TIMM8A
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).
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.
Involvement in disease
Mohr-Tranebjaerg syndrome
MTS
An X-linked recessive disorder characterized by postlingual sensorineural deafness with onset in early childhood, dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the small Tim family.
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.
Cellular localization
- Mitochondrion inner membrane
- Peripheral membrane protein
- Intermembrane side
Alternative names
DDP, DDP1, TIM8A, TIMM8A, Mitochondrial import inner membrane translocase subunit Tim8 A, Deafness dystonia protein 1, X-linked deafness dystonia protein
Database links
swissprot:O60220 omim:300356 genbank:NP_004076 entrezGene:1678