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Q8NFA2 (NOXO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:NOXO1
Synonyms:P41NOX, SH3PXD5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length376 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subunit structure

Interacts with NOX1, NOXA1, CYBA/p22phox and NCF2/p67phox. Interacts with SH3PXD2A and SH3PXD2B. Ref.3 Ref.9 Ref.10 Ref.12

Subcellular location

Isoform 3: Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Isoform 3 associates with the plasma membrane in a lipid-dependent manner. Ref.4

Tissue specificity

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. Ref.2 Ref.5 Ref.7

Developmental stage

Isoform 3 is expressed in fetal liver. Ref.5

Domain

The PX domain mediates lipid-binding, localization to the plasma membrane and is required for NOX1 activation. Ref.3 Ref.4

The SH3 domains mediate interaction with CYBA/p22phox. Also mediates intramolecular interaction with the proline-rich region. Ref.3 Ref.4

Sequence similarities

Contains 1 PX (phox homology) domain.

Contains 2 SH3 domains.

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8NFA2-1)

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.
Isoform 2 (identifier: Q8NFA2-2)

Also known as: NOXO1delta;

The sequence of this isoform differs from the canonical sequence as follows:
     49-49: Missing.
Isoform 3 (identifier: Q8NFA2-3)

Also known as: NOXO1beta;

The sequence of this isoform differs from the canonical sequence as follows:
     74-78: Missing.
Isoform 4 (identifier: Q8NFA2-4)

Also known as: NOXO1alpha;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 376376NADPH oxidase organizer 1
PRO_0000227594

Regions

Domain1 – 131131PX
Domain163 – 22563SH3 1
Domain237 – 29660SH3 2
Region328 – 33710Proline-rich region; mediates mutually exclusive interactions with itself and NOXA1

Natural variations

Alternative sequence491Missing in isoform 2 and isoform 4.
VSP_017560
Alternative sequence74 – 785Missing in isoform 3 and isoform 4.
VSP_017561

Experimental info

Mutagenesis401R → Q: Loss of ability to activate NOX1 associated with loss of lipid-binding and plasma membrane localization. Ref.4
Mutagenesis2021W → R: Loss of ability to activate NOX3 and interact with CYBA. Induces interaction with NOXA1 in vitro. Ref.8 Ref.10
Mutagenesis2741W → R: Induces interaction with NOXA1 in vitro. Ref.10
Mutagenesis3321P → A: Loss of intramolecular interaction. Ref.10
Mutagenesis3341R → A: Loss of intramolecular interaction. Ref.10

Secondary structure

...................... 376
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (NOXO1gamma) [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 2E9525A8BADDB360

FASTA37641,253
        10         20         30         40         50         60 
MAGPRYPVSV QGAALVQIKR LQTFAFSVRW SDGSDTFVRR SWDEFRQLKK TLKETFPVEA 

        70         80         90        100        110        120 
GLLRRSDRVL PKLLGQASLD APLLGRVGRT SRGLARLQLL ETYSRRLLAT AERVARSPTI 

       130        140        150        160        170        180 
TGFFAPQPLD LEPALPPGSR VILPTPEEQP LSRAAGRLSI HSLEAQSLRC LQPFCTQDTR 

       190        200        210        220        230        240 
DRPFQAQAQE SLDVLLRHPS GWWLVENEDR QTAWFPAPYL EEAAPGQGRE GGPSLGSSGP 

       250        260        270        280        290        300 
QFCASRAYES SRADELSVPA GARVRVLETS DRGWWLCRYG DRAGLLPAVL LRPEGLGALL 

       310        320        330        340        350        360 
SGTGFRGGDD PAGEARGFPE PSQATAPPPT VPTRPSPGAI QSRCCTVTRR ALERRPRRQG 

       370 
RPRGCVDSVP HPTTEQ 

« Hide

Isoform 2 (NOXO1delta) [UniParc].

Checksum: 85E41025A14AEA80
Show »

FASTA37541,125
Isoform 3 (NOXO1beta) [UniParc].

Checksum: 39E13C3FF491797E
Show »

FASTA37140,796
Isoform 4 (NOXO1alpha) [UniParc].

Checksum: 1EB8DCE8BC50551F
Show »

FASTA37040,668

References

« Hide 'large scale' references
[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]"NOX3, a superoxide-generating NADPH oxidase of the inner ear."
Banfi B., Malgrange B., Knisz J., Steger K., Dubois-Dauphin M., Krause K.-H.
J. Biol. Chem. 279:46065-46072(2004) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10454.1. [Q8NFA2-4]
CCDS10455.1. [Q8NFA2-3]
CCDS42101.1. [Q8NFA2-1]
CCDS58406.1. [Q8NFA2-2]
RefSeqNP_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]
UniGeneHs.191762.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L73NMR-A1-149[»]
ProteinModelPortalQ8NFA2.
SMRQ8NFA2. Positions 2-149, 192-302.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8NFA2. 2 interactions.
MINTMINT-7147796.
STRING9606.ENSP00000380450.

PTM databases

PhosphoSiteQ8NFA2.

Polymorphism databases

DMDM74751269.

Proteomic databases

PaxDbQ8NFA2.
PRIDEQ8NFA2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354249; ENSP00000346195; ENSG00000196408. [Q8NFA2-4]
ENST00000356120; ENSP00000348435; ENSG00000196408. [Q8NFA2-3]
ENST00000397280; ENSP00000380450; ENSG00000196408. [Q8NFA2-1]
ENST00000566005; ENSP00000456800; ENSG00000196408. [Q8NFA2-2]
GeneID124056.
KEGGhsa:124056.
UCSCuc002cnx.4. human. [Q8NFA2-1]
uc002cny.4. human. [Q8NFA2-3]
uc002cnz.4. human. [Q8NFA2-4]
uc002coa.4. human. [Q8NFA2-2]

Organism-specific databases

CTD124056.
GeneCardsGC16M002028.
HGNCHGNC:19404. NOXO1.
MIM611256. gene.
neXtProtNX_Q8NFA2.
PharmGKBPA134896072.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG150477.
HOGENOMHOG000113833.
HOVERGENHBG082053.
InParanoidQ8NFA2.
KOK17934.
OMATFVRRSW.
OrthoDBEOG70GMG8.
PhylomeDBQ8NFA2.
TreeFamTF329347.

Gene expression databases

ArrayExpressQ8NFA2.
BgeeQ8NFA2.
CleanExHS_NOXO1.
GenevestigatorQ8NFA2.

Family and domain databases

Gene3D3.30.1520.10. 1 hit.
InterProIPR001683. Phox.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00787. PX. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTSM00326. SH3. 2 hits.
[Graphical view]
SUPFAMSSF50044. SSF50044. 2 hits.
SSF64268. SSF64268. 1 hit.
PROSITEPS50195. PX. 1 hit.
PS50002. SH3. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNOXO1.
GenomeRNAi124056.
NextBio81216.
PROQ8NFA2.
SOURCESearch...

Entry information

Entry nameNOXO1_HUMAN
AccessionPrimary (citable) accession number: Q8NFA2
Secondary accession number(s): Q86YM1, Q8NFA3, Q96B73
Entry history
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM