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Protein

NADPH oxidase 1

Gene

NOX1

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

Functioni

NOH-1S is a voltage-gated proton channel that mediates the H+ currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H+ ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

The oxidase activity is potentiated by NOXA1 and NOXO1.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi101Iron (heme axial ligand)Curated1
Metal bindingi115Iron (heme axial ligand)Curated1
Metal bindingi209Iron (heme axial ligand)Curated1
Metal bindingi221Iron (heme axial ligand)Curated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi338 – 344FADSequence analysis7

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • NADP binding Source: BHF-UCL
  • Rac GTPase binding Source: BHF-UCL
  • superoxide-generating NADPH oxidase activity Source: UniProtKB
  • voltage-gated proton channel activity Source: BHF-UCL

GO - Biological processi

  • angiogenesis Source: BHF-UCL
  • cell migration Source: BHF-UCL
  • cellular response to hyperoxia Source: Ensembl
  • cellular stress response to acidic pH Source: BHF-UCL
  • extracellular matrix organization Source: Ensembl
  • hydrogen peroxide metabolic process Source: BHF-UCL
  • inflammatory response Source: BHF-UCL
  • intracellular pH elevation Source: BHF-UCL
  • NADP metabolic process Source: BHF-UCL
  • oxidation-reduction process Source: BHF-UCL
  • oxygen metabolic process Source: Ensembl
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of integrin biosynthetic process Source: BHF-UCL
  • positive regulation of JNK cascade Source: Ensembl
  • positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: Ensembl
  • positive regulation of smooth muscle cell proliferation Source: BHF-UCL
  • positive regulation of vascular endothelial growth factor production Source: BHF-UCL
  • proton transport Source: BHF-UCL
  • regulation of blood pressure Source: BHF-UCL
  • regulation of systemic arterial blood pressure by renin-angiotensin Source: Ensembl
  • respiratory burst Source: BHF-UCL
  • signal transduction Source: BHF-UCL
  • superoxide anion generation Source: BHF-UCL
  • superoxide metabolic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Oxidoreductase, Voltage-gated channel

Keywords - Biological processi

Electron transport, Ion transport, Transport

Keywords - Ligandi

FAD, Flavoprotein, Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciZFISH:HS00225-MONOMER.
ReactomeiR-HSA-5668599. RHO GTPases Activate NADPH Oxidases.

Protein family/group databases

PeroxiBasei5410. HsNOx01.
TCDBi5.B.1.1.3. the phagocyte (gp91(phox)) nadph oxidase family.

Names & Taxonomyi

Protein namesi
Recommended name:
NADPH oxidase 1 (EC:1.-.-.-)
Short name:
NOX-1
Alternative name(s):
Mitogenic oxidase 1
Short name:
MOX-1
NADH/NADPH mitogenic oxidase subunit P65-MOX
NOH-1
Gene namesi
Name:NOX1
Synonyms:MOX1, NOH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:7889. NOX1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 9CytoplasmicSequence analysis9
Transmembranei10 – 30HelicalSequence analysisAdd BLAST21
Topological domaini31 – 44ExtracellularSequence analysisAdd BLAST14
Transmembranei45 – 72HelicalSequence analysisAdd BLAST28
Topological domaini73 – 102CytoplasmicSequence analysisAdd BLAST30
Transmembranei103 – 123HelicalSequence analysisAdd BLAST21
Topological domaini124 – 168ExtracellularSequence analysisAdd BLAST45
Transmembranei169 – 189HelicalSequence analysisAdd BLAST21
Topological domaini190 – 206CytoplasmicSequence analysisAdd BLAST17
Transmembranei207 – 227HelicalSequence analysisAdd BLAST21
Topological domaini228 – 396ExtracellularSequence analysisAdd BLAST169
Transmembranei397 – 417HelicalSequence analysisAdd BLAST21
Topological domaini418 – 564CytoplasmicSequence analysisAdd BLAST147

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • early endosome Source: BHF-UCL
  • integral component of membrane Source: BHF-UCL
  • invadopodium membrane Source: UniProtKB
  • NADPH oxidase complex Source: BHF-UCL
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in NOX1 may play a role in the pathogenesis of very early onset inflammatory bowel disease (VEOIBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology diagnosed before 6 years of age. VEOIBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but the phenotype of children with onset of Crohn disease occurring younger than the age of 10 is predominantly colonic, with a lower risk of ileal disease. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.

Organism-specific databases

DisGeNETi27035.
OpenTargetsiENSG00000007952.
PharmGKBiPA31690.

Chemistry databases

ChEMBLiCHEMBL1287628.

Polymorphism and mutation databases

BioMutaiNOX1.
DMDMi8134597.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002101481 – 564NADPH oxidase 1Add BLAST564

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi162N-linked (GlcNAc...)1 Publication1
Glycosylationi236N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9Y5S8.
PeptideAtlasiQ9Y5S8.
PRIDEiQ9Y5S8.

PTM databases

iPTMnetiQ9Y5S8.
PhosphoSitePlusiQ9Y5S8.

Expressioni

Tissue specificityi

NOH-1L is detected in colon, uterus, prostate, and colon carcinoma, but not in peripheral blood leukocytes. NOH-1S is detected only in colon and colon carcinoma cells.

Gene expression databases

BgeeiENSG00000007952.
CleanExiHS_NOX1.
ExpressionAtlasiQ9Y5S8. baseline and differential.
GenevisibleiQ9Y5S8. HS.

Organism-specific databases

HPAiHPA035299.
HPA035300.

Interactioni

Subunit structurei

NOX1, NOXA1, NOXO1, RAC1 and CYBA forms a functional multimeric complex supporting reactive oxygen species (ROS) production. Interacts with NOXA1 and NOXO1.2 Publications

GO - Molecular functioni

  • Rac GTPase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi117966. 3 interactors.
DIPiDIP-60457N.
STRINGi9606.ENSP00000362057.

Chemistry databases

BindingDBiQ9Y5S8.

Structurei

3D structure databases

ProteinModelPortaliQ9Y5S8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 283Ferric oxidoreductaseAdd BLAST230
Domaini284 – 391FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST108

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni397 – 536Interaction with NOXO11 PublicationAdd BLAST140

Sequence similaritiesi

Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
Contains 1 ferric oxidoreductase domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0039. Eukaryota.
ENOG410XNZY. LUCA.
GeneTreeiENSGT00550000074350.
HOGENOMiHOG000216669.
HOVERGENiHBG003760.
InParanoidiQ9Y5S8.
KOiK08008.
OMAiIATSHPK.
OrthoDBiEOG091G09RV.
PhylomeDBiQ9Y5S8.
TreeFamiTF105354.

Family and domain databases

InterProiIPR000778. Cyt_b245_heavy_chain.
IPR013112. FAD-bd_8.
IPR017927. Fd_Rdtase_FAD-bd.
IPR013130. Fe3_Rdtase_TM_dom.
IPR013121. Fe_red_NAD-bd_6.
IPR029650. NOX1.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PANTHERiPTHR11972:SF71. PTHR11972:SF71. 2 hits.
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
PRINTSiPR00466. GP91PHOX.
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

Isoform NOH-1L (identifier: Q9Y5S8-1) [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
MGNWVVNHWF SVLFLVVWLG LNVFLFVDAF LKYEKADKYY YTRKILGSTL
60 70 80 90 100
ACARASALCL NFNSTLILLP VCRNLLSFLR GTCSFCSRTL RKQLDHNLTF
110 120 130 140 150
HKLVAYMICL HTAIHIIAHL FNFDCYSRSR QATDGSLASI LSSLSHDEKK
160 170 180 190 200
GGSWLNPIQS RNTTVEYVTF TSIAGLTGVI MTIALILMVT SATEFIRRSY
210 220 230 240 250
FEVFWYTHHL FIFYILGLGI HGIGGIVRGQ TEESMNESHP RKCAESFEMW
260 270 280 290 300
DDRDSHCRRP KFEGHPPESW KWILAPVILY ICERILRFYR SQQKVVITKV
310 320 330 340 350
VMHPSKVLEL QMNKRGFSME VGQYIFVNCP SISLLEWHPF TLTSAPEEDF
360 370 380 390 400
FSIHIRAAGD WTENLIRAFE QQYSPIPRIE VDGPFGTASE DVFQYEVAVL
410 420 430 440 450
VGAGIGVTPF ASILKSIWYK FQCADHNLKT KKIYFYWICR ETGAFSWFNN
460 470 480 490 500
LLTSLEQEME ELGKVGFLNY RLFLTGWDSN IVGHAALNFD KATDIVTGLK
510 520 530 540 550
QKTSFGRPMW DNEFSTIATS HPKSVVGVFL CGPRTLAKSL RKCCHRYSSL
560
DPRKVQFYFN KENF
Length:564
Mass (Da):64,871
Last modified:May 1, 2000 - v2
Checksum:iC3BE290F4E6DBC9A
GO
Isoform NOH-1S (identifier: Q9Y5S8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     159-190: QSRNTTVEYVTFTSIAGLTGVIMTIALILMVT → HPHITPTVYMFTVTFDMVLSSVNSNLLFLLIK
     191-564: Missing.

Show »
Length:190
Mass (Da):21,704
Checksum:i75C0B809E9AE8E3D
GO
Isoform NOH-1LV (identifier: Q9Y5S8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     433-481: Missing.

Show »
Length:515
Mass (Da):58,972
Checksum:i1D79577159D69688
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti173I → V in AAD38133 (PubMed:10615049).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049101315R → H.Corresponds to variant rs2071756dbSNPEnsembl.1
Natural variantiVAR_075548330P → S Found in a patient with very early onset inflammatory bowel disease; unknown pathological significance; no effect on subcellular location; significantly reduced basal and phorbol ester-stimulated ROS generation, which may decrease resistance to infection by enteric pathogens, such as Campylobacter jejuni. 1 Publication1
Natural variantiVAR_061176360D → N Found in a patient with very early onset inflammatory bowel disease; unknown pathological significance; no effect on subcellular location; significantly reduced basal and phorbol ester-stimulated ROS generation, which may decrease resistance to infection by enteric pathogens, such as Campylobacter jejuni. 1 PublicationCorresponds to variant rs34688635dbSNPEnsembl.1
Natural variantiVAR_049102378R → K.Corresponds to variant rs35404864dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001577159 – 190QSRNT…ILMVT → HPHITPTVYMFTVTFDMVLS SVNSNLLFLLIK in isoform NOH-1S. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_001578191 – 564Missing in isoform NOH-1S. 1 PublicationAdd BLAST374
Alternative sequenceiVSP_001579433 – 481Missing in isoform NOH-1LV. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF127763 mRNA. Translation: AAD38133.1.
AF166326 mRNA. Translation: AAF23232.1.
AF166327 mRNA. Translation: AAF23233.1.
AF166328 mRNA. Translation: AAF23234.1.
DQ314883 Genomic DNA. Translation: ABC40742.1.
AK292201 mRNA. Translation: BAF84890.1.
Z83819 Genomic DNA. Translation: CAI42336.1.
Z83819 Genomic DNA. Translation: CAI42337.1.
CH471115 Genomic DNA. Translation: EAX02820.1.
BC075014 mRNA. Translation: AAH75014.1.
BC075015 mRNA. Translation: AAH75015.1.
CCDSiCCDS14474.1. [Q9Y5S8-1]
CCDS14475.1. [Q9Y5S8-3]
RefSeqiNP_001258744.1. NM_001271815.1.
NP_008983.2. NM_007052.4. [Q9Y5S8-1]
NP_039249.1. NM_013955.2. [Q9Y5S8-3]
UniGeneiHs.592227.

Genome annotation databases

EnsembliENST00000217885; ENSP00000217885; ENSG00000007952. [Q9Y5S8-3]
ENST00000372966; ENSP00000362057; ENSG00000007952. [Q9Y5S8-1]
GeneIDi27035.
KEGGihsa:27035.
UCSCiuc004egj.3. human. [Q9Y5S8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF127763 mRNA. Translation: AAD38133.1.
AF166326 mRNA. Translation: AAF23232.1.
AF166327 mRNA. Translation: AAF23233.1.
AF166328 mRNA. Translation: AAF23234.1.
DQ314883 Genomic DNA. Translation: ABC40742.1.
AK292201 mRNA. Translation: BAF84890.1.
Z83819 Genomic DNA. Translation: CAI42336.1.
Z83819 Genomic DNA. Translation: CAI42337.1.
CH471115 Genomic DNA. Translation: EAX02820.1.
BC075014 mRNA. Translation: AAH75014.1.
BC075015 mRNA. Translation: AAH75015.1.
CCDSiCCDS14474.1. [Q9Y5S8-1]
CCDS14475.1. [Q9Y5S8-3]
RefSeqiNP_001258744.1. NM_001271815.1.
NP_008983.2. NM_007052.4. [Q9Y5S8-1]
NP_039249.1. NM_013955.2. [Q9Y5S8-3]
UniGeneiHs.592227.

3D structure databases

ProteinModelPortaliQ9Y5S8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117966. 3 interactors.
DIPiDIP-60457N.
STRINGi9606.ENSP00000362057.

Chemistry databases

BindingDBiQ9Y5S8.
ChEMBLiCHEMBL1287628.

Protein family/group databases

PeroxiBasei5410. HsNOx01.
TCDBi5.B.1.1.3. the phagocyte (gp91(phox)) nadph oxidase family.

PTM databases

iPTMnetiQ9Y5S8.
PhosphoSitePlusiQ9Y5S8.

Polymorphism and mutation databases

BioMutaiNOX1.
DMDMi8134597.

Proteomic databases

PaxDbiQ9Y5S8.
PeptideAtlasiQ9Y5S8.
PRIDEiQ9Y5S8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000217885; ENSP00000217885; ENSG00000007952. [Q9Y5S8-3]
ENST00000372966; ENSP00000362057; ENSG00000007952. [Q9Y5S8-1]
GeneIDi27035.
KEGGihsa:27035.
UCSCiuc004egj.3. human. [Q9Y5S8-1]

Organism-specific databases

CTDi27035.
DisGeNETi27035.
GeneCardsiNOX1.
HGNCiHGNC:7889. NOX1.
HPAiHPA035299.
HPA035300.
MIMi300225. gene.
neXtProtiNX_Q9Y5S8.
OpenTargetsiENSG00000007952.
PharmGKBiPA31690.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0039. Eukaryota.
ENOG410XNZY. LUCA.
GeneTreeiENSGT00550000074350.
HOGENOMiHOG000216669.
HOVERGENiHBG003760.
InParanoidiQ9Y5S8.
KOiK08008.
OMAiIATSHPK.
OrthoDBiEOG091G09RV.
PhylomeDBiQ9Y5S8.
TreeFamiTF105354.

Enzyme and pathway databases

BioCyciZFISH:HS00225-MONOMER.
ReactomeiR-HSA-5668599. RHO GTPases Activate NADPH Oxidases.

Miscellaneous databases

ChiTaRSiNOX1. human.
GeneWikiiNOX1.
GenomeRNAii27035.
PROiQ9Y5S8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000007952.
CleanExiHS_NOX1.
ExpressionAtlasiQ9Y5S8. baseline and differential.
GenevisibleiQ9Y5S8. HS.

Family and domain databases

InterProiIPR000778. Cyt_b245_heavy_chain.
IPR013112. FAD-bd_8.
IPR017927. Fd_Rdtase_FAD-bd.
IPR013130. Fe3_Rdtase_TM_dom.
IPR013121. Fe_red_NAD-bd_6.
IPR029650. NOX1.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PANTHERiPTHR11972:SF71. PTHR11972:SF71. 2 hits.
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
PRINTSiPR00466. GP91PHOX.
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOX1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5S8
Secondary accession number(s): A8K836, O95691, Q2PP02
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 150 of the entry and version 2 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 X
    Human chromosome X: 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.