rho-1 promotes ROS production and this interaction may be modulated by
CC memo-1, in order to control the oxidative stress response and longevity
CC (PubMed:28085666). {ECO:0000269|PubMed:11514595,
CC ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:19406744,
CC ECO:0000269|PubMed:23028364, ECO:0000269|PubMed:25480962,
CC ECO:0000269|PubMed:27974198, ECO:0000269|PubMed:28085666}.
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:11514595};
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:11514595};
CC -!- ACTIVITY REGULATION: Peroxidase activity is inhibited by
CC aminobenzohydrazide. {ECO:0000269|PubMed:11514595}.
CC -!- SUBUNIT: Interacts with doxa-1 and tsp-15 (PubMed:23028364). Interacts
CC with rho-1 (PubMed:28085666). {ECO:0000269|PubMed:23028364,
CC ECO:0000269|PubMed:28085666}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in hypodermal cells.
CC {ECO:0000269|PubMed:11514595}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in a blistered
CC cuticle phenotype (PubMed:23028364, PubMed:25480962). Resistant to
CC iodide toxicity (PubMed:25480962). RNAi-mediated knockdown in
CC combination with proline supplementation suppresses the effects of
CC exogenous proline alone and increases reactive oxygen species
CC production and reduces the expression of skn-1 transcriptional targets
CC including gst-4 following infection by P.aeruginosa (PubMed:27974198).
CC RNAi-mediated knockdown rescues the enhanced longevity and increased
CC reactive oxygen species production defects in memo-1 mutants
CC (PubMed:28085666). RNAi-mediated knockdown suppresses the nuclear
CC localization of transcription factor skn-1 in memo-1 RNAi mutants
CC (PubMed:28085666). {ECO:0000269|PubMed:23028364,
CC ECO:0000269|PubMed:25480962, ECO:0000269|PubMed:27974198,
CC ECO:0000269|PubMed:28085666}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the peroxidase
CC family. {ECO:0000305}.
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DR EMBL; AF229855; AAF71303.1; -; mRNA.
DR EMBL; BX284601; CCD71714.1; -; Genomic_DNA.
DR PIR; T29025; T29025.
DR RefSeq; NP_490686.3; NM_058285.4.
DR AlphaFoldDB; O61213; -.
DR SMR; O61213; -.
DR BioGRID; 37112; 6.
DR ComplexPortal; CPX-1020; BLI-3/DOXA-1/TSP-15 dual oxidase complex.
DR STRING; 6239.F56C11.1; -.
DR PeroxiBase; 3349; CelDuOx01.
DR iPTMnet; O61213; -.
DR EPD; O61213; -.
DR PaxDb; O61213; -.
DR PeptideAtlas; O61213; -.
DR PRIDE; O61213; -.
DR EnsemblMetazoa; F56C11.1.1; F56C11.1.1; WBGene00000253.
DR EnsemblMetazoa; F56C11.1.2; F56C11.1.2; WBGene00000253.
DR GeneID; 171608; -.
DR KEGG; cel:CELE_F56C11.1; -.
DR UCSC; F56C11.1; c. elegans.
DR CTD; 171608; -.
DR WormBase; F56C11.1; CE28463; WBGene00000253; bli-3.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000163963; -.
DR HOGENOM; CLU_004482_1_0_1; -.
DR InParanoid; O61213; -.
DR OMA; KDVFMWR; -.
DR OrthoDB; 27424at2759; -.
DR PhylomeDB; O61213; -.
DR BRENDA; 1.6.3.1; 1045.
DR Reactome; R-CEL-209968; Thyroxine biosynthesis.
DR PRO; PR:O61213; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000253; Expressed in larva and 3 other tissues.
DR GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central.
DR GO; GO:1990204; C:oxidoreductase complex; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IDA:WormBase.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IMP:WormBase.
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; IDA:WormBase.
DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IBA:GO_Central.
DR GO; GO:0040002; P:collagen and cuticulin-based cuticle development; IDA:ComplexPortal.
DR GO; GO:0042338; P:cuticle development involved in collagen and cuticulin-based cuticle molting cycle; IMP:WormBase.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0050832; P:defense response to fungus; IMP:WormBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:WormBase.
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:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0018149; P:peptide cross-linking; IDA:WormBase.
DR GO; GO:0040032; P:post-embryonic body morphogenesis; IMP:WormBase.
DR GO; GO:0006979; P:response to oxidative stress; IGI:WormBase.
DR GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central.
DR CDD; cd09820; dual_peroxidase_like; 1.
DR Gene3D; 1.10.640.10; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR029595; DUOX1/Duox.
DR InterPro; IPR034821; DUOX_peroxidase.
DR InterPro; IPR011992; EF-hand-dom_pair.
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:SF175; PTHR11972:SF175; 1.
DR Pfam; PF03098; An_peroxidase; 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 SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF48113; SSF48113; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 1: Evidence at protein level;
KW Calcium; FAD; Flavoprotein; Glycoprotein; Hydrogen peroxide; Membrane;
KW NADP; Oxidoreductase; Peroxidase; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1497
FT /note="Dual oxidase 1"
FT /id="PRO_0000223348"
FT TOPO_DOM 22..587
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 588..608
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 609..986
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 987..1007
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1008..1024
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1025..1045
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1046..1068
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1069..1089
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1090..1134
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1135..1155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1156..1163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1164..1184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1185..1189
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1190..1210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1211..1497
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 817..852
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 853..888
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 1030..1210
FT /note="Ferric oxidoreductase"
FT DOMAIN 1211..1318
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 26..590
FT /note="Peroxidase-like; mediates peroxidase activity"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17761667"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 586
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 246
FT /note="G->D: In e767; growth arrest, severe blistering of
FT the cuticle, incomplete molting and mild shorter and
FT stouter body shape. Resistant to iodide toxicity. Reduced
FT catalase activity. In a pah-1(tm520) mutant background,
FT growth arrest in early larval development, severe cuticle
FT abnormalities with large blisters and increased superoxide
FT dismutase activity."
FT /evidence="ECO:0000269|PubMed:18460651,
FT ECO:0000269|PubMed:25480962"
FT MUTAGEN 1263
FT /note="A->T: In mac40; blistered cuticle phenotype in some
FT animals with blisters containing cellular material.
FT Resistant to iodide toxicity."
FT /evidence="ECO:0000269|PubMed:25480962"
FT MUTAGEN 1311
FT /note="P->L: In im10; blistered cuticle phenotype with
FT accumulation of cellular material in blisters."
FT /evidence="ECO:0000269|PubMed:23028364"
FT CONFLICT 105
FT /note="Y -> H (in Ref. 1; AAF71303)"
FT /evidence="ECO:0000305"
FT CONFLICT 829
FT /note="T -> I (in Ref. 1; AAF71303)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1497 AA; 170416 MW; 6C648F193796A730 CRC64;
MRSKHVLYIA ILFSSIFGGK GIQQNEEFQR YDGWYNNLAN SEWGSAGSRL HRDARSYYSD
GVYSVNNSLP SARELSDILF KGESGIPNTR GCTTLLAFFS QVVAYEIMQS NGVSCPLETL
KIQVPLCDNV FDKECEGKTE IPFTRAKYDK ATGNGLNSPR EQINERTSWI DGSFIYGTTQ
PWVSSLRSFK QGRLAEGVPG YPPLNNPHIP LNNPAPPQVH RLMSPDRLFM LGDSRVNENP
GLLSFGLILF RWHNYNANQI HREHPDWTDE QIFQAARRLV IASMQKIIAY DFVPGLLGED
VRLSNYTKYM PHVPPGISHA FGAAAFRFPH SIVPPAMLLR KRGNKCEFRT EVGGYPALRL
CQNWWNAQDI VKEYSVDEII LGMASQIAER DDNIVVEDLR DYIFGPMHFS RLDVVASSIM
RGRDNGVPPY NELRRTFGLA PKTWETMNED FYKKHTAKVE KLKELYGGNI LYLDAYVGGM
LEGGENGPGE LFKEIIKDQF TRIRDGDRFW FENKLNGLFT DEEVQMIHSI TLRDIIKATT
DIDETMLQKD VFFFKEGDPC PQPFQVNTTG LEPCVPFMQS TYWTDNDTTY VFTLIGLACV
PLICYGIGRY LVNRRIAIGH NSACDSLTTD FANDDCGAKG DIYGVNALEW LQEEYIRQVR
IEIENTTLAV KKPRGGILRK IRFETGQKIE LFHSMPNPSA MHGPFVLLSQ KNNHHLVIRL
SSDRDLSKFL DQIRQAASGI NAEVIIKDEE NSILLSQAIT KERRQDRLDL FFREAYAKAF
NDSELQDSET SFDSSNDDIL NETISREELA SAMGMKANNE FVKRMFAMTA KHNEDSLSFN
EFLTVLREFV NAPQKQKLQT LFKMCDLEGK NKVLRKDLAE LVKSLNQTAG VHITESVQLR
LFNEVLHYAG VSNDAKYLTY DDFNALFSDI PDKQPVGLPF NRKNYQPSIG ETSSLNSFAV
VDRSINSSAP LTLIHKVSAF LETYRQHVFI VFCFVAINLV LFFERFWHYR YMAENRDLRR
VMGAGIAITR GAAGALSFCM ALILLTVCRN IITLLRETVI AQYIPFDSAI AFHKIVALFA
AFWATLHTVG HCVNFYHVGT QSQEGLACLF QEAFFGSNFL PSISYWFFST ITGLTGIALV
AVMCIIYVFA LPCFIKRAYH AFRLTHLLNI AFYALTLLHG LPKLLDSPKF GYYVVGPIVL
FVIDRIIGLM QYYKKLEIVN AEILPSDIIY IEYRRPREFK YKSGQWVTVS SPSISCTFNE
SHAFSIASSP QDENMKLYIK AVGPWTWKLR SELIRSLNTG SPFPLIHMKG PYGDGNQEWM
DYEVAIMVGA GIGVTPYAST LVDLVQRTSS DSFHRVRCRK VYFLWVCSTH KNYEWFVDVL
KNVEDQARSG ILETHIFVTQ TFHKFDLRTT MLYICEKHFR ATNSGISMFT GLHAKNHFGR
PNFKAFFQFI QSEHKEQSKI GVFSCGPVNL NESIAEGCAD ANRQRDAPSF AHRFETF
