CY24B_MOUSE
ID CY24B_MOUSE Reviewed; 570 AA.
AC Q61093;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Cytochrome b-245 heavy chain;
DE EC=1.-.-.-;
DE AltName: Full=CGD91-phox;
DE AltName: Full=Cytochrome b(558) subunit beta;
DE Short=Cytochrome b558 subunit beta;
DE AltName: Full=Heme-binding membrane glycoprotein gp91phox;
DE AltName: Full=Neutrophil cytochrome b 91 kDa polypeptide;
DE AltName: Full=gp91-1;
DE AltName: Full=gp91-phox;
DE AltName: Full=p22 phagocyte B-cytochrome;
GN Name=Cybb {ECO:0000312|MGI:MGI:88574}; Synonyms=Cgd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8634451;
RA Bjorgvinsdottir H., Zhen L., Dinauer M.C.;
RT "Cloning of murine gp91phox cDNA and functional expression in a human X-
RT linked chronic granulomatous disease cell line.";
RL Blood 87:2005-2010(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary gland;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP INTERACTION WITH NCF2 AND GBP7.
RX PubMed=21551061; DOI=10.1126/science.1201711;
RA Kim B.H., Shenoy A.R., Kumar P., Das R., Tiwari S., MacMicking J.D.;
RT "A family of IFN-gamma-inducible 65-kD GTPases protects against bacterial
RT infection.";
RL Science 332:717-721(2011).
RN [5]
RP INTERACTION WITH NRROS, AND FUNCTION.
RX PubMed=24739962; DOI=10.1038/nature13152;
RA Noubade R., Wong K., Ota N., Rutz S., Eidenschenk C., Valdez P.A., Ding J.,
RA Peng I., Sebrell A., Caplazi P., Devoss J., Soriano R.H., Sai T., Lu R.,
RA Modrusan Z., Hackney J., Ouyang W.;
RT "NRROS negatively regulates reactive oxygen species during host defence and
RT autoimmunity.";
RL Nature 509:235-239(2014).
RN [6]
RP UBIQUITINATION AT LYS-159; LYS-161; LYS-255; LYS-294; LYS-299; LYS-306;
RP LYS-328; LYS-334; LYS-381; LYS-506 AND LYS-567.
RX PubMed=26194095; DOI=10.1038/ncomms8838;
RA Graham D.B., Becker C.E., Doan A., Goel G., Villablanca E.J., Knights D.,
RA Mok A., Ng A.C., Doench J.G., Root D.E., Clish C.B., Xavier R.J.;
RT "Functional genomics identifies negative regulatory nodes controlling
RT phagocyte oxidative burst.";
RL Nat. Commun. 6:7838-7838(2015).
RN [7]
RP DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=28351984; DOI=10.1084/jem.20161382;
RA Thomas D.C., Clare S., Sowerby J.M., Pardo M., Juss J.K., Goulding D.A.,
RA van der Weyden L., Storisteanu D., Prakash A., Espeli M., Flint S.,
RA Lee J.C., Hoenderdos K., Kane L., Harcourt K., Mukhopadhyay S., Umrania Y.,
RA Antrobus R., Nathan J.A., Adams D.J., Bateman A., Choudhary J.S.,
RA Lyons P.A., Condliffe A.M., Chilvers E.R., Dougan G., Smith K.G.;
RT "Eros is a novel transmembrane protein that controls the phagocyte
RT respiratory burst and is essential for innate immunity.";
RL J. Exp. Med. 214:1111-1128(2017).
CC -!- FUNCTION: Critical component of the membrane-bound oxidase of
CC phagocytes that generates superoxide. It is the terminal component of a
CC respiratory chain that transfers single electrons from cytoplasmic
CC NADPH across the plasma membrane to molecular oxygen on the exterior.
CC Also functions as a voltage-gated proton channel that mediates the H(+)
CC currents of resting phagocytes. {ECO:0000269|PubMed:24739962}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- SUBUNIT: Composed of a heavy chain (beta) and a light chain (alpha).
CC Component of an NADPH oxidase complex composed of a heterodimer formed
CC by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1,
CC NCF2 and NCF4. Interacts with NCF1. Interacts with calprotectin
CC (S100A8/9) (By similarity). Interacts with NRROS; the interaction is
CC direct and impairs formation of a stable NADPH oxidase complex
CC (PubMed:24739962). Interacts with CYBC1; CYBC1 may act as a chaperone
CC stabilizing Cytochrome b-245 heterodimer (By similarity). Interacts
CC with NCF2; the interaction is enhanced in the presence of GBP7
CC (PubMed:21551061). The CYBA-CYBB complex interacts with GBP7
CC (PubMed:21551061). {ECO:0000250|UniProtKB:P04839,
CC ECO:0000269|PubMed:21551061, ECO:0000269|PubMed:24739962}.
CC -!- INTERACTION:
CC Q61093; Q61462: Cyba; NbExp=4; IntAct=EBI-6654585, EBI-15795776;
CC Q61093; Q8BMT4: Nrros; NbExp=4; IntAct=EBI-6654585, EBI-16102695;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Note=As unassembled monomer may localize to the endoplasmic reticulum.
CC {ECO:0000305|PubMed:28351984}.
CC -!- PTM: Glycosylated.
CC -!- PTM: Phosphorylated on Ser and Thr residues. {ECO:0000250}.
CC -!- PTM: Undergoes 'Lys-48'-linked polyubiquitination, likely by RNF145,
CC triggering endoplasmic reticulum-associated degradation.
CC {ECO:0000269|PubMed:26194095}.
CC -!- DISRUPTION PHENOTYPE: Mutants have a very sever defect in controlling
CC bacterial replication. {ECO:0000269|PubMed:28351984}.
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DR EMBL; U43384; AAB05997.1; -; mRNA.
DR EMBL; BC071229; AAH71229.1; -; mRNA.
DR CCDS; CCDS30010.1; -.
DR RefSeq; NP_031833.3; NM_007807.5.
DR RefSeq; XP_006527628.1; XM_006527565.3.
DR AlphaFoldDB; Q61093; -.
DR SMR; Q61093; -.
DR BioGRID; 198990; 29.
DR DIP; DIP-60841N; -.
DR IntAct; Q61093; 6.
DR MINT; Q61093; -.
DR STRING; 10090.ENSMUSP00000015484; -.
DR PeroxiBase; 5957; MmNOx02.
DR GlyGen; Q61093; 1 site.
DR iPTMnet; Q61093; -.
DR PhosphoSitePlus; Q61093; -.
DR SwissPalm; Q61093; -.
DR jPOST; Q61093; -.
DR MaxQB; Q61093; -.
DR PaxDb; Q61093; -.
DR PRIDE; Q61093; -.
DR ProteomicsDB; 285357; -.
DR Antibodypedia; 24864; 513 antibodies from 40 providers.
DR DNASU; 13058; -.
DR Ensembl; ENSMUST00000015484; ENSMUSP00000015484; ENSMUSG00000015340.
DR GeneID; 13058; -.
DR KEGG; mmu:13058; -.
DR UCSC; uc009spv.3; mouse.
DR CTD; 1536; -.
DR MGI; MGI:88574; Cybb.
DR VEuPathDB; HostDB:ENSMUSG00000015340; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000160244; -.
DR HOGENOM; CLU_005646_3_1_1; -.
DR InParanoid; Q61093; -.
DR OMA; KPSMKYK; -.
DR OrthoDB; 936110at2759; -.
DR PhylomeDB; Q61093; -.
DR TreeFam; TF105354; -.
DR Reactome; R-MMU-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-MMU-1236973; Cross-presentation of particulate exogenous antigens (phagosomes).
DR Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR BioGRID-ORCS; 13058; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Cybb; mouse.
DR PRO; PR:Q61093; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q61093; protein.
DR Bgee; ENSMUSG00000015340; Expressed in granulocyte and 120 other tissues.
DR ExpressionAtlas; Q61093; baseline and differential.
DR Genevisible; Q61093; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043020; C:NADPH oxidase complex; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0009055; F:electron transfer activity; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0016175; F:superoxide-generating NAD(P)H oxidase activity; IDA:MGI.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0071276; P:cellular response to cadmium ion; IEA:Ensembl.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR GO; GO:1904845; P:cellular response to L-glutamine; IEA:Ensembl.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0050665; P:hydrogen peroxide biosynthetic process; IMP:MGI.
DR GO; GO:0097411; P:hypoxia-inducible factor-1alpha signaling pathway; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0045730; P:respiratory burst; ISO:MGI.
DR GO; GO:1904044; P:response to aldosterone; IEA:Ensembl.
DR GO; GO:1990776; P:response to angiotensin; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0042554; P:superoxide anion generation; ISO:MGI.
DR GO; GO:0006801; P:superoxide metabolic process; IMP:UniProtKB.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR000778; Cyt_b245_heavy_chain.
DR InterPro; IPR013112; FAD-bd_8.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR InterPro; IPR013121; Fe_red_NAD-bd_6.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF08022; FAD_binding_8; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR Pfam; PF08030; NAD_binding_6; 1.
DR PRINTS; PR00466; GP91PHOX.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Electron transport; FAD; Flavoprotein; Glycoprotein; Heme;
KW Ion channel; Ion transport; Iron; Isopeptide bond; Membrane; Metal-binding;
KW NADP; Oxidoreductase; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..570
FT /note="Cytochrome b-245 heavy chain"
FT /id="PRO_0000210146"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..48
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 70..102
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..169
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..261
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..570
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 54..286
FT /note="Ferric oxidoreductase"
FT DOMAIN 287..397
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 101
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000305"
FT BINDING 115
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000305"
FT BINDING 209
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000305"
FT BINDING 222
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000305"
FT BINDING 338..344
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 161
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 255
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 294
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 306
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 328
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 334
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 381
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 506
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
FT CROSSLNK 567
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26194095"
SQ SEQUENCE 570 AA; 65305 MW; 8816274E3D253DFA CRC64;
MGNWAVNEGL SIFVILVWLG LNVFLFINYY KVYDDGPKYN YTRKLLGSAL ALARAPAACL
NFNCMLILLP VCRNLLSFLR GSSACCSTRI RRQLDRNLTF HKMVAWMIAL HTAIHTIAHL
FNVEWCVNAR VGISDRYSIA LSDIGDNENE EYLNFAREKI KNPEGGLYVA VTRLAGITGI
VITLCLILII TSSTKTIRRS YFEVFWYTHH LFVIFFIGLA IHGAERIVRG QTAESLEEHN
LDICADKIEE WGKIKECPVP KFAGNPPMTW KWIVGPMFLY LCERLVRFWR SQQKVVITKV
VTHPFKTIEL QMKKKGFKME VGQYIFVKCP KVSKLEWHPF TLTSAPEEDF FSIHIRIVGD
WTEGLFNACG CDKQEFQDAW KLPKIAVDGP FGTASEDVFS YEVVMLVGAG IGVTPFASIL
KSVWYKYCDN ATSLKLKKIY FYWLCRDTHA FEWFADLLQL LETQMQERNN ANFLSYNIYL
TGWDESQANH FAVHHDEEKD VITGLKQKTL YGRPNWDNEF KTIASEHPNT TIGVFLCGPE
ALAETLSKQS ISNSESGPRG VHFIFNKENF
