Ncf4 neutrophil cytosolic factor 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ncf4provided by MGI
Official Full Name: neutrophil cytosolic factor 4provided by MGI
Primary source: MGI:MGI:109186
See related: Ensembl:ENSMUSG00000071715 AllianceGenome:MGI:109186
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: p40phox
Summary: Predicted to enable phosphatidylinositol-3-phosphate binding activity and superoxide-generating NADPH oxidase activator activity. Predicted to be involved in superoxide anion generation. Located in cytoplasm. Is expressed in liver; lower urinary tract; stomach; and testis. Human ortholog(s) of this gene implicated in autosomal recessive chronic granulomatous disease cytochrome b-positive type III and rheumatoid arthritis. Orthologous to human NCF4 (neutrophil cytosolic factor 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in spleen adult (RPKM 34.0), liver E18 (RPKM 15.5) and 13 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 E1; 15 37.1 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (78128324..78146782)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (78244164..78262582)

Chromosome 15 - NC_000081.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation.
Title: NCF4 dependent intracellular reactive oxygen species regulate plasma cell formation.
These studies demonstrate a critical role of phosphatidylinositol 3-phosphate-p40(phox) binding for optimal activation of the NADPH oxidase in macrophages.
Title: PI(3)P-p40phox binding regulates NADPH oxidase activation in mouse macrophages and magnitude of inflammatory responses in vivo.
Our data reveal a specific role for NCF4-mediated intracellular ROS production in regulating autoimmunity and chronic inflammation.
Title: A Reduction in Intracellular Reactive Oxygen Species Due to a Mutation in NCF4 Promotes Autoimmune Arthritis in Mice.
p40phox deficiency leads to upregulation of chemokine receptor 1 and downregulation of fucosyltransferases and sialyltransferases involved in glycan modifications during experimental intestinal inflammation.
Title: p40phox expression regulates neutrophil recruitment and function during the resolution phase of intestinal inflammation.
cooperation of p40(phox) with p47(phox) for Nox2-based NADPH oxidase activation during Fcgamma receptor (FcgammaR)-mediated phagocytosis
Title: Cooperation of p40(phox) with p47(phox) for Nox2-based NADPH oxidase activation during Fcγ receptor (FcγR)-mediated phagocytosis: mechanism for acquisition of p40(phox) phosphatidylinositol 3-phosphate (PI(3)P) binding.
p40(phox) is prephosphorylated in resting endothelial cells and can compensate p47(phox) in keeping basal ROS production.
Title: Knockout of p47 phox uncovers a critical role of p40 phox in reactive oxygen species production in microvascular endothelial cells.
Class III PI3K Vps34 is responsible for the synthesis of PtdIns(3)P on phagosomes containing either S aureus or E coli. PtdIns(3)P binding to p40(phox) is important for CD18-dependent activation oxidase activation in response to S aureus and E coli
Title: CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks.
binding of the ternary complex to phagosomes can be temporally regulated by switching between adaptor proteins that have PX domains with distinct lipid-binding specificities
Title: Sequential binding of cytosolic Phox complex to phagosomes through regulated adaptor proteins: evaluation using the novel monomeric Kusabira-Green System and live imaging of phagocytosis.
The defect in Reactive Oxygen Species production and killing of s aureus by p40(phox-/-) neutrophils defines p40(phox) as an essential component in bacterial killing.
Title: Neutrophils from p40phox-/- mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing.
p40(phoxR58A/R58A) embryos do not develop normally but p40(phoxR58A/-) mice are viable and neutrophils from these animals exhibit significantly reduced oxidase responses compared to those from their p40(phox+/-) siblings.
Title: PtdIns3P binding to the PX domain of p40phox is a physiological signal in NADPH oxidase activation.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI451400 (e-PCR)
- UniSTS:180793

AB002665 (e-PCR)
- UniSTS:160483

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-3-phosphate binding	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in phagocytosis	IEA Inferred from Electronic Annotation more info
involved_in respiratory burst	IEA Inferred from Electronic Annotation more info
involved_in superoxide anion generation	IBA Inferred from Biological aspect of Ancestor more info
involved_in superoxide anion generation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of NADPH oxidase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of NADPH oxidase complex	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in endosome membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: neutrophil cytosol factor 4

Names: NCF-4; neutrophil NADPH oxidase factor 4; 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.

mRNA and Protein(s)

NM_001411421.1 → NP_001398350.1 neutrophil cytosol factor 4 isoform 2

Status: VALIDATED

Source sequence(s)

AL589692

Related

ENSMUSP00000121191.3, ENSMUST00000133618.3
NM_001411422.1 → NP_001398351.1 neutrophil cytosol factor 4 isoform 1

Status: VALIDATED

Source sequence(s)

AL589692

UniProtKB/Swiss-Prot

P97369, Q3TBC6
NM_001411423.1 → NP_001398352.1 neutrophil cytosol factor 4 isoform 1

Status: VALIDATED

Source sequence(s)

AL589692

UniProtKB/Swiss-Prot

P97369, Q3TBC6
NM_008677.3 → NP_032703.2 neutrophil cytosol factor 4 isoform 1

See identical proteins and their annotated locations for NP_032703.2

Status: VALIDATED

Source sequence(s)

AL589692

Consensus CDS

CCDS27610.1

UniProtKB/Swiss-Prot

P97369, Q3TBC6

UniProtKB/TrEMBL

B6DT57

Related

ENSMUSP00000094084.6, ENSMUST00000096357.12

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

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000081.7 Reference GRCm39 C57BL/6J

Range

78128324..78146782

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036159223.1 → XP_036015116.1 neutrophil cytosol factor 4 isoform X4

UniProtKB/TrEMBL

A8XU21

Conserved Domains (2) summary

cd06882
Location:19 → 141

PX_p40phox; The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase

cl17036
Location:174 → 209

SH3; Src Homology 3 domain superfamily
XM_036159222.1 → XP_036015115.1 neutrophil cytosol factor 4 isoform X3

UniProtKB/TrEMBL

Q3TC82

Conserved Domains (3) summary

cd06399
Location:144 → 235

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 ...

cd11869
Location:80 → 133

SH3_p40phox; Src Homology 3 domain of the p40phox subunit of NADPH oxidase

cl02563
Location:1 → 47

PX_domain; The Phox Homology domain, a phosphoinositide binding module