PITRM1
Function
Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing (PubMed:10360838, PubMed:16849325, PubMed:19196155, PubMed:24931469). Has an ATP-independent activity (PubMed:16849325). Specifically cleaves peptides in the range of 5 to 65 residues (PubMed:19196155). Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference (PubMed:10360838, PubMed:19196155, PubMed:24931469). Degrades the transit peptides of mitochondrial proteins after their cleavage (PubMed:19196155). Also degrades other unstructured peptides (PubMed:19196155). It is also able to degrade amyloid-beta protein 40, one of the peptides produced by APP processing, when it accumulates in mitochondrion (PubMed:16849325, PubMed:24931469, PubMed:26697887). It is a highly efficient protease, at least toward amyloid-beta protein 40 (PubMed:24931469, PubMed:29383861, PubMed:29764912). Cleaves that peptide at a specific position and is probably not processive, releasing digested peptides intermediates that can be further cleaved subsequently (PubMed:24931469). It is also able to degrade amyloid-beta protein 42 (PubMed:29764912).
Involvement in disease
Spinocerebellar ataxia, autosomal recessive, 30
SCAR30
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR30 is a progressive disease characterized by childhood-onset global developmental delay with variably impaired intellectual development, motor dysfunction, and cerebellar ataxia. Affected individuals may also have psychiatric abnormalities.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
A disulfide bond locks the enzyme in the closed conformation preventing substrate entry into the catalytic chamber.
Sequence Similarities
Belongs to the peptidase M16 family. PreP subfamily.
Tissue Specificity
Widely expressed. Expressed at higher level in muscle and heart compared to brain, pancreas, liver, lung and placenta.
Cellular localization
- Mitochondrion
- Mitochondrion matrix
Alternative names
KIAA1104, MP1, PREP, PITRM1, hPreP, Pitrilysin metalloproteinase 1, Metalloprotease 1, hMP1