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   27-MAR-2024, entry version 153.
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, FUNCTION, AND CATALYTIC ACTIVITY.
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, INTERACTION WITH
RP   CYBA, AND CATALYTIC ACTIVITY.
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 that catalyzes the generation of superoxide
CC       from molecular oxygen utilizing NADPH as an electron donor, upon
CC       formation of a complex with CYBA/p22phox (PubMed:15181005,
CC       PubMed:15824103). Plays a role in the biogenesis of otoconia/otolith,
CC       which are crystalline structures of the inner ear involved in the
CC       perception of gravity (By similarity). {ECO:0000250|UniProtKB:Q672J9,
CC       ECO:0000269|PubMed:15181005, ECO:0000269|PubMed:15824103}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=NADPH + 2 O2 = H(+) + NADP(+) + 2 superoxide;
CC         Xref=Rhea:RHEA:63180, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:18421, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:15181005, ECO:0000269|PubMed:15824103};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:Q672J9};
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.
CC       {ECO:0000250|UniProtKB:Q672J9, ECO:0000269|PubMed:15181005,
CC       ECO:0000269|PubMed:15824103}.
CC   -!- SUBUNIT: Interacts with CYBA/p22phox (PubMed:15824103).
CC       Heterodimerization with CYBA/p22phox is essential for its activity and
CC       cell membrane localization (By similarity).
CC       {ECO:0000250|UniProtKB:Q672J9, ECO:0000269|PubMed:15824103}.
CC   -!- INTERACTION:
CC       Q9HBY0; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-13069010, EBI-2680384;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q672J9};
CC       Multi-pass membrane protein {ECO:0000255}.
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}.
CC   -!- PTM: N-glycosylated in a CYBA/p22phox-dependent manner.
CC       {ECO:0000250|UniProtKB:Q672J9}.
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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   BindingDB; Q9HBY0; -.
DR   ChEMBL; CHEMBL1741216; -.
DR   PeroxiBase; 5960; HsNOx03.
DR   TCDB; 5.B.1.1.4; the phagocyte (gp91(phox)) nadph oxidase family.
DR   GlyCosmos; Q9HBY0; 2 sites, No reported glycans.
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; 9606-ENSP00000159060; -.
DR   PeptideAtlas; Q9HBY0; -.
DR   ProteomicsDB; 81611; -.
DR   Antibodypedia; 46722; 244 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   AGR; HGNC:7890; -.
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; DENQAIH; -.
DR   OrthoDB; 367877at2759; -.
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 1136 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 cell types or tissues.
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; ISS:UniProtKB.
DR   GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IDA:UniProtKB.
DR   GO; GO:0106292; F:superoxide-generating NADPH oxidase activity; IEA:RHEA.
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   CDD; cd06186; NOX_Duox_like_FAD_NADP; 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; 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; IPR017938; Riboflavin_synthase-like_b-brl.
DR   PANTHER; PTHR11972; NADPH OXIDASE; 1.
DR   PANTHER; PTHR11972:SF12; NADPH OXIDASE 3; 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   SFLD; SFLDS00052; Ferric_Reductase_Domain; 1.
DR   SFLD; SFLDG01168; Ferric_reductase_subgroup_(FRE; 1.
DR   SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1.
DR   SUPFAM; SSF63380; Riboflavin synthase domain-like; 1.
DR   PROSITE; PS51384; FAD_FR; 1.
DR   Genevisible; Q9HBY0; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Glycoprotein; Heme; Iron; Membrane; Metal-binding;
KW   Oxidoreductase; Reference proteome; Transmembrane; 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
//