UQCRFS1

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.[5] 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,UQCRQ ("11kDa protein"), UQCRH (cyt c1 Hinge protein), UCRC ("cyt. c1 associated protein"), and UQCR ("Rieske-associated protein").[6]

UQCRFS1
Identifiers
Aliases	UQCRFS1, RIP1, RIS1, RISP, UQCR5, ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, MC3DN10
External IDs	OMIM: 191327 MGI: 1913944 HomoloGene: 4378 GeneCards: UQCRFS1
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q12 Start 29,205,320 bp[1] End 29,213,151 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 A3.2 Start 30,540,308 bp[2] End 30,545,362 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • ubiquinol-cytochrome-c reductase activity • GO:0032403 macromolecular complex binding • iron-sulfur cluster binding • metal ion binding • oxidoreductase activity • 2 iron, 2 sulfur cluster binding • oxidoreductase activity, acting on diphenols and related substances as donors • GO:0001948 protein binding Cellular component • integral component of membrane • membrane • mitochondrial membranes • myelin • mitochondrion • mitochondrial inner membrane • electron transport • mitochondrial respiratory chain complex III • mitochondrial respiratory chain complex IV Biological process • hydrogen ion transmembrane transport • response to antibiotic • response to hormone • oxidation-reduction process • response to drug • mitochondrial electron transport, ubiquinol to cytochrome c Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7386	66694
Ensembl	ENSG00000169021	ENSMUSG00000038462
UniProt	P47985	Q9CR68
RefSeq (mRNA)	NM_006003	NM_025710
RefSeq (protein)	NP_005994	NP_079986
Location (UCSC)	Chr 19: 29.21 – 29.21 Mb	Chr 13: 30.54 – 30.55 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

UQCRFS1 is located on the q arm of chromosome 19 in position 12, has 2 exons, and spans 5,969 base pairs.[5] The UQCRFS1 gene produces a 29.7 kDa protein composed of 274 amino acids.[7][8] 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.[9] The primary structure of UQCRFS1 from cDNA analysis is composed of a 78 amino acid long N-terminal extension sequence.[10]

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.[11] 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.[12] 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.[6][12]

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.[13] In addition, Acute myeloid leukemia (AML) has been found to be associated with the amplification of UQCRFS1 gene.[14] In contrast, UQCRFS1 and complex III has been absent in renal cell carcinoma, though the mechanism is unknown.[15]

Interactions

In addition to co-complexes, UQCRFS1 has protein-protein interactions with UQCRB, BCS1L, COX6B1, UQCRQ, NDUFA9, and other proteins.[16]

References

1. GRCh38: Ensembl release 89: ENSG00000169021 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038462 - 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: UQCRFS1 ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1". This article incorporates text from this source, which is in the public domain.
6. "UQCRFS1 - Cytochrome b-c1 complex subunit Rieske, mitochondrial". The UniProt Consortium.
7. 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 (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.
8. Yao D. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-07-27.
9. 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 (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.
10. Nishikimi M, Hosokawa Y, Toda H, Suzuki H, Ozawa T (1990). "The primary structure of human Rieske iron-sulfur protein of mitochondrial cytochrome bc1 complex deduced from cDNA analysis". Biochemistry International. 20 (1): 155–60. PMID 2158323.
11. Pennacchio LA, Bergmann A, Fukushima A, Okubo K, Salemi A, Lennon GG (April 1995). "Structure, sequence and location of the UQCRFS1 gene for the human Rieske Fe-S protein". Gene. 155 (2): 207–11. doi:10.1016/0378-1119(94)00683-j. PMID 7721092.
12. Bottani E, Cerutti R, Harbour ME, Ravaglia S, Dogan SA, Giordano C, Fearnley IM, D'Amati G, Viscomi C, Fernandez-Vizarra E, Zeviani M (July 2017). "TTC19 Plays a Husbandry Role on UQCRFS1 Turnover in the Biogenesis of Mitochondrial Respiratory Complex III". Molecular Cell. 67 (1): 96–105.e4. doi:10.1016/j.molcel.2017.06.001. PMID 28673544.
13. Ohashi Y, Kaneko SJ, Cupples TE, Young SR (April 2004). "Ubiquinol cytochrome c reductase (UQCRFS1) gene amplification in primary breast cancer core biopsy samples". Gynecologic Oncology. 93 (1): 54–8. doi:10.1016/j.ygyno.2004.01.019. PMID 15047214.
14. Sait SN, Qadir MU, Conroy JM, Matsui S, Nowak NJ, Baer MR (May 2002). "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. doi:10.1002/gcc.10038. PMID 11921281.
15. Sarto C, Marocchi A, Sanchez JC, Giannone D, Frutiger S, Golaz O, Wilkins MR, Doro G, Cappellano F, Hughes G, Hochstrasser DF, Mocarelli P (1997). "Renal cell carcinoma and normal kidney protein expression". Electrophoresis. 18 (3–4): 599–604. doi:10.1002/elps.1150180343. PMID 9150947.
16. 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 (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

• Shimomura Y, Nishikimi M, Ozawa T (December 1985). "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. PMID 2999105.
• Duncan AM, Anderson L, Duff C, Ozawa T, Suzuki H, Worton R, Rozen R (May 1994). "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. doi:10.1006/geno.1994.1260. PMID 8088805.
• Sarto C, Marocchi A, Sanchez JC, Giannone D, Frutiger S, Golaz O, Wilkins MR, Doro G, Cappellano F, Hughes G, Hochstrasser DF, Mocarelli P (1997). "Renal cell carcinoma and normal kidney protein expression". Electrophoresis. 18 (3–4): 599–604. doi:10.1002/elps.1150180343. PMID 9150947.
• Kaneko SJ, Gerasimova T, Smith ST, Lloyd KO, Suzumori K, Young SR (July 2003). "CA125 and UQCRFS1 FISH studies of ovarian carcinoma". Gynecologic Oncology. 90 (1): 29–36. doi:10.1016/S0090-8258(03)00144-6. PMID 12821338.
• Ohashi Y, Kaneko SJ, Cupples TE, Young SR (April 2004). "Ubiquinol cytochrome c reductase (UQCRFS1) gene amplification in primary breast cancer core biopsy samples". Gynecologic Oncology. 93 (1): 54–8. doi:10.1016/j.ygyno.2004.01.019. PMID 15047214.

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