ID NOX3_MOUSE Reviewed; 568 AA.
AC Q672J9; Q6Y4Q8;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 27-MAR-2024, entry version 125.
DE RecName: Full=NADPH oxidase 3;
DE EC=1.6.3.- {ECO:0000269|PubMed:15326186, ECO:0000269|PubMed:17140397};
GN Name=Nox3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF GLY-408 AND LYS-542,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=C3Heb/FeJ;
RX PubMed=15014044; DOI=10.1101/gad.1172504;
RA Paffenholz R., Bergstrom R.A., Pasutto F., Wabnitz P., Munroe R.J.,
RA Jagla W., Heinzmann U., Marquardt A., Bareiss A., Laufs J., Russ A.,
RA Stumm G., Schimenti J.C., Bergstrom D.E.;
RT "Vestibular defects in head-tilt mice result from mutations in Nox3,
RT encoding an NADPH oxidase.";
RL Genes Dev. 18:486-491(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, TISSUE
RP SPECIFICITY, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RC STRAIN=C57BL/6J; TISSUE=Inner ear;
RX PubMed=15326186; DOI=10.1074/jbc.m403046200;
RA Banfi B., Malgrange B., Knisz J., Steger K., Dubois-Dauphin M.,
RA Krause K.-H.;
RT "NOX3, a superoxide-generating NADPH oxidase of the inner ear.";
RL J. Biol. Chem. 279:46065-46072(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP INTERACTION WITH CYBA, GLYCOSYLATION, AND COFACTOR.
RX PubMed=17140397; DOI=10.1042/bj20060819;
RA Nakano Y., Banfi B., Jesaitis A.J., Dinauer M.C., Allen L.A., Nauseef W.M.;
RT "Critical roles for p22phox in the structural maturation and subcellular
RT targeting of Nox3.";
RL Biochem. J. 403:97-108(2007).
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:15326186,
CC PubMed:17140397). 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 (PubMed:15014044). {ECO:0000269|PubMed:15014044,
CC ECO:0000269|PubMed:15326186, ECO:0000269|PubMed:17140397}.
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:15326186, ECO:0000269|PubMed:17140397};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:17140397};
CC -!- ACTIVITY REGULATION: Activated by the ototoxic drug cisplatin.
CC Activated by NOXO1. Cooperatively activated by NCF1 and NCF2 or NOXA1
CC in a phorbol 12-myristate 13-acetate (PMA)-dependent manner. Inhibited
CC by diphenyleneiodonium chloride. {ECO:0000269|PubMed:15326186,
CC ECO:0000269|PubMed:17140397}.
CC -!- SUBUNIT: Forms a heterodimer with CYBA/p22phox which is essential for
CC its activity and cell membrane localization.
CC {ECO:0000269|PubMed:17140397}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17140397};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in inner ear by the spiral
CC glanglion neurons, the vestibular system and the sensory epithelial
CC cell layer of the saccule. Weakly expressed in skull and brain.
CC {ECO:0000269|PubMed:15326186}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal kidney.
CC {ECO:0000269|PubMed:15326186}.
CC -!- PTM: N-glycosylated in a CYBA/p22phox-dependent manner.
CC {ECO:0000269|PubMed:17140397}.
CC -!- DISRUPTION PHENOTYPE: Mice display balance defects, a tilted position
CC of the head and abnormal performances in motor coordination tests. This
CC is associated with the absence of otoconia in both the utricle and
CC saccule of the inner ear. {ECO:0000269|PubMed:15014044}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI06863.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO65981.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY182377; AAO65981.1; ALT_INIT; mRNA.
DR EMBL; AY573240; AAT80344.1; -; mRNA.
DR EMBL; BC106862; AAI06863.1; ALT_INIT; mRNA.
DR CCDS; CCDS28364.2; -.
DR RefSeq; NP_945196.2; NM_198958.2.
DR AlphaFoldDB; Q672J9; -.
DR SMR; Q672J9; -.
DR STRING; 10090.ENSMUSP00000111466; -.
DR PeroxiBase; 5959; MmNOx03.
DR GlyCosmos; Q672J9; 1 site, No reported glycans.
DR GlyGen; Q672J9; 1 site.
DR iPTMnet; Q672J9; -.
DR PhosphoSitePlus; Q672J9; -.
DR PaxDb; 10090-ENSMUSP00000111466; -.
DR ABCD; Q672J9; 5 sequenced antibodies.
DR Antibodypedia; 46722; 244 antibodies from 28 providers.
DR DNASU; 224480; -.
DR Ensembl; ENSMUST00000115800.2; ENSMUSP00000111466.2; ENSMUSG00000023802.5.
DR GeneID; 224480; -.
DR KEGG; mmu:224480; -.
DR UCSC; uc008aev.2; mouse.
DR AGR; MGI:2681162; -.
DR CTD; 50508; -.
DR MGI; MGI:2681162; Nox3.
DR VEuPathDB; HostDB:ENSMUSG00000023802; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000160501; -.
DR HOGENOM; CLU_005646_3_1_1; -.
DR InParanoid; Q672J9; -.
DR OMA; DENQAIH; -.
DR OrthoDB; 367877at2759; -.
DR PhylomeDB; Q672J9; -.
DR TreeFam; TF105354; -.
DR BRENDA; 1.6.3.1; 3474.
DR Reactome; R-MMU-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR BioGRID-ORCS; 224480; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Nox3; mouse.
DR PRO; PR:Q672J9; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q672J9; Protein.
DR Bgee; ENSMUSG00000023802; Expressed in spermatid and 1 other cell type or tissue.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0043020; C:NADPH oxidase complex; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA: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; IMP:MGI.
DR GO; GO:0048840; P:otolith development; IMP:MGI.
DR GO; GO:0009629; P:response to gravity; IMP:MGI.
DR GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central.
DR GO; GO:0001659; P:temperature homeostasis; IMP:MGI.
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.
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_0000227597"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..49
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 50..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..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 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 408
FT /note="G->R: Defects in otoconia biogenesis."
FT /evidence="ECO:0000269|PubMed:15014044"
FT MUTAGEN 542
FT /note="K->E: Defects in otoconia biogenesis."
FT /evidence="ECO:0000269|PubMed:15014044"
FT CONFLICT 161
FT /note="D -> Y (in Ref. 2; AAT80344)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 568 AA; 64495 MW; 345FD67494ADB8F2 CRC64;
MPVCWILNES GSFVVALLWL AVNAYLFIDT FFWYTEEEAF FYTRVILGSA LAWARASAVC
LNFNCMLILL PVSRNFISLV RGTSVCCRGP WRRQLDKNLN FHKLVAYGIA VNSVIHIVAH
LFNLERYHLG QAKDAEGLLA ALSKLGDAPN ESYLNPVRTF DMGTTTELLM TVSGITGLGI
SLALVFIMTS STEFIRRSSY ELFWYTHHIF VFFFISLAIH GGGRIIRGQT PESLRLHNVT
YCRDHYAEWQ AAALCPVPQF SGKEPSAWKW ALGPVVLYAC ERIIRFWRSH QEVVITKVVS
HPSAVLELHM KKRDFKMAPG QYIFIQCPSV SPLEWHPFTL TSAPQEDFFS VHIRASGDWT
EALLKAFRVE GQAPSELCSM PRLAVDGPFG GSLADVFHYP VSVCIATGIG VTPFASLLKS
VWYKCCESQS LPELSKVYFY WICRDAGAFE WFADLLLSLE TRMSEQGKAH LLSYHIYLTG
WDENQAIHIA LHWDESLDVI TGLKQKAFYG RPNWNDEFKQ IAYNHPSSSI GVFFCGSKAM
SKTLQKMCRL YSSVDPRGVH FYYNKENF
//
