MIPEP

Mitochondrial intermediate peptidase is an is_associated_with::enzyme that in humans is encoded by the MIPEP is_associated_with::gene. This protein is a critical component of human mitochondrial protein import machinery involved in the maturing process of nuclear coded mitochondrial proteins that with a mitochondrial translocation peptide, especially those OXPHOS-related proteins.

Gene
The gene MIPEP encodes one metalloprotease that hydrolyzes peptide fragment of eight amino acids in lengths to process mitochondria-targeted proteins. a. The human gene MIPEP has 21 Exons and locates at chromosome band13q12. Evidences showed that the human gene  MIPEP is highly expressed in the heart, skeletal muscle, and pancreas, three organ systems that are frequently reported with OXPHOS disorders.

Protein
The human protein Mitochondrial intermediate peptidase is 80.6 kDa in size and composed of 713 amino acids. It contains a mitonchondria targeting peptide (Amino acid 1-35 of the peptide sequence). The mature protein has a theoretical pI of 6.03.

Function
Working in concert with general mitochondrial processing peptidase (MPP), MIPEP plays critical role in the maturation of a specific class of nuclear-encoded precursor proteins characterized by the motif, XRX(f)(F/L/I)XX(T/S/G)XXXX(f). Initially, peptidase MPP cleaves the precursors at positions two peptide bonds from the R residue, leaving a typical octapeptide at the protein N- terminus; subsequently, MIP cleaves the octapeptide, completing the final maturation of processed protein. A recent study showed that mitochondrial intermediate peptidase can degrade the transmembrane receptor is_associated_with::Notch at its S5 site and assist Notch protein maturation.

Clinical significance
Since MIPEP plays critical roles in mitochondrial protein maturation, it has been linked to many diseases associated with mitochondrial dysfunctions. In a GWAS study of Chinese population, a significant association between high is_associated_with::myopia and a variant at chromosome band region 13q12.12. Gene MIPEP locates in the same locus and appears to expressed in the retina and retinal pigment epithelium (RPE) and are more likely associated with high myopia.