CYBB

CYBB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3A1F
Identifiers
Aliases	CYBB, AMCBX2, CGD, GP91-1, GP91-PHOX, GP91PHOX, IMD34, NOX2, p91-PHOX, cytochrome b-245 beta chain
External IDs	OMIM: 300481 MGI: 88574 HomoloGene: 68054 GeneCards: CYBB
Gene ontology Molecular function • flavin adenine dinucleotide binding • superoxide-generating NADPH oxidase activity • metal ion binding • voltage-gated ion channel activity • protein binding • heme binding • protein heterodimerization activity • electron carrier activity • oxidoreductase activity Cellular component • cytoplasm • integral component of membrane • phagocytic vesicle membrane • membrane • plasma membrane • integral component of plasma membrane • NADPH oxidase complex • mitochondrion • perinuclear region of cytoplasm • phagocytic vesicle • Golgi apparatus • endoplasmic reticulum • neuronal cell body • intracellular • endoplasmic reticulum membrane • rough endoplasmic reticulum • dendrite • nuclear envelope Biological process • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent • regulation of ion transmembrane transport • ion transport • cell redox homeostasis • superoxide anion generation • respiratory burst • vascular endothelial growth factor receptor signaling pathway • hydrogen peroxide biosynthetic process • innate immune response • inflammatory response • oxidation-reduction process • superoxide metabolic process • cellular response to L-glutamine • response to reactive oxygen species • positive regulation of angiogenesis • response to angiotensin • response to nutrient • cellular response to hypoxia • hypoxia-inducible factor-1alpha signaling pathway • cellular response to cadmium ion • cellular response to ethanol • response to drug • response to aldosterone • positive regulation of tumor necrosis factor biosynthetic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1536	13058
Ensembl	ENSG00000165168	ENSMUSG00000015340
UniProt	P04839	Q61093
RefSeq (mRNA)	NM_000397	NM_007807
RefSeq (protein)	NP_000388.2	NP_031833.3
Location (UCSC)	Chr X: 37.78 – 37.81 Mb	Chr X: 9.44 – 9.49 Mb
PubMed search	[1]	[2]
Wikidata

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Cytochrome b-245 heavy chain also known as cytochrome b(558) subunit beta or NADPH oxidase 2 or Nox2 is a protein that in humans is encoded by the CYBB gene.^[3] The protein is a super-oxide generating enzyme which forms reactive oxygen species (ROS).

Function

Nox2, or Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes.^[3]

Also, many of the functions for Nox2 are linked through the many functions of NADPH oxidase since Nox2 is one of the several isoforms of the gp91^phox catalytic subunit of NADPH oxidase.^[4]

There has been recent evidence that shows that it plays an important role in atherosclerotic lesion development in the aortic arch, thoracic, and abdominal aorta.^[4]

It has also been shown to play a part in determining the size of a myocardial infarction due to its connection to ROS which play a role in myocardial reperfusion injury. This was a result of the relation between Nox2 and the signalling towards neutrophil invasion.^[5] Also, it increases golbal post-reperfusion oxidative stress probably due to decreased STAT3 and Erk phosphorylation.^[5]

As well, it appears that hippocampal oxidative stress is increase in septic animals due to the actions of Nox2. This connection also came about through the actions of the chemically active ROS which work as one of the main components that help in the development of neuroinflammation associated with Sepsis-associated encephalopathy (SAE).^[6]

Lastly, due to recent experiments, it seems that Nox2 also plays an important role in angiotensin II-mediated inward remodelling in cerebral arterioles due to the emittance of superoxides from Nox2-containing NADPH oxidases.^[7]

Clinical significance

CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this disorder, there is decreased activity of phagocyte NADPH oxidase; neutrophils are able to phagocytize bacteria but cannot kill them in the phagocytic vacuoles. The cause of the killing defect is an inability to increase the cell's respiration and consequent failure to deliver activated oxygen into the phagocytic vacuole.^[3]

Since Nox2 was shown to play a huge part in determining the size of a myocardial infarction, this transforms the protein into a possible future target through drug medication due to its negative effect on myocardial reperfusion.^[5]

Recent evidence highly suggests that Nox2 generates ROS which contribute to reduce flow-mediated dilation (FMD) in patients with periphery artery disease (PAD). Scientists have gone to conclude that administering an antioxidant helps with inhibiting Nox2 activity and allowing in the improvement of arterial dilation.^[8]

Lastly, targeting Nox2 in the bone marrow could be a great therapeutic attempt at treating vascular injury during diabetic retinopathy (damage to the retina), because the Nox2-generated ROS which are produced by the bone-marrow derived cells & local retinal cells are accumulating the vascular injury in the diabetic retina area.^[9]

Interactions

Nox2 has been shown to interact directly with podocyte TRPC6 channels.^[10]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. "Entrez Gene: CYBB cytochrome b-245, beta polypeptide (chronic granulomatous disease)".
4. "Nox2 is required for macrophage chemotaxis towards CSF-1".
5. Braunersreuther V, Montecucco F, Asrih M, Pelli G, Galan K, Frias M, Burger F, Quinderé AL, Montessuit C, Krause KH, Mach F, Jaquet V (Nov 2013). "Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury". J Mol Cell Cardiol. 64: 99–107. doi:10.1016/j.yjmcc.2013.09.007. PMID 24051369.
6. Hernandes MS, D'Avila JC, Trevelin SC, Reis PA, Kinjo ER, Lopes LR, Castro-Faria-Neto HC, Cunha FQ, Britto LR, Bozza FA (27 Feb 2014). "The role of Nox2-derived ROS in the development of cognitive impairment after sepsis". J Neuroinflammation. 11 (1): 36. doi:10.1186/1742-2094-11-36. PMC 3974031. PMID 24571599.
7. Chan SL, Baumbach GL (26 June 2013). "Deficiency of Nox2 prevents angiotensin II-induced inward remodeling in cerebral arterioles". Front Physiol. 4: 133. doi:10.3389/fphys.2013.00133. PMC 3693079. PMID 23805104.
8. Loffredo, Lorenzo; Carnevale, Roberto; Cangemi, Roberto; Angelico, Francesco; Augelletti, Teresa; Di Santo, Serena; Calabrese, Cinzia M.; Della Volpe, Luigi; Pignatelli, Pasquale; Perri, Ludovica; Basili, Stefania; Violi, Francesco (2013). "NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease". International Journal of Cardiology. 165 (1): 184–192. doi:10.1016/j.ijcard.2012.01.069. ISSN 0167-5273. PMID 22336250.
9. "Requirement of NOX2 Expression in Both Retina and Bone Marrow for Diabetes-Induced Retinal Vascular Injury".
10. Kim EY, Anderson M, Wilson C, Hagmann H, Benzing T, Dryer SE (1 Nov 2013). "NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex.". Am J Physiol Cell Physiol. 305 (9): C960–71. doi:10.1152/ajpcell.00191.2013. PMID 23948707.

Further reading

• Bolscher BG, de Boer M, de Klein A, et al. (1991). "Point mutations in the beta-subunit of cytochrome b558 leading to X-linked chronic granulomatous disease". Blood. 77 (11): 2482–7. PMID 1710153.
• Nong Y, Kandil O, Tobin EH, et al. (1991). "The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1". Cell. Immunol. 132 (1): 10–6. doi:10.1016/0008-8749(91)90002-S. PMID 1905983.
• Dinauer MC, Pierce EA, Bruns GA, et al. (1990). "Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease". J. Clin. Invest. 86 (5): 1729–37. doi:10.1172/JCI114898. PMC 296926. PMID 2243141.
• Royer-Pokora B, Kunkel LM, Monaco AP, et al. (1986). "Cloning the gene for an inherited human disorder--chronic granulomatous disease--on the basis of its chromosomal location". Nature. 322 (6074): 32–8. doi:10.1038/322032a0. PMID 2425263.
• Dinauer MC, Curnutte JT, Rosen H, Orkin SH (1990). "A missense mutation in the neutrophil cytochrome b heavy chain in cytochrome-positive X-linked chronic granulomatous disease". J. Clin. Invest. 84 (6): 2012–6. doi:10.1172/JCI114393. PMC 304086. PMID 2556453.
• Dinauer MC, Orkin SH, Brown R, et al. (1987). "The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complex". Nature. 327 (6124): 717–20. doi:10.1038/327717a0. PMID 3600768.
• Teahan C, Rowe P, Parker P, et al. (1987). "The X-linked chronic granulomatous disease gene codes for the beta-chain of cytochrome b-245". Nature. 327 (6124): 720–1. doi:10.1038/327720a0. PMID 3600769.
• Rabbani H, de Boer M, Ahlin A, et al. (1994). "A 40-base-pair duplication in the gp91-phox gene leading to X-linked chronic granulomatous disease". Eur. J. Haematol. 51 (4): 218–22. doi:10.1111/j.1600-0609.1993.tb00634.x. PMID 7694872.
• Pollock JD, Williams DA, Gifford MA, et al. (1995). "Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production". Nat. Genet. 9 (2): 202–9. doi:10.1038/ng0295-202. PMID 7719350.
• Ariga T, Sakiyama Y, Matsumoto S (1994). "Two novel point mutations in the cytochrome b 558 heavy chain gene, detected in two Japanese patients with X-linked chronic granulomatous disease". Hum. Genet. 94 (4): 441. doi:10.1007/BF00201609. PMID 7927345.
• Leto TL, Adams AG, de Mendez I (1994). "Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline-rich targets". Proc. Natl. Acad. Sci. U.S.A. 91 (22): 10650–4. doi:10.1073/pnas.91.22.10650. PMC 45079. PMID 7938008.
• Ariga T, Sakiyama Y, Tomizawa K, et al. (1993). "A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid, in a patient with cytochrome b positive X-linked chronic granulomatous disease". Eur. J. Pediatr. 152 (6): 469–72. doi:10.1007/BF01955051. PMID 8101486.
• Leusen JH, de Boer M, Bolscher BG, et al. (1994). "A point mutation in gp91-phox of cytochrome b558 of the human NADPH oxidase leading to defective translocation of the cytosolic proteins p47-phox and p67-phox". J. Clin. Invest. 93 (5): 2120–6. doi:10.1172/JCI117207. PMC 294341. PMID 8182143.
• Meindl A, Carvalho MR, Herrmann K, et al. (1996). "A gene (SRPX) encoding a sushi-repeat-containing protein is deleted in patients with X-linked retinitis pigmentosa". Hum. Mol. Genet. 4 (12): 2339–46. doi:10.1093/hmg/4.12.2339. PMID 8634708.
• Sathyamoorthy M, de Mendez I, Adams AG, Leto TL (1997). "p40(phox) down-regulates NADPH oxidase activity through interactions with its SH3 domain". J. Biol. Chem. 272 (14): 9141–6. doi:10.1074/jbc.272.14.9141. PMID 9083043.
• Eklund EA, Kakar R (1997). "Identification and characterization of TF1(phox), a DNA-binding protein that increases expression of gp91(phox) in PLB985 myeloid leukemia cells". J. Biol. Chem. 272 (14): 9344–55. doi:10.1074/jbc.272.14.9344. PMID 9083071.
• Jendrossek V, Ritzel A, Neubauer B, et al. (1997). "An in-frame triplet deletion within the gp91-phox gene in an adult X-linked chronic granulomatous disease patient with residual NADPH-oxidase activity". Eur. J. Haematol. 58 (2): 78–85. doi:10.1111/j.1600-0609.1997.tb00928.x. PMID 9111587.
• Rae J, Newburger PE, Dinauer MC, et al. (1998). "X-Linked chronic granulomatous disease: mutations in the CYBB gene encoding the gp91-phox component of respiratory-burst oxidase". Am. J. Hum. Genet. 62 (6): 1320–31. doi:10.1086/301874. PMC 1377153. PMID 9585602.
• Ariga T, Furuta H, Cho K, Sakiyama Y (1998). "Genetic analysis of 13 families with X-linked chronic granulomatous disease reveals a low proportion of sporadic patients and a high proportion of sporadic carriers". Pediatr. Res. 44 (1): 85–92. doi:10.1203/00006450-199807000-00014. PMID 9667376.
• Kumatori A, Faizunnessa NN, Suzuki S, et al. (1998). "Nonhomologous recombination between the cytochrome b558 heavy chain gene (CYBB) and LINE-1 causes an X-linked chronic granulomatous disease". Genomics. 53 (2): 123–8. doi:10.1006/geno.1998.5510. PMID 9790760.

External links

• gp91phox protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)