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NCF4 neutrophil cytosolic factor 4 [ Homo sapiens (human) ]

Gene ID: 4689, updated on 2-Nov-2024

Summary

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Official Symbol
NCF4provided by HGNC
Official Full Name
neutrophil cytosolic factor 4provided by HGNC
Primary source
HGNC:HGNC:7662
See related
Ensembl:ENSG00000100365 MIM:601488; AllianceGenome:HGNC:7662
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
NCF; CGD3; P40PHOX; SH3PXD4
Summary
The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
Expression
Biased expression in bone marrow (RPKM 51.6), appendix (RPKM 18.9) and 11 other tissues See more
Orthologs
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Genomic context

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See NCF4 in Genome Data Viewer
Location:
22q12.3
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (36861006..36878015)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (37316866..37336974)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (37257048..37274057)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene CACNG2 divergent transcript Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:37161913-37163112 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13671 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr22:37171863-37172426 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:37172992-37173555 Neighboring gene intraflagellar transport 27 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:37194619-37195541 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr22:37203445-37204171 Neighboring gene parvalbumin Neighboring gene NCF4 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:37267835-37268373 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:37275012-37275204 Neighboring gene uncharacterized LOC105373022 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr22:37291564-37292117 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:37296897-37297462 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:37297463-37298028 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:37307503-37308204 Neighboring gene uncharacterized LOC105373023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18942 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:37318330-37318900 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:37321546-37322745 Neighboring gene colony stimulating factor 2 receptor subunit beta

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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

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Related articles in PubMed

  1. Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: regulation by angiotensin II. Touyz RM, et al. Circ Res, 2002 Jun 14. PMID 12065324
  2. Subcellular localisation of the p40phox component of NADPH oxidase involves direct interactions between the Phox homology domain and F-actin. Shao D, et al. Int J Biochem Cell Biol, 2010 Oct. PMID 20637895, Free PMC Article
  3. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Matute JD, et al. Blood, 2009 Oct 8. PMID 19692703, Free PMC Article
  4. [Crystal structure of p40(phox) and regulation mechanism of superoxide generation]. Honbou K. Seikagaku, 2008 Aug. PMID 18807499
  5. Fc gamma R-stimulated activation of the NADPH oxidase: phosphoinositide-binding protein p40phox regulates NADPH oxidase activity after enzyme assembly on the phagosome. Tian W, et al. Blood, 2008 Nov 1. PMID 18711001, Free PMC Article

See all (87) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NCF4 attenuates colorectal cancer progression by modulating inflammasome activation and immune surveillance.
    Title: NCF4 attenuates colorectal cancer progression by modulating inflammasome activation and immune surveillance.
  2. Polymorphisms of the NCF4 Gene Increase the Risk of Chronic Heart Failure in Patients with Type 2 Diabetes Mellitus.
    Title: Polymorphisms of the NCF4 Gene Increase the Risk of Chronic Heart Failure in Patients with Type 2 Diabetes Mellitus.
  3. NCF1/2/4 Are Prognostic Biomarkers Related to the Immune Infiltration of Kidney Renal Clear Cell Carcinoma.
    Title: NCF1/2/4 Are Prognostic Biomarkers Related to the Immune Infiltration of Kidney Renal Clear Cell Carcinoma.
  4. Association of NCF2, NCF4, and CYBA Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population.
    Title: Association of NCF2, NCF4, and CYBA Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population.
  5. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another.
    Title: Inherited p40phox deficiency differs from classic chronic granulomatous disease.
  6. Tyrosine kinase substrate (Tks) proteins, analogous to the related proteins p47(phox), p40(phox) and NoxO1, also facilitate local generation of reactive oxygen species (ROS), which aid in signaling at invadopodia and/or podosomes to promote their activity. As their name suggests, Tks adaptor proteins are substrates for tyrosine kinases, especially Src. [review]
    Title: Tks adaptor proteins at a glance.
  7. Phosphoinositol 3-phosphate regulates reactive oxygen species production by maintaining p40phox and p67phox at the phagosomal membrane.
    Title: Phosphoinositol 3-phosphate acts as a timer for reactive oxygen species production in the phagosome.
  8. NCF4 polymorphism was associated with Crohn's disease, but not ulcerative colitis in Caucasian--{REVIEW}
    Title: Association between NCF4 rs4821544T/C polymorphism and inflammatory bowel disease risk in Caucasian: a meta-analysis.
  9. NCF4 may induce ex- pression of NADPH oxidase enzymes, such as p67phox, p47phox, p22phox and NOX2, which lead to increased ROS levels.
    Title: Activation of NADPH oxidase subunit NCF4 induces ROS-mediated EMT signaling in HeLa cells.
  10. Germline variation in NCF4, an innate immunity gene, is associated with an increased risk of colorectal cancer.
    Title: Germline variation in NCF4, an innate immunity gene, is associated with an increased risk of colorectal cancer.
Submit: New GeneRIF Correction See all GeneRIFs (38)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC3810

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables phosphatidylinositol-3-phosphate binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables superoxide-generating NADPH oxidase activator activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables superoxide-generating NADPH oxidase activator activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in phagocytosis IEA
Inferred from Electronic Annotation
more info
  
involved_in respiratory burst NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in superoxide anion generation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in superoxide anion generation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of NADPH oxidase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of NADPH oxidase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of NADPH oxidase complex NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in phagolysosome TAS
Traceable Author Statement
more info
  
located_in plasma membrane NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
neutrophil cytosol factor 4
Names
NCF-4
SH3 and PX domain-containing protein 4
neutrophil NADPH oxidase factor 4
neutrophil cytosolic factor 4, 40kDa
p40-phox

NCBI Reference Sequences (RefSeq)

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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.

Genomic

  1. NG_023400.1 RefSeqGene

    Range
    5001..22030
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_159

mRNA and Protein(s)

  1. NM_000631.5 → NP_000622.2  neutrophil cytosol factor 4 isoform 1

    See identical proteins and their annotated locations for NP_000622.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) lacks an internal coding segment compared to variant 2, which leads to a translation frameshift. The resulting isoform (1) has a distinct and shorter C-terminus, as compared to isoform 2.
    Source sequence(s)
    BC002798, BU076892, BX355636
    Consensus CDS
    CCDS13934.1
    UniProtKB/Swiss-Prot
    A8K4F9, O60808, Q15080, Q86U56, Q9BU98, Q9NP45
    UniProtKB/TrEMBL
    Q53FG4, Q6FGM9
    Related
    ENSP00000248899.6, ENST00000248899.11
    Conserved Domains (3) summary
    cd06399
    Location:238 → 329
    PB1_P40; The PB1 domain is essential part of the p40 adaptor protein which plays an important role in activating phagocyte NADPH oxidase during phagocytosis. The PB1 domain is a modular domain mediating specific protein-protein interaction which play a role in ...
    cd06882
    Location:19 → 141
    PX_p40phox; The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase
    cd11869
    Location:174 → 227
    SH3_p40phox; Src Homology 3 domain of the p40phox subunit of NADPH oxidase

  2. NM_013416.4 → NP_038202.2  neutrophil cytosol factor 4 isoform 2

    See identical proteins and their annotated locations for NP_038202.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longer transcript and encodes the longer isoform (2). This isoform (2) lacks the PC (Phox and Cdc24p) motif, which may be important for the interaction with NCF2.
    Source sequence(s)
    AK290924, BC002798
    Consensus CDS
    CCDS13935.1
    UniProtKB/TrEMBL
    A0A217FLJ2
    Related
    ENSP00000380334.4, ENST00000397147.7
    Conserved Domains (3) summary
    cd06882
    Location:19 → 141
    PX_p40phox; The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase
    cd11869
    Location:174 → 227
    SH3_p40phox; Src Homology 3 domain of the p40phox subunit of NADPH oxidase
    cl02720
    Location:238 → 258
    PB1; The PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development, and cell polarity. A canonical PB1-PB1 ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    36861006..36878015
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047441385.1 → XP_047297341.1  neutrophil cytosol factor 4 isoform X2

  2. XM_047441384.1 → XP_047297340.1  neutrophil cytosol factor 4 isoform X1

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NT_187631.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    81800..101331
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    37316866..37336974
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054325654.1 → XP_054181629.1  neutrophil cytosol factor 4 isoform X5

    UniProtKB/TrEMBL
    A0A494BZS1

  2. XM_054325656.1 → XP_054181631.1  neutrophil cytosol factor 4 isoform X6

  3. XM_054325653.1 → XP_054181628.1  neutrophil cytosol factor 4 isoform X4

  4. XM_054325655.1 → XP_054181630.1  neutrophil cytosol factor 4 isoform X5

    UniProtKB/TrEMBL
    A0A494BZS1

  5. XM_054325651.1 → XP_054181626.1  neutrophil cytosol factor 4 isoform X3

  6. XM_054325652.1 → XP_054181627.1  neutrophil cytosol factor 4 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q15080.2 GenPept UniProtKB/Swiss-Prot:Q15080

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