TPP1 (CLN2)

Tripeptidyl-peptidase 1 (TPP1 / CLN2) is a member of the sedolisin family of serine proteases. 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 auto-proteolyzed upon acidification. TPP1 / CLN2 May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Defects in TPP1 / CLN2 are the cause of neuronal ceroid lipofuscinosis type 2 (CLN2), a form of neuronal ceroid lipofuscinosis which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.

TPP1 (CLN2) Alternative Names

GIG1, CLN2, LPIC, TPP-1, cell growth-inhibiting gene 1 protein, growth-inhibiting protein 1, lysosomal pepstatin insensitive protease, tripeptidyl aminopeptidase, tripeptidyl-peptidase 1[Homo sapiens]

Cln2, TPP-I, LPIC, TPP-1, ceroid-lipofuscinosis, neuronal 2, lysosomal pepstatin-insensitive protease, tripeptidyl aminopeptidase, tripeptidyl peptidase-I, tripeptidyl-peptidase 1[Mus musculus]

Summaries for TPP1 (CLN2)

Entrez Gene summary for TPP1 (CLN2):

TPP1 gene encodes a member of the sedolisin family of serine proteases. 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 auto-proteolyzed upon acidification. Mutations in TPP1 gene result in late-infantile neuronal ceroid lipofuscinosis, which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome. [provided by RefSeq, Jul 2008]

OMIM - description for TPP1 (CLN2):

TPP1 is a lysosomal exopeptidase that sequentially removes tripeptides from the N termini of proteins. It also has a minor endoprotease activity (Golabek et al., 2005).

Wikipedia summary for TPP1 (CLN2):

Tripeptidyl-peptidase 1 is an enzyme that in humans is encoded by the TPP1 gene.

Human TPP1 (CLN2) Protein General Information

 

• Protein names: Tripeptidyl-peptidase 1
  Short name=TPP1
• Sequence length: 563 AA.
• Domain: Signal
• Sequence similarities: Belongs to the peptidase S53 family.
• Post-translational modification: Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing and activity.
• Subunit structure: Monomer.
• Subcellular location: Lysosome. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
• Tissue specificity: Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues.
• Involvement in disease: Defects in TPP1 are the cause of neuronal ceroid lipofuscinosis type 2 (CLN2) . A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles.
• Cofactor: Binds 1 calcium ion per subunit.
• Catalytic activity: Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.
• Sequence caution: The sequence AAM08412.1 differs from that shown. Reason: Incorrectly indicated as originating from bovine.
  The sequence AAQ88866.1 differs from that shown. Reason: Frameshift at position 551.

General information above from UniProt

Function for TPP1 (CLN2) Protein

UniProtKB:

TPP1 is lysosomal serine protease with tripeptidyl-peptidase I activity. TPP1 may act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. TPP1 requires substrates with an unsubstituted N-terminus.

Genatlas:

• TPP1 is pepstatin-insensitive, carboxyl-dependent tripeptidyl-peptidase
• TPP1 acts as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases
• TPP1 is a minor endoprotease activity
• TPP1 is predominant proteolytic enzyme responsible for the intracellular degradation of neuromedin B
• TPP1 catalyzes the cleavage of Bid (Autefage 2009)
• TPP1 plays a role in TNF-induced cell death (Autefage 2009)

Homology for human TPP1 (CLN2)

• homolog to murine Tpp1
• homolog to rattus Cln2

Phenotype Information for TPP1 (CLN2)

• Gene/Locus: TPP1, CLN2
• Phenotype: Ceroid lipofuscinosis, neuronal, 2

Phenotype Information for TPP1 (CLN2) from OMIM (Online Mendelian Inheritance in Man)