UQCRB

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.[5]

UQCRB
Identifiers
AliasesUQCRB, MC3DN3, QCR7, QP-C, QPC, UQBC, UQBP, UQCR6, UQPC, ubiquinol-cytochrome c reductase binding protein
External IDsOMIM: 191330 MGI: 1914780 HomoloGene: 38164 GeneCards: UQCRB
Gene location (Human)
Chr.Chromosome 8 (human)[1]
Band8q22.1Start96,225,920 bp[1]
End96,235,634 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

7381

67530

Ensembl

ENSG00000156467

ENSMUSG00000021520

UniProt

P14927

Q9D855
Q9CQB4

RefSeq (mRNA)

NM_001199975
NM_001254752
NM_006294

NM_026219

RefSeq (protein)

NP_001186904
NP_001241681
NP_006285

NP_080495

Location (UCSC)Chr 8: 96.23 – 96.24 MbChr 13: 66.9 – 66.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

UQCRB is located on the q arm of chromosome 8 in position 22.1, has 18 exons, and spans 8,958 base pairs.[5] The UQCRB gene produces a 5.9 kDa protein composed of 161 amino acids.[6][7] 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.[5]

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.[5] 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 mitochondrial ROS (reactive oxygen species). In addition, UQCRB keeps maintenance of complex III.[8][9][10]

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.[11] 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.[11] Other phenotypes include mitochondrial encephalomyopathy, mitochondrial myopathy, Leber hereditary optic neuropathy, muscle weakness, myoglobinuria, blood acidosis, renal tubulopathy, and more.[11][12] Complex III deficiency is known to be rare among mitochondrial diseases.[12]

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.[13]

References
  1. GRCh38: Ensembl release 89: ENSG00000156467 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000021520 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: UQCRB ubiquinol-cytochrome c reductase binding protein". This article incorporates text from this source, which is in the public domain.
  6. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  7. Yao D. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-07-27.
  8. Chang J, Jung HJ, Jeong SH, Kim HK, Han J, Kwon HJ (December 2014). "A mutation in the mitochondrial protein UQCRB promotes angiogenesis through the generation of mitochondrial reactive oxygen species". Biochemical and Biophysical Research Communications. 455 (3–4): 290–7. doi:10.1016/j.bbrc.2014.11.005. PMID 25446085.
  9. Jung HJ, Cho M, Kim Y, Han G, Kwon HJ (October 2014). "Development of a novel class of mitochondrial ubiquinol-cytochrome c reductase binding protein (UQCRB) modulators as promising antiangiogenic leads". Journal of Medicinal Chemistry. 57 (19): 7990–8. doi:10.1021/jm500863j. PMID 25244355.
    • Jung HJ, Kim KH, Kim ND, Han G, Kwon HJ (February 2011). "Identification of a novel small molecule targeting UQCRB of mitochondrial complex III and its anti-angiogenic activity". Bioorganic & Medicinal Chemistry Letters. 21 (3): 1052–6. doi:10.1016/j.bmcl.2010.12.002. PMID 21215626.
  11. "UQCRB - Cytochrome b-c1 complex subunit 7". The UniProt Consortium.
  12. Gil Borlado MC, Moreno Lastres D, Gonzalez Hoyuela M, Moran M, Blazquez A, Pello R, et al. (September 2010). "Impact of the mitochondrial genetic background in complex III deficiency". PLOS ONE. 5 (9): e12801. doi:10.1371/journal.pone.0012801. PMC 2941448. PMID 20862300.
  13. Kerrien S, Alam-Faruque Y, Aranda B, Bancarz I, Bridge A, Derow C, et al. (January 2007). "IntAct--open source resource for molecular interaction data". Nucleic Acids Research. 35 (Database issue): D561-5. doi:10.1093/nar/gkl958. PMC 1751531. PMID 17145710.

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. S2CID 13973232.
  • 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. hdl:10722/42534. 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. S2CID 24273072.
  • 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. S2CID 4427026.

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