Human Gene TIMM8A (ENST00000372902.4) Description and Page Index
Description: Homo sapiens translocase of inner mitochondrial membrane 8A (TIMM8A), transcript variant 1, mRNA. (from RefSeq NM_004085) RefSeq Summary (NM_004085): This translocase is involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS) and it is postulated that MTS/DDS is a mitochondrial disease caused by a defective mitochondrial protein import system. Defects in this gene also cause Jensen syndrome; an X-linked disease with opticoacoustic nerve atrophy and muscle weakness. This protein, along with TIMM13, forms a 70 kDa heterohexamer. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Mar 2009]. Gencode Transcript: ENST00000372902.4 Gencode Gene: ENSG00000126953.8 Transcript (Including UTRs) Position: hg38 chrX:101,345,661-101,348,742 Size: 3,082 Total Exon Count: 2 Strand: - Coding Region Position: hg38 chrX:101,346,499-101,348,664 Size: 2,166 Coding Exon Count: 2
ID:TIM8A_HUMAN DESCRIPTION: RecName: Full=Mitochondrial import inner membrane translocase subunit Tim8 A; AltName: Full=Deafness dystonia protein 1; AltName: Full=X-linked deafness dystonia protein; FUNCTION: Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. Probably necessary for normal neurologic development. SUBUNIT: Heterohexamer; composed of 3 copies of TIMM8A and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22. SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side. TISSUE SPECIFICITY: Highly expressed in fetal and adult brain, followed by fetal lung, liver and kidney. Also expressed in heart, placenta, lung, liver, kidney, pancreas, skeletal muscle and heart. DOMAIN: The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity). DISEASE: Defects in TIMM8A are the cause of Mohr-Tranebjaerg syndrome (MTS) [MIM:304700]; also known as dystonia-deafness syndrome (DDS) or X-linked progressive deafness type 1 (DFN-1). It is a recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness. DISEASE: Defects in TIMM8A are the cause of Jensen syndrome (JENSS) [MIM:311150]; also known as opticoacoustic nerve atrophy with dementia. This X-linked disease is characterized by deafness, blindness and muscle weakness. SIMILARITY: Belongs to the small Tim family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TIMM8A";
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.
Pfam Domains: PF02953 - Tim10/DDP family zinc finger
ModBase Predicted Comparative 3D Structure on O60220
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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.