Ncf2 neutrophil cytosolic factor 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ncf2provided by MGI
Official Full Name: neutrophil cytosolic factor 2provided by MGI
Primary source: MGI:MGI:97284
See related: Ensembl:ENSMUSG00000026480 AllianceGenome:MGI:97284
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: NOXA2; Ncf-2; p67phox
Summary: Enables small GTPase binding activity. Contributes to superoxide-generating NAD(P)H oxidase activity. Acts upstream of or within superoxide anion generation. Located in acrosomal vesicle. Is expressed in several structures, including hemolymphoid system; limb; and liver. Human ortholog(s) of this gene implicated in Alzheimer's disease; autosomal recessive chronic granulomatous disease cytochrome b-positive type II; and rheumatoid arthritis. Orthologous to human NCF2 (neutrophil cytosolic factor 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in genital fat pad adult (RPKM 19.6), spleen adult (RPKM 10.2) and 13 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 G3; 1 65.05 cM

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (152675904..152712743)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (152800153..152836990)

Chromosome 1 - NC_000067.7 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?

we propose that SRF integrates transcriptional activation of NCF1/NCF2 and ROS production to promote liver fibrosis.
Title: Serum response factor (SRF) promotes ROS generation and hepatic stellate cell activation by epigenetically stimulating NCF1/2 transcription.
we found that ROS formation and expression of p47(phox) and p67(phox), subunits of NADPH oxidase, were increased in AppTg mice but attenuated in AppTg/Cebpd(-/-) mice. Cebpd can up-regulate p47(phox) and p67(phox) transcription via a direct binding on their promoters, which results in an increase in intracellular oxidative stress
Title: Astrocytic CCAAT/Enhancer-binding protein delta contributes to reactive oxygen species formation in neuroinflammation.
Just as patients with chronic granulomatous disease who lack NADPH oxidase rarely develop SLE, NCF-2-null mice on a nonautoimmune background were susceptible to a chronic granulomatous disease-like opportunistic infection but did not develop lupus. In contrast, on a lupus-prone background, even haploinsufficiency of NCF-2 accelerated the development of full-blown lupus disease.
Title: Haploinsufficiency of NADPH Oxidase Subunit Neutrophil Cytosolic Factor 2 Is Sufficient to Accelerate Full-Blown Lupus in NZM 2328 Mice.
p67(phox) binds to phosphoPrdx6 and inhibits its PLA2 activity, an interaction that could function to terminate the PLA2-mediated NOX2 activation signal.
Title: p67(phox) terminates the phospholipase A(2)-derived signal for activation of NADPH oxidase (NOX2).
The results of this study suggested that repeated stress promotes depressive behavior through the upregulation of NADPH oxidasesubunit (67kDa) and the resultant metabolic oxidative stress.
Title: NADPH oxidase mediates depressive behavior induced by chronic stress in mice.
Data suggest that a cytosolic source of reactive oxygen species, probably p67(phox) subunit of cardiac NADPH oxidase 2 (NOX2), may contribute to the hypertrophic phenotype in glucose transporter 4 gene (GLUT4-/-) mice.
Title: Cytosolic, but not mitochondrial, oxidative stress is a likely contributor to cardiac hypertrophy resulting from cardiac specific GLUT4 deletion in mice.
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.
This study demonstrates the involvement of ROS from NADPH oxidase in mediating paraquat cytotoxicity in BV-2 microglial cells and this process is mediated through PKCdelta- and ERK-dependent pathways.
Title: Cytotoxicity of paraquat in microglial cells: Involvement of PKCdelta- and ERK1/2-dependent NADPH oxidase.
This report evaluates neutrophil cytosolic factor 2 (Ncf2) as a candidate Salmonella susceptibility gene for Ity3.
Title: Sequencing, expression, and functional analyses support the candidacy of Ncf2 in susceptibility to Salmonella typhimurium infection in wild-derived mice.

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Variation

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Alleles

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

Targeted (4) 1 citation
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC156340P1 (e-PCR)
- UniSTS:271393

AB002664 (e-PCR)
- UniSTS:180601

Ncf2 (e-PCR), detects polymorphism
- UniSTS:548045

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to superoxide-generating NAD(P)H oxidase activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to superoxide-generating NAD(P)H oxidase activity	ISO Inferred from Sequence Orthology 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
acts_upstream_of_or_within NADP catabolic process	ISO Inferred from Sequence Orthology more info	PubMed
involved_in cellular response to hormone stimulus	ISO Inferred from Sequence Orthology more info
involved_in phagocytosis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of blood pressure	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of reactive oxygen species biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in respiratory burst	IEA Inferred from Electronic Annotation more info
involved_in response to glucose	ISO Inferred from Sequence Orthology more info
involved_in response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in response to organic cyclic compound	ISO Inferred from Sequence Orthology more info
involved_in superoxide anion generation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within superoxide anion generation	IDA Inferred from Direct Assay more info	PubMed
involved_in superoxide anion generation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within superoxide metabolic process	ISO Inferred from Sequence Orthology more info	PubMed

Component	Evidence Code	Pubs
part_of NADPH oxidase complex	ISO Inferred from Sequence Orthology more info
located_in acrosomal vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info	PubMed
located_in membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: neutrophil cytosol factor 2

Names: 67 kDa neutrophil oxidase factor; NADPH oxidase activator 2; NADPH oxidase subunit (67kDa); neutrophil NADPH oxidase factor 2

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_001420384.1 → NP_001407313.1 neutrophil cytosol factor 2 isoform 1

Status: VALIDATED

Source sequence(s)

AC123613

UniProtKB/Swiss-Prot

O70145, Q3TC92, Q3U5S4
NM_001420385.1 → NP_001407314.1 neutrophil cytosol factor 2 isoform 1

Status: VALIDATED

Source sequence(s)

AC123613

UniProtKB/Swiss-Prot

O70145, Q3TC92, Q3U5S4
NM_001420386.1 → NP_001407315.1 neutrophil cytosol factor 2 isoform 2

Status: VALIDATED

Source sequence(s)

AC123613
NM_001420387.1 → NP_001407316.1 neutrophil cytosol factor 2 isoform 3

Status: VALIDATED

Source sequence(s)

AC123613
NM_010877.6 → NP_035007.1 neutrophil cytosol factor 2 isoform 1

See identical proteins and their annotated locations for NP_035007.1

Status: VALIDATED

Source sequence(s)

AC123613

Consensus CDS

CCDS15367.1

UniProtKB/Swiss-Prot

O70145, Q3TC92, Q3U5S4

UniProtKB/TrEMBL

Q1PCS1

Related

ENSMUSP00000140404.2, ENSMUST00000186568.7

Conserved Domains (6) summary

cd06406
Location:350 → 428

PB1_P67; A PB1 domain is present in p67 proteins which forms a signaling complex with p40, a crucial step for activation of NADPH oxidase during phagocytosis. PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in ...

cd11871
Location:244 → 297

SH3_p67phox_N; N-terminal (or first) Src Homology 3 domain of the p67phox subunit of NADPH oxidase

cd12046
Location:460 → 511

SH3_p67phox_C; C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase

COG0457
Location:6 → 117

TPR; Tetratricopeptide (TPR) repeat [General function prediction only]

sd00006
Location:6 → 32

TPR; TPR repeat [structural motif]

pfam00515
Location:71 → 99

TPR_1; Tetratricopeptide repeat