Tripeptidyl peptidase I

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

Gene
The human gene TPP1 encodes a member of the is_associated_with::sedolisin family of is_associated_with::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 is_associated_with::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 is_associated_with::shelterin that is composed of six proteins: is_associated_with::TRF1, is_associated_with::TRF2, is_associated_with::RAP1, is_associated_with::TIN2, is_associated_with::POT1 and is_associated_with::TPP1.

Clinical significance
The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders with pathological phenotypes that auto fluorescent lipopigments present in neurons and other cell types. Over the past two decades, accumulating evidences indicates that NCLs are caused by mutations in eight different genes, including genes encoding several soluble proteins (is_associated_with::cathepsin D, is_associated_with::PPT1, and is_associated_with::TPP1). Mutations of gene TPP1 result in late-infantile is_associated_with::neuronal ceroid lipofuscinosis which is associated with the failure to degrade specific neuropeptides and a subunit of is_associated_with::ATP synthase in the is_associated_with::lysosome.