UQCRB

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External IDs	GeneCards: [1]
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Species	Human	Mouse
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Ubiquinol-cytochrome c reductase binding protein, also known as UQCRB, Complex III subunit 7, QP-C, or Ubiquinol-cytochrome c reductase complex 14 kDa protein is a protein which in humans is encoded by the UQCRB gene.This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X.

Structure

UQCRB is located on the q arm of chromosome 8 in position 22.1, has 18 exons, and spans 8,958 base pairs. The UQCRB gene produces a 5.9 kDa protein composed of 161 amino acids. The gene product of UQCRB is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex; E.C. 1.10.2.2), which consists of the products of one mitochondrially encoded gene, MTCYTB (mitochondrial cytochrome b) and ten nuclear genes: UQCRC1, UQCRC2, Cytochrome c1, UQCRFS1 (Rieske protein), UQCRB, "14kDa protein", UQCRH (cyt c1 Hinge protein), Rieske Protein presequence, "cyt. c1 associated protein", and "Rieske-associated protein". After processing, the cleaved leader sequence of the iron-sulfur protein is retained as subunit 9, giving 11 subunits from 10 genes.

Function

The ubiquinone-binding protein is a nucleus-encoded component of ubiquinol-cytochrome c oxidoreductase (Complex III) in the mitochondrial respiratory chain and plays an important role in electron transfer as a complex of ubiquinone and QP-C. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. It is a target of a protein named natural anti-angiogenic small molecule terpestacin, which enables the role of the ubiquinone-binding protein as cellular oxygen sensors and participants in angiogenesis. This angiogenesis, which is the development of new blood vessels, is hypoxia induced and is facilitated by signaling mediated by ROS (mitochondrial reactive oxygen) species. In addition, UQCRB keeps maintenance of complex III.

Clinical significance

Mutations in UQCRB can result in mitochondrial deficiencies and associated disorders. It is majorly associated with a complex III deficiency, a deficiency in an enzyme complex which catalyzes electron transfer from coenzyme Q to cytochrome c in the mitochondrial respiratory chain. A complex III deficiency can result in a highly variable phenotype depending on which tissues are affected. Most frequent clinical manifestations include progressive exercise intolerance and cardiomyopathy. Occasional multisystem disorders accompanied by exercise intolerance may arise as well, in forms of deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, and epilepsy. Other phenotypes include mitochondrial encephalomyopathy, mitochondrial myopathy, Leber hereditary optic neuropathy, muscle weakness, myoglobinuria, blood acidosis, renal tubulopathy, and more. Complex III deficiency is known to be rare among mitochondrial diseases.

Interactions

UQCRB has binary interactions with 3 proteins, including MAGA4, Q1RN33, and 1A1L1. In addition, SDHAF2 has 69 protein-protein interactions, including COX6B1, CYC1, MYO18A, UHRF1, and others.

Further reading

• Chang J, Jung HJ, Park HJ, Cho SW, Lee SK, Kwon HJ (September 2015). "Cell-permeable mitochondrial ubiquinol-cytochrome c reductase binding protein induces angiogenesis in vitro and in vivo". Cancer Letters. 366 (1): 52–60. doi:10.1016/j.canlet.2015.06.013. PMID 26118773.
• Cho YS, Jung HJ, Seok SH, Payumo AY, Chen JK, Kwon HJ (April 2013). "Functional inhibition of UQCRB suppresses angiogenesis in zebrafish". Biochemical and Biophysical Research Communications. 433 (4): 396–400. doi:10.1016/j.bbrc.2013.02.082. PMC 3691074. PMID 23454382.
• Jung HJ, Kwon HJ (May 2013). "Exploring the role of mitochondrial UQCRB in angiogenesis using small molecules". Molecular bioSystems. 9 (5): 930–9. doi:10.1039/c3mb25426g. PMID 23475074.
• Jung HJ, Kim Y, Chang J, Kang SW, Kim JH, Kwon HJ (September 2013). "Mitochondrial UQCRB regulates VEGFR2 signaling in endothelial cells". Journal of Molecular Medicine. 91 (9): 1117–28. doi:10.1007/s00109-013-1049-6. PMID 23708980.
• Suzuki H, Hosokawa Y, Toda H, Nishikimi M, Ozawa T (May 1990). "Common protein-binding sites in the 5'-flanking regions of human genes for cytochrome c1 and ubiquinone-binding protein". The Journal of Biological Chemistry. 265 (14): 8159–63. PMID 2159470.
• Hosokawa Y, Suzuki H, Nishikimi M, Matsukage A, Yoshida MC, Ozawa T (1990). "Chromosomal assignment of the gene for the ubiquinone-binding protein of human mitochondrial cytochrome bc1 complex". Biochemistry International. 21 (1): 41–4. PMID 2167087.
• Suzuki H, Hosokawa Y, Toda H, Nishikimi M, Ozawa T (May 1989). "Isolation of a single nuclear gene encoding human ubiquinone-binding protein in complex III of mitochondrial respiratory chain". Biochemical and Biophysical Research Communications. 161 (1): 371–8. doi:10.1016/0006-291X(89)91607-0. PMID 2543413.
• Wakabayashi S, Takao T, Shimonishi Y, Kuramitsu S, Matsubara H, Wang T, Zhang Z, King TE (January 1985). "Complete amino acid sequence of the ubiquinone binding protein (QP-C), a protein similar to the 14,000-dalton subunit of the yeast ubiquinol-cytochrome c reductase complex". The Journal of Biological Chemistry. 260 (1): 337–43. PMID 2981208.
• Suzuki H, Hosokawa Y, Toda H, Nishikimi M, Ozawa T (October 1988). "Cloning and sequencing of a cDNA for human mitochondrial ubiquinone-binding protein of complex III". Biochemical and Biophysical Research Communications. 156 (2): 987–94. doi:10.1016/S0006-291X(88)80941-0. PMID 3056408.
• Malaney S, Heng HH, Tsui LC, Shi XM, Robinson BH (1996). "Localization of the human gene encoding the 13.3-kDa subunit of mitochondrial complex III (UQCRB) to 8q22 by in situ hybridization". Cytogenetics and Cell Genetics. 73 (4): 297–9. doi:10.1159/000134360. PMID 8751380.
• Haut S, Brivet M, Touati G, Rustin P, Lebon S, Garcia-Cazorla A, Saudubray JM, Boutron A, Legrand A, Slama A (July 2003). "A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis". Human Genetics. 113 (2): 118–22. doi:10.1007/s00439-003-0946-0. PMID 12709789.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.