NCF4

Protein identityUniProt · HPA

UniProt accession

Q15080

Gene

NCF4

Ensembl

ENSG00000100365

Chromosome

22

Canonical length

339 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

339 residues, UniProt reviewed canonical sequence.

>Q15080|NCF4
     1  MAVAQQLRAE SDFEQLPDDV AISANIADIE EKRGFTSHFV FVIEVKTKGG SKYLIYRRYR
    61  QFHALQSKLE ERFGPDSKSS ALACTLPTLP AKVYVGVKQE IAEMRIPALN AYMKSLLSLP
   121  VWVLMDEDVR IFFYQSPYDS EQVPQALRRL RPRTRKVKSV SPQGNSVDRM AAPRAEALFD
   181  FTGNSKLELN FKAGDVIFLL SRINKDWLEG TVRGATGIFP LSFVKILKDF PEEDDPTNWL
   241  RCYYYEDTIS TIKDIAVEED LSSTPLLKDL LELTRREFQR EDIALNYRDA EGDLVRLLSD
   301  EDVALMVRQA RGLPSQKRLF PWKLHITQKD NYRVYNTMP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NCF4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

170 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NCF4.

Disease | AllUniProt

Conditions NCF4 is implicated in, by any mechanism.

• Granulomatous disease, chronic, autosomal recessive, 3 (CGD3) MIM:613960

Disease | GeneticClinVar

27 pathogenic / likely-pathogenic of 445 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3
• Chronic granulomatous disease

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.2

gnomAD pLI

0

gnomAD missense Z

-0.23

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• phagocytosis
• respiratory burst
• superoxide anion generation

Molecular functions

• phosphatidylinositol-3-phosphate binding
• superoxide-generating NADPH oxidase activator activity

Cellular components

• cytoplasm
• cytosol
• endosome membrane
• membrane
• NADPH oxidase complex
• phagolysosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• PB1 domain
• SH3 domain
• Phox homology
• SH3-like domain superfamily
• PX domain superfamily
• NADPH Oxidase and PX Domain-Containing
• PB1-like domain
• SH3 domain
• PB1 domain
• PX domain
• Neutrophil cytosol factor P40
• Neutrophil cytosol factor P40, PB1 domain
• Neutrophil cytosol factor 4, PX domain
• Neutrophil cytosol factor P40, SH3 domain

KeywordsUniProt

• Chronic granulomatous disease
• Cytoplasm
• Endosome
• Lipid-binding
• Membrane
• Phosphoprotein
• SH3 domain

InteractionsUniProt · HPA

Protein binding partners of NCF4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GBP7
• NCF1
• NCF2