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 24-JAN-2024, entry version 220. 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9. 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; 5. DR MINT; Q15080; -. DR STRING; 9606.ENSP00000380334; -. DR DrugBank; DB00514; Dextromethorphan. DR GlyGen; Q15080; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15080; -. DR PhosphoSitePlus; Q15080; -. DR BioMuta; NCF4; -. DR DMDM; 108884815; -. DR jPOST; Q15080; -. DR MassIVE; Q15080; -. DR MaxQB; Q15080; -. DR PaxDb; 9606-ENSP00000380334; -. DR PeptideAtlas; Q15080; -. DR PRIDE; Q15080; -. DR ProteomicsDB; 60430; -. [Q15080-1] DR ProteomicsDB; 60432; -. [Q15080-3] DR Antibodypedia; 11797; 625 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 AGR; HGNC:7662; -. 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; 2997622at2759; -. 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 1153 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 101 other cell types or tissues. DR ExpressionAtlas; Q15080; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. 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; NAS: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; NAS: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; Phox-like domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 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; NEUTROPHIL CYTOSOL FACTOR 4; 1. DR PANTHER; PTHR15706; SH3 MULTIPLE DOMAIN; 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; SSF54277; CAD & PB1 domains; 1. DR SUPFAM; SSF64268; PX domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS51745; PB1; 1. DR PROSITE; PS50195; PX; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q15080; HS. 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 //