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Information on EC 3.4.16.2 - lysosomal Pro-Xaa carboxypeptidase and Organism(s) Mus musculus and UniProt Accession Q7TMR0

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Mus musculus
UNIPROT: Q7TMR0 not found.
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Cleavage of a -Pro-/-Xaa bond to release a C-terminal amino acid
Synonyms
carboxypeptidase, plasma carboxypeptidase, prolyl carboxypeptidase, lysosomal carboxypeptidase, carboxypeptidase a6, angiotensinase c, lysosomal pro-x carboxypeptidase, matrix pk activator, serine protease prolylcarboxypeptidase, proline carboxypeptidase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
prolylcarboxypeptidase
-
aminoacylproline carboxypeptidase
-
-
-
-
angiotensinase C
-
-
-
-
Carboxypeptidase P
-
-
-
-
Carboxypeptidase R
-
-
carboxypeptidase, aminoacylproline
-
-
-
-
carboxypeptidase, peptidylprolylamino acid
-
-
-
-
lysosomal carboxypeptidase
-
-
-
-
lysosomal carboxypeptidase C
-
-
-
-
PCP
-
-
-
-
plasma carboxypeptidase
-
-
plasma procarboxypeptidase B
-
-
procarboxypeptidase U
-
-
proline carboxypeptidase
-
-
-
-
proline-specific carboxypeptidase P
-
-
-
-
prolyl carboxypeptidase
-
-
-
-
prolylcarboxypeptidase
TAFI
-
-
thrombin-activatable fibrinolysis inhibitor
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
9075-64-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha-melanocyte-stimulating hormone + H2O
?
show the reaction diagram
evidence is provided that in mice, PRCP degrades alpha-melanocyte-stimulating hormone to an inactive form that is unable to inhibit food intake
-
-
?
alpha-melanocyte-stimulating hormone + H2O
?
show the reaction diagram
-
using recombinant PRCP it is shown that PRCP removes the C-terminal amino acid of alpha-melanocyte-stimulating hormone1-13, producing alpha-melanocyte-stimulating hormone1-12, which is not neuroactive
-
-
?
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
alpha-melanocyte-stimulating hormone + H2O
?
show the reaction diagram
evidence is provided that in mice, PRCP degrades alpha-melanocyte-stimulating hormone to an inactive form that is unable to inhibit food intake
-
-
?
alpha-melanocyte-stimulating hormone + H2O
?
show the reaction diagram
-
using recombinant PRCP it is shown that PRCP removes the C-terminal amino acid of alpha-melanocyte-stimulating hormone1-13, producing alpha-melanocyte-stimulating hormone1-12, which is not neuroactive
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3R,4R)-4-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-1-(2,2-dimethylpropyl)-3-(4-fluorophenyl)piperidine
-
compound shows improved oral bioavailabilities
2-[4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-1-(2-phenylethyl)piperidin-4-yl]pyridine
-
most potent compound in the series
N-benzyloxycarbonyl-prolyl-prolinal
-
the inhibition of PRCP activity by small molecule protease inhibitors administered peripherally or centrally decreased food intake in both wild-type and obese mice
potato carboxypeptidase inhibitor
-
-
-
t-butyl carbamate-prolyl-prolinal
-
the inhibition of PRCP activity by small molecule protease inhibitors administered peripherally or centrally decreased food intake in both wild-type and obese mice
Z-prolyl-prolinal
-
-
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(2,5-dichlorophenyl)amino]-3-iminobut-1-en-1-yl]piperidin-1-yl)methanone
-
compound has good levels of unbound compound in pure plasma
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(3-chloro-4-fluorophenyl)amino]-3-iminoprop-1-en-1-yl]piperidin-1-yl)methanone
-
compound achieves greater than 99% plasma target engagement with low brain exposure and has good levels of unbound compound in pure plasma
[4-[1-(3-chloro-4-fluorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl][(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone
-
compound has a superior in vivo profile, and also maintains a low brain to plasma ratio
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
thrombin
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000004 - 0.0000009
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(2,5-dichlorophenyl)amino]-3-iminobut-1-en-1-yl]piperidin-1-yl)methanone
0.0000005 - 0.0000014
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(3-chloro-4-fluorophenyl)amino]-3-iminoprop-1-en-1-yl]piperidin-1-yl)methanone
0.0000003 - 0.0000013
[4-[1-(3-chloro-4-fluorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl][(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00018
(3R,4R)-4-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-1-(2,2-dimethylpropyl)-3-(4-fluorophenyl)piperidine
Mus musculus
-
pH not specified in the publication, temperature not specified in the publication
0.0000007
2-[4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-1-(2-phenylethyl)piperidin-4-yl]pyridine
Mus musculus
-
pH not specified in the publication, temperature not specified in the publication
0.0000004
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(2,5-dichlorophenyl)amino]-3-iminobut-1-en-1-yl]piperidin-1-yl)methanone
Mus musculus
-
pH not specified in the publication, temperature not specified in the publication
0.0000003
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(3-chloro-4-fluorophenyl)amino]-3-iminoprop-1-en-1-yl]piperidin-1-yl)methanone
Mus musculus
-
pH not specified in the publication, temperature not specified in the publication
0.0000002
[4-[1-(3-chloro-4-fluorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl][(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone
Mus musculus
-
pH not specified in the publication, temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.1
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
greatest level of signals are detected in the cerebral cortex with very strong labeling in the cingulate and piriform cortex. Other areas of the cortex show moderate signal intensity
Manually annotated by BRENDA team
-
within the limbic system, strong signal is detected in the hippocampus and in the amygdaloid complex
Manually annotated by BRENDA team
-
enzyme mRNA detected in the zona incerta and the ventral tegmental area
Manually annotated by BRENDA team
-
strong expression
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
Prcp-null (Prcp-/-) mice eat less and have even less fat than the mice with partial loss of the enzyme. Knockout mice are resistant to diet-induced obesity
physiological function
PRCP expression promotes obesity, while inhibitors of the enzyme counteract obesity
malfunction
-
Prcp-null mice have elevated levels of alpha-melanocyte-stimulating hormone 1-13 in the hypothalamus and aree leaner and shorter than the wild-type controls on a regular chow diet. They are also resistant to high-fat diet-induced obesity
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PCP_MOUSE
491
0
55027
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
51000
-
predicted molecular mass of recombinant PRCP
60000
-
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
an inhibitor of activated TAFI might be used as a therapeutic agent in venous thrombotic diseases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wang, X.; Smith, P.L.; Hsu, M.Y.; Tamasi, J.A.; Bird, E.; Schumacher, W.A.
Deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI) protected mice from ferric chloride-induced vena cava thrombosis
J. Thromb. Thrombolysis
23
41-49
2007
Mus musculus
Manually annotated by BRENDA team
Palmiter, R.D.
Reduced levels of neurotransmitter-degrading enzyme PRCP promote obesity
J. Clin. Invest.
119
2130-2133
2009
Mus musculus (Q7TMR0)
Manually annotated by BRENDA team
Wallingford, N.; Perroud, B.; Gao, Q.; Coppola, A.; Gyengesi, E.; Liu, Z.W.; Gao, X.B.; Diament, A.; Haus, K.A.; Shariat-Madar, Z.; Mahdi, F.; Wardlaw, S.L.; Schmaier, A.H.; Warden, C.H.; Diano, S.
Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents
J. Clin. Invest.
119
2291-2303
2009
Mus musculus
Manually annotated by BRENDA team
Graham, T.H.; Liu, W.; Verras, A.; Sebhat, I.K.; Xiong, Y.; Bleasby, K.; Bhatt, U.R.; Chen, Q.; Garcia-Calvo, M.; Geissler, W.M.; Gorski, J.N.; He, H.; Lassman, M.E.; Lisnock, J.; Li, X.; Shen, Z.; Tong, X.; Tung, E.C.; Wiltsie, J.; Xiao, J.; Xie, D.; Xu, S.; Hale, J.J.; Pinto, S.; Shen, D.M.
A new class of prolylcarboxypeptidase inhibitors, part 1: discovery and evaluation
Bioorg. Med. Chem. Lett.
22
2811-2817
2012
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Graham, T.H.; Liu, W.; Verras, A.; Reibarkh, M.; Bleasby, K.; Bhatt, U.R.; Chen, Q.; Garcia-Calvo, M.; Geissler, W.M.; Gorski, J.N.; He, H.; Lassman, M.E.; Lisnock, J.; Li, X.; Shen, Z.; Tong, X.; Tung, E.C.; Wiltsie, J.; Xie, D.; Xu, S.; Xiao, J.; Hale, J.J.; Pinto, S.; Shen, D.M.
A new class of prolylcarboxypeptidase inhibitors, part 2: the aminocyclopentanes
Bioorg. Med. Chem. Lett.
22
2818-2822
2012
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Graham, T.H.; Shu, M.; Verras, A.; Chen, Q.; Garcia-Calvo, M.; Li, X.; Lisnock, J.; Tong, X.; Tung, E.C.; Wiltsie, J.; Hale, J.J.; Pinto, S.; Shen, D.M.
Pyrazoles as non-classical bioisosteres in prolylcarboxypeptidase (PrCP) inhibitors
Bioorg. Med. Chem. Lett.
24
1657-1660
2014
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Jeong, J.K.; Diano, S.
Prolyl carboxypeptidase mRNA expression in the mouse brain
Brain Res.
1542
85-92
2014
Mus musculus
Manually annotated by BRENDA team
Grobe, N.; Weir, N.M.; Leiva, O.; Ong, F.S.; Bernstein, K.E.; Schmaier, A.H.; Morris, M.; Elased, K.M.
Identification of prolyl carboxypeptidase as an alternative enzyme for processing of renal angiotensin II using mass spectrometry
Am. J. Physiol. Cell Physiol.
304
C945-C953
2013
Mus musculus
Manually annotated by BRENDA team