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NOX4 NADPH oxidase 4 [ Homo sapiens (human) ]

Gene ID: 50507, updated on 11-Sep-2019

Summary

Official Symbol
NOX4provided by HGNC
Official Full Name
NADPH oxidase 4provided by HGNC
Primary source
HGNC:HGNC:7891
See related
Ensembl:ENSG00000086991 MIM:605261
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
KOX; KOX-1; RENOX
Summary
This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]
Expression
Biased expression in kidney (RPKM 23.6) and endometrium (RPKM 1.5) See more
Orthologs

Genomic context

See NOX4 in Genome Data Viewer
Location:
11q14.3
Exon count:
29
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 11 NC_000011.10 (89324353..89589557, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (89057521..89322779, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984363 Neighboring gene tyrosinase 5' upstream regulatory sequence Neighboring gene tyrosinase Neighboring gene chromobox 3 pseudogene 7 Neighboring gene folate hydrolase 1B Neighboring gene UBTF like 10 (pseudogene)

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
NHGRI GWA Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Knockdown of NOX2 and NOX4 by siRNA abrogates HIV-1 gp120-induced reactive oxygen species (ROS), suggesting that NOX2 and NOX4 are involved in ROS production through CYP2E1 in astrocytes PubMed
env HIV-1 gp120 binding to CXCR4 induces NADPH oxidase-mediated production of superoxide radicals in neurons, which is involved in the activation of neutral sphingomyelinase PubMed
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 inhibits the cellular immune response and enhances oxidative stress mediated by NADPH oxidase PubMed
Nef nef NADPH oxidase is required for HIV-1 Nef-induced ROS production and endothelial apoptosis in human coronary arterial endothelial cells PubMed
Tat tat HIV-1 Tat C downregulates the expression of miR-17 to increase the expression of NOX2 and NOX4; overexpression of miR-17 inhibits NOX2 and NOX4 expression in human microglial cells PubMed
tat HIV-1 Tat C upregulates NOX2 and NOX4 expression and increases ROS production in human brain cells PubMed
tat PDGF-BB inhibits NADPH oxidase-mediated reactive oxygen species production induced by HIV-1 Tat and morphine treatment in neuroblastoma cells PubMed
tat HIV-1 Tat increases CXCL10 expression in IFN-gamma and TNF-alpha stimulated human astrocytes via NADPH oxidase PubMed
tat Knocking down oxidase Nox4 completely suppresses Tat-dependent Ras and ERK activation downstream of Rac1 and RhoA and blocks Tat-dependent proliferation PubMed
tat NOX4-mediated K-Ras activation on the ER endomembrane results in Tat-induced unfolded-protein response PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Cellular responses to stress, organism-specific biosystem (from REACTOME)
    Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
  • Detoxification of Reactive Oxygen Species, organism-specific biosystem (from REACTOME)
    Detoxification of Reactive Oxygen Species, organism-specific biosystemReactive oxygen species such as superoxide (O2.-), peroxides (ROOR), singlet oxygen, peroxynitrite (ONOO-), and hydroxyl radical (OH.) are generated by cellular processes such as respiration (reviewe...
  • Oxidative Stress, organism-specific biosystem (from WikiPathways)
    Oxidative Stress, organism-specific biosystemOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to rep...
  • Signaling events mediated by PTP1B, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by PTP1B, organism-specific biosystem
    Signaling events mediated by PTP1B
  • Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
    Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NAD(P)H oxidase activity TAS
Traceable Author Statement
more info
PubMed 
electron transfer activity TAS
Traceable Author Statement
more info
PubMed 
flavin adenine dinucleotide binding TAS
Traceable Author Statement
more info
PubMed 
heme binding TAS
Traceable Author Statement
more info
PubMed 
modified amino acid binding IDA
Inferred from Direct Assay
more info
PubMed 
nucleotide binding TAS
Traceable Author Statement
more info
PubMed 
oxygen sensor activity TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein tyrosine kinase binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
superoxide-generating NADPH oxidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
bone resorption IEA
Inferred from Electronic Annotation
more info
 
cardiac muscle cell differentiation IEA
Inferred from Electronic Annotation
more info
 
cell aging ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cell morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cellular response to cAMP IEA
Inferred from Electronic Annotation
more info
 
cellular response to gamma radiation IEA
Inferred from Electronic Annotation
more info
 
cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to oxidative stress TAS
Traceable Author Statement
more info
 
cellular response to transforming growth factor beta stimulus IEA
Inferred from Electronic Annotation
more info
 
defense response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
electron transport chain IEA
Inferred from Electronic Annotation
more info
 
gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
heart process IGI
Inferred from Genetic Interaction
more info
PubMed 
homocysteine metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
inflammatory response TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
oxidation-reduction process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
oxidation-reduction process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of DNA biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of ERK1 and ERK2 cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of MAP kinase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein kinase B signaling IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein tyrosine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of reactive oxygen species metabolic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of smooth muscle cell migration IEA
Inferred from Electronic Annotation
more info
 
positive regulation of stress fiber assembly IEA
Inferred from Electronic Annotation
more info
 
reactive oxygen species biosynthetic process NAS
Non-traceable Author Statement
more info
PubMed 
reactive oxygen species metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
superoxide anion generation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
superoxide anion generation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
superoxide metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
NADPH oxidase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
apical plasma membrane IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
focal adhesion IEA
Inferred from Electronic Annotation
more info
 
integral component of membrane TAS
Traceable Author Statement
more info
PubMed 
mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
nucleolus IEA
Inferred from Electronic Annotation
more info
 
nucleus IDA
Inferred from Direct Assay
more info
 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
perinuclear endoplasmic reticulum ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
perinuclear region of cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
stress fiber IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
NADPH oxidase 4
Names
kidney oxidase-1
kidney superoxide-producing NADPH oxidase
renal NAD(P)H-oxidase
NP_001137308.2
NP_001137309.2
NP_001278855.2
NP_001278856.1
NP_001278858.2
NP_001287924.1
NP_058627.2
XP_006718912.1
XP_011541159.1
XP_016873330.1
XP_016873331.1
XP_016873332.1
XP_016873333.1
XP_016873334.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001143836.3NP_001137308.2  NADPH oxidase 4 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (NOX4B), lacks an exon in the coding region compared to variant 1. The encoded isoform (b) is shorter compared to isoform a.
    Source sequence(s)
    AP001815, AP002404
    Consensus CDS
    CCDS44695.1
    Related
    ENSP00000436892.1, ENST00000534731.5
  2. NM_001143837.2NP_001137309.2  NADPH oxidase 4 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding region compared to variant 1. These differences cause translation initiation at a downstream AUG and result in a protein (isoform c) with a shorter N-terminus compared to isoform a.
    Source sequence(s)
    AP001815, AP002404, AP003400
    Consensus CDS
    CCDS44696.1
    Related
    ENSP00000412446.1, ENST00000424319.5
  3. NM_001291926.2NP_001278855.2  NADPH oxidase 4 isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in its 5' UTR, and uses a downstream start codon, compared to variant 1. The encoded isoform (d) has a shorter N-terminus, compared to isoform a.
    Source sequence(s)
    AP001815, AP002404
  4. NM_001291927.1NP_001278856.1  NADPH oxidase 4 isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (e) has a longer and distinct N-terminus, compared to isoform a.
    Source sequence(s)
    AB041035, AK298328, AP001815, AP002404
    UniProtKB/Swiss-Prot
    Q9NPH5
    UniProtKB/TrEMBL
    B7Z523
    Conserved Domains (2) summary
    cd06186
    Location:332598
    NOX_Duox_like_FAD_NADP; NADPH oxidase (NOX) catalyzes the generation of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. ROS were originally identified as bactericidal agents in phagocytes, but are now also implicated in cell signaling and metabolism. NOX ...
    pfam01794
    Location:90225
    Ferric_reduct; Ferric reductase like transmembrane component
  5. NM_001291929.2NP_001278858.2  NADPH oxidase 4 isoform f

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (f) has a shorter and distinct N-terminus, compared to isoform a.
    Source sequence(s)
    AP001815, AP002404
    Consensus CDS
    CCDS73362.1
    Related
    ENSP00000436970.1, ENST00000528341.5
  6. NM_001300995.1NP_001287924.1  NADPH oxidase 4 isoform g

    See identical proteins and their annotated locations for NP_001287924.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) differs in the 5' UTR and coding sequence and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (g) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform a.
    Source sequence(s)
    AK057189, AK291830, AK298323, AP001815
    Consensus CDS
    CCDS73361.1
    UniProtKB/Swiss-Prot
    Q9NPH5
    UniProtKB/TrEMBL
    B3KQ17
    Related
    ENSP00000434924.1, ENST00000532825.5
    Conserved Domains (2) summary
    cd06186
    Location:295513
    NOX_Duox_like_FAD_NADP; NADPH oxidase (NOX) catalyzes the generation of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. ROS were originally identified as bactericidal agents in phagocytes, but are now also implicated in cell signaling and metabolism. NOX ...
    pfam01794
    Location:45180
    Ferric_reduct; Ferric reductase like transmembrane component
  7. NM_016931.5NP_058627.2  NADPH oxidase 4 isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform (a).
    Source sequence(s)
    AP001815, AP002404
    Consensus CDS
    CCDS8285.1
    Related
    ENSP00000263317.4, ENST00000263317.9
    Conserved Domains (2) summary
    cd06186
    Location:319577
    NOX_Duox_like_FAD_NADP; NADPH oxidase (NOX) catalyzes the generation of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. ROS were originally identified as bactericidal agents in phagocytes, but are now also implicated in cell signaling and metabolism. NOX ...
    cl26813
    Location:69479
    PLN02844; oxidoreductase/ferric-chelate reductase

RNA

  1. NR_120406.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks several exons and uses an alternate 3'-terminal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AB041035, AP002404, BC051371
    Related
    ENST00000393282.2

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p13 Primary Assembly

    Range
    89324353..89589557 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011542857.2XP_011541159.1  NADPH oxidase 4 isoform X3

    UniProtKB/Swiss-Prot
    Q9NPH5
    Related
    ENSP00000433797.1, ENST00000527956.5
    Conserved Domains (2) summary
    cd06186
    Location:295553
    NOX_Duox_like_FAD_NADP; NADPH oxidase (NOX) catalyzes the generation of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. ROS were originally identified as bactericidal agents in phagocytes, but are now also implicated in cell signaling and metabolism. NOX ...
    pfam01794
    Location:45180
    Ferric_reduct; Ferric reductase like transmembrane component
  2. XM_017017844.1XP_016873333.1  NADPH oxidase 4 isoform X6

  3. XM_017017841.2XP_016873330.1  NADPH oxidase 4 isoform X1

  4. XM_006718849.4XP_006718912.1  NADPH oxidase 4 isoform X2

    Conserved Domains (2) summary
    cd06186
    Location:340558
    NOX_Duox_like_FAD_NADP; NADPH oxidase (NOX) catalyzes the generation of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. ROS were originally identified as bactericidal agents in phagocytes, but are now also implicated in cell signaling and metabolism. NOX ...
    pfam01794
    Location:90225
    Ferric_reduct; Ferric reductase like transmembrane component
  5. XM_017017845.1XP_016873334.1  NADPH oxidase 4 isoform X6

    Related
    ENSP00000436093.1, ENST00000527626.5
  6. XM_017017842.1XP_016873331.1  NADPH oxidase 4 isoform X4

  7. XM_017017843.2XP_016873332.1  NADPH oxidase 4 isoform X5

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