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Protein

Neutrophil cytosol factor 4

Gene

NCF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • ARF guanyl-nucleotide exchange factor activity Source: GO_Central
  • phosphatidylinositol-3-phosphate binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB
  • superoxide-generating NADPH oxidase activator activity Source: UniProtKB

GO - Biological processi

  • immune response Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • phagocytosis Source: InterPro
  • respiratory burst Source: InterPro
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome
  • vesicle-mediated transport Source: GO_Central

Keywordsi

LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-1236973 Cross-presentation of particulate exogenous antigens (phagosomes)
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-5668599 RHO GTPases Activate NADPH Oxidases
SIGNORiQ15080

Names & Taxonomyi

Protein namesi
Recommended name:
Neutrophil cytosol factor 4
Short name:
NCF-4
Alternative name(s):
Neutrophil NADPH oxidase factor 4
SH3 and PX domain-containing protein 4
p40-phox
Short name:
p40phox
Gene namesi
Name:NCF4
Synonyms:SH3PXD4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100365.14
HGNCiHGNC:7662 NCF4
MIMi601488 gene
neXtProtiNX_Q15080

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Granulomatous disease, chronic, cytochrome-b-positive 3, autosomal recessive (CGD3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.
See also OMIM:613960
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065949105R → Q in CGD3; the protein remains cytosolic, does not localize to phagosomes or endosomes and is unable to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) in a lipid-binding assay; unable to rescue the NADPH-oxidase defect of NCF4 functionally null cells. 1 PublicationCorresponds to variant dbSNP:rs387906808EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi58R → Q: Abolishes interaction with membranes enriched in phosphatidylinositol 3-phosphate. 1 Publication1
Mutagenesisi60R → A: Strongly reduces interaction with membranes enriched in phosphatidylinositol 3-phosphate. 1 Publication1
Mutagenesisi92K → A: Abolishes interaction with membranes enriched in phosphatidylinositol 3-phosphate. 1 Publication1
Mutagenesisi94Y → A: Slightly reduces interaction with membranes enriched in phosphatidylinositol 3-phosphate. 1 Publication1
Mutagenesisi105R → A: Abolishes interaction with membranes enriched in phosphatidylinositol 3-phosphate. 1 Publication1
Mutagenesisi154T → A: Reduces phosphorylation. 1 Publication1
Mutagenesisi211T → A: No effect on phosphorylation. 1 Publication1
Mutagenesisi251T → A: No effect on phosphorylation. 1 Publication1
Mutagenesisi274T → A: No effect on phosphorylation. 1 Publication1
Mutagenesisi315S → A: Reduces phosphorylation. 1 Publication1
Mutagenesisi327T → A: No effect on phosphorylation. 1 Publication1

Keywords - Diseasei

Chronic granulomatous disease, Disease mutation

Organism-specific databases

DisGeNETi4689
GeneReviewsiNCF4
MalaCardsiNCF4
MIMi613960 phenotype
OpenTargetsiENSG00000100365
Orphaneti379 Chronic granulomatous disease
206 Crohn disease
PharmGKBiPA31465

Chemistry databases

DrugBankiDB00514 Dextromethorphan

Polymorphism and mutation databases

BioMutaiNCF4
DMDMi108884815

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000967641 – 339Neutrophil cytosol factor 4Add BLAST339

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei154Phosphothreonine1 Publication1
Modified residuei315Phosphoserine1 Publication1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ15080
PaxDbiQ15080
PeptideAtlasiQ15080
PRIDEiQ15080
ProteomicsDBi60430
60432 [Q15080-3]

PTM databases

iPTMnetiQ15080
PhosphoSitePlusiQ15080

Expressioni

Tissue specificityi

Expression is restricted to hematopoietic cells.

Gene expression databases

BgeeiENSG00000100365
CleanExiHS_NCF4
ExpressionAtlasiQ15080 baseline and differential
GenevisibleiQ15080 HS

Organism-specific databases

HPAiCAB010146
HPA036156
HPA057975

Interactioni

Subunit structurei

Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. NCF4 interacts primarily with NCF2 to form a complex with NCF1.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ARF guanyl-nucleotide exchange factor activity Source: GO_Central
  • protein dimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi110769, 6 interactors
DIPiDIP-17019N
IntActiQ15080, 5 interactors
MINTiQ15080
STRINGi9606.ENSP00000380334

Structurei

Secondary structure

1339
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 15Combined sources13
Beta strandi21 – 32Combined sources12
Beta strandi34 – 36Combined sources3
Beta strandi38 – 47Combined sources10
Beta strandi52 – 58Combined sources7
Helixi59 – 73Combined sources15
Helixi80 – 82Combined sources3
Helixi98 – 116Combined sources19
Helixi121 – 124Combined sources4
Helixi127 – 133Combined sources7
Helixi137 – 140Combined sources4
Beta strandi174 – 179Combined sources6
Beta strandi184 – 188Combined sources5
Beta strandi196 – 202Combined sources7
Beta strandi204 – 212Combined sources9
Beta strandi215 – 220Combined sources6
Helixi221 – 223Combined sources3
Beta strandi224 – 226Combined sources3
Beta strandi238 – 246Combined sources9
Beta strandi249 – 257Combined sources9
Helixi267 – 278Combined sources12
Beta strandi281 – 288Combined sources8
Beta strandi290 – 292Combined sources3
Beta strandi294 – 296Combined sources3
Helixi300 – 309Combined sources10
Beta strandi324 – 328Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H6HX-ray1.70A2-144[»]
1OEYX-ray2.00J/K/L/M237-339[»]
1W6XX-ray2.00A/B174-228[»]
1W70X-ray1.46A/B174-228[»]
1Z9QNMR-A168-233[»]
2DYBX-ray3.15A/B1-339[»]
ProteinModelPortaliQ15080
SMRiQ15080
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15080

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 140PXPROSITE-ProRule annotationAdd BLAST122
Domaini170 – 229SH3PROSITE-ProRule annotationAdd BLAST60
Domaini237 – 329PB1PROSITE-ProRule annotationAdd BLAST93

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni58 – 60Phosphatidylinositol 3-phosphate binding3
Regioni92 – 94Phosphatidylinositol 3-phosphate binding3

Domaini

The PB1 domain mediates the association with NCF2/p67-PHOX.
The PX domain mediates interaction with membranes enriched in phosphatidylnositol 3-phosphate.

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG4773 Eukaryota
ENOG410YBFF LUCA
GeneTreeiENSGT00510000048561
HOGENOMiHOG000013076
HOVERGENiHBG006452
InParanoidiQ15080
KOiK08012
OMAiLFPWKLH
OrthoDBiEOG091G0CKP
PhylomeDBiQ15080

Family and domain databases

CDDicd06399 PB1_P40, 1 hit
cd06882 PX_p40phox, 1 hit
cd11869 SH3_p40phox, 1 hit
Gene3Di3.30.1520.10, 1 hit
InterProiView protein in InterPro
IPR000919 p40phox
IPR035541 p40phox_SH3
IPR000270 PB1_dom
IPR034853 PB1_P40
IPR001683 Phox
IPR036871 PX_dom_sf
IPR034912 PX_p40phox
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR44898 PTHR44898, 1 hit
PfamiView protein in Pfam
PF00564 PB1, 1 hit
PF00787 PX, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00497 P40PHOX
SMARTiView protein in SMART
SM00666 PB1, 1 hit
SM00312 PX, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF64268 SSF64268, 1 hit
PROSITEiView protein in PROSITE
PS51745 PB1, 1 hit
PS50195 PX, 1 hit
PS50002 SH3, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15080-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAVAQQLRAE SDFEQLPDDV AISANIADIE EKRGFTSHFV FVIEVKTKGG
60 70 80 90 100
SKYLIYRRYR QFHALQSKLE ERFGPDSKSS ALACTLPTLP AKVYVGVKQE
110 120 130 140 150
IAEMRIPALN AYMKSLLSLP VWVLMDEDVR IFFYQSPYDS EQVPQALRRL
160 170 180 190 200
RPRTRKVKSV SPQGNSVDRM AAPRAEALFD FTGNSKLELN FKAGDVIFLL
210 220 230 240 250
SRINKDWLEG TVRGATGIFP LSFVKILKDF PEEDDPTNWL RCYYYEDTIS
260 270 280 290 300
TIKDIAVEED LSSTPLLKDL LELTRREFQR EDIALNYRDA EGDLVRLLSD
310 320 330
EDVALMVRQA RGLPSQKRLF PWKLHITQKD NYRVYNTMP
Length:339
Mass (Da):39,032
Last modified:May 30, 2006 - v2
Checksum:iD82FE9E5BA12890B
GO
Isoform 3 (identifier: Q15080-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     254-339: DIAVEEDLSS...DNYRVYNTMP → SVAWEGGACP...WRKISAALPY

Show »
Length:348
Mass (Da):39,017
Checksum:i0C787E82434C16C6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065949105R → Q in CGD3; the protein remains cytosolic, does not localize to phagosomes or endosomes and is unable to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) in a lipid-binding assay; unable to rescue the NADPH-oxidase defect of NCF4 functionally null cells. 1 PublicationCorresponds to variant dbSNP:rs387906808EnsemblClinVar.1
Natural variantiVAR_009314147L → I2 Publications1
Natural variantiVAR_034136153R → H. Corresponds to variant dbSNP:rs35160112Ensembl.1
Isoform 3 (identifier: Q15080-3)
Natural varianti272L → P. Corresponds to variant dbSNP:rs2075939Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042681254 – 339DIAVE…YNTMP → SVAWEGGACPAFLPSLRPLP LTSPSHGSLSHSKAPSGSQM SHNAVTSHQRPGWPGQPHSP FPHPTPHFQPDASLLQPVTP LGTSRWRKISAALPY in isoform 3. 4 PublicationsAdd BLAST86

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X77094 mRNA Translation: CAA54372.1
U50729
, U50720, U50721, U50722, U50723, U50724, U50725, U50726, U50727, U50728 Genomic DNA Translation: AAB39970.1
AB025220 mRNA Translation: BAA89792.1
AB025219 mRNA Translation: BAA89791.1
CR456528 mRNA Translation: CAG30414.1
BT007346 mRNA Translation: AAP36010.1
AK290924 mRNA Translation: BAF83613.1
DQ314880 Genomic DNA Translation: ABC40739.1
AL008637 Genomic DNA No translation available.
BC002798 mRNA Translation: AAH02798.1
CCDSiCCDS13934.1 [Q15080-1]
CCDS13935.1 [Q15080-3]
PIRiS39768
RefSeqiNP_000622.2, NM_000631.4 [Q15080-1]
NP_038202.2, NM_013416.3 [Q15080-3]
UniGeneiHs.474781

Genome annotation databases

EnsembliENST00000248899; ENSP00000248899; ENSG00000100365 [Q15080-1]
ENST00000397147; ENSP00000380334; ENSG00000100365 [Q15080-3]
GeneIDi4689
KEGGihsa:4689
UCSCiuc003apy.5 human [Q15080-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNCF4_HUMAN
AccessioniPrimary (citable) accession number: Q15080
Secondary accession number(s): A8K4F9
, O60808, Q86U56, Q9BU98, Q9NP45
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2006
Last modified: June 20, 2018
This is version 188 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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