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

    Gene ID: 4689, updated on 5-Dec-2018

    Summary

    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
    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

    Genomic context

    See NCF4 in Genome Data Viewer
    Location:
    22q12.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 22 NC_000022.11 (36860988..36878017)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (37257030..37274059)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373021 Neighboring gene intraflagellar transport 27 Neighboring gene parvalbumin Neighboring gene NCF4 antisense RNA 1 Neighboring gene uncharacterized LOC105373022 Neighboring gene uncharacterized LOC105373023 Neighboring gene colony stimulating factor 2 receptor beta common subunit

    Genomic regions, transcripts, and products

    Expression

    • Project title: 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 Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Pathways from BioSystems

    • 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 ...
    • Cellular responses to stress, organism-specific biosystem (from REACTOME)
      Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
    • 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...
    • Detoxification of Reactive Oxygen Species, organism-specific biosystem (from REACTOME)
      Detoxification of Reactive Oxygen Species, organism-specific biosystemReactive oxygen species such as superoxide (O2.-), peroxides (ROOR), singlet oxygen, peroxynitrite (ONOO-), and hydroxyl radical (OH.) are generated by cellular processes such as respiration (reviewe...
    • 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...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • 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...
    • 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...
    • RHO GTPase Effectors, organism-specific biosystem (from REACTOME)
      RHO GTPase Effectors, organism-specific biosystemRHO GTPases regulate cell behaviour by activating a number of downstream effectors that regulate cytoskeletal organization, intracellular trafficking and transcription (reviewed by Sahai and Marshall...
    • RHO GTPases Activate NADPH Oxidases, organism-specific biosystem (from REACTOME)
      RHO GTPases Activate NADPH Oxidases, organism-specific biosystemNADPH oxidases (NOX) are membrane-associated enzymatic complexes that use NADPH as an electon donor to reduce oxygen and produce superoxide (O2-) that serves as a secondary messenger (Brown and Grien...
    • ROS, RNS production in phagocytes, organism-specific biosystem (from REACTOME)
      ROS, RNS production in phagocytes, organism-specific biosystemThe first line of defense against infectious agents involves an active recruitment of phagocytes to the site of infection. Recruited cells include polymorhonuclear (PMN) leukocytes (i.e., neutrophils...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
      Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...
    • Signaling by VEGF, organism-specific biosystem (from REACTOME)
      Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
    • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
      VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • MGC3810

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    phosphatidylinositol binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    superoxide-generating NADPH oxidase activator activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    oxidation-reduction process TAS
    Traceable Author Statement
    more info
    PubMed 
    phagocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of catalytic activity IEA
    Inferred from Electronic Annotation
    more info
     
    respiratory burst IEA
    Inferred from Electronic Annotation
    more info
     
    superoxide metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    vascular endothelial growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    NADPH oxidase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    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
     

    General protein information

    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)

    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_000631.5NP_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
      Q15080
      Related
      ENSP00000248899.6, ENST00000248899.10
      Conserved Domains (3) summary
      cd06399
      Location:238329
      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
      PX_p40phox; The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase
      cd11869
      Location:174227
      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 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, BU076892
      Consensus CDS
      CCDS13935.1
      UniProtKB/Swiss-Prot
      Q15080
      Related
      ENSP00000380334.4, ENST00000397147.6
      Conserved Domains (3) summary
      cd06882
      Location:19141
      PX_p40phox; The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase
      cd11869
      Location:174227
      SH3_p40phox; Src Homology 3 domain of the p40phox subunit of NADPH oxidase
      cl02720
      Location:238258
      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 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000022.11 Reference GRCh38.p12 Primary Assembly

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

    mRNA and Protein(s)

    1. XM_017028808.1XP_016884297.1  neutrophil cytosol factor 4 isoform X1

    Reference GRCh38.p12 ALT_REF_LOCI_1

    Genomic

    1. NT_187631.1 Reference GRCh38.p12 ALT_REF_LOCI_1

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