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Protein

Neutrophil cytosol factor 1

Gene

NCF1

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

Functioni

NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).3 Publications

GO - Molecular functioni

  • electron transfer activity Source: UniProtKB
  • phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol binding Source: UniProtKB
  • SH3 domain binding Source: BHF-UCL
  • superoxide-generating NADPH oxidase activator activity Source: GO_Central
  • superoxide-generating NADPH oxidase activity Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: Ensembl
  • cellular defense response Source: ProtInc
  • cellular response to cadmium ion Source: CAFA
  • cellular response to reactive oxygen species Source: CAFA
  • innate immune response Source: BHF-UCL
  • podosome assembly Source: GO_Central
  • positive regulation of epidermal growth factor-activated receptor activity Source: CAFA
  • positive regulation of JNK cascade Source: CAFA
  • positive regulation of p38MAPK cascade Source: CAFA
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: CAFA
  • positive regulation of transcription, DNA-templated Source: CAFA
  • protein targeting to membrane Source: UniProtKB
  • respiratory burst Source: BHF-UCL
  • superoxide anion generation Source: UniProtKB
  • superoxide metabolic process Source: BHF-UCL
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome

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
SIGNORiP14598

Names & Taxonomyi

Protein namesi
Recommended name:
Neutrophil cytosol factor 1
Short name:
NCF-1
Alternative name(s):
47 kDa autosomal chronic granulomatous disease protein
47 kDa neutrophil oxidase factor
NCF-47K
Neutrophil NADPH oxidase factor 1
Nox organizer 2
Nox-organizing protein 2
SH3 and PX domain-containing protein 1A
p47-phox
Gene namesi
Name:NCF1
Synonyms:NOXO2, SH3PXD1A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000158517.13
HGNCiHGNC:7660 NCF1
MIMi608512 gene
neXtProtiNX_P14598

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, Membrane

Pathology & Biotechi

Involvement in diseasei

Granulomatous disease, chronic, cytochrome-b-positive 1, autosomal recessive (CGD1)2 Publications
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:233700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01247642R → Q in CGD1. 1 PublicationCorresponds to variant dbSNP:rs119103270EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi43R → Q: Reduces affinity for membranes enriched in phosphatidylinositol 3,4-bisphosphate. 1 Publication1
Mutagenesisi90R → A: Reduces affinity for membranes enriched in phosphatidylinositol 3,4-bisphosphate. 1
Mutagenesisi263W → R: Abolishes autoinhibition and promotes phospholipid binding. 1 Publication1
Mutagenesisi303S → E: Abolishes autoinhibition and promotes phospholipid binding; when associated with E-304; E-328; E-359 and E-370. 1 Publication1
Mutagenesisi304S → E: Abolishes autoinhibition and promotes phospholipid binding; when associated with E-303; E-328; E-359 and E-370. 1 Publication1
Mutagenesisi328S → E: Abolishes autoinhibition and promotes phospholipid binding; when associated with E-303; E-304; E-359 and E-370. 1 Publication1
Mutagenesisi359S → E: Abolishes autoinhibition and promotes phospholipid binding; when associated with E-303; E-304; E-328 and E-370. 1 Publication1
Mutagenesisi370S → E: Abolishes autoinhibition and promotes phospholipid binding; when associated with E-303; E-304; E-328 and E-359. 1 Publication1

Keywords - Diseasei

Chronic granulomatous disease, Disease mutation

Organism-specific databases

DisGeNETi653361
GeneReviewsiNCF1
MalaCardsiNCF1
MIMi233700 phenotype
OpenTargetsiENSG00000158517
Orphaneti379 Chronic granulomatous disease
PharmGKBiPA31463

Chemistry databases

DrugBankiDB00514 Dextromethorphan

Polymorphism and mutation databases

DMDMi325511390

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000967621 – 390Neutrophil cytosol factor 1Add BLAST390

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei303Phosphoserine1 Publication1
Modified residuei304Phosphoserine1 Publication1
Modified residuei320Phosphoserine1 Publication1
Modified residuei328Phosphoserine1 Publication1
Modified residuei345Phosphoserine1 Publication1
Modified residuei348Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated by PRKCD; phosphorylation induces activation of NCF1 and NADPH oxidase activity.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP14598
PaxDbiP14598
PeptideAtlasiP14598
PRIDEiP14598
ProteomicsDBi53060
53061 [P14598-2]

PTM databases

iPTMnetiP14598
PhosphoSitePlusiP14598

Expressioni

Tissue specificityi

Detected in peripheral blood monocytes and neutrophils (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000158517
ExpressionAtlasiP14598 baseline and differential
GenevisibleiP14598 HS

Organism-specific databases

HPAiCAB004524
HPA047836
HPA052095

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. Interacts (via C-terminus) with NCF2 (via the C-terminal SH3 domain). Interacts with NCF4. Interacts with CYBB. Interacts (via the second SH3 domain) with CYBA. Interacts with NOXA1. Interacts with ADAM15. Interacts with TRAF4. Interacts with FASLG. Interacts with PARK7 (via C-terminus); the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (By similarity).By similarity11 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • SH3 domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi575724, 39 interactors
DIPiDIP-126N
ELMiP14598
IntActiP14598, 17 interactors
MINTiP14598
STRINGi9606.ENSP00000289473

Chemistry databases

BindingDBiP14598

Structurei

Secondary structure

1390
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 17Combined sources12
Beta strandi19 – 21Combined sources3
Beta strandi23 – 32Combined sources10
Beta strandi37 – 42Combined sources6
Helixi44 – 57Combined sources14
Turni59 – 63Combined sources5
Helixi67 – 69Combined sources3
Helixi78 – 80Combined sources3
Helixi84 – 101Combined sources18
Helixi106 – 109Combined sources4
Helixi112 – 118Combined sources7
Helixi122 – 125Combined sources4
Beta strandi137 – 140Combined sources4
Beta strandi153 – 155Combined sources3
Beta strandi159 – 162Combined sources4
Beta strandi171 – 174Combined sources4
Beta strandi182 – 187Combined sources6
Beta strandi195 – 198Combined sources4
Beta strandi202 – 206Combined sources5
Helixi207 – 209Combined sources3
Beta strandi210 – 214Combined sources5
Beta strandi229 – 235Combined sources7
Beta strandi241 – 244Combined sources4
Beta strandi252 – 257Combined sources6
Beta strandi262 – 268Combined sources7
Beta strandi271 – 276Combined sources6
Helixi277 – 279Combined sources3
Beta strandi280 – 282Combined sources3
Helixi287 – 292Combined sources6
Helixi302 – 304Combined sources3
Helixi321 – 328Combined sources8
Helixi371 – 376Combined sources6
Helixi380 – 385Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GD5NMR-A1-128[»]
1K4UNMR-P359-390[»]
1KQ6X-ray1.18A1-141[»]
1NG2X-ray1.70A156-340[»]
1O7KX-ray2.00A/B/C1-123[»]
1OV3X-ray1.80A/B156-285[»]
1UECX-ray1.82A151-340[»]
1W70X-ray1.46C/D360-372[»]
1WLPNMR-B151-286[»]
ProteinModelPortaliP14598
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14598

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 125PXPROSITE-ProRule annotationAdd BLAST122
Domaini156 – 215SH3 1PROSITE-ProRule annotationAdd BLAST60
Domaini226 – 285SH3 2PROSITE-ProRule annotationAdd BLAST60

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi211 – 254Asp/Glu-rich (highly acidic)Add BLAST44
Compositional biasi292 – 390Arg/Lys-rich (highly basic)Add BLAST99

Domaini

The PX domain mediates interaction with phosphatidylinositol 3,4-bisphosphate and other anionic phospholipids. In the autoinhibited, unphosphorylated state an intramolecular interaction with the C-terminal SH3 domain precludes phospholipid binding and interaction with CYBA. Phosphorylation disrupts the autoinhibited state.2 Publications

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiENOG410IRR3 Eukaryota
ENOG410YYZE LUCA
GeneTreeiENSGT00530000063010
HOVERGENiHBG002055
InParanoidiP14598
KOiK08011
OrthoDBiEOG091G0CBF
PhylomeDBiP14598
TreeFamiTF329347

Family and domain databases

CDDicd06887 PX_p47phox, 1 hit
cd12021 SH3_p47phox_1, 1 hit
cd12022 SH3_p47phox_2, 1 hit
Gene3Di3.30.1520.10, 1 hit
InterProiView protein in InterPro
IPR015039 NADPH_oxidase_p47Phox_C
IPR035756 NCF1_SH3_1
IPR035757 NCF1_SH3_2
IPR032136 NECFESHC
IPR001655 P47PHOX
IPR001683 Phox
IPR036871 PX_dom_sf
IPR034909 PX_p47phox
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR15706:SF6 PTHR15706:SF6, 1 hit
PfamiView protein in Pfam
PF16621 NECFESHC, 1 hit
PF08944 p47_phox_C, 1 hit
PF00787 PX, 1 hit
PF00018 SH3_1, 2 hits
PRINTSiPR00498 P47PHOX
SMARTiView protein in SMART
SM00312 PX, 1 hit
SM00326 SH3, 2 hits
SUPFAMiSSF50044 SSF50044, 2 hits
SSF64268 SSF64268, 1 hit
PROSITEiView protein in PROSITE
PS50195 PX, 1 hit
PS50002 SH3, 2 hits

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P14598-1) [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
MGDTFIRHIA LLGFEKRFVP SQHYVYMFLV KWQDLSEKVV YRRFTEIYEF
60 70 80 90 100
HKTLKEMFPI EAGAINPENR IIPHLPAPKW FDGQRAAENR QGTLTEYCST
110 120 130 140 150
LMSLPTKISR CPHLLDFFKV RPDDLKLPTD NQTKKPETYL MPKDGKSTAT
160 170 180 190 200
DITGPIILQT YRAIANYEKT SGSEMALSTG DVVEVVEKSE SGWWFCQMKA
210 220 230 240 250
KRGWIPASFL EPLDSPDETE DPEPNYAGEP YVAIKAYTAV EGDEVSLLEG
260 270 280 290 300
EAVEVIHKLL DGWWVIRKDD VTGYFPSMYL QKSGQDVSQA QRQIKRGAPP
310 320 330 340 350
RRSSIRNAHS IHQRSRKRLS QDAYRRNSVR FLQQRRRQAR PGPQSPGSPL
360 370 380 390
EEERQTQRSK PQPAVPPRPS ADLILNRCSE STKRKLASAV
Length:390
Mass (Da):44,682
Last modified:April 25, 2018 - v4
Checksum:i3D91EDC99A1B6417
GO
Isoform 2 (identifier: P14598-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     193-193: W → QTSHLTGLLP...LDGYGTVCSL
     194-390: Missing.

Note: Due to intron retention.
Show »
Length:278
Mass (Da):30,811
Checksum:iEF0F962E9881E8A0
GO

Sequence cautioni

The sequence BAF84783 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG54596 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti200A → T in AAK19516 (PubMed:11740866).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01247642R → Q in CGD1. 1 PublicationCorresponds to variant dbSNP:rs119103270EnsemblClinVar.1
Natural variantiVAR_01473590R → H Polymorphism; may influence susceptibility to systemic lupus erythematosus. 1 PublicationCorresponds to variant dbSNP:rs13447Ensembl.1
Natural variantiVAR_01847999S → G2 PublicationsCorresponds to variant dbSNP:rs10614Ensembl.1
Natural variantiVAR_012477160T → S2 Publications1
Natural variantiVAR_012478166N → D4 PublicationsCorresponds to variant dbSNP:rs782555266Ensembl.1
Natural variantiVAR_018476258K → E1 Publication1
Natural variantiVAR_012479262G → S1 Publication1
Natural variantiVAR_012480308A → V2 PublicationsCorresponds to variant dbSNP:rs13739Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035032193W → QTSHLTGLLPLVLRNPQPQA PCQGSGSLAPGRTPALLGAL NVLPTLWVAFCLSVHPVVAV GICAWQAGAGHVCVFCLDGY GTVCSL in isoform 2. 1 Publication1
Alternative sequenceiVSP_035033194 – 390Missing in isoform 2. 1 PublicationAdd BLAST197

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25665 mRNA Translation: AAA57209.1
M55067 mRNA Translation: AAA59901.1
AH005796 Genomic DNA Translation: AAB95193.1
AF184614 Genomic DNA Translation: AAF34737.1
AF330625 mRNA Translation: AAK19516.1
AF330626 mRNA Translation: AAK19517.1
AF330627 mRNA Translation: AAK19518.1
AK127905 mRNA Translation: BAG54596.1 Different initiation.
AK292094 mRNA Translation: BAF84783.1 Different initiation.
AK223217 mRNA Translation: BAD96937.1
AC004883 Genomic DNA No translation available.
AC083884 Genomic DNA Translation: AAS07465.1
AC124781 Genomic DNA No translation available.
BC002816 mRNA Translation: AAH02816.1
BC065731 mRNA Translation: AAH65731.1
U25793 mRNA Translation: AAA93232.1
DQ314878 Genomic DNA Translation: ABC40737.1
CCDSiCCDS34657.1 [P14598-1]
PIRiA35926 A39249
RefSeqiNP_000256.4, NM_000265.5 [P14598-1]
UniGeneiHs.647047
Hs.648940
Hs.655201

Genome annotation databases

EnsembliENST00000289473; ENSP00000289473; ENSG00000158517 [P14598-1]
GeneIDi653361
KEGGihsa:653361
UCSCiuc003ubb.5 human [P14598-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNCF1_HUMAN
AccessioniPrimary (citable) accession number: P14598
Secondary accession number(s): A6NEH2
, A8K7S9, O43842, Q2PP07, Q53FR5, Q9BU90, Q9BXI7, Q9BXI8, Q9UDV9, Q9UMU2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 25, 2018
Last modified: June 20, 2018
This is version 219 of the entry and version 4 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, Reference proteome

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