Tripeptidyl peptidase I

Tripeptidyl-peptidase 1, also known as Lysosomal pepstatin-insensitive protease, is an enzyme that in humans is encoded by the TPP1 gene.

Gene

The human gene TPP1 encodes a member of the sedolisin family of serine proteases. The human gene has 13 Exons and locates at the chromosome band 11p15.

Structure

The human tripeptidyl-peptidase 1 is 61kDa in size and composed of 563 amino acids. An isoform of 34.5kDa and 320 amino acids is generated by alternative splicing and a peptide fragment of 1-243 amino acid is missing.

Function

The protease functions in the lysosome to cleave N-terminal tripeptides from substrates and has weaker endopeptidase activity. It is synthesized as a catalytically inactive enzyme which is activated and autoproteolyzed upon acidification. Interestingly, TPP1 has been found to regulate the length of telomeres. Telomeres are the ends of linear eukaryotic chromosomes and consist of multiple repeats of a short DNA sequence.The mammalian chromosome end is capped by a protein complex known as shelterin that is composed of six proteins: TRF1, TRF2, RAP1, TIN2, POT1 and TPP1.