UQCRFS1 explained

Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, also known as UQCRFS1, Rieske iron-sulfur (Fe-S) protein, Cytochrome b-c1 complex subunit 5, or Complex III subunit 5 is a protein which in humans is encoded by the UQCRFS1 gene.^[1] UQCRFS1 is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex), which consists of the products of one mitochondrially encoded gene, MTCYTB (mitochondrial cytochrome b) and ten nuclear genes UQCRC1, UQCRC2, Cytochrome C1, UQCRFS1 (this protein, a type of Rieske protein), UQCRB, ("11kDa protein"), UQCRH (cyt c1 Hinge protein), UCRC ("cyt. c1 associated protein"), and ("Rieske-associated protein").

Structure

UQCRFS1 is located on the q arm of chromosome 19 in position 12, has 2 exons, and spans 5,969 base pairs. The UQCRFS1 gene produces a 29.7 kDa protein composed of 274 amino acids.^{[2] [3]} UQCRFS1 is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex). The structure of the complex is a symmetric homodimer composed of one mitochondrial genome encoded cytochrome b subunit and ten other nucleus encoded subunits.^[4] The primary structure of UQCRFS1 from cDNA analysis is composed of a 78 amino acid long N-terminal extension sequence.^[5]

Function

The UQCRFS1 gene encodes for an iron-sulfur protein, which is an essential subunit of the Ubiquinol Cytochrome c Reductase or Complex III in the mitochondrial respiratory chain.^[6] Complex III is responsible for electron transfer from coenzyme Q to cytochrome c as well as the proton transfer from the extracellular matrix to the intermembrane space which leads to ATP-coupled electrochemical potential generation. Incorporation of the subunit UQCRFS1 is the second to last step in complex III assembly.^[7] Once it is incorporated, UQCRFS1 undergoes proteolytic processing, which is essential for the correct insertion into Complex III. Preventions of the insertion may occur due to UQCRFS1-derived fragments, leading to a loss of Complex III structure and function.^[8]

Clinical significance

The UQCRFS1 gene has been shown to be involved in carcinogenesis of some cancers. It is mainly associated with more aggressive tumors, and results in the development of more aggressive phenotypes of breast cancers. The association was found with a grade 3 amplification of the UQCRFS1 gene.^[9] In addition, Acute myeloid leukemia (AML) has been found to be associated with the amplification of UQCRFS1 gene.^[10] In contrast, UQCRFS1 and complex III has been absent in renal cell carcinoma, though the mechanism is unknown.^[11]

Interactions

In addition to co-complexes, UQCRFS1 has protein-protein interactions with UQCRB, BCS1L, COX6B1, UQCRQ, NDUFA9, and other proteins.^[12]

Further reading

• Shimomura Y, Nishikimi M, Ozawa T . Novel purification of cytochrome c1 from mitochondrial Complex III. Reconstitution of antimycin-insensitive electron transfer with the iron-sulfur protein and cytochrome c1 . The Journal of Biological Chemistry . 260 . 28 . 15075–80 . December 1985 . 10.1016/S0021-9258(18)95704-2 . 2999105 . free .
• Duncan AM, Anderson L, Duff C, Ozawa T, Suzuki H, Worton R, Rozen R . Assignment of the gene (UQCRFS1) for the Rieske iron-sulfur protein subunit of the mitochondrial cytochrome bc1 complex to the 22q13 and 19q12-q13.1 regions of the human genome . Genomics . 21 . 1 . 281–3 . May 1994 . 8088805 . 10.1006/geno.1994.1260 .
• Sarto C, Marocchi A, Sanchez JC, Giannone D, Frutiger S, Golaz O, Wilkins MR, Doro G, Cappellano F, Hughes G, Hochstrasser DF, Mocarelli P . Renal cell carcinoma and normal kidney protein expression . Electrophoresis . 18 . 3–4 . 599–604 . 1997 . 9150947 . 10.1002/elps.1150180343 . 26023225 .
• Kaneko SJ, Gerasimova T, Smith ST, Lloyd KO, Suzumori K, Young SR . CA125 and UQCRFS1 FISH studies of ovarian carcinoma . Gynecologic Oncology . 90 . 1 . 29–36 . July 2003 . 12821338 . 10.1016/S0090-8258(03)00144-6 .
• Ohashi Y, Kaneko SJ, Cupples TE, Young SR . Ubiquinol cytochrome c reductase (UQCRFS1) gene amplification in primary breast cancer core biopsy samples . Gynecologic Oncology . 93 . 1 . 54–8 . April 2004 . 15047214 . 10.1016/j.ygyno.2004.01.019 .

Notes and References

1. Web site: Entrez Gene: UQCRFS1 ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1.
2. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P . Integration of cardiac proteome biology and medicine by a specialized knowledgebase . Circulation Research . 113 . 9 . 1043–53 . October 2013 . 23965338 . 4076475 . 10.1161/CIRCRESAHA.113.301151 .
3. Web site: Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information . Yao. Daniel . vanc . amino.heartproteome.org. 2018-07-27.
4. Gil Borlado MC, Moreno Lastres D, Gonzalez Hoyuela M, Moran M, Blazquez A, Pello R, Marin Buera L, Gabaldon T, Garcia Peñas JJ, Martín MA, Arenas J, Ugalde C . Impact of the mitochondrial genetic background in complex III deficiency . PLOS ONE . 5 . 9 . September 2010 . 20862300 . 10.1371/journal.pone.0012801 . 2941448 . e12801. 2010PLoSO...512801G . free .
5. Nishikimi M, Hosokawa Y, Toda H, Suzuki H, Ozawa T . The primary structure of human Rieske iron-sulfur protein of mitochondrial cytochrome bc1 complex deduced from cDNA analysis . Biochemistry International . 20 . 1 . 155–60 . 1990 . 2158323 .
6. Pennacchio LA, Bergmann A, Fukushima A, Okubo K, Salemi A, Lennon GG . Structure, sequence and location of the UQCRFS1 gene for the human Rieske Fe-S protein . Gene . 155 . 2 . 207–11 . April 1995 . 7721092 . 10.1016/0378-1119(94)00683-j.
7. Bottani E, Cerutti R, Harbour ME, Ravaglia S, Dogan SA, Giordano C, Fearnley IM, D'Amati G, Viscomi C, Fernandez-Vizarra E, Zeviani M . TTC19 Plays a Husbandry Role on UQCRFS1 Turnover in the Biogenesis of Mitochondrial Respiratory Complex III . Molecular Cell . 67 . 1 . 96–105.e4 . July 2017 . 28673544 . 10.1016/j.molcel.2017.06.001 . free .
8. Web site: UQCRFS1 - Cytochrome b-c1 complex subunit Rieske, mitochondrial. The UniProt Consortium.
9. Ohashi Y, Kaneko SJ, Cupples TE, Young SR . Ubiquinol cytochrome c reductase (UQCRFS1) gene amplification in primary breast cancer core biopsy samples . Gynecologic Oncology . 93 . 1 . 54–8 . April 2004 . 15047214 . 10.1016/j.ygyno.2004.01.019 .
10. Sait SN, Qadir MU, Conroy JM, Matsui S, Nowak NJ, Baer MR . Double minute chromosomes in acute myeloid leukemia and myelodysplastic syndrome: identification of new amplification regions by fluorescence in situ hybridization and spectral karyotyping . Genes, Chromosomes & Cancer . 34 . 1 . 42–7 . May 2002 . 11921281 . 10.1002/gcc.10038. 23839582 .
11. Sarto C, Marocchi A, Sanchez JC, Giannone D, Frutiger S, Golaz O, Wilkins MR, Doro G, Cappellano F, Hughes G, Hochstrasser DF, Mocarelli P . Renal cell carcinoma and normal kidney protein expression . Electrophoresis . 18 . 3–4 . 599–604 . 1997 . 9150947 . 10.1002/elps.1150180343 . 26023225 .
12. Kerrien S, Alam-Faruque Y, Aranda B, Bancarz I, Bridge A, Derow C, Dimmer E, Feuermann M, Friedrichsen A, Huntley R, Kohler C, Khadake J, Leroy C, Liban A, Lieftink C, Montecchi-Palazzi L, Orchard S, Risse J, Robbe K, Roechert B, Thorneycroft D, Zhang Y, Apweiler R, Hermjakob H . IntAct--open source resource for molecular interaction data . Nucleic Acids Research . 35 . Database issue . D561-5 . January 2007 . 17145710 . 10.1093/nar/gkl958 . 1751531.