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(pGlu)LYENKPRRRPYIL + H2O
(pGlu)L + YENKPRRRPYIL
-
i.e. neurotensin, 15.0% degradation after 16 h
-
?
Ala-Ala-Ala-4-nitroanilide + H2O
Ala-Ala-Ala + 4-nitroaniline
Ala-Ala-Phe-4-nitroanilide + H2O
Ala-Ala-Phe + 4-nitroaniline
Ala-Ala-Phe-7-amido-4-carbamoylmethylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-carbamoylmethylcoumarin
-
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
Ala-Ala-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Ala-Ala-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
Ala-Ala-Pro-4-nitroanilide + H2O
Ala-Ala-Pro + 4-nitroaniline
-
-
-
-
?
Ala-Arg-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Ala-Arg-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
Ala-Asp-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Ala-Asp-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
Ala-His-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Ala-His-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
Ala-Nle-Leu-7-amido-4-carbamoylmethylcoumarin + H2O
Ala-Nle-Leu + 7-amino-4-carbamoylmethylcoumarin
-
-
-
-
?
Ala-Nle-Nle-7-amido-4-carbamoylmethylcoumarin + H2O
Ala-Nle-Nle + 7-amino-4-carbamoylmethylcoumarin
-
-
-
-
?
Ala-Nva-Nle-7-amido-4-carbamoylmethylcoumarin + H2O
Ala-Nva-Nle + 7-amino-4-carbamoylmethylcoumarin
-
-
-
-
?
Ala-Phe-Pro-4-nitroanilide + H2O
Ala-Phe-Pro + 4-nitroaniline
-
-
-
-
?
Ala-Pro-Gly-Asp-Arg-Ile-Tyr-Val-His-Pro-Phe + H2O
Ala-Pro-Gly + Asp-Arg-Ile + Tyr-Val-His-Pro-Phe
SedB
-
-
?
Ala-Ser-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Ala-Ser-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
amyloid-beta + H2O
?
AbetaCy3 peptides are released from the nanofibrils due to TPP1 activity
-
-
?
amyloid-beta1-42 + H2O
?
the 34 Abeta end of the substrate shows integrated peak areas for peptide fragments 21-34, 22-34, and 23-34, indicative of cleavage after residue L34. The most abundant cleavages occur after residues Y10, G33, L34, and A30, and these cleavages occur more rapidly at pH 3.0 than at pH 4.5, consistent with endopeptidase activity. Peptides ending at residues E11, L17, F20, G37, and G38, are detected with lower abundances. At later times, the abundance of some of the peptides may decrease due to further proteolysis by TPP1. TPP1 can proteolyze monomeric Abeta1-42 efficiently at acidic pH
-
-
?
angiotensin II + H2O
? + Asp-Arg-Val
-
-
-
-
?
Arg-Ala-Phe-7-amido-4-methylcoumarin + H2O
Arg-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
Arg-Ala-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Arg-Ala-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
Arg-Pro-Phe-7-amido-4-carbamoylmethylcoumarin + H2O
Arg-Pro-Phe + 7-amino-4-carbamoylmethylcoumarin
-
-
-
-
?
Asp-Ala-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Asp-Ala-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
Cholecystokinin + H2O
?
-
-
-
-
?
DRVYIHPF + H2O
DRV + YIHPF
DRVYIHPFHL + H2O
DRV + YIHPFHL
-
i.e. angiotensin I, 11.3% degradation after 16 h
-
?
epsilon-aminocaproyl-WFFIQ-[N-(2,4-dinitrophenyl)-ethylenediamine] + H2O
epsilon-aminocaproyl-WF + FIQ-[N-(2,4-dinitrophenyl)-ethylenediamine]
-
-
-
?
GKPIPFFRLK + H2O
GKPIP + FFRLK
-
endo-type substrate, 24.5% degradation after 16 h
-
?
Gly-L-Pro-L-Met-2-anthraquinonyl hydrazide + H2O
Gly-L-Pro-L-Met + 2-anthraquinonyl hydrazine
-
-
-
-
?
Gly-L-Pro-L-Met-4-hydrazino-N-hexyl-1,8-naphthalimide + H2O
?
Gly-L-Pro-L-Met-L-anthraquinonyl hydrazide + H2O
?
-
-
-
?
Gly-Lys-Pro-Ile-Pro-Phe-Phe-Arg-Leu-Lys + H2O
Gly-Lys-Pro-Ile-Pro-Phe + Phe-Arg-Leu-Lys
-
-
-
-
?
Gly-Pro-Ala 4-nitroanilide + H2O
Gly-Pro-Ala + 4-nitroaniline
-
at 20% the rate of Gly-Pro-Met 4-nitroanilide hydrolysis
-
-
?
Gly-Pro-Arg-7-amido-4-methylcoumarin + H2O
?
-
at 10% the rate of Gly-Pro-Met 4-methylcoumarin 7-amide hydrolysis
-
-
?
Gly-Pro-Leu 2-naphthylamide + H2O
Gly-Pro-Leu + 2-naphthylamine
Gly-Pro-Met 2-naphthylamide + H2O
Gly-Pro-Met + 2-naphthylamine
Gly-Pro-Met 4-nitroanilide + H2O
Gly-Pro-Met + 4-nitroaniline
-
-
-
-
?
Gly-Pro-Met-7-amido-4-methylcoumarin + H2O
Gly-Pro-Met + 7-amino-4-methylcoumarin
-
-
-
-
?
GNLWATGHFM-NH2 + H2O
GNL + WATGHFM-NH2
-
i.e. neuromedin B, complete degradation after 16 h
-
?
His-Ala-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
His-Ala-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
KWFFIQ-EDDnp + H2O
KWF + FIQ-EDDnp
KWFFIQ-[N-(2,4-dinitrophenyl)-ethylenediamine] + H2O
KWF + FIQ-[N-(2,4-dinitrophenyl)-ethylenediamine]
-
-
-
?
L-Ala-L-Ala-L-Phe-4-hydrazino-N-hexyl-1,8-naphthalimide + H2O
?
L-Ala-L-Ala-L-Phe-7-amido-4-methylcoumarin + H2O
L-Ala-L-Ala-L-Phe + 7-amino-4-methylcoumarin
L-Arg-L-Nle-L-Nle-7-amido-4-methylcoumarin + H2O
L-Arg-L-Nle-L-Nle + 7-amino-4-methylcoumarin
-
-
-
?
L-Asp-L-Ala-L-Phe-4-nitroanilide + H2O
L-Asp-L-Ala-L-Phe + 4-nitroaniline
-
-
-
?
Neuromedin B + H2O
?
-
-
-
-
?
Phe-Pro-Ala 2-naphthylamide + H2O
Phe-Pro-Ala + 2-naphthylamine
-
synthetic peptide modeled after NH2-terminal tripeptide sequence of the phenylalanyl monomer of bovine or rat growth hormone, fluorogenic substrate
-
?
Phe-Pro-Ala-4-nitroanilide + H2O
Phe-Pro-Ala + 4-nitroaniline
phenylalanyl monomer of bovine growth hormone + H2O
?
-
cleaves 11 tripeptides sequentially from the NH2-terminus
-
-
?
poly(Gly-Pro-Ala) + H2O
Gly-Pro-Ala
-
-
-
?
RVYIHPF + H2O
RVY + IHPF
-
i.e. angiotensin III, 95.0% degradation after 15 min
-
?
RWFFIQ-EDDnp + H2O
RWF + FIQ-EDDnp
RWFFIQ-[N-(2,4-dinitrophenyl)-ethylenediamine] + H2O
RWF + FIQ-[N-(2,4-dinitrophenyl)-ethylenediamine]
FRET substrate
-
-
?
RWFVIQ-EDDnp + H2O
RWF + VIQ-EDDnp
RWFVIQ-[N-(2,4-dinitrophenyl)-ethylenediamine] + H2O
RWF + VIQ-[N-(2,4-dinitrophenyl)-ethylenediamine]
-
-
-
?
Ser-Ala-Phe-p-nitrophenylalanyl-Arg-Leu + H2O
Ser-Ala-Phe + p-nitrophenylalanyl-Arg-Leu
-
-
-
-
?
subunit C of mitochondrial ATP synthase + H2O
?
-
-
-
-
?
synthetic collagen-like polypetides + H2O
Gly-Pro-Xaa tripeptides
-
-
-
?
Val-Pro-Arg 4-nitroanilide + H2O
Val-Pro-Arg + 4-nitroaniline
-
at 11% the rate of Gly-Pro-Met 4-nitroanilide hydrolysis
-
-
?
YGGFLRKYP + H2O
YGG + FLRKYP
-
i.e. beta-neo-endorphin, 28% degradation after 16 h
-
?
[Ala-Ala-Phe]2-rhodamine 110 + H2O
[Ala-Ala-Phe]2 + rhodamine 110
-
specific substrate for determining TPP-I activity and intracellular localization in living cells
-
-
?
[Arg-Nle-Nle]2-rhodamine 110 + H2O
[Ala-Ala-Phe]2 + rhodamine 110
-
specific substrate for determining TPP-I activity and intracellular localization in living cells
-
-
?
glucagon + H2O
additional information
-
Ala-Ala-Ala-4-nitroanilide + H2O
Ala-Ala-Ala + 4-nitroaniline
-
-
-
-
?
Ala-Ala-Ala-4-nitroanilide + H2O
Ala-Ala-Ala + 4-nitroaniline
-
-
-
-
?
Ala-Ala-Phe-4-nitroanilide + H2O
Ala-Ala-Phe + 4-nitroaniline
SedB
-
-
?
Ala-Ala-Phe-4-nitroanilide + H2O
Ala-Ala-Phe + 4-nitroaniline
SedC
-
-
?
Ala-Ala-Phe-4-nitroanilide + H2O
Ala-Ala-Phe + 4-nitroaniline
SedD
-
-
?
Ala-Ala-Phe-4-nitroanilide + H2O
Ala-Ala-Phe + 4-nitroaniline
-
-
-
-
?
Ala-Ala-Phe-4-nitroanilide + H2O
Ala-Ala-Phe + 4-nitroaniline
-
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
33.8% degradation within 60 min
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
DRVYIHPF + H2O
DRV + YIHPF
-
-
-
?
DRVYIHPF + H2O
DRV + YIHPF
-
i.e. angiotensin II, 18.2% degradation after 16 h
-
?
Gly-L-Pro-L-Met-4-hydrazino-N-hexyl-1,8-naphthalimide + H2O
?
-
-
-
-
?
Gly-L-Pro-L-Met-4-hydrazino-N-hexyl-1,8-naphthalimide + H2O
?
-
-
-
-
?
Gly-Pro-Leu 2-naphthylamide + H2O
Gly-Pro-Leu + 2-naphthylamine
-
25% of the activity with Gly-Pro-Met 2-naphthylamide, Ala-Ala-Phe-4-nitroanilide or Ala-Ala-Phe-7-amido-4-methylcoumarin
-
-
?
Gly-Pro-Leu 2-naphthylamide + H2O
Gly-Pro-Leu + 2-naphthylamine
-
at 30% the rate of Gly-Pro-Met 2-naphthylamide hydrolysis
-
-
?
Gly-Pro-Met 2-naphthylamide + H2O
Gly-Pro-Met + 2-naphthylamine
-
-
-
?
Gly-Pro-Met 2-naphthylamide + H2O
Gly-Pro-Met + 2-naphthylamine
-
-
-
-
?
Gly-Pro-Met 2-naphthylamide + H2O
Gly-Pro-Met + 2-naphthylamine
-
-
-
-
?
KWFFIQ-EDDnp + H2O
KWF + FIQ-EDDnp
rat spleen and kidney homogenates cleave only at F-F bond
-
-
?
KWFFIQ-EDDnp + H2O
KWF + FIQ-EDDnp
rat spleen and kidney homogenates cleave only at F-F bond
-
-
?
L-Ala-L-Ala-L-Phe-4-hydrazino-N-hexyl-1,8-naphthalimide + H2O
?
-
-
-
-
?
L-Ala-L-Ala-L-Phe-4-hydrazino-N-hexyl-1,8-naphthalimide + H2O
?
-
-
-
-
?
L-Ala-L-Ala-L-Phe-7-amido-4-methylcoumarin + H2O
L-Ala-L-Ala-L-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
L-Ala-L-Ala-L-Phe-7-amido-4-methylcoumarin + H2O
L-Ala-L-Ala-L-Phe + 7-amino-4-methylcoumarin
-
-
-
?
L-Ala-L-Ala-L-Phe-7-amido-4-methylcoumarin + H2O
L-Ala-L-Ala-L-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
L-Ala-L-Ala-L-Phe-7-amido-4-methylcoumarin + H2O
L-Ala-L-Ala-L-Phe + 7-amino-4-methylcoumarin
-
-
-
-
?
Phe-Pro-Ala-4-nitroanilide + H2O
Phe-Pro-Ala + 4-nitroaniline
SedB
-
-
?
Phe-Pro-Ala-4-nitroanilide + H2O
Phe-Pro-Ala + 4-nitroaniline
SedC
-
-
?
Phe-Pro-Ala-4-nitroanilide + H2O
Phe-Pro-Ala + 4-nitroaniline
SedD
-
-
?
RWFFIQ-EDDnp + H2O
RWF + FIQ-EDDnp
best substrate, rat spleen and kidney homogenates cleave only at F-F bond
-
-
?
RWFFIQ-EDDnp + H2O
RWF + FIQ-EDDnp
best substrate, rat spleen and kidney homogenates cleave only at F-F bond
-
-
?
RWFVIQ-EDDnp + H2O
RWF + VIQ-EDDnp
rat spleen and kidney homogenates cleave only at F-V bond
-
-
?
RWFVIQ-EDDnp + H2O
RWF + VIQ-EDDnp
rat spleen and kidney homogenates cleave only at F-V bond
-
-
?
glucagon + H2O
additional information
-
-
-
all nine tripeptides and the C-terminal pentapeptide are identified
?
additional information
?
-
-
no substrates are Ala-Phe-Pro-beta-naphthylamide (modeled after NH2-terminal tripeptide sequence of the alanyl monomer of bovine growth hormone), alanyl monomer of bovine growth hormone
-
-
?
additional information
?
-
-
no significant aminopeptidase activity
-
-
?
additional information
?
-
TPP1F is binding partner of Dictyostelium discoideum intracellular transmembrane protein GPHR, i.e. Golgi pH regulator. A region encompassing the DUF3735 (GPHR_N) domain of GPHR is responsible for the interaction. In TPP1F, the binding site is located in the prodomain of the protein. GPHR is present in subcellular membranous compartments reaching from endoplasmic reticulum membranes to membranes of the endo-lysosomal system
-
-
?
additional information
?
-
-
TPP1F is binding partner of Dictyostelium discoideum intracellular transmembrane protein GPHR, i.e. Golgi pH regulator. A region encompassing the DUF3735 (GPHR_N) domain of GPHR is responsible for the interaction. In TPP1F, the binding site is located in the prodomain of the protein. GPHR is present in subcellular membranous compartments reaching from endoplasmic reticulum membranes to membranes of the endo-lysosomal system
-
-
?
additional information
?
-
-
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin, succinyl-Gly-Pro-Leu 4-methylcoumarin 7-amide, Gly-Pro-7-amido-4-methylcoumarin, Gly-7-amido-4-methylcoumarin, Pro-7-amido-4-methylcoumarin, Met-7-amido-4-methylcoumarin, Ala 7-amido-4-methylcoumarin, Phe-7-amido-4-methylcoumarin, or Leu-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
-
the enzyme removes tripeptides from the free N-termini of small polypeptides and also shows a minor endoprotease activity
-
-
?
additional information
?
-
-
absolute requirement for unsubstituted amino-terminus
-
-
?
additional information
?
-
-
involved in degradation of bone collagen
-
-
?
additional information
?
-
-
classical late infantile neuronal ceroid lipofuscinosis is an autosomal recessive disease caused by mutations in the CLN2 gene resulting in functional defects of the gene product tripeptidyl-peptidase I. This disease is associated with a progressive neurodegenerative course beginning at the age of two years with developmental stagnation, finally leading to a complete loss of motor function, vision and speech by the age of 10 years
-
-
?
additional information
?
-
-
elevated enzyme activity of tripeptidyl peptidase I and other lysosomal enzymes in Sjoegren's syndrome patients may play a role in tissue damage by accelerated breakdown of glycoproteins in lysosomes
-
-
?
additional information
?
-
-
TPP I is the predominant proteolytic enzyme responsible for the intracellular degradation of neuromedin B. The inability of cells from patients with late-infantile neuronal ceroid lipofuscinosis (CNL2) to degrade neuromedin B and other neuropeptides may contribute to the pathogenesis of the disease
-
-
?
additional information
?
-
-
determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates
-
-
?
additional information
?
-
-
prefers Leu, Phe and Nle at the P1 position, whereas Asn, His, Lys, Arg, Ser, Val, Ile, Thr, Gly and Pro are highly unfavored in this position, showing less than 1% of the activity of the best substrates
-
-
?
additional information
?
-
-
TPP I acts preferentially on small, unstructured oligopeptides of less than 5 kDa
-
-
?
additional information
?
-
validation and evaluation of a rapid and simple fluorometric tripeptidyl peptidase 1 (TPP1) assay using dried blood specimens to diagnose CLN2 disease
-
-
?
additional information
?
-
-
validation and evaluation of a rapid and simple fluorometric tripeptidyl peptidase 1 (TPP1) assay using dried blood specimens to diagnose CLN2 disease
-
-
?
additional information
?
-
-
dipeptidyl-peptidase I cannot functionally compensate for the loss of tripeptidyl-peptidase I
-
-
?
additional information
?
-
-
substrates not cleaved after 24 h of digestion: dynorphin, beta-casomorphin-7, Leu-enkephalin, Met-enkephalin, neurokinin-A, LVV-hemorphin, bradykinin
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
an inherited deficiency of tripeptidyl peptidase I activity causes a fatal lysosomal storage disorder, classic late infantile neuronal ceroid lipofuscinosis, CLN2
-
-
?
additional information
?
-
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
-
-
?
additional information
?
-
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
-
-
?
additional information
?
-
-
N-terminal exopeptidase that removes tripeptide units provided the P3 residue is unsubstituted
-
-
?
additional information
?
-
-
Met-2-naphthylamide, succinyl-Gly-Pro-Met 2-naphthylamide, Pro-Met-7-amido-4-methylcoumarin, Met-7-amido-4-methylcoumarin, methoxysuccinyl-Gly-Pro-Met-7-amido-4-methylcoumarin, benzyloxy-Arg-Arg-7-amido-4-methylcoumarin, Arg-7-amido-4-methylcoumarin, Pro-Ala-4-nitroanilide, Ala 4-nitroanilide, tert-butyloxycarbonyl-Gly-Pro-Ala 4-nitroanilide, benzoyl-Val-Pro-Arg 4-nitroanilide
-
-
?
additional information
?
-
-
exopeptidase involved in intracellular (lysosomal) degradation of collagen fibrils
-
-
?
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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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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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D276A
kcat/Km is 21% of the wild-type value
D327A
kcat/Km is 6% of the wild-type value
D517A
lack of enzyme activity and processing
D81A
-
not expressed in Sf9 cells
E272A
kcat/Km is 3% of the wild-type value
E343K
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
E343L
-
decreased activity
E77A
-
very low activity with Ala-Arg-Phe-p-nitrophenylalanyl-Arg-Leu
G473R
the mutation probably compromises the active center and results in loss of proteolytic activity
K428N
no apparent conformational destabilization is observed for the missense mutation
N286Q
-
the secreted proenzyme formes non-native, interchain disulfide bridges and displays only residual TPP I activity upon acidification. A small portion of the mutant enzyme reaches the lysosome and is processed to an active species, however, it shows low thermal and pH stability
Q248P
the mutation probably compromises the active center and results in loss of proteolytic activity
Q442H
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
R208X
-
mutation is identified in patients with late infantile ceroid lipofuscinosis, no detection of any translational product for the mutant
R266Q
no apparent conformational destabilization is observed for the missense mutation
S475
inactive mutant enzyme
T353P
-
mutation is identified in patients with late infantile ceroid lipofuscinosis, enzyme shows 5.5% of wild-type enzyme when expressed in HEK cells, blocked processing to mature size peptidase leads to protein retention in the endoplasmic reticulum and rapid degradation in non-lysosomal compartments
V216M
no apparent conformational destabilization is observed for the missense mutation
V227M
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
C365R
-
decreased activity
C365R
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
D360A
lack of enzyme activity and processing
D360A
kcat/Km is 3% of the wild-type value
G284V
-
decreased activity
G284V
the mutation probably compromises the active center and results in loss of proteolytic activity
G284V
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
G77R
-
decreased activity
G77R
-
the mutation is associated with classic late infantile neuronal ceroid lipofuscinosis
G77R
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, 1% of wild-type activity
I287N
-
decreased activity
I287N
-
mutation is identified in patients with late infantile ceroid lipofuscinosis, enzyme shows 4.1% of wild-type enzyme when expressed in HEK cells, blocked processing to mature size peptidase leads to protein retention in the endoplasmic reticulum and rapid degradation in non-lysosomal compartments
I287N
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
N286S
-
decreased activity
N286S
-
mutation is identified in patients with late infantile ceroid lipofuscinosis, enzyme shows 5.8% of wild-type enzyme when expressed in HEK cells, blocked processing to mature size peptidase leads to protein retention in the endoplasmic reticulum and rapid degradation in non-lysosomal compartments
N286S
the substitution results in loss of one glycosylation site, which leads to almost complete loss of protease activity
N286S
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
P202L
-
decreased activity
P202L
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, no enzymatic activity
P544S
-
decreased activity
P544S
-
demonstrates a normal polypeptide pattern on Western blots, enzyme activity, and lysosomal localization
P544S
protein processing similar to wild-type, lysosomal localisation, 32.8% of wild-type activity
Q422H
-
decreased activity
Q422H
-
mutation is identified in patients with late infantile ceroid lipofuscinosis, enzyme shows 4.7% of wild-type enzyme when expressed in HEK cells, blocked processing to mature size peptidase leads to protein retention in the endoplasmic reticulum and rapid degradation in non-lysosomal compartments
R127Q
-
decreased activity
R127Q
-
mutation is identified in patients with late infantile ceroid lipofuscinosis, enzyme shows 74.3% of wild-type enzyme when expressed in HEK cells
R127Q
-
demonstrates a normal polypeptide pattern on Western blots, enzyme activity, and lysosomal localization
R127Q
protein processing similar to wild-type,lysosomal localization, 43% of wild-type activity
R206C
-
decreased activity
R206C
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, 0.7% of wild-type activity
R447H
-
decreased activity
R447H
protein processing different from wild-type, mutant is not localized in lysosomes, intracellular trafficking of mutant is altered compared to wild-type, 1.8% of wild-type activity
S475L
-
inactive
S475L
-
decreased activity
S475L
kcat/Km is 0.4% of the wild-type value
S475L
the mutation probably compromises the active center and results in loss of proteolytic activity
S475L
protein processing similar to wild-type, lysosomal localization, no enzymatic activity
V277M
-
decreased activity
V277M
the mutation probably compromises the active center and results in loss of proteolytic activity
R446H
the Tpp1f allele produces normal levels of properly spliced transcript, albeit with the Arg446His mutation
R446H
-
the Tpp1f allele produces normal levels of properly spliced transcript, albeit with the Arg446His mutation
-
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
-
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
-
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
-
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Doebber, T.W.; Divor, A.R.; Ellis, S.
Identification of a tripeptidyl aminopeptidase in the anterior pituitary gland: effect on the chemical and biological properties of rat and bovine growth hormones
Endocrinology
103
1794-1804
1978
Bos taurus
brenda
McDonald, J.K.; Hoisington, A.R.; Eisenhauer, D.A.
Partial purification and characterization of an ovarian tripeptidyl peptidase: a lysosomal exopeptidase that sequentially releases collagen-related (Gly-Pro-X) triplets
Biochem. Biophys. Res. Commun.
126
63-71
1985
Sus scrofa
brenda
Page, A.E.; Fuller, K.; Chambers, T.J.; Warburton, M.J.
Purification and characterization of a tripeptidyl peptidase I from human osteoclastomas: evidence for its role in bone resorption
Arch. Biochem. Biophys.
306
354-359
1993
Homo sapiens
brenda
Krimper, R.P.; Jones, T.H.
Purification and characterization of tripeptidyl peptidase I from Dictyostelium discoideum
Biochem. Mol. Biol. Int.
47
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1999
Dictyostelium discoideum
brenda
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
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2001
Rattus norvegicus
brenda
Golabek, A.A.; Kida, E.; Walus, M.; Wujek, P.; Mehta, P.; Wisniewski, K.E.
Biosynthesis, glycosylation, and enzymatic processing in vivo of human tripeptidyl-peptidase I
J. Biol. Chem.
278
7135-7145
2003
Homo sapiens
brenda
Lin, L.; Sohar, I.; Lackland, H.; Lobel, P.
The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH
J. Biol. Chem.
276
2249-2255
2001
Homo sapiens (O14773), Homo sapiens
brenda
Vines, D.; Warburton, M.J.
Purification and characterisation of a tripeptidyl aminopeptidase I from rat spleen
Biochim. Biophys. Acta
1384
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1998
Rattus norvegicus
brenda
Reichard, U.; Lechenne, B.; Asif, A.R.; Streit, F.; Grouzmann, E.; Jousson, O.; Monod, M.
Sedolisins, a new class of secreted proteases from Aspergillus fumigatus with endoprotease or tripeptidyl-peptidase activity at acidic pHs
Appl. Environ. Microbiol.
72
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2006
Aspergillus fumigatus (Q70GH4), Aspergillus fumigatus (Q70J58), Aspergillus fumigatus (Q70J59)
brenda
Kopan, S.; Sivasubramaniam, U.; Warburton, M.J.
The lysosomal degradation of neuromedin B is dependent on tripeptidyl peptidase-I: evidence for the impairment of neuropeptide degradation in late-infantile neuronal ceroid lipofuscinosis
Biochem. Biophys. Res. Commun.
319
58-65
2004
Homo sapiens
brenda
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
brenda
Sohar, N.; Sohar, I.; Hammer, H.
Lysosomal enzyme activities: new potential markers for Sjoegrens syndrome
Clin. Biochem.
38
1120-1126
2005
Homo sapiens
brenda
Kohan, R.; Noher de Halac, I.; Anzolini, V.T.; Cismondi, A.; Oller Ramirez, A.M.; Capra, A.P.; Dodelson de Kremer, R.
Palmitoyl protein thioesterase 1 (PPT1) and tripeptidyl peptidase-I (TPP-I) are expressed in the human saliva. A reliable and non-invasive source for the diagnosis of infantile (CLN1) and late infantile (CLN2) neuronal ceroid lipofuscinoses
Clin. Biochem.
38
492-494
2005
Homo sapiens
brenda
Walus, M.; Kida, E.; Wisniewski, K.E.; Golabek, A.A.
Ser475, Glu272, Asp276, Asp327, and Asp360 are involved in catalytic activity of human tripeptidyl-peptidase I
FEBS Lett.
579
1383-1388
2005
Homo sapiens (O14773), Homo sapiens
brenda
Sondhi, D.; Peterson, D.A.; Giannaris, E.L.; Sanders, C.T.; Mendez, B.S.; De, B.; Rostkowski, A.B.; Blanchard, B.; Bjugstad, K.; Sladek, J.R.; Redmond, D.E.; Leopold, P.L.; Kaminsky, S.M.; Hackett, N.R.; Crystal, R.G.
AAV2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for LINCL
Gene Ther.
12
1618-1632
2005
Chlorocebus sabaeus
brenda
Steinfeld, R.; Steinke, H.B.; Isbrandt, D.; Kohlschuetter, A.; Gaertner, J.
Mutations in classical late infantile neuronal ceroid lipofuscinosis disrupt transport of tripeptidyl-peptidase I to lysosomes
Hum. Mol. Genet.
13
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2004
Homo sapiens
brenda
Oyama, H.; Fujisawa, T.; Suzuki, T.; Dunn, B.M.; Wlodawer, A.; Oda, K.
Catalytic residues and substrate specificity of recombinant human tripeptidyl peptidase I (CLN2)
J. Biochem.
138
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2005
Homo sapiens
brenda
Wujek, P.; Kida, E.; Walus, M.; Wisniewski, K.E.; Golabek, A.A.
N-glycosylation is crucial for folding, trafficking, and stability of human tripeptidyl-peptidase I
J. Biol. Chem.
279
12827-12839
2004
Homo sapiens
brenda
Golabek, A.A.; Wujek, P.; Walus, M.; Bieler, S.; Soto, C.; Wisniewski, K.E.; Kida, E.
Maturation of human tripeptidyl-peptidase I in vitro
J. Biol. Chem.
279
31058-31067
2004
Homo sapiens
brenda
Golabek, A.A.; Walus, M.; Wisniewski, K.E.; Kida, E.
Glycosaminoglycans modulate activation, activity, and stability of tripeptidyl-peptidase I in vitro and in vivo
J. Biol. Chem.
280
7550-7561
2005
Homo sapiens
brenda
Tian, Y.; Sohar, I.; Taylor, J.W.; Lobel, P.
Determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates
J. Biol. Chem.
281
6559-6572
2006
Homo sapiens
brenda
Steinfeld, R.; Fuhrmann, J.C.; Gaertner, J.
Detection of tripeptidyl peptidase I activity in living cells by fluorogenic substrates
J. Histochem. Cytochem.
54
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2006
Homo sapiens
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Kyttaelae, A.; Lahtinen, U.; Braulke, T.; Hofmann, S.L.
Functional biology of the neuronal ceroid lipofuscinoses (NCL) proteins
Biochim. Biophys. Acta
1762
920-933
2006
Homo sapiens
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Golabek, A.A.; Kida, E.
Tripeptidyl-peptidase I in health and disease
Biol. Chem.
387
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2006
Homo sapiens
brenda
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
-
brenda
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
brenda
Schroeder, B.; Elsaesser, H.P.; Schmidt, B.; Hasilik, A.
Characterisation of lipofuscin-like lysosomal inclusion bodies from human placenta
FEBS Lett.
581
102-108
2007
Homo sapiens (O14773), Homo sapiens
brenda
Leman, A.R.; Polochock, S.; Mole, S.E.; Pearce, D.A.; Rothberg, P.G.
Homogeneous PCR nucleobase quenching assays to detect four mutations that cause neuronal ceroid lipofuscinosis: T75P and R151X in CLN1, and IVS5-1G>C and R208X in CLN2
J. Neurosci. Methods
157
124-131
2006
Homo sapiens
brenda
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
brenda
Bessa, C.; Teixeira, C.A.; Dias, A.; Alves, M.; Rocha, S.; Lacerda, L.; Loureiro, L.; Guimaraes, A.; Ribeiro, M.G.
CLN2/TPP1 deficiency: the novel mutation IVS7-10A>G causes intron retention and is associated with a mild disease phenotype
Mol. Genet. Metab.
93
66-73
2008
Homo sapiens
brenda
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
brenda
Cabrera-Salazar, M.A.; Roskelley, E.M.; Bu, J.; Hodges, B.L.; Yew, N.; Dodge, J.C.; Shihabuddin, L.S.; Sohar, I.; Sleat, D.E.; Scheule, R.K.; Davidson, B.L.; Cheng, S.H.; Lobel, P.; Passini, M.A.
Timing of therapeutic intervention determines functional and survival outcomes in a mouse model of late infantile batten disease
Mol. Ther.
15
1782-1788
2007
Homo sapiens (O14773), Homo sapiens
brenda
Sondhi, D.; Hackett, N.R.; Peterson, D.A.; Stratton, J.; Baad, M.; Travis, K.M.; Wilson, J.M.; Crystal, R.G.
Enhanced survival of the LINCL mouse following CLN2 gene transfer using the rh.10 rhesus macaque-derived adeno-associated virus vector
Mol. Ther.
15
481-491
2007
Homo sapiens
brenda
Chang, M.; Cooper, J.D.; Sleat, D.E.; Cheng, S.H.; Dodge, J.C.; Passini, M.A.; Lobel, P.; Davidson, B.L.
Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis
Mol. Ther.
16
649-656
2008
Homo sapiens
brenda
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
brenda
Tye, C.E.; Lorenz, R.L.; Bartlett, J.D.
Lysosomal protease expression in mature enamel
Cells Tissues Organs
189
111-114
2009
Mus musculus
brenda
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
brenda
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
brenda
Golabek, A.A.; Dolzhanskaya, N.; Walus, M.; Wisniewski, K.E.; Kida, E.
Prosegment of tripeptidyl peptidase I is a potent, slow-binding inhibitor of its cognate enzyme
J. Biol. Chem.
283
16497-16504
2008
Homo sapiens
brenda
Pal, A.; Kraetzner, R.; Gruene, T.; Grapp, M.; Schreiber, K.; Gronborg, M.; Urlaub, H.; Becker, S.; Asif, A.R.; Gaertner, J.; Sheldrick, G.M.; Steinfeld, R.
Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis
J. Biol. Chem.
284
3976-3984
2009
Homo sapiens (O14773)
brenda
Guhaniyogi, J.; Sohar, I.; Das, K.; Stock, A.M.; Lobel, P.
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
Homo sapiens (O14773), Homo sapiens
brenda
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
brenda
Walus, M.; Kida, E.; Golabek, A.A.
Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I
Hum. Mutat.
31
710-721
2010
Homo sapiens (O14773), Homo sapiens
brenda
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
brenda
Atanasova, D.; Lazarov, N.
Histochemical demonstration of tripeptidyl aminopeptidase I in the rat carotid body
Acta Histochem.
117
219-222
2015
Rattus norvegicus
brenda
Zhu, L.; Nemoto, T.; Yoon, J.; Maruyama, J.; Kitamoto, K.
Improved heterologous protein production by a tripeptidyl peptidase gene (AosedD) disruptant of the filamentous fungus Aspergillus oryzae
J. Gen. Appl. Microbiol.
58
199-209
2012
Aspergillus oryzae (Q2U9N2), Aspergillus oryzae ATCC 42149 (Q2U9N2)
brenda
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)
brenda
Lukacs, Z.; Nickel, M.; Murko, S.; Nieves Cobos, P.; Schulz, A.; Santer, R.; Kohlschuetter, A.
Validity of a rapid and simple fluorometric tripeptidyl peptidase 1 (TPP1) assay using dried blood specimens to diagnose CLN2 disease
Clin. Chim. Acta
492
69-71
2019
Homo sapiens (O14773), Homo sapiens
brenda
Stumpf, M.; Mueller, R.; Gassen, B.; Wehrstedt, R.; Fey, P.; Karow, M.; Eichinger, L.; Gloeckner, G.; Noegel, A.
A tripeptidyl peptidase 1 is a binding partner of the Golgi pH regulator (GPHR) in Dictyostelium
Dis. Model. Mech.
10
897-907
2017
Dictyostelium discoideum (Q54TD0), Dictyostelium discoideum
brenda
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)
brenda
Nemtsova, Y.; Wiseman, J.; El-Banna, M.; Lobel, P.; Sleat, D.
Inducible transgenic expression of tripeptidyl peptidase 1 in a mouse model of late-infantile neuronal ceroid lipofuscinosis
PLoS ONE
13
e0192286
2018
Mus musculus (O89023), Mus musculus, Mus musculus C57BL/6 (O89023)
brenda
Sole-Domenech, S.; Rojas, A.V.; Maisuradze, G.G.; Scheraga, H.A.; Lobel, P.; Maxfield, F.R.
Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar Abeta by multiple endoproteolytic cleavages within the beta-sheet domain
Proc. Natl. Acad. Sci. USA
115
1493-1498
2018
Homo sapiens (O14773)
brenda