Tripeptidyl Peptidase I (TPP1)

CLN2; GIG1; LPIC; Tripeptidyl aminopeptidase; Lysosomal pepstatin-insensitive protease; Ceroid-Lipofuscinosis,Neuronal 2,Late Infantile; Cell growth-inhibiting gene 1 protein

SPN	U029
HGNC	2073
MGI	1336194
PubMed	24513288
RGD	621296
UniProt	O14773
Wiki	TPP1

Tripeptidyl-peptidase 1 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. Mutations in this 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.Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues.

Reference

"Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis."
Science 277:1802-1805(1997) [PubMed] [Europe PMC] [Abstract]

"Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis."
Genomics 50:206-212(1998) [PubMed] [Europe PMC] [Abstract]

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Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH."
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"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
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Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]

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Hum. Mutat. 14:199-215(1999) [PubMed] [Europe PMC] [Abstract]

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BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

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J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis."
J. Biol. Chem. 284:3976-3984(2009) [PubMed] [Europe PMC] [Abstract]

"Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis."
J. Biol. Chem. 284:3985-3997(2009) [PubMed] [Europe PMC] [Abstract]

"Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder."
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Genet. Med. 2:312-318(2000) [PubMed] [Europe PMC] [Abstract]

"Two novel CLN2 gene mutations in a Chinese patient with classical late-infantile neuronal ceroid lipofuscinosis."
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"New mutations in the neuronal ceroid lipofuscinosis genes."
Eur. J. Paediatr. Neurol. 5:7-10(2001) [PubMed] [Europe PMC] [Abstract]

"Expression and analysis of CLN2 variants in CHO cells: Q100R represents a polymorphism, and G389E and R447H represent loss-of-function mutations."
Hum. Mutat. 18:165-165(2001) [PubMed] [Europe PMC] [Abstract]

"Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations."
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"Identification of novel CLN2 mutations shows Canadian specific NCL2 alleles."
J. Med. Genet. 39:822-825(2002) [PubMed] [Europe PMC] [Abstract]

"Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation."
Vopr. Med. Khim. 48:594-598(2002) [PubMed] [Europe PMC] [Abstract]

"Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity."
Glycobiology 14:1C-5C(2004) [PubMed] [Europe PMC] [Abstract]

"Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis."
Brain 132:810-819(2009) [PubMed] [Europe PMC] [Abstract]

"Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I."
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"Targeted next generation sequencing as a diagnostic tool in epileptic disorders."
Epilepsia 53:1387-1398(2012) [PubMed] [Europe PMC] [Abstract]

"Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses."
Hum. Mutat. 33:42-63(2012) [PubMed] [Europe PMC] [Abstract]

"Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease)."
Hum. Mutat. 34:706-713(2013) [PubMed] [Europe PMC] [Abstract]