DOXA2_HUMAN
ID DOXA2_HUMAN Reviewed; 320 AA.
AC Q1HG44; B2RPI9; H0YNQ6;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Dual oxidase maturation factor 2;
DE AltName: Full=Dual oxidase activator 2;
GN Name=DUOXA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND VARIANT GLY-100.
RC TISSUE=Thyroid;
RX PubMed=16651268; DOI=10.1074/jbc.c600095200;
RA Grasberger H., Refetoff S.;
RT "Identification of the maturation factor for dual oxidase. Evolution of an
RT eukaryotic operon equivalent.";
RL J. Biol. Chem. 281:18269-18272(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INVOLVEMENT IN TDH5.
RX PubMed=18042646; DOI=10.1210/jc.2007-2020;
RA Zamproni I., Grasberger H., Cortinovis F., Vigone M.C., Chiumello G.,
RA Mora S., Onigata K., Fugazzola L., Refetoff S., Persani L., Weber G.;
RT "Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2)
RT gene as a novel cause of congenital hypothyroidism.";
RL J. Clin. Endocrinol. Metab. 93:605-610(2008).
RN [7]
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=25761904; DOI=10.1089/ars.2015.6265;
RA Carre A., Louzada R.A., Fortunato R.S., Ameziane-El-Hassani R., Morand S.,
RA Ogryzko V., de Carvalho D.P., Grasberger H., Leto T.L., Dupuy C.;
RT "When an intramolecular disulfide bridge governs the interaction of DUOX2
RT with its partner DUOXA2.";
RL Antioxid. Redox Signal. 23:724-733(2015).
RN [8]
RP VARIANT TDH5 MET-26, AND CHARACTERIZATION OF VARIANT TDH5 MET-26.
RX PubMed=25675383; DOI=10.1210/jc.2014-3964;
RA Liu S., Liu L., Niu X., Lu D., Xia H., Yan S.;
RT "A novel missense mutation (I26M) in DUOXA2 causing congenital goiter
RT hypothyroidism impairs NADPH oxidase activity but not protein expression.";
RL J. Clin. Endocrinol. Metab. 100:1225-1229(2015).
CC -!- FUNCTION: Required for the maturation and the transport from the
CC endoplasmic reticulum to the plasma membrane of functional DUOX2. May
CC play a role in thyroid hormone synthesis.
CC {ECO:0000269|PubMed:16651268}.
CC -!- SUBUNIT: Heterodimer with DUXA2; disulfide-linked.
CC {ECO:0000269|PubMed:25761904}.
CC -!- INTERACTION:
CC Q1HG44; Q9NRD8: DUOX2; NbExp=5; IntAct=EBI-25589731, EBI-12740885;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16651268}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16651268}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q1HG44-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q1HG44-2; Sequence=VSP_046554, VSP_046555;
CC -!- TISSUE SPECIFICITY: Specifically expressed in thyroid. Also detected in
CC salivary glands. {ECO:0000269|PubMed:16651268}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16651268}.
CC -!- DISEASE: Thyroid dyshormonogenesis 5 (TDH5) [MIM:274900]: A disorder
CC due to thyroid dyshormonogenesis, causing hypothyroidism, goiter, and
CC variable mental deficits derived from unrecognized and untreated
CC hypothyroidism. {ECO:0000269|PubMed:18042646,
CC ECO:0000269|PubMed:25675383}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DUOXA family. {ECO:0000305}.
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DR EMBL; DQ489734; ABF48256.1; -; mRNA.
DR EMBL; BX537581; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC091117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77289.1; -; Genomic_DNA.
DR EMBL; BC137465; AAI37466.1; -; mRNA.
DR CCDS; CCDS10118.2; -. [Q1HG44-1]
DR RefSeq; NP_997464.2; NM_207581.3. [Q1HG44-1]
DR AlphaFoldDB; Q1HG44; -.
DR SMR; Q1HG44; -.
DR BioGRID; 135714; 63.
DR IntAct; Q1HG44; 1.
DR STRING; 9606.ENSP00000319705; -.
DR GlyGen; Q1HG44; 3 sites.
DR iPTMnet; Q1HG44; -.
DR PhosphoSitePlus; Q1HG44; -.
DR BioMuta; DUOXA2; -.
DR DMDM; 215274003; -.
DR jPOST; Q1HG44; -.
DR MassIVE; Q1HG44; -.
DR PaxDb; Q1HG44; -.
DR PeptideAtlas; Q1HG44; -.
DR PRIDE; Q1HG44; -.
DR ProteomicsDB; 61216; -. [Q1HG44-1]
DR Antibodypedia; 2475; 100 antibodies from 18 providers.
DR DNASU; 405753; -.
DR Ensembl; ENST00000323030.6; ENSP00000319705.5; ENSG00000140274.14. [Q1HG44-1]
DR Ensembl; ENST00000491993.2; ENSP00000454110.1; ENSG00000140274.14. [Q1HG44-2]
DR GeneID; 405753; -.
DR KEGG; hsa:405753; -.
DR MANE-Select; ENST00000323030.6; ENSP00000319705.5; NM_207581.4; NP_997464.2.
DR UCSC; uc001zuo.4; human. [Q1HG44-1]
DR CTD; 405753; -.
DR DisGeNET; 405753; -.
DR GeneCards; DUOXA2; -.
DR HGNC; HGNC:32698; DUOXA2.
DR HPA; ENSG00000140274; Tissue enhanced (gallbladder, urinary bladder).
DR MalaCards; DUOXA2; -.
DR MIM; 274900; phenotype.
DR MIM; 612772; gene.
DR neXtProt; NX_Q1HG44; -.
DR OpenTargets; ENSG00000140274; -.
DR Orphanet; 95716; Familial thyroid dyshormonogenesis.
DR PharmGKB; PA145008523; -.
DR VEuPathDB; HostDB:ENSG00000140274; -.
DR eggNOG; KOG3921; Eukaryota.
DR GeneTree; ENSGT00390000008240; -.
DR HOGENOM; CLU_045258_0_0_1; -.
DR InParanoid; Q1HG44; -.
DR OMA; IGLMHIN; -.
DR OrthoDB; 835845at2759; -.
DR PhylomeDB; Q1HG44; -.
DR TreeFam; TF312996; -.
DR PathwayCommons; Q1HG44; -.
DR SignaLink; Q1HG44; -.
DR BioGRID-ORCS; 405753; 17 hits in 1064 CRISPR screens.
DR ChiTaRS; DUOXA2; human.
DR GenomeRNAi; 405753; -.
DR Pharos; Q1HG44; Tbio.
DR PRO; PR:Q1HG44; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q1HG44; protein.
DR Bgee; ENSG00000140274; Expressed in pancreatic ductal cell and 100 other tissues.
DR Genevisible; Q1HG44; HS.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0031252; C:cell leading edge; IGI:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042743; P:hydrogen peroxide metabolic process; IEA:Ensembl.
DR GO; GO:2000147; P:positive regulation of cell motility; IDA:UniProtKB.
DR GO; GO:0010729; P:positive regulation of hydrogen peroxide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0008104; P:protein localization; IGI:UniProtKB.
DR GO; GO:0051604; P:protein maturation; IGI:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:2000609; P:regulation of thyroid hormone generation; IEA:Ensembl.
DR InterPro; IPR018469; Dual_oxidase_maturation_fac.
DR PANTHER; PTHR31158; PTHR31158; 1.
DR Pfam; PF10204; DuoxA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Congenital hypothyroidism; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Protein transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..320
FT /note="Dual oxidase maturation factor 2"
FT /id="PRO_0000264245"
FT TOPO_DOM 1..21
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..183
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..206
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 228..247
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 167
FT /note="Interchain (with C-568 in DUXA2)"
FT /evidence="ECO:0000269|PubMed:25761904"
FT DISULFID 233
FT /note="Interchain (with C-582 in DUXA2)"
FT /evidence="ECO:0000269|PubMed:25761904"
FT VAR_SEQ 50..121
FT /note="RWFWLVRVLLSLFIGAEIVAVHFSAEWFVGTVNTNTSYKAFSAARVTARVRL
FT LVGLEGINITLTGTPVHQLN -> EYLHSHLLPSEIRLGPPSSEGGDPCVPSTSGLTEP
FT HQAVTGPGGRTRTRRQTARGVKVVEECQEVGVEGRCC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_046554"
FT VAR_SEQ 122..320
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_046555"
FT VARIANT 26
FT /note="I -> M (in TDH5; unknown pathological significance;
FT impairs hydrogen peroxide metabolic process)"
FT /evidence="ECO:0000269|PubMed:25675383"
FT /id="VAR_074025"
FT VARIANT 100
FT /note="R -> G (in dbSNP:rs2576090)"
FT /evidence="ECO:0000269|PubMed:16651268"
FT /id="VAR_047367"
SQ SEQUENCE 320 AA; 34787 MW; 5B2F58E575A30E72 CRC64;
MTLWNGVLPF YPQPRHAAGF SVPLLIVILV FLALAASFLL ILPGIRGHSR WFWLVRVLLS
LFIGAEIVAV HFSAEWFVGT VNTNTSYKAF SAARVTARVR LLVGLEGINI TLTGTPVHQL
NETIDYNEQF TWRLKENYAA EYANALEKGL PDPVLYLAEK FTPSSPCGLY HQYHLAGHYA
SATLWVAFCF WLLSNVLLST PAPLYGGLAL LTTGAFALFG VFALASISSV PLCPLRLGSS
ALTTQYGAAF WVTLATGVLC LFLGGAVVSL QYVRPSALRT LLDQSAKDCS QERGGSPLIL
GDPLHKQAAL PDLKCITTNL
