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NCF4 neutrophil cytosolic factor 4, 40kDa [ Homo sapiens (human) ]

Gene ID: 4689, updated on 21-Apr-2014
Official Symbol
NCF4provided by HGNC
Official Full Name
neutrophil cytosolic factor 4, 40kDaprovided by HGNC
Primary source
HGNC:7662
Locus tag
CTA-833B7.1
See related
Ensembl:ENSG00000100365; HPRD:03289; MIM:601488; Vega:OTTHUMG00000150548
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; 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]
Location :
22q13.1
Sequence :
Chromosome: 22; NC_000022.11 (36860988..36878017)
See NCF4 in Epigenomics, MapViewer

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene intraflagellar transport 27 homolog (Chlamydomonas) Neighboring gene parvalbumin Neighboring gene colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) Neighboring gene colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) pseudogene 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Antigen processing-Cross presentation, organism-specific biosystem (from REACTOME)
    Antigen processing-Cross presentation, organism-specific biosystemMHC class I molecules generally present peptide antigens derived from proteins synthesized by the cell itself to CD8+ T cells. However, in some circumstances, antigens from extracellular environment ...
  • Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
    Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
  • Cross-presentation of particulate exogenous antigens (phagosomes), organism-specific biosystem (from REACTOME)
    Cross-presentation of particulate exogenous antigens (phagosomes), organism-specific biosystemDendritic cells (DCs) take up and process exogenous particulate or cell-associated antigens such as microbes or tumor cells for MHC-I cross-presentation. Particulate antigens have been reported to be...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystem (from REACTOME)
    Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystemInfection by Mycobacterium tuberculosis (Mtb) is soon countered by the host's immune system, the organism is however almost never eradicated; ten per cent of infections will develop into "open tuberc...
  • Leishmaniasis, organism-specific biosystem (from KEGG)
    Leishmaniasis, organism-specific biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Leishmaniasis, conserved biosystem (from KEGG)
    Leishmaniasis, conserved biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Leukocyte transendothelial migration, organism-specific biosystem (from KEGG)
    Leukocyte transendothelial migration, organism-specific biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
  • Leukocyte transendothelial migration, conserved biosystem (from KEGG)
    Leukocyte transendothelial migration, conserved biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
  • Osteoclast differentiation, organism-specific biosystem (from KEGG)
    Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
  • Osteoclast differentiation, conserved biosystem (from KEGG)
    Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
  • Phagosomal maturation (early endosomal stage), organism-specific biosystem (from REACTOME)
    Phagosomal maturation (early endosomal stage), organism-specific biosystemAlveolar macrophages normally develop their phagosome along the endolysosomal pathway. However, after having internalized Mtb, this development is arrested at an early stage and only includes acidifi...
  • Phagosome, organism-specific biosystem (from KEGG)
    Phagosome, organism-specific biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Phagosome, conserved biosystem (from KEGG)
    Phagosome, conserved biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
phosphatidylinositol-3-phosphate binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein dimerization activity TAS
Traceable Author Statement
more info
PubMed 
superoxide-generating NADPH oxidase activator activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
NADPH oxidase complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endosome membrane IDA
Inferred from Direct Assay
more info
PubMed 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
phagolysosome TAS
Traceable Author Statement
more info
 
Preferred Names
neutrophil cytosol factor 4
Names
neutrophil cytosol factor 4
NCF-4
p40-phox
neutrophil NADPH oxidase factor 4
SH3 and PX domain-containing protein 4

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_000631.4NP_000622.2  neutrophil cytosol factor 4 isoform 1

    See proteins identical to 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
    Q15080
    Related
    ENSP00000248899, OTTHUMP00000197809, ENST00000248899, OTTHUMT00000318863
    Conserved Domains (3) summary
    cd06399
    Location:238329
    Blast Score: 443
    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:19141
    Blast Score: 581
    PX_p40phox; The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase
    cd11869
    Location:174227
    Blast Score: 269
    SH3_p40phox; Src Homology 3 domain of the p40phox subunit of NADPH oxidase
  2. NM_013416.3NP_038202.2  neutrophil cytosol factor 4 isoform 2

    See proteins identical to 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, BU076892
    Consensus CDS
    CCDS13935.1
    UniProtKB/Swiss-Prot
    Q15080
    Related
    ENSP00000380334, OTTHUMP00000197810, ENST00000397147, OTTHUMT00000318864
    Conserved Domains (3) summary
    cd06882
    Location:19141
    Blast Score: 600
    PX_p40phox; The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase
    cd11869
    Location:174227
    Blast Score: 278
    SH3_p40phox; Src Homology 3 domain of the p40phox subunit of NADPH oxidase
    cl02720
    Location:238258
    Blast Score: 92
    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: Homo sapiens Annotation Release 106

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

Reference GRCh38 ALT_REF_LOCI_1

Genomic

  1. NT_187631.1 Reference GRCh38 ALT_REF_LOCI_1

    Range
    81782..101331
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38 Primary Assembly

    Range
    36860988..36878017
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000154.1 Alternate HuRef

    Range
    20219193..20235709
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018933.2 Alternate CHM1_1.1

    Range
    37215777..37232815
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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