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Information on EC 3.4.14.9 - tripeptidyl-peptidase I and Organism(s) Rattus norvegicus and UniProt Accession Q9EQV6
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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: Rattus norvegicus
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
tripeptidyl peptidase
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tripeptidyl peptidase I
tripeptidyl aminopeptidase I
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tripeptidyl peptidase I
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tripeptidyl peptidase I
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shows tripeptidyl peptidase activity and pepstatin insensitive carboxyl endopeptidase activity
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity
the S4 subsite of TPP-I is occluded and there is an electrostatic interaction of the positively charged substrate N-terminus amino group and a negative locus in the region of the enzyme active site
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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?
KWFFIQ-EDDnp + H2O
KWF + FIQ-EDDnp
rat spleen and kidney homogenates cleave only at F-F bond
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-
?
RWFFIQ-EDDnp + H2O
RWF + FIQ-EDDnp
best substrate, rat spleen and kidney homogenates cleave only at F-F bond
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?
RWFVIQ-EDDnp + H2O
RWF + VIQ-EDDnp
rat spleen and kidney homogenates cleave only at F-V bond
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?
(pGlu)LYENKPRRRPYIL + H2O
(pGlu)L + YENKPRRRPYIL
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i.e. neurotensin, 15.0% degradation after 16 h
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?
DRVYIHPFHL + H2O
DRV + YIHPFHL
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i.e. angiotensin I, 11.3% degradation after 16 h
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?
GKPIPFFRLK + H2O
GKPIP + FFRLK
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endo-type substrate, 24.5% degradation after 16 h
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?
Gly-L-Pro-L-Met-2-anthraquinonyl hydrazide + H2O
Gly-L-Pro-L-Met + 2-anthraquinonyl hydrazine
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?
Gly-Lys-Pro-Ile-Pro-Phe-Phe-Arg-Leu-Lys + H2O
Gly-Lys-Pro-Ile-Pro-Phe + Phe-Arg-Leu-Lys
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-
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?
Gly-Pro-Leu 2-naphthylamide + H2O
Gly-Pro-Leu + 2-naphthylamine
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25% of the activity with Gly-Pro-Met 2-naphthylamide, Ala-Ala-Phe-4-nitroanilide or Ala-Ala-Phe-7-amido-4-methylcoumarin
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?
GNLWATGHFM-NH2 + H2O
GNL + WATGHFM-NH2
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i.e. neuromedin B, complete degradation after 16 h
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?
L-Asp-L-Ala-L-Phe-4-nitroanilide + H2O
L-Asp-L-Ala-L-Phe + 4-nitroaniline
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?
RVYIHPF + H2O
RVY + IHPF
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i.e. angiotensin III, 95.0% degradation after 15 min
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?
YGGFLRKYP + H2O
YGG + FLRKYP
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i.e. beta-neo-endorphin, 28% degradation after 16 h
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?
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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33.8% degradation within 60 min
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?
DRVYIHPF + H2O
DRV + YIHPF
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i.e. angiotensin II, 18.2% degradation after 16 h
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?
additional information
?
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development of fluorescence resonance energy transfer (FRET) peptides using tryptophan as the fluorophore to study TPP-I hydrolytic properties. Solvent kinetic isotope effects show the importance of the free N-terminus amino group of the substrates, whose absence results in a more complex solvent-dependent enzyme-substrate interaction and catalytic process. To investigate the exopeptidase activity of TPP-I, the randomized sequence MCA-GXXFXXQ-EDDnp is assayed and the products of hydrolysis analyzed by Edman degradation. TTP-I retains its N-terminus tripeptidase character even in randomized sequences and the preferences at the prime sites are similar to those reported for tripeptidyl amino peptidase
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?
glucagon + H2O
additional information
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all nine tripeptides and the C-terminal pentapeptide are identified
?
additional information
?
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substrates not cleaved after 24 h of digestion: dynorphin, beta-casomorphin-7, Leu-enkephalin, Met-enkephalin, neurokinin-A, LVV-hemorphin, bradykinin
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?
additional information
?
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the enzymne cleaves tripeptides from synthetic substrates provided that the N-terminus is unsubstituted and the amino acid in the P1 position is not charged. The enzyme also cleaves small peptides, angiotensin II and glucagon, releasing tripeptides but does not appear to demonstrate any preference for amino acids on either side of the cleavage site. Substrates with a charged amino acid in the P1 position appear to be resistant to hydrolysis
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?
additional information
?
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an inherited deficiency of tripeptidyl peptidase I activity causes a fatal lysosomal storage disorder, classic late infantile neuronal ceroid lipofuscinosis, CLN2
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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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an inherited deficiency of tripeptidyl peptidase I activity causes a fatal lysosomal storage disorder, classic late infantile neuronal ceroid lipofuscinosis, CLN2
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?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
the enzyme is not inhibited by pepstatin, E-64, EDTA or PMSF. The enzyme shows resistance to hydrolysis by cathepsin D
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
tripeptidylamino peptidase activity is enhanced by the presence of amino acids in the prime side
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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the optimum pH of TPP 1 is dependent on the substrate used
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.5 - 5
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pH 3.5: about 25% of maximal activity, pH 5.0: about 45% of maximal activity, hydrolysis of Ala-Ala-Phe-7-amido-4-methylcoumarin
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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enzyme histochemistry show high activity of TPP I in carotid body glomeruli. The glomus cells contain many TPP I-positive granules, while the glial-like sustentacular cells display a slightly fainter reaction
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activity in neuroglia cells, no activity in small granule cells, Purkinje cells, remified dendrites and myelinated fibers
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activity in corpus luteum and corpus albicus, no activity in follicles
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activity in ducts, no activity in acinar cells and islets of Langerhans
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activity in excretory duct and stereocilia, no activity in glandular acinus and intercalated portion
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activity in spermatogonia, spermatozoa, Sertoli cells and Leygig cells, no activity in basement cells
additional information
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activity in proximal tubules, distal tubules, collecting tubules and transitional cells, no activity in glomerulus and Bowmans capsule
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heterogenous distribution of TPP I positive macrophages, leukocytes and reticular fibroblasts in the red and white pulp
additional information
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morphological changes in the studied brain parts at different time periods following a single i.p. injection of sodium nitrite and altered TPPI activity in the brain, immunohistochemic analysis of the enzyme in brain regions and different neurons, overview
additional information
morphological changes in the studied brain parts at different time periods following a single i.p. injection of sodium nitrite and altered TPPI activity in the brain, immunohistochemic analysis of the enzyme in brain regions and different neurons, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
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
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_RAT
563
0
61332
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 6
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at pH 3.0 the activity of TPP I is less than 75% of its maximal activity at pH 4.5, most stable at pH 3-4, no activity at pH above 6.0
679200
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
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fluorescent method for the histochemical detection of tripeptidyl peptidase I using glycyl-L-prolyl-L-Met-2-anthraquinonyl hydrazide as substrate
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Du, P.G.; Kato, S.; Li, Y.H.; Maeda, T.; Yamane, T.; Yamamoto, S.; Fujiwara, M.; Yamamoto, Y.; Nishi, K.; Ohkubo, I.
Rat tripeptidyl peptidase I: molecular cloning, functional expression, tissue localization and enzymatic characterization
Biol. Chem.
382
1715-1725
2001
Rattus norvegicus
Vines, D.; Warburton, M.J.
Purification and characterisation of a tripeptidyl aminopeptidase I from rat spleen
Biochim. Biophys. Acta
1384
233-242
1998
Rattus norvegicus
Dikov, A.; Dimitrova, M.; Krieg, R.; Halbhuber, K.
New fluorescent method for the histochemical detection of tripeptidyl peptidase I using glycyl-L-prolyl-L-Met-2-anthraquinonyl hydrazide as substrate
Cell. Mol. Biol.
50
OL565-OL568
2004
Rattus norvegicus
Du, P.; An, L.; Qiu, F.; Lu, G.
Peptidase activities of tripeptidyl peptidase I (TPP I): exopeptidase and endopeptidase
Chem. Res. Chin. Univ.
22
65-67
2006
Rattus norvegicus
-
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
Atanasova, D.; Lazarov, N.
Histochemical demonstration of tripeptidyl aminopeptidase I in the rat carotid body
Acta Histochem.
117
219-222
2015
Rattus norvegicus
Petrova, E.B.; Dimitrova, M.B.; Ivanov, I.P.; Pavlova, V.G.; Dimitrova, S.G.; Kadiysky, D.S.
Effect of acute hypoxic shock on the rat brain morphology and tripeptidyl peptidase I activity
Acta Histochem.
118
496-504
2016
Rattus norvegicus, Rattus norvegicus (Q9EQV6)
Kondo, M.Y.; Gouvea, I.E.; Okamoto, D.N.; Santos, J.A.; Souccar, C.; Oda, K.; Juliano, L.; Juliano, M.A.
Analysis of catalytic properties of tripeptidyl peptidase I (TTP-I), a serine carboxyl lysosomal protease, and its detection in tissue extracts using selective FRET peptide substrate
Peptides
76
80-86
2016
Homo sapiens (O14773), Rattus norvegicus (Q9EQV6), Rattus norvegicus Wistar (Q9EQV6)
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