BCS1L: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: HTTP→HTTPS)
imported>Boghog
(fixed interaction database link)
 
Line 19: Line 19:
| CDD =  
| CDD =  
}}
}}
'''Mitochondrial chaperone BCS1''' is a [[protein]] that in humans is encoded by the ''BCS1L'' [[gene]].<ref name="pmid9878253">{{cite journal | vauthors = Petruzzella V, Tiranti V, Fernandez P, Ianna P, Carrozzo R, Zeviani M | title = Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain | journal = Genomics | volume = 54 | issue = 3 | pages = 494–504 |date=Feb 1999| pmid = 9878253 | pmc = | doi = 10.1006/geno.1998.5580 }}</ref><ref name="pmid17314340">{{cite journal | vauthors = Hinson JT, Fantin VR, Schonberger J, Breivik N, Siem G, McDonough B, Sharma P, Keogh I, Godinho R, Santos F, Esparza A, Nicolau Y, Selvaag E, Cohen BH, Hoppel CL, Tranebjaerg L, Eavey RD, Seidman JG, Seidman CE | title = Missense mutations in the BCS1L gene as a cause of the Bjornstad syndrome | journal = N Engl J Med | volume = 356 | issue = 8 | pages = 809–19 |date=Feb 2007| pmid = 17314340 | pmc = | doi = 10.1056/NEJMoa055262 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BCS1L BCS1-like (yeast)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=617| accessdate = }}</ref>
'''Mitochondrial chaperone BCS1 (BCS1L),''' also known as '''BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone (h-BCS1),''' is a [[protein]] that in humans is encoded by the ''BCS1L'' [[gene]]. BCS1L is a [[Chaperone (protein)|chaperone protein]] involved in the assembly of [[Ubiquinol-cytochrome-c reductase|Ubiquinol Cytochrome c Reductase]] ([[Coenzyme Q – cytochrome c reductase|complex III]]), which is located in the [[inner mitochondrial membrane]] and is part of the [[electron transport chain]]. [[Mutation|Mutations]] in this gene are associated with mitochondrial complex III deficiency (nuclear, 1), [[GRACILE syndrome]], and [[Björnstad syndrome|Bjoernstad syndrome]].<ref name=":0">{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=617|title=BCS1L BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2018-08-03}}{{PD-notice}}</ref><ref name=":2">{{Cite web|url=https://www.uniprot.org/uniprot/Q9Y276|title=BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-03}}{{CC-notice|cc=by4}}</ref><ref name=":3">{{cite journal | vauthors = | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158-D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 | url = https://doi.org/10.1093/nar/gkw1099 }}</ref>
== Structure ==
''BCS1L'' is located on the [[Locus (genetics)|q arm]] of [[chromosome 2]] in position 35 and has 10 [[Exon|exons]].<ref name=":0" /> The ''BCS1L'' gene produces a 47.5 kDa protein composed of 419 [[Amino acid|amino acids]].<ref name=":1">{{Cite web|url=https://amino.heartproteome.org/web/protein/Q9Y276|title=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information|last=Yao|first=Daniel | name-list-format = vanc |website=amino.heartproteome.org|access-date=2018-08-02}}</ref><ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref> The protein encoded by <i>BCS1L</i> belongs to the AAA [[ATPase]] family, BCS1 subfamily. BCS1L is a [[phosphoprotein]] and chaperone for [[Ubiquinol-cytochrome-c reductase|Ubiquinol Cytochrome c Reductase]] assembly. It contains a [[nucleotide]] binding site for [[ATP-binding motif|ATP-binding]].<ref name=":2" /><ref name=":3" /> BCS1L does not contain a mitochondrial [[Signal peptide|targeting sequence]] but experimental studies confirm that it is imported into [[Mitochondrion|mitochondria]]. A [[conserved domain]] at the [[N-terminus]] of BCS1L is responsible for the import and intramitochondrial sorting.<ref>{{cite journal | vauthors = Stan T, Brix J, Schneider-Mergener J, Pfanner N, Neupert W, Rapaport D | title = Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex | journal = Molecular and Cellular Biology | volume = 23 | issue = 7 | pages = 2239–50 | date = April 2003 | pmid = 12640110 | pmc = 150725 | doi = 10.1128/MCB.23.7.2239-2250.2003 }}</ref> Associating to the inner mitochondrial membrane, BCS1L has a [[Transmembrane domain|transmembrane]] domain in between two topological domains, passing through the inner mitochondrial membrane once. The majority of the protein is in the [[mitochondrial matrix]].<ref name=":2" /><ref name=":3" /> Several [[Alternative splicing|alternatively spliced]] transcripts encoding two different [[Protein isoform|isoforms]] have been described.<ref name="entrez">{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=617|title=Entrez Gene: BCS1L BCS1-like (yeast)|accessdate=}}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
''BCS1L'' encodes a protein that is located in the [[inner mitochondrial membrane]] and involved in the assembly of [[Ubiquinol-cytochrome-c reductase|Ubiquinol Cytochrome c Reductase]] ([[Coenzyme Q – cytochrome c reductase|complex III]]). Complex III plays an important role in the [[Electron transport chain|mitochondrial respiratory chain]] by transferring [[Electron|electrons]] from the [[Rieske protein|Rieske]] [[Iron–sulfur protein|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.<ref>{{cite journal | vauthors = Tamai S, Iida H, Yokota S, Sayano T, Kiguchiya S, Ishihara N, Hayashi J, Mihara K, Oka T | title = Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L | journal = Journal of Cell Science | volume = 121 | issue = Pt 15 | pages = 2588–600 | date = August 2008 | pmid = 18628306 | doi = 10.1242/jcs.026625 }}</ref><ref name=":2" /><ref name=":3" />
| section_title =  
| summary_text = This gene encodes a homolog of the S. cerevisiae bcs1 protein which is involved in the assembly of complex III of the mitochondrial respiratory chain. The encoded protein 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 BCS1 is responsible for the import and intramitochondrial sorting.<ref name="pmid12640110">{{Cite journal
| last1 = Stan | first1 = T.
| last2 = Brix | first2 = J.
| last3 = Schneider-Mergener | first3 = J.
| last4 = Pfanner | first4 = N.
| last5 = Neupert | first5 = W.
| last6 = Rapaport | first6 = D.
| title = Mitochondrial protein import: Recognition of internal import signals of BCS1 by the TOM complex
| journal = Molecular and Cellular Biology
| volume = 23
| issue = 7
| pages = 2239–2250
| year = 2003
| pmid = 12640110
| pmc = 150725 | doi=10.1128/mcb.23.7.2239-2250.2003
}}</ref> Mutations in this gene are associated with mitochondrial complex III deficiency and the GRACILE syndrome. Two alternatively spliced transcripts encoding the same protein have been described.<ref name="entrez" />
}}


==See also==
== Clinical Significance ==
Variants of ''BCS1L'' have been associated with mitochondrial complex III deficiency, nuclear 1, [[GRACILE syndrome]], and [[Björnstad syndrome|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 [[Multiple organ dysfunction syndrome|multi-system organ failure]]. Clinical features may include mitochondrial [[encephalopathy]], [[psychomotor retardation]], [[ataxia]], severe [[failure to thrive]], [[Liver disease|liver dysfunction]], renal [[tubulopathy]], [[muscle weakness]], [[exercise intolerance]], [[lactic acidosis]], [[hypotonia]], [[seizures]], and [[Optic Atrophy|optic atrophy]]. Pathogenic mutations have included R45C, R56X,<ref>{{cite journal | vauthors = De Meirleir L, Seneca S, Damis E, Sepulchre B, Hoorens A, Gerlo E, García Silva MT, Hernandez EM, Lissens W, Van Coster R | display-authors = 6 | title = Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene | journal = American Journal of Medical Genetics. Part A | volume = 121A | issue = 2 | pages = 126–31 | date = August 2003 | pmid = 12910490 | doi = 10.1002/ajmg.a.20171 }}</ref><ref>{{cite journal | vauthors = Ramos-Arroyo MA, Hualde J, Ayechu A, De Meirleir L, Seneca S, Nadal N, Briones P | title = Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene | journal = Clinical Genetics | volume = 75 | issue = 6 | pages = 585–7 | date = June 2009 | pmid = 19508421 | doi = 10.1111/j.1399-0004.2009.01160.x }}</ref><ref>{{cite journal | vauthors = 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 | title = Pathogenic mutations in the 5' untranslated region of BCS1L mRNA in mitochondrial complex III deficiency | journal = Mitochondrion | volume = 9 | issue = 5 | pages = 299–305 | date = September 2009 | pmid = 19389488 | doi = 10.1016/j.mito.2009.04.001 }}</ref> T50A,<ref>{{cite journal | vauthors = Blázquez A, Gil-Borlado MC, Morán M, Verdú A, Cazorla-Calleja MR, Martín MA, Arenas J, Ugalde C | title = Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient | journal = Neuromuscular Disorders | volume = 19 | issue = 2 | pages = 143–6 | date = February 2009 | pmid = 19162478 | doi = 10.1016/j.nmd.2008.11.016 }}</ref> R73C,<ref>{{cite journal | vauthors = Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M | title = Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy | journal = Human Molecular Genetics | volume = 16 | issue = 10 | pages = 1241–52 | date = May 2007 | pmid = 17403714 | doi = 10.1093/hmg/ddm072 }}</ref> P99L, R155P, V353M,<ref>{{cite journal | vauthors = 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 | title = A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure | journal = Nature Genetics | volume = 29 | issue = 1 | pages = 57–60 | date = September 2001 | pmid = 11528392 | doi = 10.1038/ng706 }}</ref> G129R,<ref>{{cite journal | vauthors = Al-Owain M, Colak D, Albakheet A, Al-Younes B, Al-Humaidi Z, Al-Sayed M, Al-Hindi H, Al-Sugair A, Al-Muhaideb A, Rahbeeni Z, Al-Sehli A, Al-Fadhli F, Ozand PT, Taylor RW, Kaya N | display-authors = 6 | title = Clinical and biochemical features associated with BCS1L mutation | journal = Journal of Inherited Metabolic Disease | volume = 36 | issue = 5 | pages = 813–20 | date = September 2013 | pmid = 22991165 | doi = 10.1007/s10545-012-9536-4 }}</ref><ref>{{cite journal | vauthors = Tuppen HA, Fehmi J, Czermin B, Goffrini P, Meloni F, Ferrero I, He L, Blakely EL, McFarland R, Horvath R, Turnbull DM, Taylor RW | title = Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation | journal = Molecular Genetics and Metabolism | volume = 100 | issue = 4 | pages = 345–8 | date = August 2010 | pmid = 20472482 | doi = 10.1016/j.ymgme.2010.04.010 }}</ref> R183C, F368I,<ref name=":4">{{cite journal | vauthors = Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M | title = Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy | journal = Human Molecular Genetics | volume = 16 | issue = 10 | pages = 1241–52 | date = May 2007 | pmid = 17403714 | doi = 10.1093/hmg/ddm072 }}</ref> and S277N. These mutations tend to affect the ATP-binding residues of BCS1L.<ref name=":5">{{cite journal | vauthors = Hinson JT, Fantin VR, Schönberger J, Breivik N, Siem G, McDonough B, Sharma P, Keogh I, Godinho R, Santos F, Esparza A, Nicolau Y, Selvaag E, Cohen BH, Hoppel CL, Tranebjaerg L, Eavey RD, Seidman JG, Seidman CE | display-authors = 6 | title = Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome | journal = The New England Journal of Medicine | volume = 356 | issue = 8 | pages = 809–19 | date = February 2007 | pmid = 17314340 | doi = 10.1056/NEJMoa055262 }}</ref><ref name=":3" /><ref name=":2" />
 
[[Delayed milestone|Growth retardation]], [[aminoaciduria]], [[cholestasis]], [[iron overload]], [[lactic acidosis]], and early death ([[GRACILE_syndrome |GRACILE]]) is a [[Dominance (genetics)|recessively inherited]] lethal disease that results in mutli-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.<ref>{{cite journal | vauthors = 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 | title = GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L | journal = American Journal of Human Genetics | volume = 71 | issue = 4 | pages = 863–76 | date = October 2002 | pmid = 12215968 | pmc = 378542 | doi = 10.1086/342773 }}</ref><ref name=":3" /><ref name=":2" />
 
Bjoernstad syndrome ia an [[Dominance (genetics)|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,<ref>{{cite journal | vauthors = Siddiqi S, Siddiq S, Mansoor A, Oostrik J, Ahmad N, Kazmi SA, Kremer H, Qamar R, Schraders M | title = Novel mutation in AAA domain of BCS1L causing Bjornstad syndrome | journal = Journal of Human Genetics | volume = 58 | issue = 12 | pages = 819–21 | date = December 2013 | pmid = 24172246 | doi = 10.1038/jhg.2013.101 }}</ref> R184C,<ref name=":4" /> G35R, R114W, R183H, Q302E, and R306H. These mutations tend to affect the protein-protein interactions of BCS1L.<ref name=":5" /><ref name=":3" /><ref name=":2" />
 
== 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]].<ref>{{Cite web | url = https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=BCS1L | title = 14 binary interactions found for search term BCS1L | work = IntAct Molecular Interaction Database | publisher = EMBL-EBI | access-date = 2018-08-25 }}</ref>
 
 
== See also ==
* [[Björnstad syndrome]]
* [[Björnstad syndrome]]
* [[GRACILE syndrome]]
* [[GRACILE syndrome]]


==References==
== References ==
{{reflist}}
{{reflist}}


==External links==
== External links ==
* {{UCSC gene info|BCS1L}}
* {{UCSC gene info|BCS1L}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
| citations =
* {{cite journal | vauthors = Fölsch H, Guiard B, Neupert W, Stuart RA | title = Internal targeting signal of the BCS1 protein: a novel mechanism of import into mitochondria | journal = The EMBO Journal | volume = 15 | issue = 3 | pages = 479–87 | date = February 1996 | pmid = 8599931 | pmc = 449966 | doi =  }}
*{{cite journal | vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–13 | date = April 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
*{{cite journal | vauthors=Fölsch H, Guiard B, Neupert W, Stuart RA |title=Internal targeting signal of the BCS1 protein: a novel mechanism of import into mitochondria |journal=EMBO J. |volume=15 |issue= 3 |pages= 479–87 |year= 1996 |pmid= 8599931 |doi= | pmc=449966 }}
* {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–8 | date = April 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
*{{cite journal | author=Andersson B |title=A "double adaptor" method for improved shotgun library construction |journal=Anal. Biochem. |volume=236 |issue= 1 |pages= 107–13 |year= 1996 |pmid= 8619474 |doi= 10.1006/abio.1996.0138 |name-list-format=vanc| author2=Wentland MA  | author3=Ricafrente JY  | display-authors=3  | last4=Liu  | first4=W  | last5=Gibbs  | first5=RA }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Yu W |title=Large-scale concatenation cDNA sequencing |journal=Genome Res. |volume=7 |issue= 4 |pages= 353–8 |year= 1997 |pmid= 9110174 |doi= 10.1101/gr.7.4.353| pmc=139146  |name-list-format=vanc| author2=Andersson B  | author3=Worley KC  | display-authors=3  | last4=Muzny  | first4=DM  | last5=Ding  | first5=Y  | last6=Liu  | first6=W  | last7=Ricafrente  | first7=JY  | last8=Wentland  | first8=MA  | last9=Lennon  | first9=G  }}
* {{cite journal | vauthors = Lubianca Neto JF, Lu L, Eavey RD, Flores MA, Caldera RM, Sangwatanaroj S, Schott JJ, McDonough B, Santos JI, Seidman CE, Seidman JG | title = The Bjornstad syndrome (sensorineural hearing loss and pili torti) disease gene maps to chromosome 2q34-36 | journal = American Journal of Human Genetics | volume = 62 | issue = 5 | pages = 1107–12 | date = May 1998 | pmid = 9545407 | pmc = 1377094 | doi = 10.1086/301837 }}
*{{cite journal | author=Suzuki Y |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 |name-list-format=vanc| author2=Yoshitomo-Nakagawa K  | author3=Maruyama K  | display-authors=3  | last4=Suyama  | first4=A  | last5=Sugano  | first5=S  }}
* {{cite journal | vauthors = Visapää I, Fellman V, Varilo T, Palotie A, Raivio KO, Peltonen L | title = Assignment of the locus for a new lethal neonatal metabolic syndrome to 2q33-37 | journal = American Journal of Human Genetics | volume = 63 | issue = 5 | pages = 1396–403 | date = November 1998 | pmid = 9792866 | pmc = 1377549 | doi = 10.1086/302123 }}
*{{cite journal | author=Lubianca Neto JF |title=The Bjornstad syndrome (sensorineural hearing loss and pili torti) disease gene maps to chromosome 2q34-36 |journal=Am. J. Hum. Genet. |volume=62 |issue= 5 |pages= 1107–12 |year= 1998 |pmid= 9545407 |doi=10.1086/301837 | pmc=1377094  |name-list-format=vanc| author2=Lu L  | author3=Eavey RD  | display-authors=3  | last4=Flores  | first4=Marco Antonio Macias  | last5=Caldera  | first5=Raul Martinez  | last6=Sangwatanaroj  | first6=Somkiat  | last7=Schott  | first7=Jean Jacques  | last8=McDonough  | first8=Barbara  | last9=Santos  | first9=Jose Ignatio  }}
* {{cite journal | vauthors = 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 | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = January 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
*{{cite journal | author=Visapää I |title=Assignment of the locus for a new lethal neonatal metabolic syndrome to 2q33-37 |journal=Am. J. Hum. Genet. |volume=63 |issue= 5 |pages= 1396–403 |year= 1998 |pmid= 9792866 |doi=10.1086/302123 | pmc=1377549  |name-list-format=vanc| author2=Fellman V  | author3=Varilo T  | display-authors=3  | last4=Palotie  | first4=Aarno  | last5=Raivio  | first5=Kari O.  | last6=Peltonen  | first6=Leena  }}
*{{cite journal | author=de Lonlay P |title=A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure |journal=Nat. Genet. |volume=29 |issue= 1 |pages= 57–60 |year= 2001 |pmid= 11528392 |doi= 10.1038/ng706  |name-list-format=vanc| author2=Valnot I  | author3=Barrientos A  | display-authors=3  | last4=Gorbatyuk  | first4=Marina  | last5=Tzagoloff  | first5=Alexander  | last6=Taanman  | first6=Jan-Willem  | last7=Benayoun  | first7=Emmanuel  | last8=Chrétien  | first8=Dominique  | last9=Kadhom  | first9=Noman }}
*{{cite journal  | author=Visapää I |title=GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L |journal=Am. J. Hum. Genet. |volume=71 |issue= 4 |pages= 863–76 |year= 2002 |pmid= 12215968 |doi=10.1086/342773  | pmc=378542  |name-list-format=vanc| author2=Fellman V  | author3=Vesa J  | display-authors=3  | last4=Dasvarma  | first4=A  | last5=Hutton  | first5=J  | last6=Kumar  | first6=V  | last7=Payne  | first7=G  | last8=Makarow  | first8=M | last9=Vancoster  | first9=R }}
*{{cite journal  | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241  |name-list-format=vanc| author2=Feingold EA  | author3=Grouse LH  | display-authors=3  | last4=Derge  | first4=JG  | last5=Klausner  | first5=RD  | last6=Collins  | first6=FS  | last7=Wagner  | first7=L  | last8=Shenmen  | first8=CM  | last9=Schuler  | first9=GD }}
*{{cite journal  | author=Ota T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285  |name-list-format=vanc| author2=Suzuki Y  | author3=Nishikawa T | display-authors=3  | last4=Otsuki  | first4=Tetsuji  | last5=Sugiyama  | first5=Tomoyasu  | last6=Irie  | first6=Ryotaro  | last7=Wakamatsu  | first7=Ai  | last8=Hayashi  | first8=Koji  | last9=Sato  | first9=Hiroyuki }}
*{{cite journal  | author=Gerhard DS |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928  |name-list-format=vanc| author2=Wagner L  | author3=Feingold EA  | display-authors=3  | last4=Shenmen  | first4=CM  | last5=Grouse  | first5=LH  | last6=Schuler  | first6=G  | last7=Klein  | first7=SL  | last8=Old  | first8=S | last9=Rasooly  | first9=R }}
*{{cite journal  | author=Kimura K |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes |journal=Genome Res. |volume=16 |issue= 1 |pages= 55–65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406  | pmc=1356129 |name-list-format=vanc| author2=Wakamatsu A  | author3=Suzuki Y  | display-authors=3  | last4=Ota  | first4=T  | last5=Nishikawa  | first5=T  | last6=Yamashita  | first6=R  | last7=Yamamoto  | first7=J  | last8=Sekine  | first8=M  | last9=Tsuritani  | first9=K }}
*{{cite journal  | author=Fernandez-Vizarra E |title=Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy |journal=Hum. Mol. Genet. |volume=16 |issue= 10 |pages= 1241–52 |year= 2007 |pmid= 17403714 |doi= 10.1093/hmg/ddm072  |name-list-format=vanc| author2=Bugiani M  | author3=Goffrini P  | display-authors=3  | last4=Carrara  | first4=F. | last5=Farina  | first5=L.  | last6=Procopio  | first6=E.  | last7=Donati  | first7=A.  | last8=Uziel  | first8=G.  | last9=Ferrero  | first9=I. }}
}}
{{refend}}
{{refend}}


<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
{{Citric acid cycle enzymes and ETC}}
{{Citric acid cycle enzymes and ETC}}


[[Category:Protein domains]]
{{NLM content}}


{{Portal bar|Mitochondria|Gene Wiki}}


{{gene-2-stub}}
[[Category:Protein domains]]

Latest revision as of 07:00, 25 August 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human
BCS1 N-terminal domain
Identifiers
SymbolBCS1_N
PfamPF08740
InterProIPR014851

Mitochondrial chaperone BCS1 (BCS1L), also known as BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone (h-BCS1), is a protein that in humans is encoded by the BCS1L gene. BCS1L is a chaperone protein involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III), which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene are associated with mitochondrial complex III deficiency (nuclear, 1), GRACILE syndrome, and Bjoernstad syndrome.[1][2][3]

Structure

BCS1L is located on the q arm of chromosome 2 in position 35 and has 10 exons.[1] The BCS1L gene produces a 47.5 kDa protein composed of 419 amino acids.[4][5] 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.[2][3] 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.[6] 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.[2][3] Several alternatively spliced transcripts encoding two different isoforms have been described.[7]

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.[8][2][3]

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,[9][10][11] T50A,[12] R73C,[13] P99L, R155P, V353M,[14] G129R,[15][16] R183C, F368I,[17] and S277N. These mutations tend to affect the ATP-binding residues of BCS1L.[18][3][2]

Growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE) is a recessively inherited lethal disease that results in mutli-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.[19][3][2]

Bjoernstad syndrome ia 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,[20] R184C,[17] G35R, R114W, R183H, Q302E, and R306H. These mutations tend to affect the protein-protein interactions of BCS1L.[18][3][2]

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.[21]


See also

References

  1. ↑ 1.0 1.1 "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.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "BCS1L - Mitochondrial chaperone BCS1 - Homo sapiens (Human) - BCS1L gene & protein". www.uniprot.org. Retrieved 2018-08-03.File:CC-BY-icon-80x15.png This article incorporates text available under the CC BY 4.0 license.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  4. ↑ Yao D. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-02.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ "Entrez Gene: BCS1L BCS1-like (yeast)".
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 17.0 17.1 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.
  18. ↑ 18.0 18.1 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ "14 binary interactions found for search term BCS1L". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.

External links

Further reading

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

Retrieved from "https://www.wikidoc.org/index.php?title=BCS1L&oldid=1531695"