Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
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.
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Founding paper identifying human BCS1L as the ortholog of yeast BCS1, involved in Complex III assembly. Mitochondrial targeting confirmed by in vitro import and protease-protection assay.
"In yeast, BCS1 is involved mainly in the assembly of complex III...Mitochondrial targeting of the human gene products, suggested by computer analysis of the protein sequences, was confirmed by an in vitro import and protease-protection assay"
A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.
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First identification of BCS1L mutations in patients with complex III deficiency. Established BCS1L as an assembly protein for Complex III.
"So far only one such gene, BCS1L, has been identified in human. BCS1L represents, therefore, an obvious candidate gene in CIII deficiency. Here, we report BCS1L mutations in six patients"
Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L.
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BCS1L interacts with LETM1 and BCS1L levels influence LETM1 complex formation. BCS1L knockdown caused disassembly of the respiratory chains, LETM1 downregulation, and distinct changes in mitochondrial morphology. The R155P MC3DN1 variant abolishes interaction with LETM1.
"LETM1 was co-precipitated with BCS1L and formation of the LETM1 complex depended on BCS1L levels, suggesting that BCS1L stimulates the assembly of the LETM1 complex. BCS1L knockdown caused disassembly of the respiratory chains as well as LETM1 downregulation and induced distinct changes in mitochondrial morphology"
A concerted ATPase cycle of the protein transporter AAA-ATPase Bcs1.
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Bcs1 is a homo-heptameric transmembrane AAA-ATPase that mediates folded Rieske iron-sulfur protein translocation across the inner mitochondrial membrane through a concerted ATPase cycle.
"Bcs1, a homo-heptameric transmembrane AAA-ATPase, facilitates folded Rieske iron-sulfur protein translocation across the inner mitochondrial membrane"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
Complex III assembly
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BCS1L is an assembly factor for Complex III. The Reactome pathway describes the assembly of the cytochrome bc1 reductase (Complex III) and notes that mutations in assembly factors can cause complex III deficiency.
"Mutations in nuclear genes coding for subunits of Complex III, as well as assembly factors, can cause complex III deficiency"
Deep research review of BCS1L gene function
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BCS1L is a dedicated AAA+ protein translocase that uses ATP hydrolysis to translocate the folded, cofactor-loaded UQCRFS1 (Rieske Fe-S protein) from the matrix across the inner membrane into the IMS for incorporation into pre-Complex III. Forms a heptameric ring in the inner membrane. Recent cryo-EM supports an airlock-like gating mechanism. Mutations cause GRACILE syndrome, Bjornstad syndrome, and MC3DN1.