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Structure

BCS1L is located on the q arm of chromosome 2 in position 35 and has 10 exons.⁴ The BCS1L gene produces a 47.5 kDa protein composed of 419 amino acids.⁵⁶ The protein encoded by BCS1L belongs to the AAA ATPase family, BCS1 subfamily. BCS1L is a phosphoprotein and chaperone for Ubiquinol Cytochrome c Reductase assembly. It contains a nucleotide binding site for ATP-binding.⁷⁸ BCS1L does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. A conserved domain at the N-terminus of BCS1L is responsible for the import and intramitochondrial sorting.⁹ Associating to the inner mitochondrial membrane, BCS1L has a transmembrane domain in between two topological domains, passing through the inner mitochondrial membrane once. The majority of the protein is in the mitochondrial matrix.¹⁰¹¹ Several alternatively spliced transcripts encoding two different isoforms have been described.¹²

Function

BCS1L encodes a protein that is located in the inner mitochondrial membrane and involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III). Complex III plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c. BCS1L is essential for this process through its role in the maintenance of mitochondrial tubular networks, respiratory chain assembly, and formation of the LETM1 complex.¹³¹⁴¹⁵

Clinical Significance

Variants of BCS1L have been associated with mitochondrial complex III deficiency, nuclear 1, GRACILE syndrome, and Bjoernstad syndrome. Mitochondrial complex III deficiency, nuclear 1 is a disorder of the mitochondrial respiratory chain resulting in reduced complex III activity and highly variable clinical features usually resulting in multi-system organ failure. Clinical features may include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness, exercise intolerance, lactic acidosis, hypotonia, seizures, and optic atrophy. Pathogenic mutations have included R45C, R56X,¹⁶¹⁷¹⁸ T50A,¹⁹ R73C,²⁰ P99L, R155P, V353M,²¹ G129R,²²²³ R183C, F368I,²⁴ and S277N. These mutations tend to affect the ATP-binding residues of BCS1L.²⁵²⁶²⁷

Growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE) is a recessively inherited lethal disease that results in multi-system organ failure. GRACILE is characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. Pathogenic mutations have included S78G, R144Q, and V327A.²⁸²⁹³⁰

Bjoernstad syndrome is an autosomal recessive disease primarily affecting hearing. This disease is characterized by congenital hearing loss and twisted hairs, a condition known as pili torti, in which hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle. Pathogenic mutations have included Y301N,³¹ R184C,³² G35R, R114W, R183H, Q302E, and R306H. These mutations tend to affect the protein-protein interactions of BCS1L.³³³⁴³⁵

Interactions

BCS1L has 11 protein-protein interactions with 8 of them being co-complex interactions. BCS1L has been found to interact with LETM1, DNAJA1, and DDX24.³⁶

See also

• Björnstad syndrome
• GRACILE syndrome

External links

• Human BCS1L genome location and BCS1L gene details page in the UCSC Genome Browser.

Further reading

• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Fölsch H, Guiard B, Neupert W, Stuart RA (February 1996). "Internal targeting signal of the BCS1 protein: a novel mechanism of import into mitochondria". The EMBO Journal. 15 (3): 479–87. doi:10.1002/j.1460-2075.1996.tb00380.x. PMC 449966. PMID 8599931.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Lubianca Neto JF, Lu L, Eavey RD, Flores MA, Caldera RM, Sangwatanaroj S, Schott JJ, McDonough B, Santos JI, Seidman CE, Seidman JG (May 1998). "The Bjornstad syndrome (sensorineural hearing loss and pili torti) disease gene maps to chromosome 2q34-36". American Journal of Human Genetics. 62 (5): 1107–12. doi:10.1086/301837. PMC 1377094. PMID 9545407.
• Visapää I, Fellman V, Varilo T, Palotie A, Raivio KO, Peltonen L (November 1998). "Assignment of the locus for a new lethal neonatal metabolic syndrome to 2q33-37". American Journal of Human Genetics. 63 (5): 1396–403. doi:10.1086/302123. PMC 1377549. PMID 9792866.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.

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

References

1. "BCS1L BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-08-03. This article incorporates text from this source, which is in the public domain. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=617 ↩

2. "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license. https://www.uniprot.org/uniprot/Q9Y276 ↩

3. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 – D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210571 ↩

4. "BCS1L BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-08-03. This article incorporates text from this source, which is in the public domain. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=617 ↩

5. Yao D. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Archived from the original on 2018-08-04. Retrieved 2018-08-02. https://web.archive.org/web/20180804013935/https://amino.heartproteome.org/web/protein/Q9Y276 ↩

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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076475 ↩

7. "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license. https://www.uniprot.org/uniprot/Q9Y276 ↩

8. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 – D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210571 ↩

9. Stan T, Brix J, Schneider-Mergener J, Pfanner N, Neupert W, Rapaport D (April 2003). "Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex". Molecular and Cellular Biology. 23 (7): 2239–50. doi:10.1128/MCB.23.7.2239-2250.2003. PMC 150725. PMID 12640110. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC150725 ↩

10. "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license. https://www.uniprot.org/uniprot/Q9Y276 ↩

11. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 – D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210571 ↩

12. "Entrez Gene: BCS1L BCS1-like (yeast)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=617 ↩

13. Tamai S, Iida H, Yokota S, Sayano T, Kiguchiya S, Ishihara N, Hayashi J, Mihara K, Oka T (August 2008). "Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L". Journal of Cell Science. 121 (Pt 15): 2588–600. doi:10.1242/jcs.026625. PMID 18628306. S2CID 10902341. /wiki/Doi_(identifier) ↩

14. "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license. https://www.uniprot.org/uniprot/Q9Y276 ↩

15. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 – D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210571 ↩

16. De Meirleir L, Seneca S, Damis E, Sepulchre B, Hoorens A, Gerlo E, et al. (August 2003). "Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene". American Journal of Medical Genetics. Part A. 121A (2): 126–31. doi:10.1002/ajmg.a.20171. PMID 12910490. S2CID 22246638. /wiki/Doi_(identifier) ↩

17. Ramos-Arroyo MA, Hualde J, Ayechu A, De Meirleir L, Seneca S, Nadal N, Briones P (June 2009). "Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene". Clinical Genetics. 75 (6): 585–7. doi:10.1111/j.1399-0004.2009.01160.x. PMID 19508421. S2CID 205407210. /wiki/Doi_(identifier) ↩

18. Gil-Borlado MC, González-Hoyuela M, Blázquez A, García-Silva MT, Gabaldón T, Manzanares J, Vara J, Martín MA, Seneca S, Arenas J, Ugalde C (September 2009). "Pathogenic mutations in the 5' untranslated region of BCS1L mRNA in mitochondrial complex III deficiency". Mitochondrion. 9 (5): 299–305. doi:10.1016/j.mito.2009.04.001. PMID 19389488. /wiki/Doi_(identifier) ↩

19. Blázquez A, Gil-Borlado MC, Morán M, Verdú A, Cazorla-Calleja MR, Martín MA, Arenas J, Ugalde C (February 2009). "Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient". Neuromuscular Disorders. 19 (2): 143–6. doi:10.1016/j.nmd.2008.11.016. PMID 19162478. S2CID 32624169. /wiki/Doi_(identifier) ↩

20. Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M (May 2007). "Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy". Human Molecular Genetics. 16 (10): 1241–52. doi:10.1093/hmg/ddm072. PMID 17403714. https://doi.org/10.1093%2Fhmg%2Fddm072 ↩

21. de Lonlay P, Valnot I, Barrientos A, Gorbatyuk M, Tzagoloff A, Taanman JW, Benayoun E, Chrétien D, Kadhom N, Lombès A, de Baulny HO, Niaudet P, Munnich A, Rustin P, Rötig A (September 2001). "A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure". Nature Genetics. 29 (1): 57–60. doi:10.1038/ng706. PMID 11528392. S2CID 10132444. /wiki/Doi_(identifier) ↩

22. Al-Owain M, Colak D, Albakheet A, Al-Younes B, Al-Humaidi Z, Al-Sayed M, et al. (September 2013). "Clinical and biochemical features associated with BCS1L mutation". Journal of Inherited Metabolic Disease. 36 (5): 813–20. doi:10.1007/s10545-012-9536-4. PMID 22991165. S2CID 13958329. /wiki/Doi_(identifier) ↩

23. Tuppen HA, Fehmi J, Czermin B, Goffrini P, Meloni F, Ferrero I, He L, Blakely EL, McFarland R, Horvath R, Turnbull DM, Taylor RW (August 2010). "Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation". Molecular Genetics and Metabolism. 100 (4): 345–8. doi:10.1016/j.ymgme.2010.04.010. PMID 20472482. https://doi.org/10.1016%2Fj.ymgme.2010.04.010 ↩

24. Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M (May 2007). "Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy". Human Molecular Genetics. 16 (10): 1241–52. doi:10.1093/hmg/ddm072. PMID 17403714. https://doi.org/10.1093%2Fhmg%2Fddm072 ↩

25. Hinson JT, Fantin VR, Schönberger J, Breivik N, Siem G, McDonough B, et al. (February 2007). "Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome". The New England Journal of Medicine. 356 (8): 809–19. doi:10.1056/NEJMoa055262. PMID 17314340. https://doi.org/10.1056%2FNEJMoa055262 ↩

26. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 – D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210571 ↩

27. "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license. https://www.uniprot.org/uniprot/Q9Y276 ↩

28. Visapää I, Fellman V, Vesa J, Dasvarma A, Hutton JL, Kumar V, Payne GS, Makarow M, Van Coster R, Taylor RW, Turnbull DM, Suomalainen A, Peltonen L (October 2002). "GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L". American Journal of Human Genetics. 71 (4): 863–76. doi:10.1086/342773. PMC 378542. PMID 12215968. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC378542 ↩

29. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 – D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210571 ↩

30. "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license. https://www.uniprot.org/uniprot/Q9Y276 ↩

31. Siddiqi S, Siddiq S, Mansoor A, Oostrik J, Ahmad N, Kazmi SA, Kremer H, Qamar R, Schraders M (December 2013). "Novel mutation in AAA domain of BCS1L causing Bjornstad syndrome". Journal of Human Genetics. 58 (12): 819–21. doi:10.1038/jhg.2013.101. PMID 24172246. https://doi.org/10.1038%2Fjhg.2013.101 ↩

32. Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M (May 2007). "Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy". Human Molecular Genetics. 16 (10): 1241–52. doi:10.1093/hmg/ddm072. PMID 17403714. https://doi.org/10.1093%2Fhmg%2Fddm072 ↩

33. Hinson JT, Fantin VR, Schönberger J, Breivik N, Siem G, McDonough B, et al. (February 2007). "Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome". The New England Journal of Medicine. 356 (8): 809–19. doi:10.1056/NEJMoa055262. PMID 17314340. https://doi.org/10.1056%2FNEJMoa055262 ↩

34. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158 – D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210571 ↩

35. "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03. This article incorporates text available under the CC BY 4.0 license. https://www.uniprot.org/uniprot/Q9Y276 ↩

36. "14 binary interactions found for search term BCS1L". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25. https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=BCS1L ↩