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Information on EC 3.4.14.9 - tripeptidyl-peptidase I and Organism(s) Mus musculus and UniProt Accession O89023
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3.4.14.9 tripeptidyl-peptidase ISpecify your search results
Word Map
- 3.4.14.9
-
infantile
- neurodegenerative
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lincl
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late-infantile
- lipofuscinoses
- batten
-
curvilinear
- palmitoyl-protein
-
pepstatin-insensitive
- cdc28p
-
serine-carboxyl
-
lipopigments
- molecular biology
- diagnostics
- medicine
- analysis
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity
Synonyms
tpp-i, tripeptidyl peptidase 1, cln2p, tripeptidyl peptidase i, tripeptidyl-peptidase i, cln2 protein, tripeptidyl-peptidase 1, tripeptidyl peptidase-i, tpp1f, ttp-i, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminopeptidase, tripeptidyl, I
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LPIC
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lysosomal pepstatin insensitive protease
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tripeptidyl aminopeptidase
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tripeptidyl aminopeptidase I
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tripeptidyl peptidase
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tripeptidyl peptidase I
tripeptidyl peptidase I
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
151662-36-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
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?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
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?
Arg-Ala-Phe-7-amido-4-methylcoumarin + H2O
Arg-Ala-Phe + 7-amino-4-methylcoumarin
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?
L-Ala-L-Ala-L-Phe-7-amido-4-methylcoumarin + H2O
L-Ala-L-Ala-L-Phe + 7-amino-4-methylcoumarin
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?
additional information
?
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dipeptidyl-peptidase I cannot functionally compensate for the loss of tripeptidyl-peptidase I
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
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dipeptidyl-peptidase I cannot functionally compensate for the loss of tripeptidyl-peptidase I
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?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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neonatally treated mice display high levels of TPP-I activity in the CNS 1 year after administration of AAVrh.10hCLN2 vector directly to the neonatal brain of CLN2 knockout mice at 2 days, 3 weeks, and 7 weeks of age, the AAVrh.10hCLN2 vector contains an expression cassette consisting of the human CLN2 cDNA driven by a CMV/beta-actin hybrid promoter consisting of the enhancer from the cytomegalovirus immediate early gene, the promoter, splice donor and intron from the chicken beta-actin gene, the splice acceptor from the rabbit beta-globin gene followed by a CLN2 cDNA with an optimized Kozak translation initiation sequence, the cDNA is followed by the polyadenylation sequence from rabbit beta-globin, the expression cassette is surrounded by the inverted terminal repeats of adeno-associated virus 2
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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TPPI is expressed ubiquitously throughout the body but disease appears restricted to the brain
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TPP1_MOUSE
562
0
61342
Swiss-Prot
Secretory Pathway (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R446H
the Tpp1f allele produces normal levels of properly spliced transcript, albeit with the Arg446His mutation
additional information
additional information
knockout mice containing the LSL-TPP1 transgene in the ROSA26 locus are referred to as TgLSL-TPP1, 5'-integration of TgLSL-TPP1 into the ROSA26 locus. A cloned PCR-amplified region of ROSA26 corresponds to nucleotides 113076032 to 113077227 of Mus musculus strain C57BL/6J chromosome 6 (GRCm38.p4). Method development for creation of mice expressing cre/ERT2 transgenes, transgenic mouse with inducible TPP1 to benchmark treatment approaches, evaluation of treatment at different stages of disease. A construct containing a loxP-flanked stop cassette inserted between the chicken-actin promoter and a sequence encoding murine TPP1 (TgLSL-TPP1) is integrated into the ROSA26 locus in mice by homologous recombination. Tested in both transfected CHO cells and in transgenic mice, the TgLSL-TPP1 does not express TPP1 until cre-mediated removal of the LSL cassette, which results in supraphysiological levels of TPP1 activity. Two of the four cre/ERT2 driver transgenes have significant cre activity in the absence of tamoxifen, while cre-mediated recombination cannot be induced by tamoxifen by two others. The germline-recombined mouse transgenic that constitutively overexpresses TPP1 allow long-term evaluation of overexposure to the enzyme and in cell culture, the inducible transgene may be a useful tool in biomarker discovery projects
additional information
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knockout mice containing the LSL-TPP1 transgene in the ROSA26 locus are referred to as TgLSL-TPP1, 5'-integration of TgLSL-TPP1 into the ROSA26 locus. A cloned PCR-amplified region of ROSA26 corresponds to nucleotides 113076032 to 113077227 of Mus musculus strain C57BL/6J chromosome 6 (GRCm38.p4). Method development for creation of mice expressing cre/ERT2 transgenes, transgenic mouse with inducible TPP1 to benchmark treatment approaches, evaluation of treatment at different stages of disease. A construct containing a loxP-flanked stop cassette inserted between the chicken-actin promoter and a sequence encoding murine TPP1 (TgLSL-TPP1) is integrated into the ROSA26 locus in mice by homologous recombination. Tested in both transfected CHO cells and in transgenic mice, the TgLSL-TPP1 does not express TPP1 until cre-mediated removal of the LSL cassette, which results in supraphysiological levels of TPP1 activity. Two of the four cre/ERT2 driver transgenes have significant cre activity in the absence of tamoxifen, while cre-mediated recombination cannot be induced by tamoxifen by two others. The germline-recombined mouse transgenic that constitutively overexpresses TPP1 allow long-term evaluation of overexposure to the enzyme and in cell culture, the inducible transgene may be a useful tool in biomarker discovery projects
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Guo, X.; Deng, Y.; Lin, Y.; Cosme-Blanco, W.; Chan, S.; He, H.; Yuan, G.; Brown, E.J.; Chang, S.
Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis
EMBO J.
26
4709-4719
2007
Mus musculus
Qian, M.; Sleat, D.E.; Zheng, H.; Moore, D.; Lobel, P.
Proteomics analysis of serum from mutant mice reveals lysosomal proteins selectively transported by each of the two mannose 6-phosphate receptors
Mol. Cell. Proteomics
7
58-70
2008
Mus musculus
Sleat, D.E.; El-Banna, M.; Sohar, I.; Kim, K.H.; Dobrenis, K.; Walkley, S.U.; Lobel, P.
Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis
Mol. Genet. Metab.
94
222-233
2008
Mus musculus
Kim, K.H.; Pham, C.T.; Sleat, D.E.; Lobel, P.
Dipeptidyl-peptidase I does not functionally compensate for the loss of tripeptidyl-peptidase I in the neurodegenerative disease late-infantile neuronal ceroid lipofuscinosis
Biochem. J.
415
225-232
2008
Mus musculus
Tye, C.E.; Lorenz, R.L.; Bartlett, J.D.
Lysosomal protease expression in mature enamel
Cells Tissues Organs
189
111-114
2009
Mus musculus
Ivanov, I.; Tasheva, D.; Todorova, R.; Dimitrova, M.
Synthesis and use of 4-peptidylhydrazido-N-hexyl-1,8-naphthalimides as fluorogenic histochemical substrates for dipeptidyl peptidase IV and tripeptidyl peptidase I
Eur. J. Med. Chem.
44
384-392
2009
Mus musculus, Rattus norvegicus
Sondhi, D.; Peterson, D.A.; Edelstein, A.M.; del Fierro, K.; Hackett, N.R.; Crystal, R.G.
Survival advantage of neonatal CNS gene transfer for late infantile neuronal ceroid lipofuscinosis
Exp. Neurol.
213
18-27
2008
Mus musculus
Xu, S.; Sleat, D.E.; Jadot, M.; Lobel, P.
Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material
Biochem. J.
428
355-362
2010
Mus musculus
Kim, K.H.; Sleat, D.E.; Bernard, O.; Lobel, P.
Genetic modulation of apoptotic pathways fails to alter disease course in tripeptidyl-peptidase 1 deficient mice
Neurosci. Lett.
453
27-30
2009
Mus musculus
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