NCF4_HUMAN
ID NCF4_HUMAN Reviewed; 339 AA.
AC Q15080; A8K4F9; O60808; Q86U56; Q9BU98; Q9NP45;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Neutrophil cytosol factor 4;
DE Short=NCF-4;
DE AltName: Full=Neutrophil NADPH oxidase factor 4;
DE AltName: Full=SH3 and PX domain-containing protein 4;
DE AltName: Full=p40-phox;
DE Short=p40phox;
GN Name=NCF4; Synonyms=SH3PXD4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, VARIANT ILE-147, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8280052; DOI=10.1042/bj2960557;
RA Wientjes F.B., Hsuan J.J., Totty N.F., Segal A.W.;
RT "p40phox, a third cytosolic component of the activation complex of the
RT NADPH oxidase to contain src homology 3 domains.";
RL Biochem. J. 296:557-561(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-147.
RX PubMed=8839867;
RA Zhan S., Vazquez N., Zhan S., Wientjes F.B., Budarf M.L., Schrock E.,
RA Ried T., Green E.D., Chanock S.J.;
RT "Genomic structure, chromosomal localization, start of transcription, and
RT tissue expression of the human p40-phox, a new component of the
RT nicotinamide adenine dinucleotide phosphate-oxidase complex.";
RL Blood 88:2714-2721(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=10437784; DOI=10.1016/s0014-5793(99)00905-9;
RA Hasebe T., Someya A., Nagaoka I.;
RT "Identification of a splice variant mRNA of p40phox, an NADPH oxidase
RT component of phagocytes.";
RL FEBS Lett. 455:257-261(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PHOSPHORYLATION AT THR-154 AND SER-315, AND MUTAGENESIS OF THR-154;
RP THR-211; THR-251; THR-274; SER-315 AND THR-327.
RX PubMed=9804763; DOI=10.1074/jbc.273.46.30097;
RA Bouin A.-P., Grandvaux N., Vignais P.V., Fuchs A.;
RT "p40(phox) is phosphorylated on threonine 154 and serine 315 during
RT activation of the phagocyte NADPH oxidase. Implication of a protein kinase
RT c-type kinase in the phosphorylation process.";
RL J. Biol. Chem. 273:30097-30103(1998).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2-144 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3-PHOSPHATE, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS
RP OF ARG-58; ARG-60; LYS-92; TYR-94 AND ARG-105, AND LIPID-BINDING.
RX PubMed=11684018; DOI=10.1016/s1097-2765(01)00372-0;
RA Bravo J., Karathanassis D., Pacold C.M., Pacold M.E., Ellson C.D.,
RA Anderson K.E., Butler P.J.G., Lavenir I., Perisic O., Hawkins P.T.,
RA Stephens L., Williams R.L.;
RT "The crystal structure of the PX domain from p40(phox) bound to
RT phosphatidylinositol 3-phosphate.";
RL Mol. Cell 8:829-839(2001).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 237-339 IN COMPLEX WITH NCF2, AND
RP INTERACTION WITH NCF2.
RX PubMed=12887891; DOI=10.1016/s1097-2765(03)00246-6;
RA Wilson M.I., Gill D.J., Perisic O., Quinn M.T., Williams R.L.;
RT "PB1 domain-mediated heterodimerization in NADPH oxidase and signaling
RT complexes of atypical protein kinase C with Par6 and p62.";
RL Mol. Cell 12:39-50(2003).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 174-228 IN COMPLEX WITH NCF1, AND
RP INTERACTION WITH NCF1.
RX PubMed=15657040; DOI=10.1074/jbc.m412897200;
RA Massenet C., Chenavas S., Cohen-Addad C., Dagher M.-C., Brandolin G.,
RA Pebay-Peyroula E., Fieschi F.;
RT "Effects of p47phox C terminus phosphorylations on binding interactions
RT with p40phox and p67phox. Structural and functional comparison of p40phox
RT and p67phox SH3 domains.";
RL J. Biol. Chem. 280:13752-13761(2005).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS), AND DOMAIN OPR/PB1.
RX PubMed=17290225; DOI=10.1038/sj.emboj.7601561;
RA Honbou K., Minakami R., Yuzawa S., Takeya R., Suzuki N.N., Kamakura S.,
RA Sumimoto H., Inagaki F.;
RT "Full-length p40phox structure suggests a basis for regulation mechanism of
RT its membrane binding.";
RL EMBO J. 26:1176-1186(2007).
RN [15]
RP VARIANT CGD3 GLN-105, AND CHARACTERIZATION OF VARIANT CGD3 GLN-105.
RX PubMed=19692703; DOI=10.1182/blood-2009-07-231498;
RA Matute J.D., Arias A.A., Wright N.A., Wrobel I., Waterhouse C.C., Li X.J.,
RA Marchal C.C., Stull N.D., Lewis D.B., Steele M., Kellner J.D., Yu W.,
RA Meroueh S.O., Nauseef W.M., Dinauer M.C.;
RT "A new genetic subgroup of chronic granulomatous disease with autosomal
RT recessive mutations in p40 phox and selective defects in neutrophil NADPH
RT oxidase activity.";
RL Blood 114:3309-3315(2009).
CC -!- FUNCTION: Component of the NADPH-oxidase, a multicomponent enzyme
CC system responsible for the oxidative burst in which electrons are
CC transported from NADPH to molecular oxygen, generating reactive oxidant
CC intermediates. It may be important for the assembly and/or activation
CC of the NADPH-oxidase complex. {ECO:0000269|PubMed:8280052}.
CC -!- SUBUNIT: Component of an NADPH oxidase complex composed of a
CC heterodimer formed by the membrane proteins CYBA and CYBB and the
CC cytosolic subunits NCF1, NCF2 and NCF4 (PubMed:8280052). Interacts with
CC NCF2 and NCF1 (PubMed:12887891, PubMed:15657040). The NCF2-NCF4 complex
CC interacts with GBP7 (via GB1/RHD3-type G domain) (By similarity).
CC {ECO:0000250|UniProtKB:P97369, ECO:0000269|PubMed:12887891,
CC ECO:0000269|PubMed:15657040, ECO:0000269|PubMed:8280052}.
CC -!- INTERACTION:
CC Q15080; P14598: NCF1; NbExp=2; IntAct=EBI-1036870, EBI-395044;
CC Q15080; P19878: NCF2; NbExp=5; IntAct=EBI-1036870, EBI-489611;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:8280052}.
CC Endosome membrane {ECO:0000269|PubMed:11684018}; Peripheral membrane
CC protein {ECO:0000269|PubMed:11684018}; Cytoplasmic side
CC {ECO:0000269|PubMed:11684018}. Membrane {ECO:0000269|PubMed:11684018};
CC Peripheral membrane protein {ECO:0000269|PubMed:11684018}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15080-1; Sequence=Displayed;
CC Name=3;
CC IsoId=Q15080-3; Sequence=VSP_042681;
CC -!- TISSUE SPECIFICITY: Expression is restricted to hematopoietic cells.
CC -!- DOMAIN: The PB1 domain mediates the association with NCF2/p67-PHOX.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched in
CC phosphatidylnositol 3-phosphate.
CC -!- DISEASE: Granulomatous disease, chronic, autosomal recessive, 3 (CGD3)
CC [MIM:613960]: A form of chronic granulomatous disease, a primary
CC immunodeficiency characterized by severe recurrent bacterial and fungal
CC infections, along with manifestations of chronic granulomatous
CC inflammation. It results from an impaired ability of phagocytes to
CC mount a burst of reactive oxygen species in response to pathogens.
CC {ECO:0000269|PubMed:19692703}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; X77094; CAA54372.1; -; mRNA.
DR EMBL; U50729; AAB39970.1; -; Genomic_DNA.
DR EMBL; U50720; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50721; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50722; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50723; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50724; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50725; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50726; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50727; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; U50728; AAB39970.1; JOINED; Genomic_DNA.
DR EMBL; AB025220; BAA89792.1; -; mRNA.
DR EMBL; AB025219; BAA89791.1; -; mRNA.
DR EMBL; CR456528; CAG30414.1; -; mRNA.
DR EMBL; BT007346; AAP36010.1; -; mRNA.
DR EMBL; AK290924; BAF83613.1; -; mRNA.
DR EMBL; DQ314880; ABC40739.1; -; Genomic_DNA.
DR EMBL; AL008637; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002798; AAH02798.1; -; mRNA.
DR CCDS; CCDS13934.1; -. [Q15080-1]
DR CCDS; CCDS13935.1; -. [Q15080-3]
DR PIR; S39768; S39768.
DR RefSeq; NP_000622.2; NM_000631.4. [Q15080-1]
DR RefSeq; NP_038202.2; NM_013416.3. [Q15080-3]
DR PDB; 1H6H; X-ray; 1.70 A; A=2-144.
DR PDB; 1OEY; X-ray; 2.00 A; J/K/L/M=237-339.
DR PDB; 1W6X; X-ray; 2.00 A; A/B=174-228.
DR PDB; 1W70; X-ray; 1.46 A; A/B=174-228.
DR PDB; 1Z9Q; NMR; -; A=168-233.
DR PDB; 2DYB; X-ray; 3.15 A; A/B=1-339.
DR PDBsum; 1H6H; -.
DR PDBsum; 1OEY; -.
DR PDBsum; 1W6X; -.
DR PDBsum; 1W70; -.
DR PDBsum; 1Z9Q; -.
DR PDBsum; 2DYB; -.
DR AlphaFoldDB; Q15080; -.
DR BMRB; Q15080; -.
DR SMR; Q15080; -.
DR BioGRID; 110769; 8.
DR ComplexPortal; CPX-1017; Phagocyte NADPH oxidase complex, RAC1 variant.
DR ComplexPortal; CPX-6134; Phagocyte NADPH oxidase complex, RAC2 variant.
DR ComplexPortal; CPX-6135; Phagocyte NADPH oxidase complex, RAC3 variant.
DR DIP; DIP-17019N; -.
DR IntAct; Q15080; 6.
DR MINT; Q15080; -.
DR STRING; 9606.ENSP00000380334; -.
DR DrugBank; DB00514; Dextromethorphan.
DR iPTMnet; Q15080; -.
DR PhosphoSitePlus; Q15080; -.
DR BioMuta; NCF4; -.
DR DMDM; 108884815; -.
DR jPOST; Q15080; -.
DR MassIVE; Q15080; -.
DR MaxQB; Q15080; -.
DR PaxDb; Q15080; -.
DR PeptideAtlas; Q15080; -.
DR PRIDE; Q15080; -.
DR ProteomicsDB; 60430; -. [Q15080-1]
DR ProteomicsDB; 60432; -. [Q15080-3]
DR Antibodypedia; 11797; 543 antibodies from 39 providers.
DR DNASU; 4689; -.
DR Ensembl; ENST00000248899.11; ENSP00000248899.6; ENSG00000100365.16. [Q15080-1]
DR Ensembl; ENST00000397147.7; ENSP00000380334.4; ENSG00000100365.16. [Q15080-3]
DR GeneID; 4689; -.
DR KEGG; hsa:4689; -.
DR MANE-Select; ENST00000248899.11; ENSP00000248899.6; NM_000631.5; NP_000622.2.
DR UCSC; uc003apy.5; human. [Q15080-1]
DR CTD; 4689; -.
DR DisGeNET; 4689; -.
DR GeneCards; NCF4; -.
DR GeneReviews; NCF4; -.
DR HGNC; HGNC:7662; NCF4.
DR HPA; ENSG00000100365; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; NCF4; -.
DR MIM; 601488; gene.
DR MIM; 613960; phenotype.
DR neXtProt; NX_Q15080; -.
DR OpenTargets; ENSG00000100365; -.
DR Orphanet; 379; Chronic granulomatous disease.
DR Orphanet; 206; NON RARE IN EUROPE: Crohn disease.
DR PharmGKB; PA31465; -.
DR VEuPathDB; HostDB:ENSG00000100365; -.
DR eggNOG; KOG4773; Eukaryota.
DR GeneTree; ENSGT00510000048561; -.
DR HOGENOM; CLU_068185_0_0_1; -.
DR InParanoid; Q15080; -.
DR OMA; KLHVTQQ; -.
DR OrthoDB; 824942at2759; -.
DR PhylomeDB; Q15080; -.
DR PathwayCommons; Q15080; -.
DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-HSA-1236973; Cross-presentation of particulate exogenous antigens (phagosomes).
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; Q15080; -.
DR SIGNOR; Q15080; -.
DR BioGRID-ORCS; 4689; 14 hits in 1075 CRISPR screens.
DR ChiTaRS; NCF4; human.
DR EvolutionaryTrace; Q15080; -.
DR GenomeRNAi; 4689; -.
DR Pharos; Q15080; Tbio.
DR PRO; PR:Q15080; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q15080; protein.
DR Bgee; ENSG00000100365; Expressed in blood and 100 other tissues.
DR ExpressionAtlas; Q15080; baseline and differential.
DR Genevisible; Q15080; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0043020; C:NADPH oxidase complex; IDA:UniProtKB.
DR GO; GO:0032010; C:phagolysosome; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IMP:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IEA:InterPro.
DR GO; GO:0045730; P:respiratory burst; IC:ComplexPortal.
DR GO; GO:0042554; P:superoxide anion generation; IMP:UniProtKB.
DR CDD; cd06399; PB1_P40; 1.
DR CDD; cd06882; PX_p40phox; 1.
DR CDD; cd11869; SH3_p40phox; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR IDEAL; IID00593; -.
DR InterPro; IPR000919; p40phox.
DR InterPro; IPR035541; p40phox_SH3.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR034853; PB1_P40.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR034912; PX_p40phox.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR15706:SF20; PTHR15706:SF20; 1.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00497; P40PHOX.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00312; PX; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chronic granulomatous disease;
KW Cytoplasm; Direct protein sequencing; Disease variant; Endosome;
KW Lipid-binding; Membrane; Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..339
FT /note="Neutrophil cytosol factor 4"
FT /id="PRO_0000096764"
FT DOMAIN 19..140
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 170..229
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 237..329
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT BINDING 58..60
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT BINDING 92..94
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT MOD_RES 154
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:9804763"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9804763"
FT VAR_SEQ 254..339
FT /note="DIAVEEDLSSTPLLKDLLELTRREFQREDIALNYRDAEGDLVRLLSDEDVAL
FT MVRQARGLPSQKRLFPWKLHITQKDNYRVYNTMP -> SVAWEGGACPAFLPSLRPLPL
FT TSPSHGSLSHSKAPSGSQMSHNAVTSHQRPGWPGQPHSPFPHPTPHFQPDASLLQPVTP
FT LGTSRWRKISAALPY (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10437784,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|Ref.5"
FT /id="VSP_042681"
FT VARIANT 105
FT /note="R -> Q (in CGD3; the protein remains cytosolic, does
FT not localize to phagosomes or endosomes and is unable to
FT bind phosphatidylinositol 3-phosphate (PtdIns(3)P) in a
FT lipid-binding assay; unable to rescue the NADPH-oxidase
FT defect of NCF4 functionally null cells; dbSNP:rs387906808)"
FT /evidence="ECO:0000269|PubMed:19692703"
FT /id="VAR_065949"
FT VARIANT 147
FT /note="L -> I"
FT /evidence="ECO:0000269|PubMed:8280052,
FT ECO:0000269|PubMed:8839867"
FT /id="VAR_009314"
FT VARIANT 153
FT /note="R -> H (in dbSNP:rs35160112)"
FT /id="VAR_034136"
FT MUTAGEN 58
FT /note="R->Q: Abolishes interaction with membranes enriched
FT in phosphatidylinositol 3-phosphate."
FT /evidence="ECO:0000269|PubMed:11684018"
FT MUTAGEN 60
FT /note="R->A: Strongly reduces interaction with membranes
FT enriched in phosphatidylinositol 3-phosphate."
FT /evidence="ECO:0000269|PubMed:11684018"
FT MUTAGEN 92
FT /note="K->A: Abolishes interaction with membranes enriched
FT in phosphatidylinositol 3-phosphate."
FT /evidence="ECO:0000269|PubMed:11684018"
FT MUTAGEN 94
FT /note="Y->A: Slightly reduces interaction with membranes
FT enriched in phosphatidylinositol 3-phosphate."
FT /evidence="ECO:0000269|PubMed:11684018"
FT MUTAGEN 105
FT /note="R->A: Abolishes interaction with membranes enriched
FT in phosphatidylinositol 3-phosphate."
FT /evidence="ECO:0000269|PubMed:11684018"
FT MUTAGEN 154
FT /note="T->A: Reduces phosphorylation."
FT /evidence="ECO:0000269|PubMed:9804763"
FT MUTAGEN 211
FT /note="T->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:9804763"
FT MUTAGEN 251
FT /note="T->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:9804763"
FT MUTAGEN 274
FT /note="T->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:9804763"
FT MUTAGEN 315
FT /note="S->A: Reduces phosphorylation."
FT /evidence="ECO:0000269|PubMed:9804763"
FT MUTAGEN 327
FT /note="T->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:9804763"
FT HELIX 3..15
FT /evidence="ECO:0007829|PDB:1H6H"
FT STRAND 21..32
FT /evidence="ECO:0007829|PDB:1H6H"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1H6H"
FT STRAND 38..47
FT /evidence="ECO:0007829|PDB:1H6H"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:1H6H"
FT HELIX 59..73
FT /evidence="ECO:0007829|PDB:1H6H"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:1H6H"
FT HELIX 98..116
FT /evidence="ECO:0007829|PDB:1H6H"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:1H6H"
FT HELIX 127..133
FT /evidence="ECO:0007829|PDB:1H6H"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:1H6H"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:1W70"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:2DYB"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:1W70"
FT STRAND 204..212
FT /evidence="ECO:0007829|PDB:1W70"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:1W70"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:1W70"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:1W70"
FT STRAND 238..246
FT /evidence="ECO:0007829|PDB:1OEY"
FT STRAND 249..257
FT /evidence="ECO:0007829|PDB:1OEY"
FT HELIX 267..278
FT /evidence="ECO:0007829|PDB:1OEY"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:1OEY"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:2DYB"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:1OEY"
FT HELIX 300..309
FT /evidence="ECO:0007829|PDB:1OEY"
FT STRAND 324..328
FT /evidence="ECO:0007829|PDB:1OEY"
FT VARIANT Q15080-3:272
FT /note="L -> P (in dbSNP:rs2075939)"
FT /evidence="ECO:0000305"
FT /id="VAR_082885"
SQ SEQUENCE 339 AA; 39032 MW; D82FE9E5BA12890B CRC64;
MAVAQQLRAE SDFEQLPDDV AISANIADIE EKRGFTSHFV FVIEVKTKGG SKYLIYRRYR
QFHALQSKLE ERFGPDSKSS ALACTLPTLP AKVYVGVKQE IAEMRIPALN AYMKSLLSLP
VWVLMDEDVR IFFYQSPYDS EQVPQALRRL RPRTRKVKSV SPQGNSVDRM AAPRAEALFD
FTGNSKLELN FKAGDVIFLL SRINKDWLEG TVRGATGIFP LSFVKILKDF PEEDDPTNWL
RCYYYEDTIS TIKDIAVEED LSSTPLLKDL LELTRREFQR EDIALNYRDA EGDLVRLLSD
EDVALMVRQA RGLPSQKRLF PWKLHITQKD NYRVYNTMP
