NCF1_HUMAN
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 03-AUG-2022, entry version 246.
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; TRP-263; SER-303; SER-304;
RP 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). {ECO:0000250|UniProtKB:Q09014,
CC ECO:0000269|PubMed:12023963, ECO:0000269|PubMed:12169629,
CC ECO:0000269|PubMed:12716910, ECO:0000269|PubMed:12732142,
CC ECO:0000269|PubMed:15657040, ECO:0000269|PubMed:16052631,
CC ECO:0000269|PubMed:16326715, ECO:0000269|PubMed:19718658,
CC ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:2550933,
CC 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/";
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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; 84.
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; P14598; -.
DR PeptideAtlas; P14598; -.
DR PRIDE; P14598; -.
DR ProteomicsDB; 53060; -. [P14598-1]
DR ProteomicsDB; 53061; -. [P14598-2]
DR Antibodypedia; 3863; 954 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 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; WWVVRKD; -.
DR OrthoDB; 1183210at2759; -.
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; 40 hits in 1065 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 99 other tissues.
DR ExpressionAtlas; P14598; baseline and differential.
DR Genevisible; P14598; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; 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:0005791; C:rough endoplasmic reticulum; IEA:Ensembl.
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:0006915; P:apoptotic process; IEA:Ensembl.
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:0034614; P:cellular response to reactive oxygen species; IDA:CAFA.
DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL.
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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:CAFA.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; 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; -; 1.
DR IDEAL; IID00597; -.
DR InterPro; IPR015039; NADPH_oxidase_p47Phox_C.
DR InterPro; IPR035756; NCF1_SH3_1.
DR InterPro; IPR035757; NCF1_SH3_2.
DR InterPro; IPR032136; NECFESHC.
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; PTHR15706:SF6; 1.
DR Pfam; PF16621; NECFESHC; 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; SSF50044; SSF50044; 2.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50002; SH3; 2.
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 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; E-
FT 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; E-
FT 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; E-
FT 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; E-
FT 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; E-
FT 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:1WLP"
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
