Mitochondrial intermediate peptidase (IPR033851)

Short name: M3A_MIP

Overlapping homologous superfamilies


Family relationships



Mitochondrial intermediate peptidase (MIP; MEROPS identifier M03.006; EC: belongs to the widespread peptidase subfamily M3A [PMID: 7674922]. MIP shows similarity to the thimet oligopeptidase (TOP). These proteins are enriched in cysteine residues, two of which are highly conserved, suggesting their importance to stability as well as in formation of metal binding sites, thus playing a role in MIP activity [PMID: 12191769].

MIP is one of three peptidases responsible for the proteolytic processing of both nuclear and mitochondrial encoded precursor polypeptides targeted to the various subcompartments of the mitochondria [PMID: 12191769,PMID: 12471903]. It cleaves intermediate-size proteins initially processed by mitochondrial processing peptidase (MPP) to yield a processing intermediate with a typical N-terminal octapeptide that is sequentially cleaved by MIP to mature-size protein [PMID: 19900404]. MIP cleaves precursor proteins of respiratory components, including subunits of the electron transport chain and tri-carboxylic acid cycle enzymes, and components of the mitochondrial genetic machinery, including ribosomal proteins, translation factors, and proteins required for mitochondrial DNA metabolism. It has been suggested that the human MIP (HMIP polypeptide; gene symbol MIPEP) may be one of the loci predicted to influence the clinical manifestations of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disease caused by lack of human frataxin [PMID: 10783257].

GO terms

Biological Process

GO:0006627 protein processing involved in protein targeting to mitochondrion

Molecular Function

GO:0004222 metalloendopeptidase activity

Cellular Component

GO:0005759 mitochondrial matrix

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.