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Q8NFA2

- NOXO1_HUMAN

UniProt

Q8NFA2 - NOXO1_HUMAN

Protein

NADPH oxidase organizer 1

Gene

NOXO1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
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    Functioni

    Constitutively potentiates the superoxide-generating activity of NOX1 and NOX3 and is required for the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity. Isoform 3 is more potent than isoform 1 in activating NOX3. Together with NOXA1, may also substitute to NCF1/p47phox and NCF2/p67phox in supporting the phagocyte NOX2/gp91phox superoxide-generating activity.8 Publications

    GO - Molecular functioni

    1. enzyme binding Source: BHF-UCL
    2. identical protein binding Source: IntAct
    3. phosphatidylinositol binding Source: InterPro
    4. phospholipid binding Source: BHF-UCL
    5. protein binding Source: IntAct
    6. superoxide-generating NADPH oxidase activator activity Source: BHF-UCL

    GO - Biological processi

    1. extracellular matrix disassembly Source: UniProtKB
    2. positive regulation of catalytic activity Source: GOC
    3. regulation of hydrogen peroxide metabolic process Source: BHF-UCL
    4. regulation of respiratory burst Source: BHF-UCL
    5. superoxide metabolic process Source: Ensembl

    Keywords - Ligandi

    Lipid-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NADPH oxidase organizer 1
    Alternative name(s):
    NADPH oxidase regulatory protein
    Nox organizer 1
    Nox-organizing protein 1
    SH3 and PX domain-containing protein 5
    Gene namesi
    Name:NOXO1
    Synonyms:P41NOX, SH3PXD5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:19404. NOXO1.

    Subcellular locationi

    Isoform 3 : Cell membrane; Peripheral membrane protein; Cytoplasmic side
    Note: Isoform 3 associates with the plasma membrane in a lipid-dependent manner.

    GO - Cellular componenti

    1. NADPH oxidase complex Source: BHF-UCL

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi40 – 401R → Q: Loss of ability to activate NOX1 associated with loss of lipid-binding and plasma membrane localization. 1 Publication
    Mutagenesisi202 – 2021W → R: Loss of ability to activate NOX3 and interact with CYBA. Induces interaction with NOXA1 in vitro. 2 Publications
    Mutagenesisi274 – 2741W → R: Induces interaction with NOXA1 in vitro. 1 Publication
    Mutagenesisi332 – 3321P → A: Loss of intramolecular interaction. 1 Publication
    Mutagenesisi334 – 3341R → A: Loss of intramolecular interaction. 1 Publication

    Organism-specific databases

    PharmGKBiPA134896072.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 376376NADPH oxidase organizer 1PRO_0000227594Add
    BLAST

    Proteomic databases

    PaxDbiQ8NFA2.
    PRIDEiQ8NFA2.

    PTM databases

    PhosphoSiteiQ8NFA2.

    Expressioni

    Tissue specificityi

    Expressed in testis, small and large intestines, liver, kidney and pancreas. Isoform 3 is mainly expressed in colon. Isoform 1 is preferentially expressed in testis.3 Publications

    Developmental stagei

    Isoform 3 is expressed in fetal liver.1 Publication

    Gene expression databases

    ArrayExpressiQ8NFA2.
    BgeeiQ8NFA2.
    CleanExiHS_NOXO1.
    GenevestigatoriQ8NFA2.

    Interactioni

    Subunit structurei

    Interacts with NOX1, NOXA1, CYBA/p22phox and NCF2/p67phox. Interacts with SH3PXD2A and SH3PXD2B.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-7130806,EBI-7130806
    CYBAP134986EBI-7130806,EBI-986058
    NOXA1Q86UR16EBI-7130806,EBI-949814

    Protein-protein interaction databases

    IntActiQ8NFA2. 2 interactions.
    MINTiMINT-7147796.
    STRINGi9606.ENSP00000380450.

    Structurei

    Secondary structure

    1
    376
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi7 – 1610
    Beta strandi19 – 213
    Beta strandi23 – 308
    Beta strandi35 – 417
    Helixi42 – 5514
    Helixi57 – 604
    Beta strandi61 – 633
    Helixi89 – 11022
    Helixi112 – 1165
    Helixi118 – 1247
    Helixi128 – 1314
    Beta strandi132 – 1343

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2L73NMR-A1-149[»]
    ProteinModelPortaliQ8NFA2.
    SMRiQ8NFA2. Positions 2-149, 192-302.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 131131PXPROSITE-ProRule annotationAdd
    BLAST
    Domaini163 – 22563SH3 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini237 – 29660SH3 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni328 – 33710Proline-rich region; mediates mutually exclusive interactions with itself and NOXA1

    Domaini

    The PX domain mediates lipid-binding, localization to the plasma membrane and is required for NOX1 activation.
    The SH3 domains mediate interaction with CYBA/p22phox. Also mediates intramolecular interaction with the proline-rich region.

    Sequence similaritiesi

    Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation
    Contains 2 SH3 domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH3 domain

    Phylogenomic databases

    eggNOGiNOG150477.
    HOGENOMiHOG000113833.
    HOVERGENiHBG082053.
    InParanoidiQ8NFA2.
    KOiK17934.
    OMAiTFVRRSW.
    OrthoDBiEOG70GMG8.
    PhylomeDBiQ8NFA2.
    TreeFamiTF329347.

    Family and domain databases

    Gene3Di3.30.1520.10. 1 hit.
    InterProiIPR001683. Phox.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF00787. PX. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    SMARTiSM00326. SH3. 2 hits.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 2 hits.
    SSF64268. SSF64268. 1 hit.
    PROSITEiPS50195. PX. 1 hit.
    PS50002. SH3. 2 hits.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8NFA2-1) [UniParc]FASTAAdd to Basket

    Also known as: NOXO1gamma

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAGPRYPVSV QGAALVQIKR LQTFAFSVRW SDGSDTFVRR SWDEFRQLKK    50
    TLKETFPVEA GLLRRSDRVL PKLLGQASLD APLLGRVGRT SRGLARLQLL 100
    ETYSRRLLAT AERVARSPTI TGFFAPQPLD LEPALPPGSR VILPTPEEQP 150
    LSRAAGRLSI HSLEAQSLRC LQPFCTQDTR DRPFQAQAQE SLDVLLRHPS 200
    GWWLVENEDR QTAWFPAPYL EEAAPGQGRE GGPSLGSSGP QFCASRAYES 250
    SRADELSVPA GARVRVLETS DRGWWLCRYG DRAGLLPAVL LRPEGLGALL 300
    SGTGFRGGDD PAGEARGFPE PSQATAPPPT VPTRPSPGAI QSRCCTVTRR 350
    ALERRPRRQG RPRGCVDSVP HPTTEQ 376
    Length:376
    Mass (Da):41,253
    Last modified:October 1, 2002 - v1
    Checksum:i2E9525A8BADDB360
    GO
    Isoform 2 (identifier: Q8NFA2-2) [UniParc]FASTAAdd to Basket

    Also known as: NOXO1delta

    The sequence of this isoform differs from the canonical sequence as follows:
         49-49: Missing.

    Show »
    Length:375
    Mass (Da):41,125
    Checksum:i85E41025A14AEA80
    GO
    Isoform 3 (identifier: Q8NFA2-3) [UniParc]FASTAAdd to Basket

    Also known as: NOXO1beta

    The sequence of this isoform differs from the canonical sequence as follows:
         74-78: Missing.

    Show »
    Length:371
    Mass (Da):40,796
    Checksum:i39E13C3FF491797E
    GO
    Isoform 4 (identifier: Q8NFA2-4) [UniParc]FASTAAdd to Basket

    Also known as: NOXO1alpha

    The sequence of this isoform differs from the canonical sequence as follows:
         49-49: Missing.
         74-78: Missing.

    Show »
    Length:370
    Mass (Da):40,668
    Checksum:i1EB8DCE8BC50551F
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei49 – 491Missing in isoform 2 and isoform 4. 3 PublicationsVSP_017560
    Alternative sequencei74 – 785Missing in isoform 3 and isoform 4. 6 PublicationsVSP_017561

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF539796 mRNA. Translation: AAN75141.1.
    AY255768 mRNA. Translation: AAP13479.1.
    AB097667 mRNA. Translation: BAC76711.1.
    AF532983 mRNA. Translation: AAM97925.1.
    AF532984 mRNA. Translation: AAM97926.1.
    AF532985 mRNA. Translation: AAM97927.1.
    AY191359 mRNA. Translation: AAO38665.1.
    BC015917 mRNA. Translation: AAH15917.1.
    CCDSiCCDS10454.1. [Q8NFA2-4]
    CCDS10455.1. [Q8NFA2-3]
    CCDS42101.1. [Q8NFA2-1]
    CCDS58406.1. [Q8NFA2-2]
    RefSeqiNP_001254650.1. NM_001267721.1. [Q8NFA2-2]
    NP_653204.1. NM_144603.3. [Q8NFA2-4]
    NP_751907.1. NM_172167.2. [Q8NFA2-3]
    NP_751908.1. NM_172168.2. [Q8NFA2-1]
    XP_005255156.1. XM_005255099.2. [Q8NFA2-1]
    UniGeneiHs.191762.

    Genome annotation databases

    EnsembliENST00000354249; ENSP00000346195; ENSG00000196408. [Q8NFA2-4]
    ENST00000356120; ENSP00000348435; ENSG00000196408. [Q8NFA2-3]
    ENST00000397280; ENSP00000380450; ENSG00000196408. [Q8NFA2-1]
    ENST00000566005; ENSP00000456800; ENSG00000196408. [Q8NFA2-2]
    GeneIDi124056.
    KEGGihsa:124056.
    UCSCiuc002cnx.4. human. [Q8NFA2-1]
    uc002cny.4. human. [Q8NFA2-3]
    uc002cnz.4. human. [Q8NFA2-4]
    uc002coa.4. human. [Q8NFA2-2]

    Polymorphism databases

    DMDMi74751269.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF539796 mRNA. Translation: AAN75141.1 .
    AY255768 mRNA. Translation: AAP13479.1 .
    AB097667 mRNA. Translation: BAC76711.1 .
    AF532983 mRNA. Translation: AAM97925.1 .
    AF532984 mRNA. Translation: AAM97926.1 .
    AF532985 mRNA. Translation: AAM97927.1 .
    AY191359 mRNA. Translation: AAO38665.1 .
    BC015917 mRNA. Translation: AAH15917.1 .
    CCDSi CCDS10454.1. [Q8NFA2-4 ]
    CCDS10455.1. [Q8NFA2-3 ]
    CCDS42101.1. [Q8NFA2-1 ]
    CCDS58406.1. [Q8NFA2-2 ]
    RefSeqi NP_001254650.1. NM_001267721.1. [Q8NFA2-2 ]
    NP_653204.1. NM_144603.3. [Q8NFA2-4 ]
    NP_751907.1. NM_172167.2. [Q8NFA2-3 ]
    NP_751908.1. NM_172168.2. [Q8NFA2-1 ]
    XP_005255156.1. XM_005255099.2. [Q8NFA2-1 ]
    UniGenei Hs.191762.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2L73 NMR - A 1-149 [» ]
    ProteinModelPortali Q8NFA2.
    SMRi Q8NFA2. Positions 2-149, 192-302.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q8NFA2. 2 interactions.
    MINTi MINT-7147796.
    STRINGi 9606.ENSP00000380450.

    PTM databases

    PhosphoSitei Q8NFA2.

    Polymorphism databases

    DMDMi 74751269.

    Proteomic databases

    PaxDbi Q8NFA2.
    PRIDEi Q8NFA2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000354249 ; ENSP00000346195 ; ENSG00000196408 . [Q8NFA2-4 ]
    ENST00000356120 ; ENSP00000348435 ; ENSG00000196408 . [Q8NFA2-3 ]
    ENST00000397280 ; ENSP00000380450 ; ENSG00000196408 . [Q8NFA2-1 ]
    ENST00000566005 ; ENSP00000456800 ; ENSG00000196408 . [Q8NFA2-2 ]
    GeneIDi 124056.
    KEGGi hsa:124056.
    UCSCi uc002cnx.4. human. [Q8NFA2-1 ]
    uc002cny.4. human. [Q8NFA2-3 ]
    uc002cnz.4. human. [Q8NFA2-4 ]
    uc002coa.4. human. [Q8NFA2-2 ]

    Organism-specific databases

    CTDi 124056.
    GeneCardsi GC16M002028.
    HGNCi HGNC:19404. NOXO1.
    MIMi 611256. gene.
    neXtProti NX_Q8NFA2.
    PharmGKBi PA134896072.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG150477.
    HOGENOMi HOG000113833.
    HOVERGENi HBG082053.
    InParanoidi Q8NFA2.
    KOi K17934.
    OMAi TFVRRSW.
    OrthoDBi EOG70GMG8.
    PhylomeDBi Q8NFA2.
    TreeFami TF329347.

    Miscellaneous databases

    GeneWikii NOXO1.
    GenomeRNAii 124056.
    NextBioi 81216.
    PROi Q8NFA2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8NFA2.
    Bgeei Q8NFA2.
    CleanExi HS_NOXO1.
    Genevestigatori Q8NFA2.

    Family and domain databases

    Gene3Di 3.30.1520.10. 1 hit.
    InterProi IPR001683. Phox.
    IPR001452. SH3_domain.
    [Graphical view ]
    Pfami PF00787. PX. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    SMARTi SM00326. SH3. 2 hits.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 2 hits.
    SSF64268. SSF64268. 1 hit.
    PROSITEi PS50195. PX. 1 hit.
    PS50002. SH3. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Two novel proteins activate superoxide generation by the NADPH oxidase NOX1."
      Banfi B., Clark R.A., Steger K., Krause K.-H.
      J. Biol. Chem. 278:3510-3513(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    2. "Proteins homologous to p47phox and p67phox support superoxide production by NAD(P)H oxidase 1 in colon epithelial cells."
      Geiszt M., Lekstrom K., Witta J., Leto T.L.
      J. Biol. Chem. 278:20006-20012(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, TISSUE SPECIFICITY.
      Tissue: Colon.
    3. "Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases."
      Takeya R., Ueno N., Kami K., Taura M., Kohjima M., Izaki T., Nunoi H., Sumimoto H.
      J. Biol. Chem. 278:25234-25246(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), INTERACTION WITH NOXA1; CYBA AND NCF2, DOMAIN.
    4. "NOXO1, regulation of lipid binding, localization, and activation of Nox1 by the Phox homology (PX) domain."
      Cheng G., Lambeth J.D.
      J. Biol. Chem. 279:4737-4742(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, MUTAGENESIS OF ARG-40, DOMAIN, SUBCELLULAR LOCATION.
      Tissue: Colon.
    5. "Alternative mRNA splice forms of NOXO1: differential tissue expression and regulation of Nox1 and Nox3."
      Cheng G., Lambeth J.D.
      Gene 356:118-126(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
      Tissue: Colon and Testis.
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
      Tissue: Colon.
    7. Cited for: FUNCTION, TISSUE SPECIFICITY.
    8. "The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators."
      Ueno N., Takeya R., Miyano K., Kikuchi H., Sumimoto H.
      J. Biol. Chem. 280:23328-23339(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF TRP-202.
    9. "Molecular interaction of NADPH oxidase 1 with betaPix and Nox Organizer 1."
      Park H.S., Park D., Bae Y.S.
      Biochem. Biophys. Res. Commun. 339:985-990(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH NOX1.
    10. "Interaction between the SH3 domains and C-terminal proline-rich region in NADPH oxidase organizer 1 (Noxo1)."
      Yamamoto A., Kami K., Takeya R., Sumimoto H.
      Biochem. Biophys. Res. Commun. 352:560-565(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CYBA AND NOXA1, MUTAGENESIS OF TRP-202; TRP-274; PRO-332 AND ARG-334.
    11. "Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1) activity."
      Gianni D., Diaz B., Taulet N., Fowler B., Courtneidge S.A., Bokoch G.M.
      Sci. Signal. 2:RA54-RA54(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Direct interaction between Tks proteins and the N-terminal proline-rich region (PRR) of NoxA1 mediates Nox1-dependent ROS generation."
      Gianni D., Dermardirossian C., Bokoch G.M.
      Eur. J. Cell Biol. 90:164-171(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NOXA1; SH3PXD2A AND SH3PXD2B.

    Entry informationi

    Entry nameiNOXO1_HUMAN
    AccessioniPrimary (citable) accession number: Q8NFA2
    Secondary accession number(s): Q86YM1, Q8NFA3, Q96B73
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 21, 2006
    Last sequence update: October 1, 2002
    Last modified: October 1, 2014
    This is version 100 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3