Human Gene NCF4 (uc003apy.4)
  Description: Homo sapiens neutrophil cytosolic factor 4, 40kDa (NCF4), transcript variant 1, mRNA.
RefSeq Summary (NM_000631): 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].
Transcript (Including UTRs)
   Position: hg19 chr22:37,257,030-37,274,059 Size: 17,030 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg19 chr22:37,257,214-37,273,865 Size: 16,652 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr22:37,257,030-37,274,059)mRNA (may differ from genome)Protein (339 aa)
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neXtProtOMIMPubMedReactomeTreefamUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: NCF4_HUMAN
DESCRIPTION: RecName: Full=Neutrophil cytosol factor 4; Short=NCF-4; AltName: Full=Neutrophil NADPH oxidase factor 4; AltName: Full=SH3 and PX domain-containing protein 4; AltName: Full=p40-phox; Short=p40phox;
FUNCTION: Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex.
SUBUNIT: p40-PHOX associates primarily with p67-PHOX to form a complex with p47-PHOX.
SUBCELLULAR LOCATION: Cytoplasm.
TISSUE SPECIFICITY: Expression is restricted to hematopoietic cells.
DOMAIN: The OPR/PB1 domain mediates the association with NCF2/p67- PHOX.
DISEASE: Defects in NCF4 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 3 (CGD3) [MIM:613960]. CGD3 is a disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.
SIMILARITY: Contains 1 OPR domain.
SIMILARITY: Contains 1 PX (phox homology) domain.
SIMILARITY: Contains 1 SH3 domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): NCF4
CDC HuGE Published Literature: NCF4
Positive Disease Associations: Dermatitis, Atopic , Inflammatory Bowel Diseases
Related Studies:
  1. Dermatitis, Atopic
    Lavinia Paternoster et al. Nature genetics 2012, Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis., Nature genetics. [PubMed 22197932]
  2. Inflammatory Bowel Diseases
    Richard H Duerr et al. Science (New York, N.Y.) 2006, A genome-wide association study identifies IL23R as an inflammatory bowel disease gene., Science (New York, N.Y.). [PubMed 17068223]

-  MalaCards Disease Associations
  MalaCards Gene Search: NCF4
Diseases sorted by gene-association score: granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type iii* (1350), chronic granulomatous disease* (897), renal tuberculosis (11), n syndrome (9), ornithosis (9), xanthogranulomatous pyelonephritis (9), urogenital tuberculosis (7), inhalation anthrax (7), phagocyte bactericidal dysfunction (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 302.46 RPKM in Whole Blood
Total median expression: 659.36 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -81.87184-0.445 Picture PostScript Text
3' UTR -62.10194-0.320 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000919 - NCF_P40
IPR000270 - OPR_PB1
IPR001683 - Phox
IPR001452 - SH3_domain

Pfam Domains:
PF00018 - SH3 domain
PF00564 - PB1 domain
PF00787 - PX domain
PF07653 - Variant SH3 domain
PF14604 - Variant SH3 domain

SCOP Domains:
50044 - SH3-domain
54277 - CAD & PB1 domains
64268 - PX domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1H6H - X-ray MuPIT 1OEY - X-ray MuPIT 1W6X - X-ray MuPIT 1W70 - X-ray MuPIT 1Z9Q - NMR MuPIT 2DYB - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q15080
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005086 ARF guanyl-nucleotide exchange factor activity
GO:0005515 protein binding
GO:0008289 lipid binding
GO:0016176 superoxide-generating NADPH oxidase activator activity
GO:0032266 phosphatidylinositol-3-phosphate binding
GO:0035091 phosphatidylinositol binding
GO:0046983 protein dimerization activity

Biological Process:
GO:0006909 phagocytosis
GO:0006955 immune response
GO:0016192 vesicle-mediated transport
GO:0043085 positive regulation of catalytic activity
GO:0045730 respiratory burst
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005802 trans-Golgi network
GO:0005829 cytosol
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0032010 phagolysosome
GO:0043020 NADPH oxidase complex


-  Descriptions from all associated GenBank mRNAs
  KJ897226 - Synthetic construct Homo sapiens clone ccsbBroadEn_06620 NCF4 gene, encodes complete protein.
BC002798 - Homo sapiens neutrophil cytosolic factor 4, 40kDa, mRNA (cDNA clone MGC:3810 IMAGE:3634177), complete cds.
AK223324 - Homo sapiens mRNA for neutrophil cytosolic factor 4 (40kD) isoform 1 variant, clone: TMS07761.
JD134161 - Sequence 115185 from Patent EP1572962.
JD120476 - Sequence 101500 from Patent EP1572962.
JD278704 - Sequence 259728 from Patent EP1572962.
JD387992 - Sequence 369016 from Patent EP1572962.
AK290924 - Homo sapiens cDNA FLJ75679 complete cds, highly similar to Homo sapiens neutrophil cytosolic factor 4, 40kDa (NCF4), transcript variant 2, mRNA.
JD441642 - Sequence 422666 from Patent EP1572962.
CR456528 - Homo sapiens NCF4 full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.NCF4.V2).
JD471224 - Sequence 452248 from Patent EP1572962.
JD073991 - Sequence 55015 from Patent EP1572962.
JD435306 - Sequence 416330 from Patent EP1572962.
JD435307 - Sequence 416331 from Patent EP1572962.
JD324372 - Sequence 305396 from Patent EP1572962.
X77094 - H.sapiens mRNA for p40phox.
AB025219 - Homo sapiens NCF4 mRNA for p40phox, complete cds.
AB025220 - Homo sapiens NCF-4 mRNA for p40phox, complete cds.
AB463139 - Synthetic construct DNA, clone: pF1KB8458, Homo sapiens NCF4 gene for neutrophil cytosolic factor 4, without stop codon, in Flexi system.
CU013416 - Homo sapiens NCF4, mRNA (cDNA clone IMAGE:100000385), complete cds, without stop codon, in Gateway system.
CU013128 - Homo sapiens NCF4, mRNA (cDNA clone IMAGE:100000481), complete cds, with stop codon, in Gateway system.
BT007346 - Homo sapiens neutrophil cytosolic factor 4, 40kDa mRNA, complete cds.
CR542078 - Homo sapiens full open reading frame cDNA clone RZPDo834E1136D for gene NCF4, neutrophil cytosolic factor 4, 40kDa; complete cds, incl. stopcodon.
JD185491 - Sequence 166515 from Patent EP1572962.
JD462913 - Sequence 443937 from Patent EP1572962.
JD475118 - Sequence 456142 from Patent EP1572962.
JD318460 - Sequence 299484 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04670 - Leukocyte transendothelial migration
hsa05140 - Leishmaniasis

Reactome (by CSHL, EBI, and GO)

Protein Q15080 (Reactome details) participates in the following event(s):

R-HSA-5218827 NADPH oxidase 2 (NOX2) complex binds RAC1
R-HSA-5668605 RAC2:GTP binds NOX2 complex
R-HSA-1222376 NOX2 generates superoxide from oxygen
R-HSA-1236967 Alkalization of the phagosomal lumen by NOX2
R-HSA-5218841 NADPH oxidase 2 generates superoxide from oxygen
R-HSA-5668629 Production of phagocyte oxygen radicals by NOX2 complex bound to RAC2:GTP
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-5668599 RHO GTPases Activate NADPH Oxidases
R-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-194138 Signaling by VEGF
R-HSA-195258 RHO GTPase Effectors
R-HSA-1236973 Cross-presentation of particulate exogenous antigens (phagosomes)
R-HSA-168249 Innate Immune System
R-HSA-2262752 Cellular responses to stress
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-194315 Signaling by Rho GTPases
R-HSA-1236975 Antigen processing-Cross presentation
R-HSA-168256 Immune System
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-162582 Signal Transduction
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-1280218 Adaptive Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A8K4F9, NCF4_HUMAN, NM_000631, NP_000622, O60808, Q15080, Q86U56, Q9BU98, Q9NP45, SH3PXD4
UCSC ID: uc003apy.4
RefSeq Accession: NM_000631
Protein: Q15080 (aka NCF4_HUMAN)
CCDS: CCDS13934.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene NCF4:
cgd (Chronic Granulomatous Disease)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000631.4
exon count: 10CDS single in 3' UTR: no RNA size: 1401
ORF size: 1020CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2109.00frame shift in genome: no % Coverage: 99.79
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.