NCF2_HUMAN
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 03-AUG-2022, entry version 236.
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-GLU-VAL-161.
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";
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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; 30.
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; P19878; -.
DR PeptideAtlas; P19878; -.
DR PRIDE; P19878; -.
DR ProteomicsDB; 20550; -.
DR ProteomicsDB; 20618; -.
DR ProteomicsDB; 53699; -. [P19878-1]
DR Antibodypedia; 702; 291 antibodies from 30 providers.
DR DNASU; 4688; -.
DR Ensembl; ENST00000367535.8; ENSP00000356505.4; ENSG00000116701.15. [P19878-1]
DR Ensembl; ENST00000367536.5; ENSP00000356506.1; ENSG00000116701.15. [P19878-1]
DR Ensembl; ENST00000413720.5; ENSP00000399294.1; ENSG00000116701.15. [P19878-3]
DR Ensembl; ENST00000418089.5; ENSP00000407217.1; ENSG00000116701.15. [P19878-4]
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 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; SKVNQDW; -.
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 1073 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 132 other tissues.
DR ExpressionAtlas; P19878; baseline and differential.
DR Genevisible; P19878; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0043020; C:NADPH oxidase complex; IDA:UniProtKB.
DR GO; GO:0032010; C:phagolysosome; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI: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; cd11871; SH3_p67phox_N; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR IDEAL; IID00299; -.
DR InterPro; IPR034889; P67-PHOX.
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; PTHR15175:SF3; 1.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00018; SH3_1; 2.
DR Pfam; PF13181; TPR_8; 2.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00326; SH3; 2.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF50044; SSF50044; 2.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS50002; SH3; 2.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 1.
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 /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
