ID NCF2_HUMAN Reviewed; 526 AA. AC P19878; B2R6Q1; B4DKQ7; B4DQA7; E9PHJ2; E9PHX3; Q2PP06; Q8NFC7; Q9BV51; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 2. DT 24-JAN-2024, entry version 244. DE RecName: Full=Neutrophil cytosol factor 2; DE Short=NCF-2; DE AltName: Full=67 kDa neutrophil oxidase factor; DE AltName: Full=NADPH oxidase activator 2; DE AltName: Full=Neutrophil NADPH oxidase factor 2; DE AltName: Full=p67-phox; GN Name=NCF2; Synonyms=NOXA2, P67PHOX; 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). RX PubMed=1692159; DOI=10.1126/science.1692159; RA Leto T.L., Lomax K.J., Volpp B.D., Nunoi H., Sechler J.M.G., Nauseef W.M., RA Clark R.A., Gallin J.I., Malech H.L.; RT "Cloning of a 67-kD neutrophil oxidase factor with similarity to a RT noncatalytic region of p60c-src."; RL Science 248:727-730(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7903171; RA Kenney R.T., Malech H.L., Epstein N.D., Roberts R.L., Leto T.L.; RT "Characterization of the p67phox gene: genomic organization and restriction RT fragment length polymorphism analysis for prenatal diagnosis in chronic RT granulomatous disease."; RL Blood 82:3739-3744(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, AND VARIANTS RP ARG-181; LYS-328 AND GLN-389. RC TISSUE=Colon adenocarcinoma; RX PubMed=12207919; DOI=10.1016/s0006-291x(02)02059-4; RA Yoshida L.S., Nishida S., Shimoyama T., Kawahara T., Rokutan K., RA Tsunawaki S.; RT "Expression of a p67(phox) homolog in Caco-2 cells giving O(2)(-)- RT reconstituting ability to cytochrome b(558) together with recombinant RT p47(phox)."; RL Biochem. Biophys. Res. Commun. 296:1322-1328(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ARG-181 RP AND GLN-389. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT RP ARG-181. RC TISSUE=Umbilical cord blood; 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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-181. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-181. RC TISSUE=Lymphoma; 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 INTERACTION WITH SYTL1. RX PubMed=11278853; DOI=10.1074/jbc.m011167200; RA McAdara Berkowitz J.K., Catz S.D., Johnson J.L., Ruedi J.M., Thon V., RA Babior B.M.; RT "JFC1, a novel tandem C2 domain-containing protein associated with the RT leukocyte NADPH oxidase."; RL J. Biol. Chem. 276:18855-18862(2001). RN [11] RP INTERACTION WITH NOXO1. RX PubMed=12716910; DOI=10.1074/jbc.m212856200; RA Takeya R., Ueno N., Kami K., Taura M., Kohjima M., Izaki T., Nunoi H., RA Sumimoto H.; RT "Novel human homologues of p47phox and p67phox participate in activation of RT superoxide-producing NADPH oxidases."; RL J. Biol. Chem. 278:25234-25246(2003). RN [12] RP INTERACTION WITH S100A8 AND CALPROTECTIN. RX PubMed=15642721; DOI=10.1096/fj.04-2377fje; RA Kerkhoff C., Nacken W., Benedyk M., Dagher M.C., Sopalla C., Doussiere J.; RT "The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase RT activation by interaction with p67phox and Rac-2."; RL FASEB J. 19:467-469(2005). RN [13] RP INTERACTION WITH NCF4, 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 [14] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-203 IN COMPLEX WITH RAC1. RX PubMed=11090627; DOI=10.1016/s1097-2765(05)00091-2; RA Lapouge K., Smith S.J., Walker P.A., Gamblin S.J., Smerdon S.J., RA Rittinger K.; RT "Structure of the TPR domain of p67phox in complex with Rac.GTP."; RL Mol. Cell 6:899-907(2000). RN [15] RP STRUCTURE BY NMR OF 455-516 IN COMPLEX WITH NCF1, AND INTERACTION WITH RP NCF1. RX PubMed=12169629; DOI=10.1093/emboj/cdf428; RA Kami K., Takeya R., Sumimoto H., Kohda D.; RT "Diverse recognition of non-PxxP peptide ligands by the SH3 domains from RT p67(phox), Grb2 and Pex13p."; RL EMBO J. 21:4268-4276(2002). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 352-429 IN COMPLEX WITH NCF4, RP SUBUNIT, CHARACTERIZATION OF VARIANT TRP-395, AND INTERACTION WITH NCF4. 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 [17] RP STRUCTURE BY NMR OF 242-297. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the 1st SH3 domain from human neutrophil cytosol RT factor 2 (NCF-2)."; RL Submitted (MAY-2006) to the PDB data bank. RN [18] RP VARIANT CGD2 GLU-78. RX PubMed=8286749; RA de Boer M., Hilarius-Stokman P.M., Hossle J.P., Verhoeven A.J., Graf N., RA Kenney R.T., Seger R., Roos D.; RT "Autosomal recessive chronic granulomatous disease with absence of the 67- RT kD cytosolic NADPH oxidase component: identification of mutation and RT detection of carriers."; RL Blood 83:531-536(1994). RN [19] RP VARIANT CGD2 160-ASP-LYS-161 DELINS GLU-VAL. RX PubMed=9070911; DOI=10.1006/bbrc.1997.6204; RA Bonizzato A., Russo M.P., Donini M., Dusi S.; RT "Identification of a double mutation (D160V-K161E) (sic) in the p67phox RT gene of a chronic granulomatous disease patient."; RL Biochem. Biophys. Res. Commun. 231:861-863(1997). RN [20] RP VARIANT CGD2 19-LYS--ASP-21 DEL, AND VARIANTS VAL-79; ARG-181; LYS-328; RP GLN-389 AND TRP-395. RX PubMed=10498624; RA Patino P.J., Rae J., Noack D., Erickson R., Ding J., Garcia de Olarte D., RA Curnutte J.T.; RT "Molecular characterization of autosomal recessive chronic granulomatous RT disease caused by a defect of the nicotinamide adenine dinucleotide RT phosphate (reduced form) oxidase component p67-phox."; RL Blood 94:2505-2514(1999). RN [21] RP INVOLVEMENT IN CGD2, VARIANTS CGD2 GLN-77 AND VAL-128, AND VARIANTS RP ARG-181; ARG-369 AND GLN-389. RX PubMed=10598813; DOI=10.1007/s004390051131; RA Noack D., Rae J., Cross A.R., Munoz J., Salmen S., Mendoza J.A., Rossi N., RA Curnutte J.T., Heyworth P.G.; RT "Autosomal recessive chronic granulomatous disease caused by novel RT mutations in NCF-2, the gene encoding the p67-phox component of phagocyte RT NADPH oxidase."; RL Hum. Genet. 105:460-467(1999). RN [22] RP VARIANT CGD2 ARG-44. RX PubMed=11112388; DOI=10.1006/bcmd.2000.0333; RA Cross A.R., Noack D., Rae J., Curnutte J.T., Heyworth P.G.; RT "Hematologically important mutations: the autosomal recessive forms of RT chronic granulomatous disease (first update)."; RL Blood Cells Mol. Dis. 26:561-565(2000). RN [23] RP VARIANT ILE-419. RX PubMed=16937026; DOI=10.1007/s10038-006-0039-8; RA El Kares R., Barbouche M.R., Elloumi-Zghal H., Bejaoui M., Chemli J., RA Mellouli F., Tebib N., Abdelmoula M.S., Boukthir S., Fitouri Z., M'Rad S., RA Bouslama K., Touiri H., Abdelhak S., Dellagi M.K.; RT "Genetic and mutational heterogeneity of autosomal recessive chronic RT granulomatous disease in Tunisia."; RL J. Hum. Genet. 51:887-895(2006). RN [24] RP VARIANTS CGD2 ARG-44 AND VAL-108. RX PubMed=18625437; DOI=10.1016/j.clim.2008.05.008; RA Yu G., Hong D.K., Dionis K.Y., Rae J., Heyworth P.G., Curnutte J.T., RA Lewis D.B.; RT "Focus on FOCIS: the continuing diagnostic challenge of autosomal recessive RT chronic granulomatous disease."; RL Clin. Immunol. 128:117-126(2008). RN [25] RP VARIANTS CGD2 GLU-93 AND VAL-202. RX PubMed=19624736; DOI=10.1111/j.1365-2362.2009.02195.x; RA Koker M.Y., Sanal O., van Leeuwen K., de Boer M., Metin A., Patiroglu T., RA Ozgur T.T., Tezcan I., Roos D.; RT "Four different NCF2 mutations in six families from Turkey and an overview RT of NCF2 gene mutations."; RL Eur. J. Clin. Invest. 39:942-951(2009). RN [26] RP VARIANTS CGD2 SER-42; CYS-44; LYS-58 DEL; GLN-77; GLU-96 DEL; PRO-102; RP ARG-137; ASP-140; GLU-169; PRO-184 AND LYS-196 DEL, AND VARIANT ILE-419. RX PubMed=20167518; DOI=10.1016/j.bcmd.2010.01.009; RA Roos D., Kuhns D.B., Maddalena A., Bustamante J., Kannengiesser C., RA de Boer M., van Leeuwen K., Koker M.Y., Wolach B., Roesler J., Malech H.L., RA Holland S.M., Gallin J.I., Stasia M.J.; RT "Hematologically important mutations: the autosomal recessive forms of RT chronic granulomatous disease (second update)."; RL Blood Cells Mol. Dis. 44:291-299(2010). RN [27] RP VARIANTS CGD2 GLU-93 AND VAL-202. RX PubMed=23910690; DOI=10.1016/j.jaci.2013.05.039; RA Koker M.Y., Camcioglu Y., van Leeuwen K., Kilic S.S., Barlan I., Yilmaz M., RA Metin A., de Boer M., Avcilar H., Patiroglu T., Yildiran A., Yegin O., RA Tezcan I., Sanal O., Roos D.; RT "Clinical, functional, and genetic characterization of chronic RT granulomatous disease in 89 Turkish patients."; RL J. Allergy Clin. Immunol. 132:1156-1163(2013). RN [28] RP VARIANT ILE-419. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). CC -!- FUNCTION: NCF2, NCF1, and a membrane bound cytochrome b558 are required CC for activation of the latent NADPH oxidase (necessary for superoxide CC production). {ECO:0000269|PubMed:12207919}. 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. Interacts with NCF4. Interacts CC (via the C-terminal SH3 domain) with NCF1 (via C-terminus). Interacts CC with SYTL1 and RAC1. May interact with NOXO1. Interacts with S100A8 and CC calprotectin (S100A8/9) (PubMed:15642721). Interacts with GBP7 (via CC GB1/RHD3-type G domain) (By similarity). Interacts with CYBB; the CC interaction is enhanced in the presence of GBP7 (By similarity). CC {ECO:0000250|UniProtKB:O70145, ECO:0000269|PubMed:11090627, CC ECO:0000269|PubMed:11278853, ECO:0000269|PubMed:12169629, CC ECO:0000269|PubMed:12207919, ECO:0000269|PubMed:12716910, CC ECO:0000269|PubMed:12887891, ECO:0000269|PubMed:15642721, CC ECO:0000269|PubMed:17290225}. CC -!- INTERACTION: CC P19878; P04899: GNAI2; NbExp=4; IntAct=EBI-489611, EBI-353997; CC P19878; P62873: GNB1; NbExp=2; IntAct=EBI-489611, EBI-357130; CC P19878; Q08379: GOLGA2; NbExp=9; IntAct=EBI-489611, EBI-618309; CC P19878; Q92845: KIFAP3; NbExp=14; IntAct=EBI-489611, EBI-954040; CC P19878; P14598: NCF1; NbExp=14; IntAct=EBI-489611, EBI-395044; CC P19878; Q15080: NCF4; NbExp=5; IntAct=EBI-489611, EBI-1036870; CC P19878; Q05655: PRKCD; NbExp=3; IntAct=EBI-489611, EBI-704279; CC P19878; P27870: Vav1; Xeno; NbExp=4; IntAct=EBI-489611, EBI-1697; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P19878-1; Sequence=Displayed; CC Name=2; CC IsoId=P19878-2; Sequence=VSP_045259, VSP_045261; CC Name=3; CC IsoId=P19878-3; Sequence=VSP_045260; CC Name=4; CC IsoId=P19878-4; Sequence=VSP_045259; CC -!- DOMAIN: The OPR/PB1 domain mediates the association with NCF4/p40-PHOX. CC {ECO:0000269|PubMed:17290225}. CC -!- DISEASE: Granulomatous disease, chronic, autosomal recessive, 2 (CGD2) CC [MIM:233710]: 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:10498624, ECO:0000269|PubMed:10598813, CC ECO:0000269|PubMed:11112388, ECO:0000269|PubMed:16937026, CC ECO:0000269|PubMed:18625437, ECO:0000269|PubMed:19624736, CC ECO:0000269|PubMed:20167518, ECO:0000269|PubMed:23910690, CC ECO:0000269|PubMed:8286749, ECO:0000269|PubMed:9070911}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the NCF2/NOXA1 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NCF2base; Note=NCF2 deficiency database; CC URL="http://structure.bmc.lu.se/idbase/NCF2base/"; CC -!- WEB RESOURCE: Name=Mendelian genes neutrophil cytosolic factor 2 CC (NCF2); Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/NCF2"; 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; M32011; AAA36379.1; -; mRNA. DR EMBL; U00788; AAB60320.1; -; Genomic_DNA. DR EMBL; U00776; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00777; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00778; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00779; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00780; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00781; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00782; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00783; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00784; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00785; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00786; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; U00787; AAB60320.1; JOINED; Genomic_DNA. DR EMBL; AF527950; AAM89263.1; -; mRNA. DR EMBL; BT007439; AAP36107.1; -; mRNA. DR EMBL; AK296672; BAG59269.1; -; mRNA. DR EMBL; AK298713; BAG60869.1; -; mRNA. DR EMBL; AK312666; BAG35548.1; -; mRNA. DR EMBL; DQ314879; ABC40738.1; -; Genomic_DNA. DR EMBL; AL137800; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91160.1; -; Genomic_DNA. DR EMBL; BC001606; AAH01606.1; -; mRNA. DR CCDS; CCDS1356.1; -. [P19878-1] DR CCDS; CCDS53446.1; -. [P19878-4] DR CCDS; CCDS53447.1; -. [P19878-3] DR PIR; A34855; A34855. DR RefSeq; NP_000424.2; NM_000433.3. [P19878-1] DR RefSeq; NP_001121123.1; NM_001127651.2. [P19878-1] DR RefSeq; NP_001177718.1; NM_001190789.1. [P19878-4] DR RefSeq; NP_001177723.1; NM_001190794.1. [P19878-3] DR RefSeq; XP_011507882.1; XM_011509580.1. [P19878-1] DR RefSeq; XP_011507883.1; XM_011509581.1. [P19878-1] DR PDB; 1E96; X-ray; 2.40 A; B=1-203. DR PDB; 1HH8; X-ray; 1.80 A; A=1-213. DR PDB; 1K4U; NMR; -; S=455-516. DR PDB; 1OEY; X-ray; 2.00 A; A/B/C/D=352-429. DR PDB; 1WM5; X-ray; 1.95 A; A=1-203. DR PDB; 2DMO; NMR; -; A=243-297. DR PDBsum; 1E96; -. DR PDBsum; 1HH8; -. DR PDBsum; 1K4U; -. DR PDBsum; 1OEY; -. DR PDBsum; 1WM5; -. DR PDBsum; 2DMO; -. DR AlphaFoldDB; P19878; -. DR BMRB; P19878; -. DR SASBDB; P19878; -. DR SMR; P19878; -. DR BioGRID; 110768; 31. 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-76N; -. DR IntAct; P19878; 21. DR MINT; P19878; -. DR STRING; 9606.ENSP00000356505; -. DR DrugBank; DB00514; Dextromethorphan. DR iPTMnet; P19878; -. DR PhosphoSitePlus; P19878; -. DR BioMuta; NCF2; -. DR DMDM; 1346669; -. DR EPD; P19878; -. DR jPOST; P19878; -. DR MassIVE; P19878; -. DR MaxQB; P19878; -. DR PaxDb; 9606-ENSP00000356505; -. DR PeptideAtlas; P19878; -. DR PRIDE; P19878; -. DR ProteomicsDB; 20550; -. DR ProteomicsDB; 20618; -. DR ProteomicsDB; 53699; -. [P19878-1] DR Antibodypedia; 702; 328 antibodies from 30 providers. DR DNASU; 4688; -. DR Ensembl; ENST00000367535.8; ENSP00000356505.4; ENSG00000116701.16. [P19878-1] DR Ensembl; ENST00000367536.5; ENSP00000356506.1; ENSG00000116701.16. [P19878-1] DR Ensembl; ENST00000413720.5; ENSP00000399294.1; ENSG00000116701.16. [P19878-3] DR Ensembl; ENST00000418089.5; ENSP00000407217.1; ENSG00000116701.16. [P19878-4] DR Ensembl; ENST00000697330.1; ENSP00000513258.1; ENSG00000116701.16. [P19878-1] DR GeneID; 4688; -. DR KEGG; hsa:4688; -. DR MANE-Select; ENST00000367535.8; ENSP00000356505.4; NM_000433.4; NP_000424.2. DR UCSC; uc001gqj.5; human. [P19878-1] DR AGR; HGNC:7661; -. DR CTD; 4688; -. DR DisGeNET; 4688; -. DR GeneCards; NCF2; -. DR GeneReviews; NCF2; -. DR HGNC; HGNC:7661; NCF2. DR HPA; ENSG00000116701; Tissue enhanced (bone marrow, lung, lymphoid tissue). DR MalaCards; NCF2; -. DR MIM; 233710; phenotype. DR MIM; 608515; gene. DR neXtProt; NX_P19878; -. DR OpenTargets; ENSG00000116701; -. DR Orphanet; 379; Chronic granulomatous disease. DR PharmGKB; PA31464; -. DR VEuPathDB; HostDB:ENSG00000116701; -. DR eggNOG; KOG4225; Eukaryota. DR GeneTree; ENSGT00530000063843; -. DR HOGENOM; CLU_041290_0_0_1; -. DR InParanoid; P19878; -. DR OMA; YATMEDW; -. DR OrthoDB; 11738at2759; -. DR PhylomeDB; P19878; -. DR TreeFam; TF329087; -. DR PathwayCommons; P19878; -. 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; P19878; -. DR SIGNOR; P19878; -. DR BioGRID-ORCS; 4688; 11 hits in 1151 CRISPR screens. DR ChiTaRS; NCF2; human. DR EvolutionaryTrace; P19878; -. DR GeneWiki; Neutrophil_cytosolic_factor_2; -. DR GenomeRNAi; 4688; -. DR Pharos; P19878; Tbio. DR PRO; PR:P19878; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P19878; Protein. DR Bgee; ENSG00000116701; Expressed in monocyte and 133 other cell types or tissues. DR ExpressionAtlas; P19878; baseline and differential. DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IDA:HPA. 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:0009055; F:electron transfer activity; TAS:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl. DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IEA:Ensembl. DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IMP:UniProtKB. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL. DR GO; GO:0006909; P:phagocytosis; IEA:InterPro. DR GO; GO:0045730; P:respiratory burst; TAS:BHF-UCL. DR GO; GO:0042554; P:superoxide anion generation; IMP:UniProtKB. DR GO; GO:0006801; P:superoxide metabolic process; TAS:BHF-UCL. DR CDD; cd06406; PB1_P67; 1. DR CDD; cd12046; SH3_p67phox_C; 1. DR CDD; cd11871; SH3_p67phox_N; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 2. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR IDEAL; IID00299; -. DR InterPro; IPR034889; NCF2_SH3. DR InterPro; IPR035546; p67phox_SH3_1. DR InterPro; IPR000270; PB1_dom. DR InterPro; IPR034885; PB1_P67. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR15175:SF3; NEUTROPHIL CYTOSOL FACTOR 2; 1. DR PANTHER; PTHR15175; NEUTROPHIL CYTOSOLIC FACTOR 2, NEUTROPHIL NADPH OXIDASE FACTOR 2; 1. DR Pfam; PF00564; PB1; 1. DR Pfam; PF00018; SH3_1; 2. DR Pfam; PF13181; TPR_8; 2. DR PRINTS; PR00499; P67PHOX. DR PRINTS; PR00452; SH3DOMAIN. DR SMART; SM00666; PB1; 1. DR SMART; SM00326; SH3; 2. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF54277; CAD & PB1 domains; 1. DR SUPFAM; SSF50044; SH3-domain; 2. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS51745; PB1; 1. DR PROSITE; PS50002; SH3; 2. DR PROSITE; PS50005; TPR; 3. DR PROSITE; PS50293; TPR_REGION; 1. DR Genevisible; P19878; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chronic granulomatous disease; KW Cytoplasm; Disease variant; Phosphoprotein; Reference proteome; Repeat; KW SH3 domain; TPR repeat. FT CHAIN 1..526 FT /note="Neutrophil cytosol factor 2" FT /id="PRO_0000106361" FT REPEAT 37..70 FT /note="TPR 1" FT REPEAT 71..104 FT /note="TPR 2" FT REPEAT 121..154 FT /note="TPR 3" FT DOMAIN 240..299 FT /note="SH3 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 351..429 FT /note="PB1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081" FT DOMAIN 457..516 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 303..346 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 433..458 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 304..318 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 233 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O70145" FT MOD_RES 399 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O70145" FT VAR_SEQ 123..203 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045259" FT VAR_SEQ 123..167 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045260" FT VAR_SEQ 502..526 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045261" FT VARIANT 19..21 FT /note="Missing (in CGD2)" FT /evidence="ECO:0000269|PubMed:10498624" FT /id="VAR_017387" FT VARIANT 42 FT /note="N -> S (in CGD2; dbSNP:rs137854514)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065002" FT VARIANT 44 FT /note="G -> C (in CGD2; dbSNP:rs137854510)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065003" FT VARIANT 44 FT /note="G -> R (in CGD2; dbSNP:rs137854510)" FT /evidence="ECO:0000269|PubMed:11112388, FT ECO:0000269|PubMed:18625437" FT /id="VAR_065004" FT VARIANT 58 FT /note="Missing (in CGD2)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065005" FT VARIANT 77 FT /note="R -> Q (in CGD2; dbSNP:rs119103275)" FT /evidence="ECO:0000269|PubMed:10598813, FT ECO:0000269|PubMed:20167518" FT /id="VAR_017388" FT VARIANT 78 FT /note="G -> E (in CGD2; dbSNP:rs137854519)" FT /evidence="ECO:0000269|PubMed:8286749" FT /id="VAR_008904" FT VARIANT 79 FT /note="M -> V (in dbSNP:rs137854512)" FT /evidence="ECO:0000269|PubMed:10498624" FT /id="VAR_065006" FT VARIANT 93 FT /note="D -> E (in CGD2; dbSNP:rs137854507)" FT /evidence="ECO:0000269|PubMed:19624736, FT ECO:0000269|PubMed:23910690" FT /id="VAR_065007" FT VARIANT 96 FT /note="Missing (in CGD2)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065008" FT VARIANT 102 FT /note="R -> P (in CGD2; dbSNP:rs137854515)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065009" FT VARIANT 108 FT /note="D -> V (in CGD2; dbSNP:rs137854509)" FT /evidence="ECO:0000269|PubMed:18625437" FT /id="VAR_065010" FT VARIANT 128 FT /note="A -> V (in CGD2; dbSNP:rs119103274)" FT /evidence="ECO:0000269|PubMed:10598813" FT /id="VAR_017389" FT VARIANT 137 FT /note="W -> R (in CGD2; dbSNP:rs137854516)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065011" FT VARIANT 140 FT /note="A -> D (in CGD2; dbSNP:rs137854520)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065012" FT VARIANT 160..161 FT /note="DK -> EV (in CGD2)" FT /evidence="ECO:0000269|PubMed:9070911" FT /id="VAR_017390" FT VARIANT 169 FT /note="Q -> E (in CGD2; dbSNP:rs137854517)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065013" FT VARIANT 181 FT /note="K -> R (in dbSNP:rs2274064)" FT /evidence="ECO:0000269|PubMed:10498624, FT ECO:0000269|PubMed:10598813, ECO:0000269|PubMed:12207919, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.4, ECO:0000269|Ref.8" FT /id="VAR_018477" FT VARIANT 184 FT /note="R -> P (in CGD2; dbSNP:rs137854518)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065014" FT VARIANT 196 FT /note="Missing (in CGD2)" FT /evidence="ECO:0000269|PubMed:20167518" FT /id="VAR_065015" FT VARIANT 202 FT /note="A -> V (in CGD2; dbSNP:rs137854508)" FT /evidence="ECO:0000269|PubMed:19624736, FT ECO:0000269|PubMed:23910690" FT /id="VAR_065016" FT VARIANT 279 FT /note="T -> M (in dbSNP:rs13306581)" FT /id="VAR_034129" FT VARIANT 297 FT /note="V -> A (in dbSNP:rs35937854)" FT /id="VAR_034130" FT VARIANT 328 FT /note="R -> K (in dbSNP:rs137854511)" FT /evidence="ECO:0000269|PubMed:10498624, FT ECO:0000269|PubMed:12207919" FT /id="VAR_018478" FT VARIANT 369 FT /note="G -> R (in dbSNP:rs137854513)" FT /evidence="ECO:0000269|PubMed:10598813" FT /id="VAR_065017" FT VARIANT 389 FT /note="H -> Q (in dbSNP:rs17849502)" FT /evidence="ECO:0000269|PubMed:10498624, FT ECO:0000269|PubMed:10598813, ECO:0000269|PubMed:12207919, FT ECO:0000269|Ref.4" FT /id="VAR_052620" FT VARIANT 395 FT /note="R -> W (impairs interaction with NCF4; FT dbSNP:rs13306575)" FT /evidence="ECO:0000269|PubMed:10498624, FT ECO:0000269|PubMed:12887891" FT /id="VAR_008905" FT VARIANT 419 FT /note="N -> I (in dbSNP:rs35012521)" FT /evidence="ECO:0000269|PubMed:16937026, FT ECO:0000269|PubMed:20167518, ECO:0000269|PubMed:27535533" FT /id="VAR_052621" FT HELIX 3..18 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 22..30 FT /evidence="ECO:0007829|PDB:1HH8" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 37..49 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 53..66 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 71..83 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 87..99 FT /evidence="ECO:0007829|PDB:1HH8" FT TURN 100..103 FT /evidence="ECO:0007829|PDB:1HH8" FT STRAND 105..108 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 110..112 FT /evidence="ECO:0007829|PDB:1HH8" FT STRAND 117..119 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 120..133 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 137..148 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 154..157 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 158..167 FT /evidence="ECO:0007829|PDB:1HH8" FT HELIX 187..191 FT /evidence="ECO:0007829|PDB:1HH8" FT STRAND 243..247 FT /evidence="ECO:0007829|PDB:2DMO" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:2DMO" FT STRAND 266..269 FT /evidence="ECO:0007829|PDB:2DMO" FT STRAND 274..276 FT /evidence="ECO:0007829|PDB:2DMO" FT STRAND 278..282 FT /evidence="ECO:0007829|PDB:2DMO" FT STRAND 285..289 FT /evidence="ECO:0007829|PDB:2DMO" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:2DMO" FT STRAND 352..366 FT /evidence="ECO:0007829|PDB:1OEY" FT HELIX 372..382 FT /evidence="ECO:0007829|PDB:1OEY" FT HELIX 387..389 FT /evidence="ECO:0007829|PDB:1OEY" FT STRAND 392..394 FT /evidence="ECO:0007829|PDB:1OEY" FT TURN 407..409 FT /evidence="ECO:0007829|PDB:1OEY" FT HELIX 410..414 FT /evidence="ECO:0007829|PDB:1OEY" FT STRAND 421..426 FT /evidence="ECO:0007829|PDB:1OEY" FT STRAND 460..463 FT /evidence="ECO:0007829|PDB:1K4U" FT STRAND 472..475 FT /evidence="ECO:0007829|PDB:1K4U" FT STRAND 483..493 FT /evidence="ECO:0007829|PDB:1K4U" FT STRAND 495..498 FT /evidence="ECO:0007829|PDB:1K4U" FT STRAND 503..506 FT /evidence="ECO:0007829|PDB:1K4U" FT HELIX 508..510 FT /evidence="ECO:0007829|PDB:1K4U" SQ SEQUENCE 526 AA; 59762 MW; EC136766E1915376 CRC64; MSLVEAISLW NEGVLAADKK DWKGALDAFS AVQDPHSRIC FNIGCMYTIL KNMTEAEKAF TRSINRDKHL AVAYFQRGML YYQTEKYDLA IKDLKEALIQ LRGNQLIDYK ILGLQFKLFA CEVLYNIAFM YAKKEEWKKA EEQLALATSM KSEPRHSKID KAMECVWKQK LYEPVVIPVG KLFRPNERQV AQLAKKDYLG KATVVASVVD QDSFSGFAPL QPQAAEPPPR PKTPEIFRAL EGEAHRVLFG FVPETKEELQ VMPGNIVFVL KKGNDNWATV MFNGQKGLVP CNYLEPVELR IHPQQQPQEE SSPQSDIPAP PSSKAPGRPQ LSPGQKQKEE PKEVKLSVPM PYTLKVHYKY TVVMKTQPGL PYSQVRDMVS KKLELRLEHT KLSYRPRDSN ELVPLSEDSM KDAWGQVKNY CLTLWCENTV GDQGFPDEPK ESEKADANNQ TTEPQLKKGS QVEALFSYEA TQPEDLEFQE GDIILVLSKV NEEWLEGECK GKVGIFPKVF VEDCATTDLE STRREV //