ID NCF1_HUMAN Reviewed; 390 AA. AC P14598; A6NEH2; A8K7S9; O43842; Q2PP07; Q53FR5; Q9BU90; Q9BXI7; Q9BXI8; AC Q9UDV9; Q9UMU2; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 25-APR-2018, sequence version 4. DT 27-MAR-2024, entry version 255. DE RecName: Full=Neutrophil cytosol factor 1; DE Short=NCF-1; DE AltName: Full=47 kDa autosomal chronic granulomatous disease protein; DE AltName: Full=47 kDa neutrophil oxidase factor; DE AltName: Full=NCF-47K; DE AltName: Full=Neutrophil NADPH oxidase factor 1; DE AltName: Full=Nox organizer 2; DE AltName: Full=Nox-organizing protein 2; DE AltName: Full=SH3 and PX domain-containing protein 1A; DE AltName: Full=p47-phox; GN Name=NCF1; Synonyms=NOXO2, SH3PXD1A; 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, AND TISSUE SPECIFICITY. RX PubMed=2550933; DOI=10.1073/pnas.86.18.7195; RA Volpp B.D., Nauseef W.M., Clark R.A.; RT "Cloning of the cDNA and functional expression of the 47-kilodalton RT cytosolic component of human neutrophil respiratory burst oxidase."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7195-7199(1989). RN [2] RP ERRATUM OF PUBMED:2550933, AND SEQUENCE REVISION. RA Volpp B.D., Nauseef W.M., Clark R.A.; RL Proc. Natl. Acad. Sci. U.S.A. 86:9563-9563(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP VARIANT ASP-166. RX PubMed=2547247; DOI=10.1126/science.2547247; RA Lomax K.J., Leto T.L., Nunoi H., Gallin J.I., Malech H.L.; RT "Recombinant 47-kilodalton cytosol factor restores NADPH oxidase in chronic RT granulomatous disease."; RL Science 245:409-412(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-166. RX PubMed=2398896; DOI=10.1128/mcb.10.10.5388-5396.1990; RA Rodaway A.R.F., Teahan C.G., Casimir C.M., Segal A.W., Bentley D.L.; RT "Characterization of the 47-kilodalton autosomal chronic granulomatous RT disease protein: tissue-specific expression and transcriptional control by RT retinoic acid."; RL Mol. Cell. Biol. 10:5388-5396(1990). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-160 AND VAL-308. RX PubMed=9329953; DOI=10.1172/jci119721; RA Gorlach A., Lee P.L., Roesler J., Hopkins P.J., Christensen B., Green E.D., RA Chanock S.J., Curnutte J.T.; RT "A p47-phox pseudogene carries the most common mutation causing p47-phox- RT deficient chronic granulomatous disease."; RL J. Clin. Invest. 100:1907-1918(1997). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-160 AND VAL-308. RX PubMed=10772875; DOI=10.1006/bcmd.2000.0274; RA Chanock S.J., Roesler J., Zhan S., Hopkins P., Lee P., Barrett D.T., RA Christensen B.L., Curnutte J.T., Goerlach A.; RT "Genomic structure of the human p47-phox (NCF1) gene."; RL Blood Cells Mol. Dis. 26:37-46(2000). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASP-166 AND GLU-258. RC TISSUE=Umbilical vein; RX PubMed=11740866; DOI=10.1006/excr.2001.5404; RA Gu Y., Xu Y.C., Wu R.F., Souza R.F., Nwariaku F.E., Terada L.S.; RT "TNFalpha activates c-jun amino terminal kinase through p47(phox)."; RL Exp. Cell Res. 272:62-74(2002). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Spleen, and Synovium; 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Spleen; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-99. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-99. 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 [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-31 (ISOFORM 1). RC TISSUE=Ovary; RX PubMed=7581362; DOI=10.1093/hmg/4.8.1259; RA Harshman K., Bell R., Rosenthal J., Katcher H., Miki Y., Swenson J., RA Gholami Z., Frye C., Ding W., Dayananth P., Eddington K., Norris F.H., RA Bristow P.K., Phelps R., Hattier T., Stone S., Shaffer D., Bayer S., RA Hussey C., Tran T., Lai M., Rosteck P.R. Jr., Skolnick M.H., RA Shattuck-Eidens D., Kamb A.; RT "Comparison of the positional cloning methods used to isolate the BRCA1 RT gene."; RL Hum. Mol. Genet. 4:1259-1266(1995). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-24, AND INVOLVEMENT IN CHRONIC RP GRANULOMATOUS DISEASE. RX PubMed=2011585; DOI=10.1073/pnas.88.7.2753; RA Casimir C.M., Bu-Ghanim H.N., Rodaway A.R., Bentley D.L., Rowe P., RA Segal A.W.; RT "Autosomal recessive chronic granulomatous disease caused by deletion at a RT dinucleotide repeat."; RL Proc. Natl. Acad. Sci. U.S.A. 88:2753-2757(1991). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 133-390, AND VARIANT ASP-166. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [15] RP PHOSPHORYLATION AT SER-303; SER-304; SER-320; SER-328; SER-345 AND SER-348. RX PubMed=8089108; DOI=10.1016/s0021-9258(17)31534-x; RA el Benna J., Faust L.P., Babior B.M.; RT "The phosphorylation of the respiratory burst oxidase component p47phox RT during neutrophil activation. Phosphorylation of sites recognized by RT protein kinase C and by proline-directed kinases."; RL J. Biol. Chem. 269:23431-23436(1994). RN [16] RP INTERACTION WITH CYBB. RX PubMed=9224653; DOI=10.1042/bj3250249; RA Adams E.R., Dratz E.A., Gizachew D., Deleo F.R., Yu L., Volpp B.D., RA Vlases M., Jesaitis A.J., Quinn M.T.; RT "Interaction of human neutrophil flavocytochrome b with cytosolic proteins: RT transferred-NOESY NMR studies of a gp91phox C-terminal peptide bound to RT p47phox."; RL Biochem. J. 325:249-257(1997). RN [17] RP INTERACTION WITH TRAF4, AND SUBCELLULAR LOCATION. RX PubMed=12023963; DOI=10.1074/jbc.m202665200; RA Xu Y.C., Wu R.F., Gu Y., Yang Y.S., Yang M.C., Nwariaku F.E., Terada L.S.; RT "Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase."; RL J. Biol. Chem. 277:28051-28057(2002). RN [18] RP INTERACTION WITH NOXA1. 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 [19] RP INTERACTION WITH TRAF4. RX PubMed=16052631; DOI=10.1002/eji.200526151; RA Takeshita F., Ishii K.J., Kobiyama K., Kojima Y., Coban C., Sasaki S., RA Ishii N., Klinman D.M., Okuda K., Akira S., Suzuki K.; RT "TRAF4 acts as a silencer in TLR-mediated signaling through the association RT with TRAF6 and TRIF."; RL Eur. J. Immunol. 35:2477-2485(2005). RN [20] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [21] RP INTERACTION WITH ADAM15. RX PubMed=19718658; DOI=10.1002/jcb.22317; RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.; RT "Alternative splicing of ADAM15 regulates its interactions with cellular RT SH3 proteins."; RL J. Cell. Biochem. 108:877-885(2009). RN [22] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=19801500; DOI=10.1189/jlb.0408230; RA Kilpatrick L.E., Sun S., Li H., Vary T.C., Korchak H.M.; RT "Regulation of TNF-induced oxygen radical production in human neutrophils: RT role of delta-PKC."; RL J. Leukoc. Biol. 87:153-164(2010). RN [23] RP STRUCTURE BY NMR OF 1-128. RX PubMed=11373621; DOI=10.1038/88591; RA Hiroaki H., Ago T., Ito T., Sumimoto H., Kohda D.; RT "Solution structure of the PX domain, a target of the SH3 domain."; RL Nat. Struct. Biol. 8:526-530(2001). RN [24] RP STRUCTURE BY NMR OF 359-390 IN COMPLEX WITH NCF2, AND INTERACTION WITH RP NCF2. 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 [25] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-123, DOMAIN, LIPID-BINDING, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-43; HIS-90; TRP-263; SER-303; RP SER-304; SER-328; SER-359 AND SER-370. RX PubMed=12356722; DOI=10.1093/emboj/cdf519; RA Karathanassis D., Stahelin R.V., Bravo J., Perisic O., Pacold C.M., Cho W., RA Williams R.L.; RT "Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4- RT bisphosphate and phosphatidic acid is masked by an intramolecular RT interaction."; RL EMBO J. 21:5057-5068(2002). RN [26] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 156-340, DOMAIN, AND INTERACTION RP WITH CYBA. RX PubMed=12732142; DOI=10.1016/s0092-8674(03)00314-3; RA Groemping Y., Lapouge K., Smerdon S.J., Rittinger K.; RT "Molecular basis of phosphorylation-induced activation of the NADPH RT oxidase."; RL Cell 113:343-355(2003). RN [27] RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 151-340. RX PubMed=15147273; DOI=10.1111/j.1356-9597.2004.00733.x; RA Yuzawa S., Suzuki N.N., Fujioka Y., Ogura K., Sumimoto H., Inagaki F.; RT "A molecular mechanism for autoinhibition of the tandem SH3 domains of RT p47phox, the regulatory subunit of the phagocyte NADPH oxidase."; RL Genes Cells 9:443-456(2004). RN [28] RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 360-372 IN COMPLEX WITH NCF4, AND RP SUBUNIT. 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 [29] RP STRUCTURE BY NMR OF 151-286 IN COMPLEX WITH CYBA, AND INTERACTION WITH RP CYBA. RX PubMed=16326715; DOI=10.1074/jbc.m505193200; RA Ogura K., Nobuhisa I., Yuzawa S., Takeya R., Torikai S., Saikawa K., RA Sumimoto H., Inagaki F.; RT "NMR solution structure of the tandem Src homology 3 domains of p47phox RT complexed with a p22phox-derived proline-rich peptide."; RL J. Biol. Chem. 281:3660-3668(2006). RN [30] RP INVOLVEMENT IN CGD1, VARIANT CGD1 GLN-42, AND VARIANT SER-262. RX PubMed=11133775; DOI=10.1182/blood.v97.1.305; RA Noack D., Rae J., Cross A.R., Ellis B.A., Newburger P.E., Curnutte J.T., RA Heyworth P.G.; RT "Autosomal recessive chronic granulomatous disease caused by defects in RT NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in RT the NCF1 pseudogenes."; RL Blood 97:305-311(2001). RN [31] RP INVOLVEMENT IN CGD1. 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 [32] RP VARIANT HIS-90. RX PubMed=28135245; DOI=10.1038/ng.3782; RA Zhao J., Ma J., Deng Y., Kelly J.A., Kim K., Bang S.Y., Lee H.S., Li Q.Z., RA Wakeland E.K., Qiu R., Liu M., Guo J., Li Z., Tan W., Rasmussen A., RA Lessard C.J., Sivils K.L., Hahn B.H., Grossman J.M., Kamen D.L., RA Gilkeson G.S., Bae S.C., Gaffney P.M., Shen N., Tsao B.P.; RT "A missense variant in NCF1 is associated with susceptibility to multiple RT autoimmune diseases."; RL Nat. Genet. 49:433-437(2017). 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:19801500, ECO:0000269|PubMed:2547247, CC ECO:0000269|PubMed:2550933}. 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 (via C-terminus) with CC NCF2 (via the C-terminal SH3 domain). Interacts with NCF4. Interacts CC with CYBB. Interacts (via the second SH3 domain) with CYBA. Interacts CC with NOXA1. Interacts with ADAM15. Interacts with TRAF4. Interacts with CC FASLG. Interacts with PARK7 (via C-terminus); the interaction is CC enhanced by LPS and modulates NCF1 phosphorylation and membrane CC translocation (By similarity). Interacts with NOXA1 (By similarity). CC {ECO:0000250|UniProtKB:Q09014, ECO:0000269|PubMed:12023963, CC ECO:0000269|PubMed:12169629, ECO:0000269|PubMed:12716910, CC ECO:0000269|PubMed:12732142, ECO:0000269|PubMed:15657040, CC ECO:0000269|PubMed:16052631, ECO:0000269|PubMed:16326715, CC ECO:0000269|PubMed:19718658, ECO:0000269|PubMed:19807924, CC ECO:0000269|PubMed:2550933, ECO:0000269|PubMed:9224653}. CC -!- INTERACTION: CC P14598; Q8IZP0: ABI1; NbExp=5; IntAct=EBI-395044, EBI-375446; CC P14598; P60709: ACTB; NbExp=3; IntAct=EBI-395044, EBI-353944; CC P14598; P78325: ADAM8; NbExp=2; IntAct=EBI-395044, EBI-2625954; CC P14598; P28329-3: CHAT; NbExp=3; IntAct=EBI-395044, EBI-25837549; CC P14598; P13498: CYBA; NbExp=7; IntAct=EBI-395044, EBI-986058; CC P14598; P22607: FGFR3; NbExp=3; IntAct=EBI-395044, EBI-348399; CC P14598; P04899: GNAI2; NbExp=2; IntAct=EBI-395044, EBI-353997; CC P14598; P06396: GSN; NbExp=3; IntAct=EBI-395044, EBI-351506; CC P14598; P11142: HSPA8; NbExp=2; IntAct=EBI-395044, EBI-351896; CC P14598; P42858: HTT; NbExp=6; IntAct=EBI-395044, EBI-466029; CC P14598; P19878: NCF2; NbExp=14; IntAct=EBI-395044, EBI-489611; CC P14598; Q15080: NCF4; NbExp=2; IntAct=EBI-395044, EBI-1036870; CC P14598; Q05513: PRKCZ; NbExp=3; IntAct=EBI-395044, EBI-295351; CC P14598; Q9BUZ4: TRAF4; NbExp=5; IntAct=EBI-395044, EBI-3650647; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:2550933}. CC Membrane {ECO:0000269|PubMed:12356722}; Peripheral membrane protein CC {ECO:0000269|PubMed:12356722}; Cytoplasmic side CC {ECO:0000269|PubMed:12356722}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P14598-1; Sequence=Displayed; CC Name=2; CC IsoId=P14598-2; Sequence=VSP_035032, VSP_035033; CC -!- TISSUE SPECIFICITY: Detected in peripheral blood monocytes and CC neutrophils (at protein level). {ECO:0000269|PubMed:2547247, CC ECO:0000269|PubMed:2550933}. CC -!- DOMAIN: The PX domain mediates interaction with phosphatidylinositol CC 3,4-bisphosphate and other anionic phospholipids. In the autoinhibited, CC unphosphorylated state an intramolecular interaction with the C- CC terminal SH3 domain precludes phospholipid binding and interaction with CC CYBA. Phosphorylation disrupts the autoinhibited state. CC {ECO:0000269|PubMed:12356722, ECO:0000269|PubMed:12732142}. CC -!- PTM: Phosphorylated by PRKCD; phosphorylation induces activation of CC NCF1 and NADPH oxidase activity. {ECO:0000269|PubMed:19801500, CC ECO:0000269|PubMed:8089108}. CC -!- DISEASE: Granulomatous disease, chronic, autosomal recessive, 1 (CGD1) CC [MIM:233700]: 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:11133775, ECO:0000269|PubMed:23910690}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron retention. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAF84783.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG54596.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NCF1base; Note=NCF1 deficiency database; CC URL="http://structure.bmc.lu.se/idbase/NCF1base/"; 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; M25665; AAA57209.1; -; mRNA. DR EMBL; M55067; AAA59901.1; -; mRNA. DR EMBL; AH005796; AAB95193.1; -; Genomic_DNA. DR EMBL; AF184614; AAF34737.1; -; Genomic_DNA. DR EMBL; AF330625; AAK19516.1; -; mRNA. DR EMBL; AF330626; AAK19517.1; -; mRNA. DR EMBL; AF330627; AAK19518.1; -; mRNA. DR EMBL; AK127905; BAG54596.1; ALT_INIT; mRNA. DR EMBL; AK292094; BAF84783.1; ALT_INIT; mRNA. DR EMBL; AK223217; BAD96937.1; -; mRNA. DR EMBL; AC004883; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC083884; AAS07465.1; -; Genomic_DNA. DR EMBL; AC124781; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002816; AAH02816.1; -; mRNA. DR EMBL; BC065731; AAH65731.1; -; mRNA. DR EMBL; U25793; AAA93232.1; -; mRNA. DR EMBL; DQ314878; ABC40737.1; -; Genomic_DNA. DR CCDS; CCDS34657.1; -. [P14598-1] DR PIR; A35926; A39249. DR RefSeq; NP_000256.4; NM_000265.5. [P14598-1] DR PDB; 1GD5; NMR; -; A=1-128. DR PDB; 1K4U; NMR; -; P=359-390. DR PDB; 1KQ6; X-ray; 1.18 A; A=1-141. DR PDB; 1NG2; X-ray; 1.70 A; A=156-340. DR PDB; 1O7K; X-ray; 2.00 A; A/B/C=1-123. DR PDB; 1OV3; X-ray; 1.80 A; A/B=156-285. DR PDB; 1UEC; X-ray; 1.82 A; A=151-340. DR PDB; 1W70; X-ray; 1.46 A; C/D=360-372. DR PDB; 1WLP; NMR; -; B=151-286. DR PDB; 7YXW; X-ray; 2.50 A; A=156-285. DR PDBsum; 1GD5; -. DR PDBsum; 1K4U; -. DR PDBsum; 1KQ6; -. DR PDBsum; 1NG2; -. DR PDBsum; 1O7K; -. DR PDBsum; 1OV3; -. DR PDBsum; 1UEC; -. DR PDBsum; 1W70; -. DR PDBsum; 1WLP; -. DR PDBsum; 7YXW; -. DR AlphaFoldDB; P14598; -. DR BMRB; P14598; -. DR SASBDB; P14598; -. DR SMR; P14598; -. DR BioGRID; 575724; 88. 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-126N; -. DR ELM; P14598; -. DR IntAct; P14598; 61. DR MINT; P14598; -. DR STRING; 9606.ENSP00000289473; -. DR BindingDB; P14598; -. DR ChEMBL; CHEMBL1613743; -. DR DrugBank; DB00514; Dextromethorphan. DR iPTMnet; P14598; -. DR PhosphoSitePlus; P14598; -. DR BioMuta; NCF1; -. DR DMDM; 325511390; -. DR jPOST; P14598; -. DR MassIVE; P14598; -. DR PaxDb; 9606-ENSP00000289473; -. DR PeptideAtlas; P14598; -. DR ProteomicsDB; 53060; -. [P14598-1] DR ProteomicsDB; 53061; -. [P14598-2] DR Pumba; P14598; -. DR Antibodypedia; 3863; 1078 antibodies from 39 providers. DR DNASU; 653361; -. DR Ensembl; ENST00000289473.11; ENSP00000289473.4; ENSG00000158517.16. [P14598-1] DR GeneID; 653361; -. DR KEGG; hsa:653361; -. DR MANE-Select; ENST00000289473.11; ENSP00000289473.4; NM_000265.7; NP_000256.4. DR UCSC; uc003ubb.5; human. [P14598-1] DR AGR; HGNC:7660; -. DR CTD; 653361; -. DR DisGeNET; 653361; -. DR GeneCards; NCF1; -. DR GeneReviews; NCF1; -. DR HGNC; HGNC:7660; NCF1. DR HPA; ENSG00000158517; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; NCF1; -. DR MIM; 233700; phenotype. DR MIM; 608512; gene. DR neXtProt; NX_P14598; -. DR OpenTargets; ENSG00000158517; -. DR Orphanet; 379; Chronic granulomatous disease. DR Orphanet; 904; Williams syndrome. DR PharmGKB; PA31463; -. DR VEuPathDB; HostDB:ENSG00000158517; -. DR eggNOG; KOG4773; Eukaryota. DR GeneTree; ENSGT00940000160014; -. DR HOGENOM; CLU_030529_0_0_1; -. DR InParanoid; P14598; -. DR OMA; TEYCNTL; -. DR OrthoDB; 2910367at2759; -. DR PhylomeDB; P14598; -. DR TreeFam; TF329347; -. DR PathwayCommons; P14598; -. 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; P14598; -. DR SIGNOR; P14598; -. DR BioGRID-ORCS; 653361; 57 hits in 1135 CRISPR screens. DR ChiTaRS; NCF1; human. DR EvolutionaryTrace; P14598; -. DR GeneWiki; Neutrophil_cytosolic_factor_1; -. DR GenomeRNAi; 653361; -. DR Pharos; P14598; Tbio. DR PRO; PR:P14598; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P14598; Protein. DR Bgee; ENSG00000158517; Expressed in granulocyte and 100 other cell types or tissues. DR ExpressionAtlas; P14598; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0043020; C:NADPH oxidase complex; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0032010; C:phagolysosome; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:CAFA. DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB. DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB. DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IPI:BHF-UCL. DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IMP:CAFA. DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IBA:GO_Central. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0071276; P:cellular response to cadmium ion; IDA:CAFA. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:CAFA. DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:CAFA. DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IMP:CAFA. DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:CAFA. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:CAFA. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:CAFA. DR GO; GO:0006612; P:protein targeting to membrane; IDA:UniProtKB. DR GO; GO:1903409; P:reactive oxygen species biosynthetic process; IEA:Ensembl. DR GO; GO:0060264; P:regulation of respiratory burst involved in inflammatory response; IEA:Ensembl. DR GO; GO:0045730; P:respiratory burst; IBA:GO_Central. DR GO; GO:0042554; P:superoxide anion generation; IMP:GO_Central. DR GO; GO:0006801; P:superoxide metabolic process; TAS:BHF-UCL. DR CDD; cd06887; PX_p47phox; 1. DR CDD; cd12021; SH3_p47phox_1; 1. DR CDD; cd12022; SH3_p47phox_2; 1. DR DisProt; DP02254; -. DR Gene3D; 3.30.1520.10; Phox-like domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 2. DR IDEAL; IID00597; -. DR InterPro; IPR015039; NCF1_C. DR InterPro; IPR032136; NCF1_PBR/AIR. DR InterPro; IPR035756; NCF1_SH3_1. DR InterPro; IPR035757; NCF1_SH3_2. DR InterPro; IPR001655; P47PHOX. DR InterPro; IPR001683; PX_dom. DR InterPro; IPR036871; PX_dom_sf. DR InterPro; IPR034909; PX_p47phox. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR15706:SF6; NEUTROPHIL CYTOSOL FACTOR 1-RELATED; 1. DR PANTHER; PTHR15706; SH3 MULTIPLE DOMAIN; 1. DR Pfam; PF16621; NCF1_PBR_AIR; 1. DR Pfam; PF08944; p47_phox_C; 1. DR Pfam; PF00787; PX; 1. DR Pfam; PF00018; SH3_1; 2. DR PRINTS; PR00498; P47PHOX. DR SMART; SM00312; PX; 1. DR SMART; SM00326; SH3; 2. DR SUPFAM; SSF64268; PX domain; 1. DR SUPFAM; SSF50044; SH3-domain; 2. DR PROSITE; PS50195; PX; 1. DR PROSITE; PS50002; SH3; 2. DR Genevisible; P14598; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chronic granulomatous disease; KW Cytoplasm; Disease variant; Lipid-binding; Membrane; Phosphoprotein; KW Reference proteome; Repeat; SH3 domain. FT CHAIN 1..390 FT /note="Neutrophil cytosol factor 1" FT /id="PRO_0000096762" FT DOMAIN 4..125 FT /note="PX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147" FT DOMAIN 156..215 FT /note="SH3 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 226..285 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 285..390 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 375..390 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 303 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8089108" FT MOD_RES 304 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8089108" FT MOD_RES 320 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8089108" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8089108" FT MOD_RES 345 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8089108" FT MOD_RES 348 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8089108" FT VAR_SEQ 193 FT /note="W -> QTSHLTGLLPLVLRNPQPQAPCQGSGSLAPGRTPALLGALNVLPTLW FT VAFCLSVHPVVAVGICAWQAGAGHVCVFCLDGYGTVCSL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_035032" FT VAR_SEQ 194..390 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_035033" FT VARIANT 42 FT /note="R -> Q (in CGD1; dbSNP:rs119103270)" FT /evidence="ECO:0000269|PubMed:11133775" FT /id="VAR_012476" FT VARIANT 90 FT /note="R -> H (may influence susceptibility to systemic FT lupus erythematosus; dbSNP:rs13447)" FT /evidence="ECO:0000269|PubMed:28135245" FT /id="VAR_014735" FT VARIANT 99 FT /note="S -> G (in dbSNP:rs10614)" FT /evidence="ECO:0000269|PubMed:12853948, FT ECO:0000269|PubMed:15489334" FT /id="VAR_018479" FT VARIANT 160 FT /note="T -> S" FT /evidence="ECO:0000269|PubMed:10772875, FT ECO:0000269|PubMed:9329953" FT /id="VAR_012477" FT VARIANT 166 FT /note="N -> D (in dbSNP:rs782555266)" FT /evidence="ECO:0000269|PubMed:11740866, FT ECO:0000269|PubMed:2398896, ECO:0000269|PubMed:2547247, FT ECO:0000269|Ref.14" FT /id="VAR_012478" FT VARIANT 258 FT /note="K -> E" FT /evidence="ECO:0000269|PubMed:11740866" FT /id="VAR_018476" FT VARIANT 262 FT /note="G -> S (in dbSNP:rs1489201208)" FT /evidence="ECO:0000269|PubMed:11133775" FT /id="VAR_012479" FT VARIANT 308 FT /note="A -> V (in dbSNP:rs13739)" FT /evidence="ECO:0000269|PubMed:10772875, FT ECO:0000269|PubMed:9329953" FT /id="VAR_012480" FT MUTAGEN 43 FT /note="R->Q: Reduces affinity for membranes enriched in FT phosphatidylinositol 3,4-bisphosphate." FT /evidence="ECO:0000269|PubMed:12356722" FT MUTAGEN 90 FT /note="R->A: Reduces affinity for membranes enriched in FT phosphatidylinositol 3,4-bisphosphate." FT /evidence="ECO:0000269|PubMed:12356722" FT MUTAGEN 263 FT /note="W->R: Abolishes autoinhibition and promotes FT phospholipid binding." FT /evidence="ECO:0000269|PubMed:12356722" FT MUTAGEN 303 FT /note="S->E: Abolishes autoinhibition and promotes FT phospholipid binding; when associated with E-304; E-328; FT E-359 and E-370." FT /evidence="ECO:0000269|PubMed:12356722" FT MUTAGEN 304 FT /note="S->E: Abolishes autoinhibition and promotes FT phospholipid binding; when associated with E-303; E-328; FT E-359 and E-370." FT /evidence="ECO:0000269|PubMed:12356722" FT MUTAGEN 328 FT /note="S->E: Abolishes autoinhibition and promotes FT phospholipid binding; when associated with E-303; E-304; FT E-359 and E-370." FT /evidence="ECO:0000269|PubMed:12356722" FT MUTAGEN 359 FT /note="S->E: Abolishes autoinhibition and promotes FT phospholipid binding; when associated with E-303; E-304; FT E-328 and E-370." FT /evidence="ECO:0000269|PubMed:12356722" FT MUTAGEN 370 FT /note="S->E: Abolishes autoinhibition and promotes FT phospholipid binding; when associated with E-303; E-304; FT E-328 and E-359." FT /evidence="ECO:0000269|PubMed:12356722" FT CONFLICT 200 FT /note="A -> T (in Ref. 7; AAK19516)" FT /evidence="ECO:0000305" FT STRAND 6..17 FT /evidence="ECO:0007829|PDB:1KQ6" FT STRAND 19..21 FT /evidence="ECO:0007829|PDB:1KQ6" FT STRAND 23..32 FT /evidence="ECO:0007829|PDB:1KQ6" FT STRAND 37..42 FT /evidence="ECO:0007829|PDB:1KQ6" FT HELIX 44..57 FT /evidence="ECO:0007829|PDB:1KQ6" FT TURN 59..63 FT /evidence="ECO:0007829|PDB:1KQ6" FT HELIX 67..69 FT /evidence="ECO:0007829|PDB:1KQ6" FT HELIX 78..80 FT /evidence="ECO:0007829|PDB:1O7K" FT HELIX 84..101 FT /evidence="ECO:0007829|PDB:1KQ6" FT HELIX 106..109 FT /evidence="ECO:0007829|PDB:1KQ6" FT HELIX 112..118 FT /evidence="ECO:0007829|PDB:1KQ6" FT HELIX 122..125 FT /evidence="ECO:0007829|PDB:1KQ6" FT STRAND 137..140 FT /evidence="ECO:0007829|PDB:1KQ6" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:1WLP" FT STRAND 159..162 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 171..174 FT /evidence="ECO:0007829|PDB:7YXW" FT STRAND 182..187 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 202..206 FT /evidence="ECO:0007829|PDB:1OV3" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 210..214 FT /evidence="ECO:0007829|PDB:1OV3" FT STRAND 229..235 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 241..244 FT /evidence="ECO:0007829|PDB:1WLP" FT STRAND 252..257 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 262..268 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 271..276 FT /evidence="ECO:0007829|PDB:1NG2" FT HELIX 277..279 FT /evidence="ECO:0007829|PDB:1NG2" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:1NG2" FT HELIX 287..292 FT /evidence="ECO:0007829|PDB:1NG2" FT HELIX 302..304 FT /evidence="ECO:0007829|PDB:1NG2" FT HELIX 321..328 FT /evidence="ECO:0007829|PDB:1NG2" FT HELIX 371..376 FT /evidence="ECO:0007829|PDB:1K4U" FT HELIX 380..385 FT /evidence="ECO:0007829|PDB:1K4U" SQ SEQUENCE 390 AA; 44682 MW; 3D91EDC99A1B6417 CRC64; MGDTFIRHIA LLGFEKRFVP SQHYVYMFLV KWQDLSEKVV YRRFTEIYEF HKTLKEMFPI EAGAINPENR IIPHLPAPKW FDGQRAAENR QGTLTEYCST LMSLPTKISR CPHLLDFFKV RPDDLKLPTD NQTKKPETYL MPKDGKSTAT DITGPIILQT YRAIANYEKT SGSEMALSTG DVVEVVEKSE SGWWFCQMKA KRGWIPASFL EPLDSPDETE DPEPNYAGEP YVAIKAYTAV EGDEVSLLEG EAVEVIHKLL DGWWVIRKDD VTGYFPSMYL QKSGQDVSQA QRQIKRGAPP RRSSIRNAHS IHQRSRKRLS QDAYRRNSVR FLQQRRRQAR PGPQSPGSPL EEERQTQRSK PQPAVPPRPS ADLILNRCSE STKRKLASAV //