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Protein

Neutrophil cytosol factor 4

Gene

NCF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • phosphatidylinositol-3-phosphate binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB
  • superoxide-generating NADPH oxidase activator activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100365-MONOMER.
ReactomeiR-HSA-1222556. ROS, RNS production in response to bacteria.
R-HSA-1236973. Cross-presentation of particulate exogenous antigens (phagosomes).
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

HGNCiHGNC:7662. NCF4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • endosome membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • NADPH oxidase complex Source: UniProtKB
  • phagolysosome Source: Reactome
Complete GO annotation...

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 rs387906808dbSNPEnsembl.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.
MalaCardsiNCF4.
MIMi613960. phenotype.
OpenTargetsiENSG00000100365.
ENSG00000275990.
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.

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.

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

WithEntry#Exp.IntActNotes
NCF1P145982EBI-1036870,EBI-395044
NCF2P198785EBI-1036870,EBI-489611

GO - Molecular functioni

  • protein dimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi110769. 6 interactors.
DIPiDIP-17019N.
IntActiQ15080. 5 interactors.
MINTiMINT-206126.
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.

Sequence similaritiesi

Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG4773. Eukaryota.
ENOG410YBFF. LUCA.
GeneTreeiENSGT00510000048561.
HOGENOMiHOG000013076.
HOVERGENiHBG006452.
InParanoidiQ15080.
KOiK08012.
OMAiRITIMRC.
OrthoDBiEOG091G0CKP.
PhylomeDBiQ15080.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR000919. NCF_P40.
IPR000270. PB1_dom.
IPR001683. Phox.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00787. PX. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00497. P40PHOX.
SMARTiSM00666. PB1. 1 hit.
SM00312. PX. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50195. PX. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 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 2 (identifier: Q15080-2) [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):39,001
Checksum:i49393E82583B7ADD
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 rs387906808dbSNPEnsembl.1
Natural variantiVAR_009314147L → I.2 Publications1
Natural variantiVAR_034136153R → H.Corresponds to variant rs35160112dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004328254 – 339DIAVE…YNTMP → SVAWEGGACPAFLPSLRPPP LTSPSHGSLSHSKAPSGSQM SHNAVTSHQRPGWPGQPHSP FPHPTPHFQPDASLLQPVTP LGTSRWRKISAALPY in isoform 2. 3 PublicationsAdd BLAST86
Alternative sequenceiVSP_042681254 – 339DIAVE…YNTMP → SVAWEGGACPAFLPSLRPLP LTSPSHGSLSHSKAPSGSQM SHNAVTSHQRPGWPGQPHSP FPHPTPHFQPDASLLQPVTP LGTSRWRKISAALPY in isoform 3. 1 PublicationAdd 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. Translation: CAQ10741.1.
AL008637 Genomic DNA. Translation: CAA15486.1.
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]
ENST00000614157; ENSP00000483977; ENSG00000275990. [Q15080-2]
ENST00000625504; ENSP00000486471; ENSG00000275990. [Q15080-2]
GeneIDi4689.
KEGGihsa:4689.
UCSCiuc003apy.5. human. [Q15080-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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. Translation: CAQ10741.1.
AL008637 Genomic DNA. Translation: CAA15486.1.
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.

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...

Protein-protein interaction databases

BioGridi110769. 6 interactors.
DIPiDIP-17019N.
IntActiQ15080. 5 interactors.
MINTiMINT-206126.
STRINGi9606.ENSP00000380334.

Chemistry databases

DrugBankiDB00514. Dextromethorphan.

PTM databases

iPTMnetiQ15080.
PhosphoSitePlusiQ15080.

Polymorphism and mutation databases

BioMutaiNCF4.
DMDMi108884815.

Proteomic databases

MaxQBiQ15080.
PaxDbiQ15080.
PeptideAtlasiQ15080.
PRIDEiQ15080.

Protocols and materials databases

DNASUi4689.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000248899; ENSP00000248899; ENSG00000100365. [Q15080-1]
ENST00000397147; ENSP00000380334; ENSG00000100365. [Q15080-3]
ENST00000614157; ENSP00000483977; ENSG00000275990. [Q15080-2]
ENST00000625504; ENSP00000486471; ENSG00000275990. [Q15080-2]
GeneIDi4689.
KEGGihsa:4689.
UCSCiuc003apy.5. human. [Q15080-1]

Organism-specific databases

CTDi4689.
DisGeNETi4689.
GeneCardsiNCF4.
GeneReviewsiNCF4.
HGNCiHGNC:7662. NCF4.
HPAiCAB010146.
HPA036156.
MalaCardsiNCF4.
MIMi601488. gene.
613960. phenotype.
neXtProtiNX_Q15080.
OpenTargetsiENSG00000100365.
ENSG00000275990.
Orphaneti379. Chronic granulomatous disease.
206. Crohn disease.
PharmGKBiPA31465.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4773. Eukaryota.
ENOG410YBFF. LUCA.
GeneTreeiENSGT00510000048561.
HOGENOMiHOG000013076.
HOVERGENiHBG006452.
InParanoidiQ15080.
KOiK08012.
OMAiRITIMRC.
OrthoDBiEOG091G0CKP.
PhylomeDBiQ15080.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100365-MONOMER.
ReactomeiR-HSA-1222556. ROS, RNS production in response to bacteria.
R-HSA-1236973. Cross-presentation of particulate exogenous antigens (phagosomes).
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-5668599. RHO GTPases Activate NADPH Oxidases.
SIGNORiQ15080.

Miscellaneous databases

ChiTaRSiNCF4. human.
EvolutionaryTraceiQ15080.
GenomeRNAii4689.
PROiQ15080.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100365.
CleanExiHS_NCF4.
ExpressionAtlasiQ15080. baseline and differential.
GenevisibleiQ15080. HS.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR000919. NCF_P40.
IPR000270. PB1_dom.
IPR001683. Phox.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00787. PX. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00497. P40PHOX.
SMARTiSM00666. PB1. 1 hit.
SM00312. PX. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50195. PX. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNCF4_HUMAN
AccessioniPrimary (citable) accession number: Q15080
Secondary accession number(s): A8K4F9
, O60808, Q86U56, Q9BU98, Q9NP45
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2006
Last modified: November 2, 2016
This is version 177 of the entry and version 2 of the sequence. [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
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.