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Protein

NADPH oxidase organizer 1

Gene

NOXO1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • enzyme binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • phosphatidylinositol binding Source: GO_Central
  • phospholipid binding Source: BHF-UCL
  • superoxide-generating NADPH oxidase activator activity Source: BHF-UCL

GO - Biological processi

  • extracellular matrix disassembly Source: UniProtKB
  • oxidation-reduction process Source: GO_Central
  • regulation of hydrogen peroxide metabolic process Source: BHF-UCL
  • regulation of respiratory burst Source: BHF-UCL
  • superoxide metabolic process Source: GO_Central

Keywordsi

LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-5668599. RHO GTPases Activate NADPH Oxidases.
SIGNORiQ8NFA2.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:19404. NOXO1.

Subcellular locationi

Isoform 3 :

GO - Cellular componenti

  • intracellular Source: GO_Central
  • NADPH oxidase complex Source: BHF-UCL
  • plasma membrane Source: Reactome

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40R → Q: Loss of ability to activate NOX1 associated with loss of lipid-binding and plasma membrane localization. 1 Publication1
Mutagenesisi202W → R: Loss of ability to activate NOX3 and interact with CYBA. Induces interaction with NOXA1 in vitro. 2 Publications1
Mutagenesisi274W → R: Induces interaction with NOXA1 in vitro. 1 Publication1
Mutagenesisi332P → A: Loss of intramolecular interaction. 1 Publication1
Mutagenesisi334R → A: Loss of intramolecular interaction. 1 Publication1

Organism-specific databases

DisGeNETi124056.
OpenTargetsiENSG00000196408.
PharmGKBiPA134896072.

Chemistry databases

DrugBankiDB05265. Ecabet.

Polymorphism and mutation databases

BioMutaiNOXO1.
DMDMi74751269.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002275941 – 376NADPH oxidase organizer 1Add BLAST376

Proteomic databases

PaxDbiQ8NFA2.
PeptideAtlasiQ8NFA2.
PRIDEiQ8NFA2.

PTM databases

iPTMnetiQ8NFA2.
PhosphoSitePlusiQ8NFA2.

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

BgeeiENSG00000196408.
CleanExiHS_NOXO1.
ExpressionAtlasiQ8NFA2. baseline and differential.
GenevisibleiQ8NFA2. HS.

Organism-specific databases

HPAiHPA071540.

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi125848. 6 interactors.
IntActiQ8NFA2. 2 interactors.
MINTiMINT-7147796.
STRINGi9606.ENSP00000380450.

Structurei

Secondary structure

1376
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 16Combined sources10
Beta strandi19 – 21Combined sources3
Beta strandi23 – 30Combined sources8
Beta strandi35 – 41Combined sources7
Helixi42 – 55Combined sources14
Helixi57 – 60Combined sources4
Beta strandi61 – 63Combined sources3
Helixi89 – 110Combined sources22
Helixi112 – 116Combined sources5
Helixi118 – 124Combined sources7
Helixi128 – 131Combined sources4
Beta strandi132 – 134Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L73NMR-A1-149[»]
ProteinModelPortaliQ8NFA2.
SMRiQ8NFA2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 131PXPROSITE-ProRule annotationAdd BLAST131
Domaini163 – 225SH3 1PROSITE-ProRule annotationAdd BLAST63
Domaini237 – 296SH3 2PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni328 – 337Proline-rich region; mediates mutually exclusive interactions with itself and NOXA110

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.

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiENOG410IX9P. Eukaryota.
ENOG410ZVBX. LUCA.
GeneTreeiENSGT00530000063010.
HOGENOMiHOG000113833.
HOVERGENiHBG082053.
InParanoidiQ8NFA2.
KOiK17934.
OMAiHPSGWWL.
OrthoDBiEOG091G0HF0.
PhylomeDBiQ8NFA2.
TreeFamiTF329347.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiView protein in InterPro
IPR001683. Phox.
IPR001452. SH3_domain.
PfamiView protein in Pfam
PF00787. PX. 1 hit.
PF14604. SH3_9. 1 hit.
SMARTiView protein in SMART
SM00326. SH3. 2 hits.
SUPFAMiSSF50044. SSF50044. 2 hits.
SSF64268. SSF64268. 1 hit.
PROSITEiView protein in PROSITE
PS50195. PX. 1 hit.
PS50002. SH3. 2 hits.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

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

        10         20         30         40         50
MAGPRYPVSV QGAALVQIKR LQTFAFSVRW SDGSDTFVRR SWDEFRQLKK
60 70 80 90 100
TLKETFPVEA GLLRRSDRVL PKLLGQASLD APLLGRVGRT SRGLARLQLL
110 120 130 140 150
ETYSRRLLAT AERVARSPTI TGFFAPQPLD LEPALPPGSR VILPTPEEQP
160 170 180 190 200
LSRAAGRLSI HSLEAQSLRC LQPFCTQDTR DRPFQAQAQE SLDVLLRHPS
210 220 230 240 250
GWWLVENEDR QTAWFPAPYL EEAAPGQGRE GGPSLGSSGP QFCASRAYES
260 270 280 290 300
SRADELSVPA GARVRVLETS DRGWWLCRYG DRAGLLPAVL LRPEGLGALL
310 320 330 340 350
SGTGFRGGDD PAGEARGFPE PSQATAPPPT VPTRPSPGAI QSRCCTVTRR
360 370
ALERRPRRQG RPRGCVDSVP HPTTEQ
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01756049Missing in isoform 2 and isoform 4. 3 Publications1
Alternative sequenceiVSP_01756174 – 78Missing in isoform 3 and isoform 4. 6 Publications5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_005255099.4. [Q8NFA2-1]
XP_016878416.1. XM_017022927.1. [Q8NFA2-1]
XP_016878417.1. XM_017022928.1. [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.5. human. [Q8NFA2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNOXO1_HUMAN
AccessioniPrimary (citable) accession number: Q8NFA2
Secondary accession number(s): Q86YM1, Q8NFA3, Q96B73
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: October 1, 2002
Last modified: August 30, 2017
This is version 124 of the entry and version 1 of the sequence. See 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