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Protein

Neutrophil cytosol factor 2

Gene

NCF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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).1 Publication

GO - Molecular functioni

  • electron carrier activity Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • Rac GTPase binding Source: Ensembl
  • superoxide-generating NADPH oxidase activator activity Source: InterPro
  • superoxide-generating NADPH oxidase activity Source: Ensembl

GO - Biological processi

  • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
  • cell redox homeostasis Source: Reactome
  • cellular defense response Source: ProtInc
  • cellular response to oxidative stress Source: Reactome
  • innate immune response Source: BHF-UCL
  • phagocytosis Source: InterPro
  • respiratory burst Source: BHF-UCL
  • superoxide anion generation Source: BHF-UCL
  • superoxide metabolic process Source: BHF-UCL
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome

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.
SIGNORiP19878.

Names & Taxonomyi

Protein namesi
Recommended name:
Neutrophil cytosol factor 2
Short name:
NCF-2
Alternative name(s):
67 kDa neutrophil oxidase factor
NADPH oxidase activator 2
Neutrophil NADPH oxidase factor 2
p67-phox
Gene namesi
Name:NCF2
Synonyms:NOXA2, P67PHOX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:7661. NCF2.

Subcellular locationi

GO - Cellular componenti

  • acrosomal vesicle Source: Ensembl
  • cytosol Source: HPA
  • NADPH oxidase complex Source: BHF-UCL
  • nucleolus Source: HPA
  • phagolysosome Source: Reactome

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Granulomatous disease, chronic, cytochrome-b-positive 2, autosomal recessive (CGD2)10 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:233710
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01738719 – 21Missing in CGD2. 1 Publication3
Natural variantiVAR_06500242N → S in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854514Ensembl.1
Natural variantiVAR_06500344G → C in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854510Ensembl.1
Natural variantiVAR_06500444G → R in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs137854510Ensembl.1
Natural variantiVAR_06500558Missing in CGD2. 1 Publication1
Natural variantiVAR_01738877R → Q in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs119103275Ensembl.1
Natural variantiVAR_00890478G → E in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854519Ensembl.1
Natural variantiVAR_06500793D → E in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs137854507Ensembl.1
Natural variantiVAR_06500896Missing in CGD2. 1 Publication1
Natural variantiVAR_065009102R → P in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854515Ensembl.1
Natural variantiVAR_065010108D → V in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854509Ensembl.1
Natural variantiVAR_017389128A → V in CGD2. 1 PublicationCorresponds to variant dbSNP:rs119103274Ensembl.1
Natural variantiVAR_065011137W → R in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854516Ensembl.1
Natural variantiVAR_065012140A → D in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854520Ensembl.1
Natural variantiVAR_017390160 – 161DK → EV in CGD2. 2
Natural variantiVAR_065013169Q → E in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854517Ensembl.1
Natural variantiVAR_065014184R → P in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854518Ensembl.1
Natural variantiVAR_065015196Missing in CGD2. 1 Publication1
Natural variantiVAR_065016202A → V in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs137854508Ensembl.1

Keywords - Diseasei

Chronic granulomatous disease, Disease mutation

Organism-specific databases

DisGeNETi4688.
GeneReviewsiNCF2.
MalaCardsiNCF2.
MIMi233710. phenotype.
OpenTargetsiENSG00000116701.
Orphaneti379. Chronic granulomatous disease.
PharmGKBiPA31464.

Chemistry databases

DrugBankiDB00514. Dextromethorphan.

Polymorphism and mutation databases

BioMutaiNCF2.
DMDMi1346669.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001063611 – 526Neutrophil cytosol factor 2Add BLAST526

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei233PhosphothreonineBy similarity1
Modified residuei399PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP19878.
MaxQBiP19878.
PaxDbiP19878.
PeptideAtlasiP19878.
PRIDEiP19878.

PTM databases

iPTMnetiP19878.
PhosphoSitePlusiP19878.

Expressioni

Gene expression databases

BgeeiENSG00000116701.
CleanExiHS_NCF2.
ExpressionAtlasiP19878. baseline and differential.
GenevisibleiP19878. HS.

Organism-specific databases

HPAiCAB022160.
HPA002327.
HPA006040.

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 with NCF4. Interacts (via the C-terminal SH3 domain) with NCF1 (via C-terminus). Interacts with SYTL1 and RAC1. May interact with NOXO1. Interacts with S100A8 and calprotectin (S100A8/9).8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB
  • Rac GTPase binding Source: Ensembl

Protein-protein interaction databases

BioGridi110768. 24 interactors.
DIPiDIP-76N.
IntActiP19878. 13 interactors.
MINTiMINT-151560.
STRINGi9606.ENSP00000356505.

Structurei

Secondary structure

1526
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 18Combined sources16
Helixi22 – 30Combined sources9
Beta strandi32 – 34Combined sources3
Helixi37 – 49Combined sources13
Helixi53 – 66Combined sources14
Helixi71 – 83Combined sources13
Helixi87 – 99Combined sources13
Turni100 – 103Combined sources4
Beta strandi105 – 108Combined sources4
Helixi110 – 112Combined sources3
Beta strandi117 – 119Combined sources3
Helixi120 – 133Combined sources14
Helixi137 – 148Combined sources12
Helixi154 – 157Combined sources4
Helixi158 – 167Combined sources10
Helixi187 – 191Combined sources5
Beta strandi243 – 247Combined sources5
Beta strandi255 – 258Combined sources4
Beta strandi266 – 269Combined sources4
Beta strandi274 – 276Combined sources3
Beta strandi278 – 282Combined sources5
Beta strandi285 – 289Combined sources5
Beta strandi294 – 296Combined sources3
Beta strandi352 – 366Combined sources15
Helixi372 – 382Combined sources11
Helixi387 – 389Combined sources3
Beta strandi392 – 394Combined sources3
Turni407 – 409Combined sources3
Helixi410 – 414Combined sources5
Beta strandi421 – 426Combined sources6
Beta strandi460 – 463Combined sources4
Beta strandi472 – 475Combined sources4
Beta strandi483 – 493Combined sources11
Beta strandi495 – 498Combined sources4
Beta strandi503 – 506Combined sources4
Helixi508 – 510Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1E96X-ray2.40B1-203[»]
1HH8X-ray1.80A1-213[»]
1K4UNMR-S455-516[»]
1OEYX-ray2.00A/B/C/D352-429[»]
1WM5X-ray1.95A1-203[»]
2DMONMR-A243-297[»]
ProteinModelPortaliP19878.
SMRiP19878.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19878.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati37 – 70TPR 1Add BLAST34
Repeati71 – 104TPR 2Add BLAST34
Repeati121 – 154TPR 3Add BLAST34
Domaini240 – 299SH3 1PROSITE-ProRule annotationAdd BLAST60
Domaini351 – 429PB1PROSITE-ProRule annotationAdd BLAST79
Domaini457 – 516SH3 2PROSITE-ProRule annotationAdd BLAST60

Domaini

The OPR/PB1 domain mediates the association with NCF4/p40-PHOX.1 Publication

Sequence similaritiesi

Belongs to the NCF2/NOXA1 family.Curated

Keywords - Domaini

Repeat, SH3 domain, TPR repeat

Phylogenomic databases

eggNOGiKOG4225. Eukaryota.
ENOG41110AD. LUCA.
GeneTreeiENSGT00530000063843.
HOGENOMiHOG000237312.
HOVERGENiHBG001521.
InParanoidiP19878.
KOiK08010.
OMAiCNYLEPV.
OrthoDBiEOG091G04T7.
PhylomeDBiP19878.
TreeFamiTF329087.

Family and domain databases

CDDicd06406. PB1_P67. 1 hit.
cd11871. SH3_p67phox_N. 1 hit.
Gene3Di1.25.40.10. 3 hits.
InterProiView protein in InterPro
IPR034889. P67-PHOX.
IPR035546. p67phox_SH3_1.
IPR000270. PB1_dom.
IPR034885. PB1_P67.
IPR001452. SH3_domain.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
PANTHERiPTHR15175:SF7. PTHR15175:SF7. 1 hit.
PfamiView protein in Pfam
PF00564. PB1. 1 hit.
PF00018. SH3_1. 2 hits.
PF13181. TPR_8. 2 hits.
PRINTSiPR00452. SH3DOMAIN.
SMARTiView protein in SMART
SM00666. PB1. 1 hit.
SM00326. SH3. 2 hits.
SM00028. TPR. 3 hits.
SUPFAMiSSF48452. SSF48452. 1 hit.
SSF50044. SSF50044. 2 hits.
PROSITEiView protein in PROSITE
PS51745. PB1. 1 hit.
PS50002. SH3. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19878-1) [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
MSLVEAISLW NEGVLAADKK DWKGALDAFS AVQDPHSRIC FNIGCMYTIL
60 70 80 90 100
KNMTEAEKAF TRSINRDKHL AVAYFQRGML YYQTEKYDLA IKDLKEALIQ
110 120 130 140 150
LRGNQLIDYK ILGLQFKLFA CEVLYNIAFM YAKKEEWKKA EEQLALATSM
160 170 180 190 200
KSEPRHSKID KAMECVWKQK LYEPVVIPVG KLFRPNERQV AQLAKKDYLG
210 220 230 240 250
KATVVASVVD QDSFSGFAPL QPQAAEPPPR PKTPEIFRAL EGEAHRVLFG
260 270 280 290 300
FVPETKEELQ VMPGNIVFVL KKGNDNWATV MFNGQKGLVP CNYLEPVELR
310 320 330 340 350
IHPQQQPQEE SSPQSDIPAP PSSKAPGRPQ LSPGQKQKEE PKEVKLSVPM
360 370 380 390 400
PYTLKVHYKY TVVMKTQPGL PYSQVRDMVS KKLELRLEHT KLSYRPRDSN
410 420 430 440 450
ELVPLSEDSM KDAWGQVKNY CLTLWCENTV GDQGFPDEPK ESEKADANNQ
460 470 480 490 500
TTEPQLKKGS QVEALFSYEA TQPEDLEFQE GDIILVLSKV NEEWLEGECK
510 520
GKVGIFPKVF VEDCATTDLE STRREV
Length:526
Mass (Da):59,762
Last modified:February 1, 1996 - v2
Checksum:iEC136766E1915376
GO
Isoform 2 (identifier: P19878-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     123-203: Missing.
     502-526: Missing.

Note: No experimental confirmation available.
Show »
Length:420
Mass (Da):47,515
Checksum:iD45BFF944F0CE53C
GO
Isoform 3 (identifier: P19878-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     123-167: Missing.

Note: No experimental confirmation available.
Show »
Length:481
Mass (Da):54,446
Checksum:i4A15D34EA01887D6
GO
Isoform 4 (identifier: P19878-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     123-203: Missing.

Note: No experimental confirmation available.
Show »
Length:445
Mass (Da):50,337
Checksum:i88E274CACEDFFBC7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01738719 – 21Missing in CGD2. 1 Publication3
Natural variantiVAR_06500242N → S in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854514Ensembl.1
Natural variantiVAR_06500344G → C in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854510Ensembl.1
Natural variantiVAR_06500444G → R in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs137854510Ensembl.1
Natural variantiVAR_06500558Missing in CGD2. 1 Publication1
Natural variantiVAR_01738877R → Q in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs119103275Ensembl.1
Natural variantiVAR_00890478G → E in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854519Ensembl.1
Natural variantiVAR_06500679M → V1 PublicationCorresponds to variant dbSNP:rs137854512Ensembl.1
Natural variantiVAR_06500793D → E in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs137854507Ensembl.1
Natural variantiVAR_06500896Missing in CGD2. 1 Publication1
Natural variantiVAR_065009102R → P in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854515Ensembl.1
Natural variantiVAR_065010108D → V in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854509Ensembl.1
Natural variantiVAR_017389128A → V in CGD2. 1 PublicationCorresponds to variant dbSNP:rs119103274Ensembl.1
Natural variantiVAR_065011137W → R in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854516Ensembl.1
Natural variantiVAR_065012140A → D in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854520Ensembl.1
Natural variantiVAR_017390160 – 161DK → EV in CGD2. 2
Natural variantiVAR_065013169Q → E in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854517Ensembl.1
Natural variantiVAR_018477181K → R7 PublicationsCorresponds to variant dbSNP:rs2274064Ensembl.1
Natural variantiVAR_065014184R → P in CGD2. 1 PublicationCorresponds to variant dbSNP:rs137854518Ensembl.1
Natural variantiVAR_065015196Missing in CGD2. 1 Publication1
Natural variantiVAR_065016202A → V in CGD2. 2 PublicationsCorresponds to variant dbSNP:rs137854508Ensembl.1
Natural variantiVAR_034129279T → M. Corresponds to variant dbSNP:rs13306581Ensembl.1
Natural variantiVAR_034130297V → A. Corresponds to variant dbSNP:rs35937854Ensembl.1
Natural variantiVAR_018478328R → K2 PublicationsCorresponds to variant dbSNP:rs137854511Ensembl.1
Natural variantiVAR_065017369G → R1 PublicationCorresponds to variant dbSNP:rs137854513Ensembl.1
Natural variantiVAR_052620389H → Q4 PublicationsCorresponds to variant dbSNP:rs17849502Ensembl.1
Natural variantiVAR_008905395R → W Impairs interaction with NCF4. 2 PublicationsCorresponds to variant dbSNP:rs13306575Ensembl.1
Natural variantiVAR_052621419N → I3 PublicationsCorresponds to variant dbSNP:rs35012521Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045259123 – 203Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_045260123 – 167Missing in isoform 3. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_045261502 – 526Missing in isoform 2. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32011 mRNA. Translation: AAA36379.1.
U00788
, U00776, U00777, U00778, U00779, U00780, U00781, U00782, U00783, U00784, U00785, U00786, U00787 Genomic DNA. Translation: AAB60320.1.
AF527950 mRNA. Translation: AAM89263.1.
BT007439 mRNA. Translation: AAP36107.1.
AK296672 mRNA. Translation: BAG59269.1.
AK298713 mRNA. Translation: BAG60869.1.
AK312666 mRNA. Translation: BAG35548.1.
DQ314879 Genomic DNA. Translation: ABC40738.1.
AL137800 Genomic DNA. Translation: CAC19686.1.
CH471067 Genomic DNA. Translation: EAW91160.1.
BC001606 mRNA. Translation: AAH01606.1.
CCDSiCCDS1356.1. [P19878-1]
CCDS53446.1. [P19878-4]
CCDS53447.1. [P19878-3]
PIRiA34855.
RefSeqiNP_000424.2. NM_000433.3. [P19878-1]
NP_001121123.1. NM_001127651.2. [P19878-1]
NP_001177718.1. NM_001190789.1. [P19878-4]
NP_001177723.1. NM_001190794.1. [P19878-3]
XP_011507882.1. XM_011509580.1. [P19878-1]
XP_011507883.1. XM_011509581.1. [P19878-1]
UniGeneiHs.587558.

Genome annotation databases

EnsembliENST00000367535; ENSP00000356505; ENSG00000116701. [P19878-1]
ENST00000367536; ENSP00000356506; ENSG00000116701. [P19878-1]
ENST00000413720; ENSP00000399294; ENSG00000116701. [P19878-3]
ENST00000418089; ENSP00000407217; ENSG00000116701. [P19878-4]
GeneIDi4688.
KEGGihsa:4688.
UCSCiuc001gqj.5. human. [P19878-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNCF2_HUMAN
AccessioniPrimary (citable) accession number: P19878
Secondary accession number(s): B2R6Q1
, B4DKQ7, B4DQA7, E9PHJ2, E9PHX3, Q2PP06, Q8NFC7, Q9BV51
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1996
Last modified: August 30, 2017
This is version 202 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, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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