Q9Y276 (BCS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial chaperone BCS1
Short name=h-BCS1

Alternative name(s):
BCS1-like protein

Gene names

Name:	BCS1L
Synonyms:	BCS1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	419 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Chaperone necessary for the assembly of mitochondrial respiratory chain complex III. Plays an important role in the maintenance of mitochondrial tubular networks, respiratory chain assembly and formation of the LETM1 complex. Ref.9
Subunit structure	Interacts with LETM1. Ref.9
Subcellular location	Mitochondrion inner membrane; Single-pass membrane protein Ref.1 Ref.9.
Tissue specificity	Ubiquitous. Ref.1
Involvement in disease	Defects in BCS1L are the cause of GRACILE syndrome (GRACILE) [MIM:603358]. GRACILE stands for 'growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death'. It is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. Ref.3 Ref.14 Defects in BCS1L are a cause of mitochondrial complex III deficiency (MT-C3D) [MIM:124000]. A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance. Ref.2 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Defects in BCS1L are the cause of Bjoernstad syndrome (BJS) [MIM:262000]. BJS is an autosomal recessive condition characterized by sensorineural hearing loss and pili torti. The hearing loss in BJS is congenital and of variable severity. Pili torti (twisted hairs), a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle, is usually recognized early in childhood. Ref.14
Sequence similarities	Belongs to the AAA ATPase family. BCS1 subfamily.

Ontologies

Keywords
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Disease	Deafness Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chaperone
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mitochondrial respiratory chain complex I assembly Inferred from mutant phenotype Ref.9. Source: UniProtKB mitochondrial respiratory chain complex III assembly Inferred from mutant phenotype Ref.9. Source: UniProtKB mitochondrial respiratory chain complex IV assembly Inferred from mutant phenotype Ref.9. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial respiratory chain complex III Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 419	419	Mitochondrial chaperone BCS1		PRO_0000084772
Regions
	Topological domain	1 – 15	15	Mitochondrial intermembrane Potential
	Transmembrane	16 – 32	17	Helical; Potential
	Topological domain	33 – 419	387	Mitochondrial matrix Potential
	Nucleotide binding	230 – 237	8	ATP Potential
Amino acid modifications
	Modified residue	181	1	Phosphotyrosine Ref.10
Natural variations
	Natural variant	35	1	G → R in BJS; with mild mitochondrial complex III deficiency. Ref.14		VAR_032086
	Natural variant	45	1	R → C in MT-C3D. Ref.12		VAR_032087
	Natural variant	50	1	T → A in MT-C3D. Ref.15		VAR_064615
	Natural variant	73	1	R → C in MT-C3D. Ref.13		VAR_064616
	Natural variant	78	1	S → G in GRACILE. Ref.3 Ref.14 Corresponds to variant rs28937590 [ dbSNP | Ensembl ].		VAR_018149
	Natural variant	99	1	P → L in MT-C3D. Ref.2 Ref.14		VAR_018159
	Natural variant	114	1	R → W in BJS. Ref.14		VAR_032088
	Natural variant	144	1	R → Q in GRACILE. Ref.3 Ref.14		VAR_018160
	Natural variant	155	1	R → P in MT-C3D; abolishes interaction with LETM1. Ref.2 Ref.9 Ref.14		VAR_018161
	Natural variant	183	1	R → C in MT-C3D; causes a decreased incorporation of the Rieske iron-sulfur protein UQCRFS1 into complex III. Ref.13		VAR_064617
	Natural variant	183	1	R → H in BJS. Ref.14		VAR_032089
	Natural variant	184	1	R → C in MT-C3D and BJS; with mild mitochondrial complex III deficiency; causes a decreased incorporation of the Rieske iron-sulfur protein UQCRFS1 into complex III. Ref.13 Ref.14		VAR_032090
	Natural variant	277	1	S → N in MT-C3D. Ref.2 Ref.14		VAR_018162
	Natural variant	302	1	Q → E in BJS. Ref.14		VAR_032091
	Natural variant	306	1	R → H in BJS. Ref.14		VAR_032092
	Natural variant	327	1	V → A in GRACILE. Ref.3 Ref.14		VAR_018163
	Natural variant	353	1	V → M in MT-C3D. Ref.2 Ref.14		VAR_018164
	Natural variant	368	1	F → I in MT-C3D. Ref.13		VAR_064618
Experimental info
	Sequence conflict	394	1	A → T in CAE11877. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q9Y276 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 7F0F98BA62F2CBB8	FASTA	419	47,534
	10 20 30 40 50 60 MPLSDFILAL KDNPYFGAGF GLVGVGTALA LARKGVQLGL VAFRRHYMIT LEVPARDRSY 70 80 90 100 110 120 AWLLSWLTRH STRTQHLSVE TSYLQHESGR ISTKFEFVPS PGNHFIWYRG KWIRVERSRE 130 140 150 160 170 180 MQMIDLQTGT PWESVTFTAL GTDRKVFFNI LEEARELALQ QEEGKTVMYT AVGSEWRPFG 190 200 210 220 230 240 YPRRRRPLNS VVLQQGLADR IVRDVQEFID NPKWYTDRGI PYRRGYLLYG PPGCGKSSFI 250 260 270 280 290 300 TALAGELEHS ICLLSLTDSS LSDDRLNHLL SVAPQQSLVL LEDVDAAFLS RDLAVENPVK 310 320 330 340 350 360 YQGLGRLTFS GLLNALDGVA STEARIVFMT TNHVDRLDPA LIRPGRVDLK EYVGYCSHWQ 370 380 390 400 410 LTQMFQRFYP GQAPSLAENF AEHVLRATNQ ISPAQVQGYF MLYKNDPVGA IHNAESLRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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." Petruzzella V., Tiranti V., Fernandez P., Ianna P., Carrozzo R., Zeviani M. Genomics 54:494-504(1998) [PubMed: 9878253] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure." de Lonlay P., Valnot I., Barrientos A., Gorbatyuk M., Tzagoloff A., Taanman J.-W., Benayoun E., Chretien D., Kadhom N., Lombes A., Ogier de Baulny H., Niaudet P., Munnich A., Rustin P., Roetig A. Nat. Genet. 29:57-60(2001) [PubMed: 11528392] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MT-C3D LEU-99; PRO-155; ASN-277 AND MET-353.
[3]	"GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L." Visapaeae I., Fellman V., Vesa J., Dasvarma A., Hutton J.L., Kumar V., Payne G.S., Makarow M., Van Coster R., Taylor R.W., Turnbull D.M., Suomalainen A., Peltonen L. Am. J. Hum. Genet. 71:863-876(2002) [PubMed: 12215968] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS GRACILE GLY-78; GLN-144 AND ALA-327.
[4]	"Large-scale concatenation cDNA sequencing." Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A. Genome Res. 7:353-358(1997) [PubMed: 9110174] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Small intestine.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[9]	"Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L." Tamai S., Iida H., Yokota S., Sayano T., Kiguchiya S., Ishihara N., Hayashi J., Mihara K., Oka T. J. Cell Sci. 121:2588-2600(2008) [PubMed: 18628306] [Abstract] Cited for: INTERACTION WITH LETM1, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT MT-C3D PRO-155.
[10]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-181, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene." De Meirleir L., Seneca S., Damis E., Sepulchre B., Hoorens A., Gerlo E., Garcia Silva M.T., Hernandez E.M., Lissens W., Van Coster R. Am. J. Med. Genet. A 121:126-131(2003) [PubMed: 12910490] [Abstract] Cited for: VARIANT MT-C3D CYS-45.
[13]	"Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy." Fernandez-Vizarra E., Bugiani M., Goffrini P., Carrara F., Farina L., Procopio E., Donati A., Uziel G., Ferrero I., Zeviani M. Hum. Mol. Genet. 16:1241-1252(2007) [PubMed: 17403714] [Abstract] Cited for: VARIANTS MT-C3D CYS-73; CYS-183; CYS-184 AND ILE-368.
[14]	"Missense mutations in the BCS1L gene as a cause of the Bjoernstad syndrome." Hinson J.T., Fantin V.R., Schoenberger J., Breivik N., Siem G., McDonough B., Sharma P., Keogh I., Godinho R., Santos F., Esparza A., Nicolau Y., Selvaag E., Cohen B.H., Hoppel C.L., Tranebjaerg L., Eavey R.D., Seidman J.G., Seidman C.E. N. Engl. J. Med. 356:809-819(2007) [PubMed: 17314340] [Abstract] Cited for: VARIANTS BJS ARG-35; TRP-114; HIS-183; CYS-184; GLU-302 AND HIS-306, VARIANTS MT-C3D LEU-99; PRO-155; ASN-277 AND MET-353, VARIANTS GRACILE GLY-78; GLN-144 AND ALA-327.
[15]	"Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient." Blazquez A., Gil-Borlado M.C., Moran M., Verdu A., Cazorla-Calleja M.R., Martin M.A., Arenas J., Ugalde C. Neuromuscul. Disord. 19:143-146(2009) [PubMed: 19162478] [Abstract] Cited for: VARIANT MT-C3D ALA-50.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF026849 mRNA. Translation: AAD08638.1. AF346835 Genomic DNA. Translation: AAK29417.1. AF516670 Genomic DNA. Translation: AAN05490.1. AF038195 mRNA. Translation: AAB97365.1. AK096210 mRNA. Translation: BAG53231.1. BX571752 mRNA. Translation: CAE11877.1. CH471063 Genomic DNA. Translation: EAW70634.1. BC000416 mRNA. Translation: AAH00416.1. BC007500 mRNA. Translation: AAH07500.1.
IPI	IPI00003985.
RefSeq	NP_001073335.1. NM_001079866.1. NP_004319.1. NM_004328.4.
UniGene	Hs.471401.
3D structure databases
ProteinModelPortal	Q9Y276.
SMR	Q9Y276. Positions 185-400.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y276. 1 interaction.
MINT	MINT-1433080.
STRING	Q9Y276.
PTM databases
PhosphoSite	Q9Y276.
Polymorphism databases
DMDM	46397351.
Proteomic databases
PeptideAtlas	Q9Y276.
PRIDE	Q9Y276.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359273; ENSP00000352219; ENSG00000074582. ENST00000392109; ENSP00000375957; ENSG00000074582. ENST00000392110; ENSP00000375958; ENSG00000074582. ENST00000392111; ENSP00000375959; ENSG00000074582. ENST00000412366; ENSP00000406494; ENSG00000074582. ENST00000431802; ENSP00000413908; ENSG00000074582. ENST00000439945; ENSP00000404999; ENSG00000074582.
GeneID	617.
KEGG	hsa:617.
UCSC	uc002vio.1. human.
Organism-specific databases
CTD	617.
GeneCards	GC02P219523.
H-InvDB	HIX0002834.
HGNC	HGNC:1020. BCS1L.
HPA	HPA037700. HPA037701.
MIM	124000. phenotype. 262000. phenotype. 603358. phenotype. 603647. gene.
neXtProt	NX_Q9Y276.
Orphanet	123. Bjoernstad syndrome. 53693. GRACILE syndrome. 1460. Isolated CoQ-cytochrome C reductase deficiency. 255249. Leigh syndrome with nephrotic syndrome. 254902. Renal tubulopathy - encephalopathy - liver failure.
PharmGKB	PA25327.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000005415.
HOGENOM	HBG521794.
HOVERGEN	HBG048759.
InParanoid	Q9Y276.
OMA	PSKDKSY.
OrthoDB	EOG4TTGJ0.
PhylomeDB	Q9Y276.
Gene expression databases
ArrayExpress	Q9Y276.
Bgee	Q9Y276.
CleanEx	HS_BCS1L.
Genevestigator	Q9Y276.
GermOnline	ENSG00000074582. Homo sapiens.
Family and domain databases
InterPro	IPR003593. ATPase_AAA+_core. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. IPR014851. BCS1_N. [Graphical view]
KO	K08900.
Pfam	PF00004. AAA. 1 hit. PF08740. BCS1_N. 1 hit. [Graphical view]
SMART	SM00382. AAA. 1 hit. SM01024. BCS1_N. 1 hit. [Graphical view]
PROSITE	PS00674. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	2497.
SOURCE	Search...

Entry information

Entry name

BCS1_HUMAN

Accession

Primary (citable) accession number: Q9Y276
Secondary accession number(s): B3KTW9, Q7Z2V7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	November 1, 1999
Last modified:	January 25, 2012
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.