ID   NOX3_HUMAN              Reviewed;         568 AA.
AC   Q9HBY0; Q9HBJ9;
DT   21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   03-AUG-2022, entry version 144.
DE   RecName: Full=NADPH oxidase 3;
DE            EC=1.6.3.-;
DE   AltName: Full=Mitogenic oxidase 2;
DE            Short=MOX-2;
DE   AltName: Full=gp91phox homolog 3;
DE            Short=GP91-3;
GN   Name=NOX3; Synonyms=MOX2;
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], AND DEVELOPMENTAL STAGE.
RC   TISSUE=Fetal kidney;
RX   PubMed=11376945; DOI=10.1016/s0378-1119(01)00449-8;
RA   Cheng G., Cao Z., Xu X., van Meir E.G., Lambeth J.D.;
RT   "Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and
RT   Nox5.";
RL   Gene 269:131-140(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 54-497, AND DEVELOPMENTAL STAGE.
RC   TISSUE=Fetal kidney;
RX   PubMed=10974555; DOI=10.1016/s0378-1119(00)00258-4;
RA   Kikuchi H., Hikage M., Miyashita H., Fukumoto M.;
RT   "NADPH oxidase subunit, gp91phox homologue, preferentially expressed in
RT   human colon epithelial cells.";
RL   Gene 254:237-243(2000).
RN   [4]
RP   ACTIVITY REGULATION.
RX   PubMed=15181005; DOI=10.1074/jbc.m400660200;
RA   Cheng G., Ritsick D., Lambeth J.D.;
RT   "Nox3 regulation by NOXO1, p47phox, and p67phox.";
RL   J. Biol. Chem. 279:34250-34255(2004).
RN   [5]
RP   FUNCTION, MUTAGENESIS OF PRO-413, ACTIVITY REGULATION, AND INTERACTION WITH
RP   CYBA.
RX   PubMed=15824103; DOI=10.1074/jbc.m414548200;
RA   Ueno N., Takeya R., Miyano K., Kikuchi H., Sumimoto H.;
RT   "The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-
RT   dependent manner: its regulation by oxidase organizers and activators.";
RL   J. Biol. Chem. 280:23328-23339(2005).
CC   -!- FUNCTION: NADPH oxidase which constitutively produces superoxide upon
CC       formation of a complex with CYBA/p22phox. Plays a role in the
CC       biogenesis of otoconia/otolith, which are crystalline structures of the
CC       inner ear involved in the perception of gravity.
CC       {ECO:0000269|PubMed:15824103}.
CC   -!- ACTIVITY REGULATION: Activated by the ototoxic drug cisplatin (By
CC       similarity). Activated by NOXO1. Cooperatively activated by NCF1 and
CC       NCF2 or NOXA1 in a phorbol 12-myristate 13-acetate (PMA)-dependent
CC       manner. Inhibited by diphenyleneiodonium chloride. {ECO:0000250,
CC       ECO:0000269|PubMed:15181005, ECO:0000269|PubMed:15824103}.
CC   -!- SUBUNIT: Interacts with and stabilizes CYBA/p22phox.
CC       {ECO:0000269|PubMed:15824103}.
CC   -!- INTERACTION:
CC       Q9HBY0; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-13069010, EBI-2680384;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000305}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in fetal kidney and to a lower extent in
CC       liver, lung and spleen. {ECO:0000269|PubMed:10974555,
CC       ECO:0000269|PubMed:11376945}.
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DR   EMBL; AF190122; AAG17121.1; -; mRNA.
DR   EMBL; AL031773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF229177; AAG15435.1; -; mRNA.
DR   CCDS; CCDS5250.1; -.
DR   RefSeq; NP_056533.1; NM_015718.2.
DR   AlphaFoldDB; Q9HBY0; -.
DR   SMR; Q9HBY0; -.
DR   BioGRID; 119079; 1.
DR   IntAct; Q9HBY0; 1.
DR   STRING; 9606.ENSP00000159060; -.
DR   ChEMBL; CHEMBL1741216; -.
DR   PeroxiBase; 5960; HsNOx03.
DR   TCDB; 5.B.1.1.4; the phagocyte (gp91(phox)) nadph oxidase family.
DR   GlyGen; Q9HBY0; 2 sites.
DR   iPTMnet; Q9HBY0; -.
DR   PhosphoSitePlus; Q9HBY0; -.
DR   BioMuta; NOX3; -.
DR   DMDM; 74752785; -.
DR   jPOST; Q9HBY0; -.
DR   MassIVE; Q9HBY0; -.
DR   PaxDb; Q9HBY0; -.
DR   PeptideAtlas; Q9HBY0; -.
DR   PRIDE; Q9HBY0; -.
DR   ProteomicsDB; 81611; -.
DR   Antibodypedia; 46722; 217 antibodies from 28 providers.
DR   DNASU; 50508; -.
DR   Ensembl; ENST00000159060.3; ENSP00000159060.2; ENSG00000074771.4.
DR   GeneID; 50508; -.
DR   KEGG; hsa:50508; -.
DR   MANE-Select; ENST00000159060.3; ENSP00000159060.2; NM_015718.3; NP_056533.1.
DR   UCSC; uc003qqm.4; human.
DR   CTD; 50508; -.
DR   DisGeNET; 50508; -.
DR   GeneCards; NOX3; -.
DR   HGNC; HGNC:7890; NOX3.
DR   HPA; ENSG00000074771; Not detected.
DR   MIM; 607105; gene.
DR   neXtProt; NX_Q9HBY0; -.
DR   OpenTargets; ENSG00000074771; -.
DR   PharmGKB; PA31691; -.
DR   VEuPathDB; HostDB:ENSG00000074771; -.
DR   eggNOG; KOG0039; Eukaryota.
DR   GeneTree; ENSGT00940000160501; -.
DR   HOGENOM; CLU_005646_3_1_1; -.
DR   InParanoid; Q9HBY0; -.
DR   OMA; MCRLYSS; -.
DR   OrthoDB; 936110at2759; -.
DR   PhylomeDB; Q9HBY0; -.
DR   TreeFam; TF105354; -.
DR   PathwayCommons; Q9HBY0; -.
DR   Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR   Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR   Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR   SignaLink; Q9HBY0; -.
DR   SIGNOR; Q9HBY0; -.
DR   BioGRID-ORCS; 50508; 12 hits in 1058 CRISPR screens.
DR   GeneWiki; NOX3; -.
DR   GenomeRNAi; 50508; -.
DR   Pharos; Q9HBY0; Tbio.
DR   PRO; PR:Q9HBY0; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q9HBY0; protein.
DR   Bgee; ENSG00000074771; Expressed in frontal cortex and 2 other tissues.
DR   Genevisible; Q9HBY0; HS.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0043020; C:NADPH oxidase complex; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IBA:GO_Central.
DR   GO; GO:0006952; P:defense response; IBA:GO_Central.
DR   GO; GO:0009590; P:detection of gravity; IEA:Ensembl.
DR   GO; GO:0048840; P:otolith development; IEA:Ensembl.
DR   GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central.
DR   GO; GO:0001659; P:temperature homeostasis; IEA:Ensembl.
DR   Gene3D; 3.40.50.80; -; 1.
DR   InterPro; IPR000778; Cyt_b245_heavy_chain.
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; IPR029653; NOX3.
DR   InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR   PANTHER; PTHR11972:SF12; PTHR11972:SF12; 1.
DR   Pfam; PF08022; FAD_binding_8; 1.
DR   Pfam; PF01794; Ferric_reduct; 1.
DR   Pfam; PF08030; NAD_binding_6; 1.
DR   PRINTS; PR00466; GP91PHOX.
DR   SUPFAM; SSF52343; SSF52343; 1.
DR   SUPFAM; SSF63380; SSF63380; 1.
DR   PROSITE; PS51384; FAD_FR; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Membrane; Oxidoreductase; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..568
FT                   /note="NADPH oxidase 3"
FT                   /id="PRO_0000227596"
FT   TOPO_DOM        1..13
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        14..34
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        35..51
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        52..72
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        73..103
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        104..124
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        125..167
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        168..188
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        189..201
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        202..222
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        223..395
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        396..416
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        417..568
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          55..284
FT                   /note="Ferric oxidoreductase"
FT   DOMAIN          285..395
FT                   /note="FAD-binding FR-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        238
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         171
FT                   /note="T -> K (in dbSNP:rs3749930)"
FT                   /id="VAR_049103"
FT   MUTAGEN         413
FT                   /note="P->H: Loss of catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:15824103"
FT   CONFLICT        328
FT                   /note="P -> S (in Ref. 3; AAG15435)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   568 AA;  64935 MW;  10BCD6BEB18D0583 CRC64;
     MMGCWILNEG LSTILVLSWL GINFYLFIDT FYWYEEEESF HYTRVILGST LAWARASALC
     LNFNCMLILI PVSRNLISFI RGTSICCRGP WRRQLDKNLR FHKLVAYGIA VNATIHIVAH
     FFNLERYHWS QSEEAQGLLA ALSKLGNTPN ESYLNPVRTF PTNTTTELLR TIAGVTGLVI
     SLALVLIMTS STEFIRQASY ELFWYTHHVF IVFFLSLAIH GTGRIVRGQT QDSLSLHNIT
     FCRDRYAEWQ TVAQCPVPQF SGKEPSAWKW ILGPVVLYAC ERIIRFWRFQ QEVVITKVVS
     HPSGVLELHM KKRGFKMAPG QYILVQCPAI SSLEWHPFTL TSAPQEDFFS VHIRAAGDWT
     AALLEAFGAE GQALQEPWSL PRLAVDGPFG TALTDVFHYP VCVCVAAGIG VTPFAALLKS
     IWYKCSEAQT PLKLSKVYFY WICRDARAFE WFADLLLSLE TRMSEQGKTH FLSYHIFLTG
     WDENQALHIA LHWDENTDVI TGLKQKTFYG RPNWNNEFKQ IAYNHPSSSI GVFFCGPKAL
     SRTLQKMCHL YSSADPRGVH FYYNKESF
//