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 27-MAR-2024, entry version 182. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 30. DR DIP; DIP-60841N; -. DR IntAct; Q61093; 6. DR MINT; Q61093; -. DR STRING; 10090.ENSMUSP00000015484; -. DR PeroxiBase; 5957; MmNOx02. DR GlyCosmos; Q61093; 1 site, No reported glycans. DR GlyGen; Q61093; 1 site. DR iPTMnet; Q61093; -. DR PhosphoSitePlus; Q61093; -. DR SwissPalm; Q61093; -. DR jPOST; Q61093; -. DR MaxQB; Q61093; -. DR PaxDb; 10090-ENSMUSP00000015484; -. DR ProteomicsDB; 285357; -. DR Antibodypedia; 24864; 590 antibodies from 40 providers. DR DNASU; 13058; -. DR Ensembl; ENSMUST00000015484.10; ENSMUSP00000015484.4; ENSMUSG00000015340.11. DR GeneID; 13058; -. DR KEGG; mmu:13058; -. DR UCSC; uc009spv.3; mouse. DR AGR; MGI:88574; -. 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; FTFAKEH; -. DR OrthoDB; 367877at2759; -. 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 77 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 122 other cell types or tissues. DR ExpressionAtlas; Q61093; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0005739; C:mitochondrion; HDA:MGI. DR GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW. DR GO; GO:0043020; C:NADPH oxidase complex; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005635; C:nuclear envelope; ISO:MGI. 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:0009055; F:electron transfer activity; IEA:Ensembl. 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: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; ISO:MGI. DR GO; GO:0006954; P:inflammatory response; IMP:UniProtKB. DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; IEA:UniProtKB-KW. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI. 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; ISO:MGI. DR GO; GO:0042554; P:superoxide anion generation; ISO:MGI. DR GO; GO:0006801; P:superoxide metabolic process; IMP:UniProtKB. DR CDD; cd06186; NOX_Duox_like_FAD_NADP; 1. DR Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1. DR Gene3D; 2.40.30.10; Translation factors; 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 PANTHER; PTHR11972:SF60; CYTOCHROME B-245 HEAVY CHAIN; 1. DR PANTHER; PTHR11972; NADPH OXIDASE; 1. 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 SFLD; SFLDS00052; Ferric_Reductase_Domain; 1. DR SFLD; SFLDG01168; Ferric_reductase_subgroup_(FRE; 1. DR SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1. DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 1. DR PROSITE; PS51384; FAD_FR; 1. DR Genevisible; Q61093; MM. 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 //