Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.4.14.10 - tripeptidyl-peptidase II and Organism(s) Mus musculus and UniProt Accession Q64514

for references in articles please use BRENDA:EC3.4.14.10
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Mus musculus
UNIPROT: Q64514 not found.
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Release of an N-terminal tripeptide from a polypeptide
Synonyms
tripeptidyl peptidase, tripeptidyl-peptidase ii, ptp-a, tripeptidylpeptidase ii, dtpp ii, tripeptidyl aminopeptidase i, tpp-ii, tpp-2, ty-21 tpp, tripeptidyl-peptidase-ii, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aminopeptidase, tripeptidyl, II
-
-
-
-
cholecystokinin-inactivating peptidase
-
-
-
-
mTPP II
-
-
TPP II
tripeptidyl aminopeptidase
-
-
-
-
tripeptidyl aminopeptidase I
-
-
tripeptidyl aminopeptidase II
tripeptidyl peptidase
-
-
-
-
tripeptidyl peptidase II
tripeptidylpeptidase II
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
101149-94-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-Ala-L-Ala-L-Ala 4-nitroanilide + H2O
L-Ala-L-Ala-L-Ala + 4-nitroaniline
show the reaction diagram
both the KM and kcat are lower for cleavage of L-Ala-L-Ala-L-Ala 4-nitroanilide than for L-Ala-L-Ala-L-Phe 4-nitroanilide, the former possibly can bind non-productively to the active site of the enzyme
-
-
?
L-Ala-L-Ala-L-Phe 4-nitroanilide + H2O
L-Ala-L-Ala-L-Phe + 4-nitroaniline
show the reaction diagram
both the KM and kcat are lower for cleavage of L-Ala-L-Ala-L-Ala 4-nitroanilide than for L-Ala-L-Ala-L-Phe 4-nitroanilide, the former possibly can bind non-productively to the active site of the enzyme
-
-
?
L-Ala-L-Ala-L-Phe-p-nitroanilide + H2O
L-Ala-L-Ala-L-Phe + p-nitroaniline
show the reaction diagram
-
-
-
?
Ala-Ala-Ala-4-nitroanilide + H2O
Ala-Ala-Ala + 4-nitroaniline
show the reaction diagram
-
-
-
?
Ala-Ala-Phe-4-nitroanilide + H2O
Ala-Ala-Phe + 4-nitroaniline
show the reaction diagram
-
-
-
?
Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
Ala-Ala-Phe + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
N-succinyl-Leu-Leu-Val-Tyr + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
the activities of both the proteasome and PTTII are regulated in a parallel manner in cancer cachexia, and both are induced by the same factor and probably have the same intracellular signalling pathways and transcription factors
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
butabindide
efficient, competitive inhibitor of TPP II
isovaleryl-L-Leu-L-Arg-L-Arg-L-Ala-L-Ser-L-Val-L-Ala
-
L-Val-L-Leu-L-Arg-L-Arg-L-Ala-L-Ser-L-Val-L-Ala
-
Ala-Ala-Phe-chloromethylketone
-
-
Ala-Ala-Phe-CMK
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008 - 20
L-Ala-L-Ala-L-Ala 4-nitroanilide
0.017 - 30
L-Ala-L-Ala-L-Phe 4-nitroanilide
0.013 - 1
L-Ala-L-Ala-L-Phe-p-nitroanilide
0.008 - 0.062
Ala-Ala-Ala-4-nitroanilide
0.017 - 0.1
Ala-Ala-Phe-4-nitroanilide
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.25 - 100
L-Ala-L-Ala-L-Ala 4-nitroanilide
0.38 - 500
L-Ala-L-Ala-L-Phe 4-nitroanilide
0.25 - 33
Ala-Ala-Ala-4-nitroanilide
0.38 - 114
Ala-Ala-Phe-4-nitroanilide
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.4 - 3900
L-Ala-L-Ala-L-Ala 4-nitroanilide
3.82 - 3500
L-Ala-L-Ala-L-Phe 4-nitroanilide
0.000005 - 0.0039
Ala-Ala-Ala-4-nitroanilide
0.0000038 - 0.0035
Ala-Ala-Phe-4-nitroanilide
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000011 - 0.14
butabindide
0.001 - 2
L-Val-L-Leu-L-Arg-L-Arg-L-Ala-L-Ser-L-Val-L-Ala
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.068
recombinant enzyme from cell lysate, at 37°C
12
after 8fold purification, at 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
7.8
-
assay at
7.9
optimal pH, substrate: Ala-Ala-Phe-4-nitroanilide
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8
optimal pH, substrate: Ala-Ala-Ala-4-nitroanilide
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
murine colon adenocarcinoma cell
Manually annotated by BRENDA team
-
gastrocnemius muscle bearing MAC16 tumour
Manually annotated by BRENDA team
TPPII is located on the sperm acrosomal region
Manually annotated by BRENDA team
-
CD8 T cell lines specific are generated from spleen cells from Listeria monocytogenes-infected BALB/c mice 2 weeks after infection
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
inner cytoplasmic membrane
Manually annotated by BRENDA team
additional information
-
radiation does not lead to nuclear translocation of TPPII
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
cell lines from primary fibroblasts are generated having conditional (floxed) TPPII alleles, transformed with both the c-myc and H-ras oncogenes. TPPII is deleted using retroviral self-deleting Cre recombinase. Clonally derived TPPIIflox/flox and TPPII-/- transformed fibroblasts show no influences of TPPII expression on basal cell survival and proliferation, nor on radiation-induced p53 activation, p21 induction, cell cycle arrest, apoptosis, or clonogenic cell death
physiological function
isoform TPPII can regulate sperm maturation by modulating intracellular Ca2+ stores via the type 3 ryanodine receptor. Tripeptidyl peptidase II antagonists strongly activate the cAMP/PKA signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation. In the absence of Ca2+, TPPII antagonists elevate the intracellular Ca2+ levels in sperm, resulting in a marked improvement in sperm movement, capacitation, acrosome reaction, and the in vitro fertilizing ability. This antagonist-induced release of intracellular Ca2+ can be blocked by the inhibitors of ryanodine receptors which are the main intracellular Ca2+ channels responsible for releasing stored Ca2+
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TPP2_MOUSE
1262
0
139879
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
145000
His-tagged TPP II, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 100000-140000, SDS-PAGE of recombinant protein, full-length TPP II and shortened versions thereof
oligomer
-
oligomeric assembly of 138000 Da subunits
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D387G
mutant shows bell-shaped pH-dependence of kcat, possibly due to an impaired protonation of the leaving group
E305K
the mutant shows extremely low activity
E305Q
the mutant shows extremely low activity
E331K
the catalytic efficiency is reduced 20000fold for the E331K variant compared to the wild type enzyme
E331Q
G375D
less than 0.1% of wild-type activity
H267A
mutant shows bell-shaped pH-dependence of kcat, possibly due to an impaired protonation of the leaving group
G375D
mutant has only 0.1% activity of wild-type at pH 7.5. Mutant shows a marked decrease in pH optimum compared to wild-type
H267A
mutant shows mostly a decresed kcat for all substrates and a highly decreased kcat/Km between 2 to fold orders of magnitude compared to wild-type. kcat shows a higher rise with pH in mutant H267A than in wild-type with substrate Ala-Ala-Phe-4-nitroanilide but at pH more than 7.6 kcat (app) decreases for substrate Ala-Ala-Phe-4-nitroanilide, resulting in a significantly better fit for a bell-shaped curve than for a sigmoidal
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni Sepharose 6 column chromatography
using polyethyleneimine precipitation, (NH4)2SO4 precipitation, dialysis, anion-exchange chromatography, hydrophobic interaction chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Pichia pastoris
expression of murine TPP2 gene optimized for high-level expression in Escherichia coli
expressed in Escherichia coli
normal and alternatively spliced cDNA variant which contains an additional 39 bp, encoding 13 amino acids in the C-terminal end of the protein, expression in human kidney 293 cells
-
overexpression in 293-cells, enzyme forms active oligomers
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
isoform TPPII can regulate sperm maturation by modulating intracellular Ca2+ stores via the type 3 ryanodine receptor. Tripeptidyl peptidase II antagonists strongly activate the cAMP/PKA signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation. In the absence of Ca2+, TPPII antagonists elevate the intracellular Ca2+ levels in sperm, resulting in a marked improvement in sperm movement, capacitation, acrosome reaction, and the in vitro fertilizing ability. This antagonist-induced release of intracellular Ca2+ can be blocked by the inhibitors of ryanodine receptors which are the main intracellular Ca2+ channels responsible for releasing stored Ca2+
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tomkinson, B.
Characterization of cDNA for murine tripeptidyl-peptidase II reveals alternative splicing [published erratum appears in Biochem J 1995 Mar 15;306(Pt 3):880]
Biochem. J.
304
517-523
1994
Mus musculus
Manually annotated by BRENDA team
Tomkinson, B.; Ni Laoi, B.; Wellington, K.
The insert within the catalytic domain of tripeptidyl-peptidase II is important for the formation of the active complex
Eur. J. Biochem.
269
1438-1443
2002
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Tomkinson, B.; Hansen, M.; Cheung, W.F.
Structure-function studies of recombinant murine tripeptidyl-peptidase II: the extra domain which is subject to alternative splicing is involved in complex formation
FEBS Lett.
405
277-280
1997
Mus musculus
Manually annotated by BRENDA team
Chand, A.; Wyke, S.M.; Tisdale, M.J.
Effect of cancer cachexia on the activity of tripeptidyl-peptidase II in skeletal muscle
Cancer Lett.
218
215-222
2005
Mus musculus
Manually annotated by BRENDA team
Naujokat, C.; Fuchs, D.; Berges, C.
Adaptive modification and flexibility of the proteasome system in response to proteasome inhibition
Biochim. Biophys. Acta
1773
1389-1397
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Huai, J.; Firat, E.; Nil, A.; Million, D.; Gaedicke, S.; Kanzler, B.; Freudenberg, M.; van Endert, P.; Kohler, G.; Pahl, H.L.; Aichele, P.; Eichmann, K.; Niedermann, G.
Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice
Proc. Natl. Acad. Sci. USA
105
5177-5182
2008
Mus musculus
Manually annotated by BRENDA team
Lindas, A.C.; Eriksson, S.; Jozsa, E.; Tomkinson, B.
Investigation of a role for Glu-331 and Glu-305 in substrate binding of tripeptidyl-peptidase II
Biochim. Biophys. Acta
1784
1899-1907
2008
Mus musculus (Q64514)
Manually annotated by BRENDA team
Firat, E.; Tsurumi, C.; Gaedicke, S.; Huai, J.; Niedermann, G.
Tripeptidyl peptidase II plays a role in the radiation response of selected primary cell types but not based on nuclear translocation and p53 Sstabilization
Cancer Res.
69
3325-3331
2009
Mus musculus
Manually annotated by BRENDA team
Tye, C.E.; Lorenz, R.L.; Bartlett, J.D.
Lysosomal protease expression in mature enamel
Cells Tissues Organs
189
111-114
2009
Mus musculus
Manually annotated by BRENDA team
Tsurumi, C.; Firat, E.; Gaedicke, S.; Huai, J.; Mandal, P.K.; Niedermann, G.
Viability and DNA damage responses of TPPII-deficient Myc- and Ras-transformed fibroblasts
Biochem. Biophys. Res. Commun.
386
563-568
2009
Mus musculus (Q64514)
Manually annotated by BRENDA team
Grauling-Halama, S.; Bahr, U.; Schenk, S.; Geginat, G.
Role of tripeptidyl peptidase II in the processing of Listeria monocytogenes-derived MHC class I-presented antigenic peptides
Microbes Infect.
11
795-802
2009
Mus musculus
Manually annotated by BRENDA team
Eklund, S.; Dogan, J.; Jemth, P.; Kalbacher, H.; Tomkinson, B.
Characterization of the endopeptidase activity of tripeptidyl-peptidase II
Biochem. Biophys. Res. Commun.
424
503-507
2012
Mus musculus
Manually annotated by BRENDA team
Eklund, S.; Lindas, A.C.; Hamnevik, E.; Widersten, M.; Tomkinson, B.
Exploring the active site of tripeptidyl-peptidase II through studies of pH dependence of reaction kinetics
Biochim. Biophys. Acta
1824
561-570
2012
Drosophila melanogaster, Drosophila melanogaster (Q9V6K1), Homo sapiens, Mus musculus, Mus musculus (Q64514)
Manually annotated by BRENDA team
Zhou, Y.; Ru, Y.; Wang, C.; Wang, S.; Zhou, Z.; Zhang, Y.
Tripeptidyl peptidase II regulates sperm function by modulating intracellular Ca(2+) stores via the ryanodine receptor
PLoS ONE
8
e66634
2013
Mus musculus, Mus musculus (Q64514)
Manually annotated by BRENDA team
Bialy, L.P.; Kuckelkorn, U.; Henklein, P.; Fayet, J.; Wilczynski, G.M.; Kaminski, A.; Mlynarczuk-Bialy, I.
Changes in spatio-temporal localization of tripeptidyl peptidase II (TPPII) in murine colon adenocarcinoma cells during aggresome formation a microscopy study based on a novel fluorescent proteasome inhibitor
Histol. Histopathol.
34
359-372
2019
Mus musculus
Manually annotated by BRENDA team