Description: Homo sapiens chromosome 10 open reading frame 2 (TWNK), transcript variant 1, mRNA. RefSeq Summary (NM_021830): This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Aug 2009]. Transcript (Including UTRs) Position: hg19 chr10:102,747,293-102,754,158 Size: 6,866 Total Exon Count: 5 Strand: + Coding Region Position: hg19 chr10:102,747,968-102,753,267 Size: 5,300 Coding Exon Count: 5
ID:PEO1_HUMAN DESCRIPTION: RecName: Full=Twinkle protein, mitochondrial; EC=3.6.4.12; AltName: Full=Progressive external ophthalmoplegia 1 protein; AltName: Full=T7 gp4-like protein with intramitochondrial nucleoid localization; AltName: Full=T7-like mitochondrial DNA helicase; Flags: Precursor; FUNCTION: Involved in mitochondrial DNA (mtDNA) metabolism. Could function as an adenine nucleotide-dependent DNA helicase. Function inferred to be critical for lifetime maintenance of mtDNA integrity. In vitro, forms in combination with POLG, a processive replication machinery, which can use double-stranded DNA (dsDNA) as template to synthesize single-stranded DNA (ssDNA) molecules. May be a key regulator of mtDNA copy number in mammals. CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. SUBUNIT: Forms multimers in vitro, including hexamers. Interacts with POLG in vitro. SUBCELLULAR LOCATION: Mitochondrion matrix, mitochondrion nucleoid. Note=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 and expression. TISSUE SPECIFICITY: High relative levels in skeletal muscle, testis and pancreas. Lower levels of expression in the heart, brain, placenta, lung, liver, kidney, spleen, thymus, prostate, ovary, small intestine, colon and leukocytes. Expression is coregulated with MRPL43. DISEASE: Defects in PEO1 are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 3 (PEOA3) [MIM:609286]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged- red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. DISEASE: Defects in PEO1 are a cause of sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]. SANDO is a clinically heterogeneous systemic disorder with variable features resulting from mitochondrial dysfunction. It shares phenotypic characteristics with autosomal recessive progressive external ophthalmoplegia and mitochondrial neurogastrointestinal encephalopathy syndrome. The clinical triad of symptoms consists of sensory ataxic, neuropathy, dysarthria, and ophthalmoparesis. DISEASE: Defects in PEO1 are the cause of mitochondrial DNA depletion syndrome type 7 (MTDPS7) [MIM:271245]; also known as spinocerebellar ataxia infantile-onset (IOSCA). A severe disease associated with mitochondrial dysfunction. Some patients are affected by progressive atrophy of the cerebellum, brain stem, the spinal cord, and sensory axonal neuropath. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. Some individuals manifest a hepatocerebral phenotype characterized by liver insufficiency, increased serum and CSF lactate, hypotonia, psychomotor retardation and peripheral neuropathy. SIMILARITY: Contains 1 SF4 helicase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/C10orf2"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/peo1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96RR1
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006260 DNA replication GO:0006264 mitochondrial DNA replication GO:0006268 DNA unwinding involved in DNA replication GO:0006390 transcription from mitochondrial promoter GO:0007005 mitochondrion organization GO:0034214 protein hexamerization GO:0051260 protein homooligomerization GO:0071333 cellular response to glucose stimulus