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Protein

NADPH oxidase activator 1

Gene

NOXA1

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

Functioni

Functions as an activator of NOX1, a superoxide-producing NADPH oxidase. Functions in the production of reactive oxygen species (ROS) which participate in a variety of biological processes including host defense, hormone biosynthesis, oxygen sensing and signal transduction. May also activate CYBB/gp91phox and NOX3.8 Publications

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • Rac GTPase binding Source: BHF-UCL
  • SH3 domain binding Source: UniProtKB
  • superoxide-generating NADPH oxidase activator activity Source: UniProtKB

GO - Biological processi

  • regulation of hydrogen peroxide metabolic process Source: BHF-UCL
  • regulation of respiratory burst Source: BHF-UCL
  • superoxide metabolic process Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:G66-33228-MONOMER.
ReactomeiR-HSA-5668599. RHO GTPases Activate NADPH Oxidases.
SIGNORiQ86UR1.

Names & Taxonomyi

Protein namesi
Recommended name:
NADPH oxidase activator 1
Short name:
NOX activator 1
Alternative name(s):
Antigen NY-CO-31
NCF2-like protein
P67phox-like factor
p51-nox
Gene namesi
Name:NOXA1
Synonyms:P51NOX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:10668. NOXA1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • NADPH oxidase complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi34P → A: Partial loss of function. 1 Publication1
Mutagenesisi37P → A: Partial loss of function. 1 Publication1
Mutagenesisi68D → A: Loss of function and loss of interaction with RAC1. 1 Publication1
Mutagenesisi103R → E: Loss of function and loss of interaction with RAC1. Loss of localization to membranes. 3 Publications1
Mutagenesisi172S → A: Loss of phosphorylation. Loss of interaction with YHAWZ; when associated with A-461. 1 Publication1
Mutagenesisi172S → E: Constitutively interacts with YWHAZ; when associated with E-461. 1 Publication1
Mutagenesisi205V → A: Unable to activate NOX2. 1 Publication1
Mutagenesisi436W → R: Loss of interaction with NOXO1 and NCF1. Loss of localization to membranes. Partial loss of function. 3 Publications1
Mutagenesisi461S → A: Loss of phosphorylation. Loss of interaction with YHAWZ; when associated with A-172. 1 Publication1
Mutagenesisi461S → E: Constitutively interacts with YWHAZ; when associated with E-172. 1 Publication1

Organism-specific databases

DisGeNETi10811.
OpenTargetsiENSG00000188747.
PharmGKBiPA35598.

Polymorphism and mutation databases

BioMutaiNOXA1.
DMDMi74759404.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003146091 – 476NADPH oxidase activator 1Add BLAST476

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei172Phosphoserine; by PKA1 Publication1
Modified residuei461Phosphoserine; by PKA1 Publication1

Post-translational modificationi

Interaction with YWHAZ depends on phosphorylation by PKA.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ86UR1.
PeptideAtlasiQ86UR1.
PRIDEiQ86UR1.

PTM databases

iPTMnetiQ86UR1.
PhosphoSitePlusiQ86UR1.

Expressioni

Tissue specificityi

Widely expressed. Detected in pancreas, liver, kidney, spleen, prostate, small intestine and colon.1 Publication

Developmental stagei

Expressed in fetal kidney.1 Publication

Gene expression databases

BgeeiENSG00000188747.
CleanExiHS_NOXA1.
GenevisibleiQ86UR1. HS.

Organism-specific databases

HPAiHPA044781.

Interactioni

Subunit structurei

NOX1, NOXA1, NOXO1, RAC1 and CYBA forms a functional multimeric complex supporting ROS production. Interaction with YWHAZ prevents the interaction of NOXA1 with NOXO1 and RAC1 and its targeting to membranes, hence reducing its ability to activate NOX1. Interacts (via N-terminus) with SH3PXD2A and SH3PXD2B; the interaction is direct.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NOXO1Q8NFA26EBI-949814,EBI-7130806
RIMBP3Q9UFD93EBI-949814,EBI-10182375

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • Rac GTPase binding Source: BHF-UCL
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116025. 13 interactors.
IntActiQ86UR1. 17 interactors.
MINTiMINT-1211202.
STRINGi9606.ENSP00000342848.

Structurei

3D structure databases

ProteinModelPortaliQ86UR1.
SMRiQ86UR1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati7 – 38TPR 1Add BLAST32
Repeati39 – 71TPR 2Add BLAST33
Repeati73 – 105TPR 3Add BLAST33
Repeati122 – 155TPR 4Add BLAST34
Domaini315 – 395PB1PROSITE-ProRule annotationAdd BLAST81
Domaini399 – 458SH3PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 224Mediates interaction with RAC1Add BLAST224

Domaini

The SH3 domain mediates interaction with NOXO1 and NCF1 and has autoregulatory function.
The TPR repeats mediate interaction with RAC1.

Sequence similaritiesi

Belongs to the NCF2/NOXA1 family.Curated
Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation
Contains 4 TPR repeats.Curated

Keywords - Domaini

Repeat, SH3 domain, TPR repeat

Phylogenomic databases

eggNOGiKOG4225. Eukaryota.
ENOG41110AD. LUCA.
GeneTreeiENSGT00530000063843.
HOGENOMiHOG000237312.
HOVERGENiHBG098043.
InParanoidiQ86UR1.
OMAiFQLERFQ.
OrthoDBiEOG091G04T7.
PhylomeDBiQ86UR1.
TreeFamiTF329087.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR000270. PB1_dom.
IPR001452. SH3_domain.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00018. SH3_1. 1 hit.
PF13176. TPR_7. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00326. SH3. 1 hit.
SM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50002. SH3. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86UR1-1) [UniParc]FASTAAdd to basket

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
MASLGDLVRA WHLGAQAVDR GDWARALHLF SGVPAPPARL CFNAGCVHLL
60 70 80 90 100
AGDPEAALRA FDQAVTKDTC MAVGFFQRGV ANFQLARFQE ALSDFWLALE
110 120 130 140 150
QLRGHAAIDY TQLGLRFKLQ AWEVLHNVAS AQCQLGLWTE AASSLREAMS
160 170 180 190 200
KWPEGSLNGL DSALDQVQRR GSLPPRQVPR GEVFRPHRWH LKHLEPVDFL
210 220 230 240 250
GKAKVVASAI PDDQGWGVRP QQPQGPGANH DARSLIMDSP RAGTHQGPLD
260 270 280 290 300
AETEVGADRC TSTAYQEQRP QVEQVGKQAP LSPGLPAMGG PGPGPCEDPA
310 320 330 340 350
GAGGAGAGGS EPLVTVTVQC AFTVALRARR GADLSSLRAL LGQALPHQAQ
360 370 380 390 400
LGQLSYLAPG EDGHWVPIPE EESLQRAWQD AAACPRGLQL QCRGAGGRPV
410 420 430 440 450
LYQVVAQHSY SAQGPEDLGF RQGDTVDVLC EVDQAWLEGH CDGRIGIFPK
460 470
CFVVPAGPRM SGAPGRLPRS QQGDQP
Length:476
Mass (Da):50,933
Last modified:June 1, 2003 - v1
Checksum:i64DFBF64C59722AD
GO
Isoform 2 (identifier: Q86UR1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     431-431: E → EEPDVPLA

Note: Mostly inactive for NOX1 activation. Does not interact with NOXO1.
Show »
Length:483
Mass (Da):51,655
Checksum:i3C3B2AC24286D2D2
GO
Isoform 3 (identifier: Q86UR1-3) [UniParc]FASTAAdd to basket
Also known as: NOXA1inhib

The sequence of this isoform differs from the canonical sequence as follows:
     168-223: Missing.
     431-431: E → EEPDVPLA

Note: Inactive for NOX1 activation. No experimental confirmation available.
Show »
Length:427
Mass (Da):45,245
Checksum:i122CD814C315AA08
GO

Sequence cautioni

The sequence AAY16126 differs from that shown. Reason: Frameshift at position 305.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51A → T in AAY16126 (PubMed:17602954).Curated1
Sequence conflicti56A → T in AAY16127 (PubMed:17602954).Curated1
Sequence conflicti73V → L in AAY16127 (PubMed:17602954).Curated1
Sequence conflicti142A → T in AAY16127 (PubMed:17602954).Curated1
Sequence conflicti261T → A in AAY16126 (PubMed:17602954).Curated1
Sequence conflicti277K → E in AAY16126 (PubMed:17602954).Curated1
Sequence conflicti278Q → V in AAC18046 (PubMed:9610721).Curated1
Sequence conflicti320C → R in AAY16127 (PubMed:17602954).Curated1
Sequence conflicti329R → G in AAC18046 (PubMed:9610721).Curated1
Sequence conflicti345 – 346LP → FL in AAC18046 (PubMed:9610721).Curated2
Sequence conflicti354L → F in AAC18046 (PubMed:9610721).Curated1
Sequence conflicti409S → R in AAC18046 (PubMed:9610721).Curated1
Sequence conflicti441C → R in AAI10841 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037985274 – 476Missing Found in a truncated form isolated from Caco-2 cells treated with butyrate. Add BLAST203
Natural variantiVAR_037986286P → L.1 PublicationCorresponds to variant rs34155071dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030335168 – 223Missing in isoform 3. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_030336431E → EEPDVPLA in isoform 2 and isoform 3. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY255769 mRNA. Translation: AAP13480.1.
AB095031 mRNA. Translation: BAC76710.1.
AY927790 mRNA. Translation: AAY16126.1. Frameshift.
AY927791 mRNA. Translation: AAY16127.1.
BX322799 Genomic DNA. Translation: CAM24776.1.
BC041594 mRNA. Translation: AAH41594.1.
BC110840 mRNA. Translation: AAI10841.1.
AF039697 mRNA. Translation: AAC18046.1.
CCDSiCCDS59157.1. [Q86UR1-3]
CCDS7042.1. [Q86UR1-2]
RefSeqiNP_001242996.1. NM_001256067.1. [Q86UR1-1]
NP_001242997.1. NM_001256068.1. [Q86UR1-3]
NP_006638.1. NM_006647.1. [Q86UR1-2]
UniGeneiHs.495554.

Genome annotation databases

EnsembliENST00000341349; ENSP00000342848; ENSG00000188747. [Q86UR1-2]
ENST00000392815; ENSP00000376562; ENSG00000188747. [Q86UR1-3]
GeneIDi10811.
KEGGihsa:10811.
UCSCiuc004cmu.4. human. [Q86UR1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY255769 mRNA. Translation: AAP13480.1.
AB095031 mRNA. Translation: BAC76710.1.
AY927790 mRNA. Translation: AAY16126.1. Frameshift.
AY927791 mRNA. Translation: AAY16127.1.
BX322799 Genomic DNA. Translation: CAM24776.1.
BC041594 mRNA. Translation: AAH41594.1.
BC110840 mRNA. Translation: AAI10841.1.
AF039697 mRNA. Translation: AAC18046.1.
CCDSiCCDS59157.1. [Q86UR1-3]
CCDS7042.1. [Q86UR1-2]
RefSeqiNP_001242996.1. NM_001256067.1. [Q86UR1-1]
NP_001242997.1. NM_001256068.1. [Q86UR1-3]
NP_006638.1. NM_006647.1. [Q86UR1-2]
UniGeneiHs.495554.

3D structure databases

ProteinModelPortaliQ86UR1.
SMRiQ86UR1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116025. 13 interactors.
IntActiQ86UR1. 17 interactors.
MINTiMINT-1211202.
STRINGi9606.ENSP00000342848.

PTM databases

iPTMnetiQ86UR1.
PhosphoSitePlusiQ86UR1.

Polymorphism and mutation databases

BioMutaiNOXA1.
DMDMi74759404.

Proteomic databases

PaxDbiQ86UR1.
PeptideAtlasiQ86UR1.
PRIDEiQ86UR1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341349; ENSP00000342848; ENSG00000188747. [Q86UR1-2]
ENST00000392815; ENSP00000376562; ENSG00000188747. [Q86UR1-3]
GeneIDi10811.
KEGGihsa:10811.
UCSCiuc004cmu.4. human. [Q86UR1-1]

Organism-specific databases

CTDi10811.
DisGeNETi10811.
GeneCardsiNOXA1.
H-InvDBHIX0018704.
HGNCiHGNC:10668. NOXA1.
HPAiHPA044781.
MIMi611255. gene.
neXtProtiNX_Q86UR1.
OpenTargetsiENSG00000188747.
PharmGKBiPA35598.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4225. Eukaryota.
ENOG41110AD. LUCA.
GeneTreeiENSGT00530000063843.
HOGENOMiHOG000237312.
HOVERGENiHBG098043.
InParanoidiQ86UR1.
OMAiFQLERFQ.
OrthoDBiEOG091G04T7.
PhylomeDBiQ86UR1.
TreeFamiTF329087.

Enzyme and pathway databases

BioCyciZFISH:G66-33228-MONOMER.
ReactomeiR-HSA-5668599. RHO GTPases Activate NADPH Oxidases.
SIGNORiQ86UR1.

Miscellaneous databases

GeneWikiiNOXA1.
GenomeRNAii10811.
PROiQ86UR1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188747.
CleanExiHS_NOXA1.
GenevisibleiQ86UR1. HS.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR000270. PB1_dom.
IPR001452. SH3_domain.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00018. SH3_1. 1 hit.
PF13176. TPR_7. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00326. SH3. 1 hit.
SM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50002. SH3. 1 hit.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOXA1_HUMAN
AccessioniPrimary (citable) accession number: Q86UR1
Secondary accession number(s): O60533
, Q29VU9, Q29VV0, Q2TAM1, Q8IUS3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: June 1, 2003
Last modified: November 30, 2016
This is version 123 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.