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twinkle protein, mitochondrial; T7 gp4-like protein with intramitochondrial nucleoid localization; T7-like mitochondrial DNA helicase; Progressive external ophthalmoplegia 1 protein (PEO1, C10orf2)
Function:
- role in mitochondrial DNA (mtDNA) metabolism.
- has helicase activity
- may be a key regulator of mtDNA copy number in mammals
- role in lifetime maintenance of mtDNA integrity
- in vitro, forms in combination with POLG, a processive replication machinery, which can use double-stranded DNA as template to synthesize single-stranded DNA
- forms multimers in vitro, including hexamers
- interacts with POLG in vitro
Structure: contains 1 SF4 helicase domain
Compartment:
- mitochondrial matrix, mitochondrial nucleoid
- colocalizes with mtDNA in mitochondrial nucleoids, a nucleoproteins complex consisting of a number of copies of proteins associated with mtDNA, probably involved in mtDNA maintenance & expression
Alternative splicing: named isoforms=3
Expression:
- high relative levels in skeletal muscle, testis & pancreas
- lower levels of expression in the heart, brain, placenta, lung, liver, kidney, spleen, thymus, prostate, ovary, small intestine, colon & leukocytes.
- expression is coregulated with MRPL43
Genetics:
- nuclear encoded mitochondrial protein
Pathology:
- defects in PEO1 are the cause
a) progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 3
b) spinocerebellar ataxia infantile-onset
- defects in PEO1 are a cause of
- sensory ataxic neuropathy dysarthria & ophthalmoparesis (SANDO)
Note:
- the name 'twinkle' derives from the unusual localization pattern reminiscent of twinkling stars [3]
Related
C10orf2 (twinkle) gene
mitochondrial nucleoid
ophthalmoplegia (ophthalmoparesis)
General
helicase (DNA unwinding protein, DNA untwisting protein)
mitochondrial protein
oligomerizing protein
Properties
SIZE: entity length = 684 aa
MW = 77 kD
COMPARTMENT: mitochondrial matrix
MOTIF: SF4 helicase {384-635}
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 415-422
Database Correlations
OMIM correlations
MORBIDMAP 606075
UniProt Q96RR1
Pfam PF06745
Entrez Gene 56652
Kegg hsa:56652
References
- UniProt :accession Q96RR1
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/C10orf2
- NIEHS-SNPs
http://egp.gs.washington.edu/data/peo1/
- OMIM :accession 606075
- Spelbrink JN et al
Human mitochondrial DNA deletions associated with mutations
in the gene encoding Twinkle, a phage T7 gene 4-like protein
localized in mitochondria.
Nature Genetics 28:223, 2001
PMID: 11431692