NOXO1_HUMAN
ID NOXO1_HUMAN Reviewed; 376 AA.
AC Q8NFA2; Q86YM1; Q8NFA3; Q96B73;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=NADPH oxidase organizer 1;
DE AltName: Full=NADPH oxidase regulatory protein;
DE AltName: Full=Nox organizer 1;
DE AltName: Full=Nox-organizing protein 1;
DE AltName: Full=SH3 and PX domain-containing protein 5;
GN Name=NOXO1; Synonyms=P41NOX, SH3PXD5;
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 3).
RX PubMed=12473664; DOI=10.1074/jbc.c200613200;
RA Banfi B., Clark R.A., Steger K., Krause K.-H.;
RT "Two novel proteins activate superoxide generation by the NADPH oxidase
RT NOX1.";
RL J. Biol. Chem. 278:3510-3513(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Colon;
RX PubMed=12657628; DOI=10.1074/jbc.m301289200;
RA Geiszt M., Lekstrom K., Witta J., Leto T.L.;
RT "Proteins homologous to p47phox and p67phox support superoxide production
RT by NAD(P)H oxidase 1 in colon epithelial cells.";
RL J. Biol. Chem. 278:20006-20012(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH NOXA1; CYBA AND
RP NCF2, AND DOMAIN.
RX PubMed=12716910; DOI=10.1074/jbc.m212856200;
RA Takeya R., Ueno N., Kami K., Taura M., Kohjima M., Izaki T., Nunoi H.,
RA Sumimoto H.;
RT "Novel human homologues of p47phox and p67phox participate in activation of
RT superoxide-producing NADPH oxidases.";
RL J. Biol. Chem. 278:25234-25246(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, MUTAGENESIS OF ARG-40,
RP DOMAIN, AND SUBCELLULAR LOCATION.
RC TISSUE=Colon;
RX PubMed=14617635; DOI=10.1074/jbc.m305968200;
RA Cheng G., Lambeth J.D.;
RT "NOXO1, regulation of lipid binding, localization, and activation of Nox1
RT by the Phox homology (PX) domain.";
RL J. Biol. Chem. 279:4737-4742(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4), FUNCTION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Colon, and Testis;
RX PubMed=15949904; DOI=10.1016/j.gene.2005.03.008;
RA Cheng G., Lambeth J.D.;
RT "Alternative mRNA splice forms of NOXO1: differential tissue expression and
RT regulation of Nox1 and Nox3.";
RL Gene 356:118-126(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Colon;
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 [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [8]
RP FUNCTION, AND MUTAGENESIS OF TRP-202.
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).
RN [9]
RP FUNCTION, AND INTERACTION WITH NOX1.
RX PubMed=16329988; DOI=10.1016/j.bbrc.2005.11.108;
RA Park H.S., Park D., Bae Y.S.;
RT "Molecular interaction of NADPH oxidase 1 with betaPix and Nox Organizer
RT 1.";
RL Biochem. Biophys. Res. Commun. 339:985-990(2006).
RN [10]
RP FUNCTION, INTERACTION WITH CYBA AND NOXA1, AND MUTAGENESIS OF TRP-202;
RP TRP-274; PRO-332 AND ARG-334.
RX PubMed=17126813; DOI=10.1016/j.bbrc.2006.11.060;
RA Yamamoto A., Kami K., Takeya R., Sumimoto H.;
RT "Interaction between the SH3 domains and C-terminal proline-rich region in
RT NADPH oxidase organizer 1 (Noxo1).";
RL Biochem. Biophys. Res. Commun. 352:560-565(2007).
RN [11]
RP FUNCTION.
RX PubMed=19755710; DOI=10.1126/scisignal.2000370;
RA Gianni D., Diaz B., Taulet N., Fowler B., Courtneidge S.A., Bokoch G.M.;
RT "Novel p47(phox)-related organizers regulate localized NADPH oxidase 1
RT (Nox1) activity.";
RL Sci. Signal. 2:RA54-RA54(2009).
RN [12]
RP INTERACTION WITH NOXA1; SH3PXD2A AND SH3PXD2B.
RX PubMed=20609497; DOI=10.1016/j.ejcb.2010.05.007;
RA Gianni D., Dermardirossian C., Bokoch G.M.;
RT "Direct interaction between Tks proteins and the N-terminal proline-rich
RT region (PRR) of NoxA1 mediates Nox1-dependent ROS generation.";
RL Eur. J. Cell Biol. 90:164-171(2011).
CC -!- FUNCTION: Constitutively potentiates the superoxide-generating activity
CC of NOX1 and NOX3 and is required for the biogenesis of
CC otoconia/otolith, which are crystalline structures of the inner ear
CC involved in the perception of gravity. Isoform 3 is more potent than
CC isoform 1 in activating NOX3. Together with NOXA1, may also substitute
CC to NCF1/p47phox and NCF2/p67phox in supporting the phagocyte
CC NOX2/gp91phox superoxide-generating activity.
CC {ECO:0000269|PubMed:12657628, ECO:0000269|PubMed:14617635,
CC ECO:0000269|PubMed:15326186, ECO:0000269|PubMed:15824103,
CC ECO:0000269|PubMed:15949904, ECO:0000269|PubMed:16329988,
CC ECO:0000269|PubMed:17126813, ECO:0000269|PubMed:19755710}.
CC -!- SUBUNIT: Interacts with NOX1, NOXA1, CYBA/p22phox and NCF2/p67phox.
CC Interacts with SH3PXD2A and SH3PXD2B. {ECO:0000269|PubMed:12716910,
CC ECO:0000269|PubMed:16329988, ECO:0000269|PubMed:17126813,
CC ECO:0000269|PubMed:20609497}.
CC -!- INTERACTION:
CC Q8NFA2; P13498: CYBA; NbExp=3; IntAct=EBI-7130806, EBI-986058;
CC Q8NFA2-3; P13498: CYBA; NbExp=3; IntAct=EBI-20557410, EBI-986058;
CC Q8NFA2-3; Q86UR1: NOXA1; NbExp=5; IntAct=EBI-20557410, EBI-949814;
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane
CC {ECO:0000269|PubMed:12716910}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12716910}; Cytoplasmic side
CC {ECO:0000269|PubMed:12716910}. Note=Isoform 3 associates with the
CC plasma membrane in a lipid-dependent manner (PubMed:12716910).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=NOXO1gamma;
CC IsoId=Q8NFA2-1; Sequence=Displayed;
CC Name=2; Synonyms=NOXO1delta;
CC IsoId=Q8NFA2-2; Sequence=VSP_017560;
CC Name=3; Synonyms=NOXO1beta;
CC IsoId=Q8NFA2-3; Sequence=VSP_017561;
CC Name=4; Synonyms=NOXO1alpha;
CC IsoId=Q8NFA2-4; Sequence=VSP_017560, VSP_017561;
CC -!- TISSUE SPECIFICITY: Expressed in testis, small and large intestines,
CC liver, kidney and pancreas. Isoform 3 is mainly expressed in colon.
CC Isoform 1 is preferentially expressed in testis.
CC {ECO:0000269|PubMed:12657628, ECO:0000269|PubMed:15326186,
CC ECO:0000269|PubMed:15949904}.
CC -!- DEVELOPMENTAL STAGE: Isoform 3 is expressed in fetal liver.
CC {ECO:0000269|PubMed:15949904}.
CC -!- DOMAIN: The PX domain mediates lipid-binding, localization to the
CC plasma membrane and is required for NOX1 activation.
CC -!- DOMAIN: The SH3 domains mediate interaction with CYBA/p22phox. Also
CC mediates intramolecular interaction with the proline-rich region.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF539796; AAN75141.1; -; mRNA.
DR EMBL; AY255768; AAP13479.1; -; mRNA.
DR EMBL; AB097667; BAC76711.1; -; mRNA.
DR EMBL; AF532983; AAM97925.1; -; mRNA.
DR EMBL; AF532984; AAM97926.1; -; mRNA.
DR EMBL; AF532985; AAM97927.1; -; mRNA.
DR EMBL; AY191359; AAO38665.1; -; mRNA.
DR EMBL; BC015917; AAH15917.1; -; mRNA.
DR CCDS; CCDS10454.1; -. [Q8NFA2-4]
DR CCDS; CCDS10455.1; -. [Q8NFA2-3]
DR CCDS; CCDS42101.1; -. [Q8NFA2-1]
DR CCDS; CCDS58406.1; -. [Q8NFA2-2]
DR RefSeq; NP_001254650.1; NM_001267721.1. [Q8NFA2-2]
DR RefSeq; NP_653204.1; NM_144603.3. [Q8NFA2-4]
DR RefSeq; NP_751907.1; NM_172167.2. [Q8NFA2-3]
DR RefSeq; NP_751908.1; NM_172168.2. [Q8NFA2-1]
DR RefSeq; XP_005255156.1; XM_005255099.4. [Q8NFA2-1]
DR RefSeq; XP_016878416.1; XM_017022927.1. [Q8NFA2-1]
DR RefSeq; XP_016878417.1; XM_017022928.1. [Q8NFA2-1]
DR PDB; 2L73; NMR; -; A=1-149.
DR PDBsum; 2L73; -.
DR AlphaFoldDB; Q8NFA2; -.
DR SMR; Q8NFA2; -.
DR BioGRID; 125848; 21.
DR IntAct; Q8NFA2; 2.
DR MINT; Q8NFA2; -.
DR STRING; 9606.ENSP00000380450; -.
DR DrugBank; DB05265; Ecabet.
DR iPTMnet; Q8NFA2; -.
DR PhosphoSitePlus; Q8NFA2; -.
DR BioMuta; NOXO1; -.
DR DMDM; 74751269; -.
DR jPOST; Q8NFA2; -.
DR MassIVE; Q8NFA2; -.
DR PaxDb; Q8NFA2; -.
DR PeptideAtlas; Q8NFA2; -.
DR PRIDE; Q8NFA2; -.
DR ProteomicsDB; 73281; -. [Q8NFA2-1]
DR ProteomicsDB; 73282; -. [Q8NFA2-2]
DR ProteomicsDB; 73283; -. [Q8NFA2-3]
DR ProteomicsDB; 73284; -. [Q8NFA2-4]
DR Antibodypedia; 23401; 212 antibodies from 33 providers.
DR DNASU; 124056; -.
DR Ensembl; ENST00000354249.8; ENSP00000346195.4; ENSG00000196408.12. [Q8NFA2-4]
DR Ensembl; ENST00000356120.9; ENSP00000348435.4; ENSG00000196408.12. [Q8NFA2-3]
DR Ensembl; ENST00000397280.8; ENSP00000380450.4; ENSG00000196408.12. [Q8NFA2-1]
DR Ensembl; ENST00000566005.5; ENSP00000456800.1; ENSG00000196408.12. [Q8NFA2-2]
DR GeneID; 124056; -.
DR KEGG; hsa:124056; -.
DR MANE-Select; ENST00000356120.9; ENSP00000348435.4; NM_172167.3; NP_751907.1. [Q8NFA2-3]
DR UCSC; uc002cnx.5; human. [Q8NFA2-1]
DR CTD; 124056; -.
DR DisGeNET; 124056; -.
DR GeneCards; NOXO1; -.
DR HGNC; HGNC:19404; NOXO1.
DR HPA; ENSG00000196408; Tissue enhanced (intestine, lymphoid tissue, testis).
DR MIM; 611256; gene.
DR neXtProt; NX_Q8NFA2; -.
DR OpenTargets; ENSG00000196408; -.
DR PharmGKB; PA134896072; -.
DR VEuPathDB; HostDB:ENSG00000196408; -.
DR eggNOG; ENOG502QW5I; Eukaryota.
DR GeneTree; ENSGT00940000158812; -.
DR HOGENOM; CLU_030529_2_0_1; -.
DR InParanoid; Q8NFA2; -.
DR OMA; QQMAWFP; -.
DR OrthoDB; 601811at2759; -.
DR PhylomeDB; Q8NFA2; -.
DR TreeFam; TF329347; -.
DR PathwayCommons; Q8NFA2; -.
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 Reactome; R-HSA-9673324; WNT5:FZD7-mediated leishmania damping.
DR SignaLink; Q8NFA2; -.
DR SIGNOR; Q8NFA2; -.
DR BioGRID-ORCS; 124056; 10 hits in 1014 CRISPR screens.
DR GeneWiki; NOXO1; -.
DR GenomeRNAi; 124056; -.
DR Pharos; Q8NFA2; Tbio.
DR PRO; PR:Q8NFA2; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8NFA2; protein.
DR Bgee; ENSG00000196408; Expressed in mucosa of transverse colon and 104 other tissues.
DR ExpressionAtlas; Q8NFA2; baseline and differential.
DR Genevisible; Q8NFA2; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043020; C:NADPH oxidase complex; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0005543; F:phospholipid binding; TAS:BHF-UCL.
DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IBA:GO_Central.
DR GO; GO:0022617; P:extracellular matrix disassembly; IMP:UniProtKB.
DR GO; GO:0010310; P:regulation of hydrogen peroxide metabolic process; TAS:BHF-UCL.
DR GO; GO:0060263; P:regulation of respiratory burst; TAS:BHF-UCL.
DR GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central.
DR CDD; cd12024; SH3_NoxO1_2; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR035758; NoxO1_SH3_2.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF14604; SH3_9; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Lipid-binding; Membrane;
KW Reference proteome; Repeat; SH3 domain.
FT CHAIN 1..376
FT /note="NADPH oxidase organizer 1"
FT /id="PRO_0000227594"
FT DOMAIN 1..131
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 163..225
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 237..296
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 302..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..337
FT /note="Proline-rich region; mediates mutually exclusive
FT interactions with itself and NOXA1"
FT COMPBIAS 348..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 49
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12657628,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:15949904"
FT /id="VSP_017560"
FT VAR_SEQ 74..78
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12473664,
FT ECO:0000303|PubMed:12657628, ECO:0000303|PubMed:12716910,
FT ECO:0000303|PubMed:14617635, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15949904"
FT /id="VSP_017561"
FT MUTAGEN 40
FT /note="R->Q: Loss of ability to activate NOX1 associated
FT with loss of lipid-binding and plasma membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:14617635"
FT MUTAGEN 202
FT /note="W->R: Loss of ability to activate NOX3 and interact
FT with CYBA. Induces interaction with NOXA1 in vitro."
FT /evidence="ECO:0000269|PubMed:15824103,
FT ECO:0000269|PubMed:17126813"
FT MUTAGEN 274
FT /note="W->R: Induces interaction with NOXA1 in vitro."
FT /evidence="ECO:0000269|PubMed:17126813"
FT MUTAGEN 332
FT /note="P->A: Loss of intramolecular interaction."
FT /evidence="ECO:0000269|PubMed:17126813"
FT MUTAGEN 334
FT /note="R->A: Loss of intramolecular interaction."
FT /evidence="ECO:0000269|PubMed:17126813"
FT STRAND 7..16
FT /evidence="ECO:0007829|PDB:2L73"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:2L73"
FT STRAND 23..30
FT /evidence="ECO:0007829|PDB:2L73"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:2L73"
FT HELIX 42..55
FT /evidence="ECO:0007829|PDB:2L73"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:2L73"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:2L73"
FT HELIX 89..110
FT /evidence="ECO:0007829|PDB:2L73"
FT HELIX 112..116
FT /evidence="ECO:0007829|PDB:2L73"
FT HELIX 118..124
FT /evidence="ECO:0007829|PDB:2L73"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:2L73"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:2L73"
SQ SEQUENCE 376 AA; 41253 MW; 2E9525A8BADDB360 CRC64;
MAGPRYPVSV QGAALVQIKR LQTFAFSVRW SDGSDTFVRR SWDEFRQLKK TLKETFPVEA
GLLRRSDRVL PKLLGQASLD APLLGRVGRT SRGLARLQLL ETYSRRLLAT AERVARSPTI
TGFFAPQPLD LEPALPPGSR VILPTPEEQP LSRAAGRLSI HSLEAQSLRC LQPFCTQDTR
DRPFQAQAQE SLDVLLRHPS GWWLVENEDR QTAWFPAPYL EEAAPGQGRE GGPSLGSSGP
QFCASRAYES SRADELSVPA GARVRVLETS DRGWWLCRYG DRAGLLPAVL LRPEGLGALL
SGTGFRGGDD PAGEARGFPE PSQATAPPPT VPTRPSPGAI QSRCCTVTRR ALERRPRRQG
RPRGCVDSVP HPTTEQ
