ID   CY24A_HUMAN             Reviewed;         195 AA.
AC   P13498; Q14090; Q9BR72;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   25-NOV-2008, entry version 90.
DE   RecName: Full=Cytochrome b-245 light chain;
DE   AltName: Full=p22 phagocyte B-cytochrome;
DE   AltName: Full=Neutrophil cytochrome b 22 kDa polypeptide;
DE   AltName: Full=p22-phox;
DE            Short=p22phox;
DE   AltName: Full=Cytochrome b(558) alpha chain;
DE   AltName: Full=Cytochrome b558 subunit alpha;
DE   AltName: Full=Superoxide-generating NADPH oxidase light chain subunit;
GN   Name=CYBA;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-26.
RX   MEDLINE=88217892; PubMed=3368442;
RA   Parkos C.A., Dinauer M.C., Walker L.E., Allen R.A., Jesaitis A.J.,
RA   Orkin S.H.;
RT   "Primary structure and unique expression of the 22-kilodalton light
RT   chain of human neutrophil cytochrome b.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:3319-3323(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-72.
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
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-123, AND VARIANT AR-CGD
RP   ARG-118.
RX   MEDLINE=91056180; PubMed=2243141;
RA   Dinauer M.C., Pierce E.A., Bruns G.A.P., Curnutte J.T., Orkin S.H.;
RT   "Human neutrophil cytochrome b light chain (p22-phox). Gene structure,
RT   chromosomal location, and mutations in cytochrome-negative autosomal
RT   recessive chronic granulomatous disease.";
RL   J. Clin. Invest. 86:1729-1737(1990).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 51-195.
RX   MEDLINE=89229402; PubMed=2469497;
RA   Verhoeven A.J., Bolscher B.G., Meerhof L.J., van Zwieten R.,
RA   Keijer J., Weening R.S., Roos D.;
RT   "Characterization of two monoclonal antibodies against cytochrome b558
RT   of human neutrophils.";
RL   Blood 73:1686-1694(1989).
RN   [6]
RP   INTERACTION WITH NOXO1, AND MUTAGENESIS OF PRO-157.
RX   MEDLINE=22716264; 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
RT   activation of superoxide-producing NADPH oxidases.";
RL   J. Biol. Chem. 278:25234-25246(2003).
RN   [7]
RP   INTERACTION WITH DUOX1; DUOX2 AND TPO.
RX   PubMed=15561711; DOI=10.1074/jbc.M407709200;
RA   Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E.,
RA   Miot F.;
RT   "Identification of a novel partner of duox: EFP1, a thioredoxin-
RT   related protein.";
RL   J. Biol. Chem. 280:3096-3103(2005).
RN   [8]
RP   FUNCTION.
RX   PubMed=15824103; DOI=10.1074/jbc.M414548200;
RA   Ueno N., Takeya R., Miyano K., Kikuchi H., Sumimoto H.;
RT   "The NADPH oxidase Nox3 constitutively produces superoxide in a
RT   p22phox-dependent manner: its regulation by oxidase organizers and
RT   activators.";
RL   J. Biol. Chem. 280:23328-23339(2005).
RN   [9]
RP   INTERACTION WITH NOX4.
RX   PubMed=15927447; DOI=10.1016/j.cellsig.2005.03.023;
RA   Martyn K.D., Frederick L.M., von Loehneysen K., Dinauer M.C.,
RA   Knaus U.G.;
RT   "Functional analysis of Nox4 reveals unique characteristics compared
RT   to other NADPH oxidases.";
RL   Cell. Signal. 18:69-82(2006).
RN   [10]
RP   VARIANTS AR-CGD GLN-90 AND ARG-94.
RX   MEDLINE=93035377; PubMed=1415254;
RA   de Boer M., de Klein A., Hossle J.-P., Seger R., Corbeel L.,
RA   Weening R.S., Roos D.;
RT   "Cytochrome b558-negative, autosomal recessive chronic granulomatous
RT   disease: two new mutations in the cytochrome b558 light chain of the
RT   NADPH oxidase (p22-phox).";
RL   Am. J. Hum. Genet. 51:1127-1135(1992).
RN   [11]
RP   VARIANT AR-CGD GLN-156.
RX   MEDLINE=92107923; PubMed=1763037;
RA   Dinauer M.C., Pierce E.A., Erickson R.W., Muhlebach T.J., Messner H.,
RA   Orkin S.H., Seger R.A., Curnutte J.T.;
RT   "Point mutation in the cytoplasmic domain of the neutrophil p22-phox
RT   cytochrome b subunit is associated with a nonfunctional NADPH oxidase
RT   and chronic granulomatous disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:11231-11235(1991).
RN   [12]
RP   CHARACTERIZATION OF VARIANT AR-CGD GLN-156.
RX   MEDLINE=95053767; PubMed=7964505; DOI=10.1084/jem.180.6.2329;
RA   Leusen J.H., Bolscher B.G., Hilarius P.M., Weening R.S.,
RA   Kaulfersch W., Seger R.A., Roos D., Verhoeven A.J.;
RT   "156Pro-->Gln substitution in the light chain of cytochrome b558 of
RT   the human NADPH oxidase (p22-phox) leads to defective translocation of
RT   the cytosolic proteins p47-phox and p67-phox.";
RL   J. Exp. Med. 180:2329-2334(1994).
RN   [13]
RP   VARIANT AR-CGD ARG-24.
RX   MEDLINE=20223064; PubMed=10759707;
RX   DOI=10.1046/j.1365-2141.2000.01857.x;
RA   Yamada M., Ariga T., Kawamura N., Ohtsu M., Imajoh-Ohmi S.,
RA   Ohshika E., Tatsuzawa O., Kobayashi K., Sakiyama Y.;
RT   "Genetic studies of three Japanese patients with p22-phox-deficient
RT   chronic granulomatous disease: detection of a possible common mutant
RT   CYBA allele in Japan and a genotype-phenotype correlation in these
RT   patients.";
RL   Br. J. Haematol. 108:511-517(2000).
CC   -!- FUNCTION: Critical component of the membrane-bound oxidase of
CC       phagocytes that generates superoxide. Associates with NOX3 to form
CC       a functional NADPH oxidase constitutively generating superoxide.
CC   -!- SUBUNIT: Composed of a heavy chain (beta) and a light chain
CC       (alpha). Interacts with DUOX1, DUOX2 and TPO. Interacts with NOX3
CC       and NOX4.
CC   -!- INTERACTION:
CC       P14598:NCF1; NbExp=4; IntAct=EBI-986058, EBI-395044;
CC   -!- SUBCELLULAR LOCATION: Membrane (Potential).
CC   -!- DISEASE: Defects in CYBA are a cause of autosomal recessive
CC       chronic granulomatous disease (AR-CGD) [MIM:233690]. AR-CGD is
CC       characterized by the failure of activated phagocytes to generate
CC       superoxide.
CC   -!- MISCELLANEOUS: The heme prosthetic group could be coordinated with
CC       residues of the light chain, the heavy chain, or both, and it is
CC       possible that more than one heme is present per cytochrome b-245.
CC   -!- SIMILARITY: Belongs to the p22phox family.
CC   -!- WEB RESOURCE: Name=CYBAbase; Note=CYBA mutation db;
CC       URL="http://bioinf.uta.fi/CYBAbase/";
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.genetests.org/query?gene=CYBA";
CC   -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC       polymorphism database;
CC       URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=C&genename=CYBB+%40+GP91-PHOX";
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DR   EMBL; M21186; AAA90925.1; -; mRNA.
DR   EMBL; BT006861; AAP35507.1; -; mRNA.
DR   EMBL; BC006465; AAH06465.1; -; mRNA.
DR   EMBL; M62818; AAA52134.1; -; Genomic_DNA.
DR   EMBL; M61106; AAA52134.1; JOINED; Genomic_DNA.
DR   EMBL; M62817; AAA52134.1; JOINED; Genomic_DNA.
DR   EMBL; M61107; AAA52134.1; JOINED; Genomic_DNA.
DR   PIR; A28201; A28201.
DR   RefSeq; NP_000092.2; -.
DR   UniGene; Hs.513803; -.
DR   PDB; 1WLP; NMR; -; A=144-168.
DR   PDBsum; 1WLP; -.
DR   IntAct; P13498; -.
DR   PeptideAtlas; P13498; -.
DR   Ensembl; ENSG00000051523; Homo sapiens.
DR   GeneID; 1535; -.
DR   KEGG; hsa:1535; -.
DR   H-InvDB; HIX0013335; -.
DR   HGNC; HGNC:2577; CYBA.
DR   HPA; CAB009492; -.
DR   MIM; 233690; phenotype.
DR   MIM; 608508; gene.
DR   PharmGKB; PA27075; -.
DR   HOGENOM; P13498; -.
DR   HOVERGEN; P13498; -.
DR   NextBio; 6349; -.
DR   ArrayExpress; P13498; -.
DR   CleanEx; HS_CYBA; -.
DR   GermOnline; ENSG00000051523; Homo sapiens.
DR   GO; GO:0043020; C:NADPH oxidase complex; IDA:UniProtKB.
DR   GO; GO:0030141; C:secretory granule; TAS:UniProtKB.
DR   GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR   GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB.
DR   GO; GO:0017004; P:cytochrome complex assembly; IDA:UniProtKB.
DR   GO; GO:0022900; P:electron transport chain; IEA:UniProtKB-KW.
DR   GO; GO:0050665; P:hydrogen peroxide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; IMP:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR   GO; GO:0045730; P:respiratory burst; IMP:UniProtKB.
DR   GO; GO:0014895; P:smooth muscle hypertrophy; ISS:UniProtKB.
DR   GO; GO:0042554; P:superoxide release; IMP:UniProtKB.
DR   GO; GO:0006810; P:transport; IEA:UniProtKB-KW.
DR   InterPro; IPR007732; Cytochr_b558a.
DR   PANTHER; PTHR15168; Cytochr_b558a; 1.
DR   Pfam; PF05038; Cytochrom_B558a; 1.
DR   PIRSF; PIRSF019635; Cytochr_b558a; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Chronic granulomatous disease;
KW   Direct protein sequencing; Disease mutation; Electron transport; Heme;
KW   Iron; Membrane; Metal-binding; NADP; Oxidoreductase; Polymorphism;
KW   Transport.
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    195       Cytochrome b-245 light chain.
FT                                /FTId=PRO_0000144907.
FT   METAL        94     94       Iron (heme axial ligand) (Potential).
FT   VARIANT      24     24       G -> R (in AR-CGD).
FT                                /FTId=VAR_012755.
FT   VARIANT      72     72       H -> Y (in dbSNP:rs4673).
FT                                /FTId=VAR_005122.
FT   VARIANT      90     90       R -> Q (in AR-CGD).
FT                                /FTId=VAR_005123.
FT   VARIANT      94     94       H -> R (in AR-CGD).
FT                                /FTId=VAR_005124.
FT   VARIANT     118    118       S -> R (in AR-CGD).
FT                                /FTId=VAR_005125.
FT   VARIANT     156    156       P -> Q (in AR-CGD).
FT                                /FTId=VAR_005126.
FT   MUTAGEN     157    157       P->Q: Loss of interaction with NOXO1.
FT   HELIX       161    165
SQ   SEQUENCE   195 AA;  20958 MW;  429E97A6A9303510 CRC64;
     MGQIEWAMWA NEQALASGLI LITGGIVATA GRFTQWYFGA YSIVAGVFVC LLEYPRGKRK
     KGSTMERWGQ KHMTAVVKLF GPFTRNYYVR AVLHLLLSVP AGFLLATILG TACLAIASGI
     YLLAAVRGEQ WTPIEPKPRE RPQIGGTIKQ PPSNPPPRPP AEARKKPSEE EAAAAAGGPP
     GGPQVNPIPV TDEVV
//