3.4.14.9: tripeptidyl-peptidase I
This is an abbreviated version!
For detailed information about tripeptidyl-peptidase I, go to the full flat file.
Word Map on EC 3.4.14.9
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3.4.14.9
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infantile
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neurodegenerative
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lincl
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late-infantile
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lipofuscinoses
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batten
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curvilinear
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palmitoyl-protein
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pepstatin-insensitive
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cdc28p
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serine-carboxyl
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lipopigments
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molecular biology
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diagnostics
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medicine
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analysis
- 3.4.14.9
-
infantile
- neurodegenerative
-
lincl
-
late-infantile
- lipofuscinoses
- batten
-
curvilinear
- palmitoyl-protein
-
pepstatin-insensitive
- cdc28p
-
serine-carboxyl
-
lipopigments
- molecular biology
- diagnostics
- medicine
- analysis
Reaction
Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity =
Synonyms
aminopeptidase, tripeptidyl, I, AO090166000084, ceroid lipofuscinosis 2 protease, CLN2, CLN2 protein, CLN2p, EC 3.4.14.8, LPIC, lysosomal pepstatin insensitive protease, N-terminal tripeptidyl exopeptidase, SedB, SedC, SedD, sedolisin B, sedolisin C, sedolisin D, TPP I, TPP-I, Tpp1, TPP1F, TPPI, tripeptidyl aminopeptidase, tripeptidyl aminopeptidase I, tripeptidyl exopeptidase, tripeptidyl peptidase, tripeptidyl peptidase 1, tripeptidyl peptidase I, tripeptidyl peptidase-I, tripeptidyl-peptidase 1, tripeptidyl-peptidase I, TTP-I, v4-7
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results (General Information
General Information on EC 3.4.14.9 - tripeptidyl-peptidase I
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
TPPI is conserved in mammals, amphibians, fish and the amoeba Dictyostelium discoideum. Tripeptidyl peptidase 1 (TPP1) enzymes belong to the group of sedolisins, serine peptidases that are present in organisms ranging from bacteria to mammals. High homology to tripeptidyl peptidase 1 (TPP) from various organisms
malfunction
physiological function
additional information
malfunction
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TPP1 knockout mice providing a mouse model for late-infantile neuronal ceroid lipofuscinosis (LINCL) generated that either lack the pro-apoptotic p53 or have increased levels of anti-apoptotic Bcl-2. Neither modification affects the shortened life-span of the LINCL mouse. These findings suggest that targeting pathways of cell death involving p53 or Bcl-2 do not represent useful directions for developing effective treatment
malfunction
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TPP1 knockout mice which serve as a mouse model for classical late-infantile neuronal ceroid lipofuscinosis (LINCL) are analysed in terms of storage material present in the brain of the mouse model. It is shown that a number of protein constituents including glial fibrillary acidic protein are elevated
malfunction
CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons. CLN2 disease has become treatable by enzyme replacement, which can only be effective when the disease is diagnosed early. Analysis of reliability of a test for TPP1 deficiency in dried blood specimens (DBS) to detect CLN2 disease, overview. Diminished TTP1 activity is carefully checked for clinical information compatible with the diagnosis of CLN2 disease, and respective patients are subject to molecular genetic testing and confirmation of CLN2 disease by detection of known variants within the CLN2 gene, phenotypes, overview
malfunction
knockout tpp1F mutants do not display any particular phenotype, and TPP1 activity is not abrogated, presumably because tpp1B compensates as it has the highest expression level of all the TPP1 genes during growth. The majority of the TPP1 mutations in NCL results in reduction or loss of enzyme activity
malfunction
late-infantile neuronal ceroid lipofuscinosis is a fatal neurodegenerative disease of children caused by mutations resulting in loss of activity of the lysosomal protease, tripeptidyl peptidase 1 (TPP1), gene therapy studies on the LINCL mouse using Tpp1-targeted mouse models for LINCL that accurately recapitulate the human disease with locomotor deficits and a reduced lifespan. Tpp1-/- mice show signs of disease progression but death typically occurs suddenly (possibly from disease-related seizures) when feeding and grooming behaviors remained normal and before they become moribund. No gender-specific effects in life-span or other phenotypes of the LINCL mouse model are observed
malfunction
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late-infantile neuronal ceroid lipofuscinosis is a fatal neurodegenerative disease of children caused by mutations resulting in loss of activity of the lysosomal protease, tripeptidyl peptidase 1 (TPP1), gene therapy studies on the LINCL mouse using Tpp1-targeted mouse models for LINCL that accurately recapitulate the human disease with locomotor deficits and a reduced lifespan. Tpp1-/- mice show signs of disease progression but death typically occurs suddenly (possibly from disease-related seizures) when feeding and grooming behaviors remained normal and before they become moribund. No gender-specific effects in life-span or other phenotypes of the LINCL mouse model are observed
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physiological function
both the total protease and tripeptidyl peptidase activities in the culture medium of a gene disruptant strain are decreased as compared to those of the control strain. The maximum yields of recombinant bovine chymosin and human lysozyme produced by the disruptants show approximately 2.9- and 1.7fold increases, respectively, as compared to their control strains. Tripeptidyl peptidase activity in the culture medium of the disruptant is decreased
physiological function
in sodium nitrite-induced acute hypoxic shocked rat brain, morphological changes in cerebral cortex, cerebellum, medulla oblongata, thalamus,mesencephalon and pons are assessed using silver-copper impregnation for neurodegeneration. TPPI activity on these brains leads to less vulnerable to oxidative stress, the studied brain areas show different histopathological changes, such as neuronal loss and tissue vacuolization, dilatation of the smallest capillaries and impairment of neuronal processes. TPPI activity is strictly regulated following the hypoxic stress. The involvement of the enzyme in rat brain response to hypoxic stress causes a temporary enzyme deficiency in all types of neurons
physiological function
tripeptidyl peptidase 1 (TPP1) is a lysosomal serine protease, that possesses endopeptidase activity and cleaves peptides between hydrophobic residues. TPP1 is able to proteolyze fibrillar amyloid-beta efficiently. Mass spectrometry analysis of peptides released from fibrillar amyloid-beta digested with TPP1 reveals several endoproteolytic cleavages including some within beta-sheet regions that are important for fibril formation. These cleavages destabilize fibrillar beta-sheet structure. N-terminal tripeptidyl exopeptidase activity with a pH optimum of 5 that catalyzes the sequential release of tripeptides from the unsubstituted N termini of proteins
physiological function
tripeptidyl peptidase 1, TPP1, is a lysosomal serine protease, which removes tripeptides from the N-terminus of proteins and is composed of an N-terminal prodomain and a catalytic domain. Isozyme TPP1F is a binding partner of the Golgi pH regulator (GPHR), an evolutionarily highly conserved intracellular transmembrane protein, in Dictyostelium discoideum. The GPHR interaction is not restricted to TPP1F but occurs also with isozyme TPP1B
physiological function
upon hypoxic shock, the studied brain areas show different histopathological changes, such as neuronal loss and tissue vacuolization, dilatation of the smallest capillaries and impairment of neuronal processes. TPPI activity is strictly regulated following the hypoxic stress. TPPI activity increases 12-24 h post-treatment, then decreases followed by a slow process of recovery. There is a temporary enzyme deficiency in all types of neurons
physiological function
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both the total protease and tripeptidyl peptidase activities in the culture medium of a gene disruptant strain are decreased as compared to those of the control strain. The maximum yields of recombinant bovine chymosin and human lysozyme produced by the disruptants show approximately 2.9- and 1.7fold increases, respectively, as compared to their control strains. Tripeptidyl peptidase activity in the culture medium of the disruptant is decreased
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additional information
molecular dynamics (MD) simulations are used to analyze the effects of each cleavage on beta-sheet and fibril stability of amyloid-beta, eight cleavage sites are selected to be simulated, namely after residues K16, F20, G33, L34, M35, V36, G38, and V40, stability of hydrogen bonds following selected TPP1 cleavages and peptide release from the fibril, molecular modeling, detailed overview
additional information
the enzyme has a prodomain (residues 25-182) and a catalytic domain (peptidases S53 domain), which extends from residue 197 to the end. In TPP1F, the catalytic domain is interrupted by a stretch of amino acids (residues 370-499). The catalytic triad, a Ca2+ binding site and a particular sequence of amino acids (S611, E272, D369 in TPP1F), which represent the catalytic residues and are highly conserved in the S53 sedolisin family of peptidases, to which TPP1 proteins belong, are also present
additional information
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the enzyme has a prodomain (residues 25-182) and a catalytic domain (peptidases S53 domain), which extends from residue 197 to the end. In TPP1F, the catalytic domain is interrupted by a stretch of amino acids (residues 370-499). The catalytic triad, a Ca2+ binding site and a particular sequence of amino acids (S611, E272, D369 in TPP1F), which represent the catalytic residues and are highly conserved in the S53 sedolisin family of peptidases, to which TPP1 proteins belong, are also present
additional information
tripeptidyl peptidase I (TPP-I), also named ceroid lipofuscinosis 2 protease (CLN2p), is a serine carboxyllysosomal protease involved in neurodegenerative diseases, and has both tripeptidyl amino- and endo-peptidase activities under different pH conditions. The enzyme shows resistance to hydrolysis by cathepsin D
additional information
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tripeptidyl peptidase I (TPP-I), also named ceroid lipofuscinosis 2 protease (CLN2p), is a serine carboxyllysosomal protease involved in neurodegenerative diseases, and has both tripeptidyl amino- and endo-peptidase activities under different pH conditions. The enzyme shows resistance to hydrolysis by cathepsin D
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