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Information on EC 3.4.14.5 - dipeptidyl-peptidase IV and Organism(s) Mus musculus and UniProt Accession P28843
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3.4.14.5 dipeptidyl-peptidase IVSpecify your search results
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- 3.4.14.5
- mellitus
- glp-1
- peptide-1
- agonist
- cardiovascular
- sitagliptin
- metformin
-
antidiabetic
- incretins
-
glycemic
- sulfonylurea
- hypoglycemia
- vildagliptin
-
monotherapy
- hemoglobin
-
placebo
- pancreatic
-
glucose-lowering
-
glucose-dependent
-
sodium-glucose
- thiazolidinediones
-
insulinotropic
-
postprandial
-
glycated
-
incretin-based
- gip
- liraglutide
-
add-on
-
double-blind
- beta-cell
-
cotransporter
-
antihyperglycemic
-
exenatide
-
excursion
-
open-label
-
placebo-controlled
- pioglitazone
-
sulphonylureas
- pemphigoid
-
long-acting
-
bullous
- exendin-4
- mers-cov
-
real-world
- biguanides
-
once-daily
- medicine
-
macrovascular
-
once-weekly
- drug development
- veterinary medicine
- analysis
- pharmacology
- glargine
- food industry
-
enteroendocrine
- diagnostics
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
release of an N-terminal dipeptide, Xaa-Yaa-/-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline
Synonyms
dpp-4, dipeptidyl peptidase-4, dpp-iv, dipeptidyl peptidase iv, dpp iv, dppiv, dipeptidyl peptidase 4, dipeptidyl peptidase-iv, dp iv, dipeptidylpeptidase iv, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ACT3
-
-
-
-
ADABP
-
-
-
-
Adenosine deaminase complexing protein
-
-
-
-
amino acyl-prolyl dipeptidyl aminopeptidase
-
-
-
-
aminopeptidase, glycylproline
-
-
-
-
Bile canaliculus domain-specific membrane glycoprotein
-
-
-
-
dipeptidyl aminopeptidase IV
dipeptidyl peptidase-IV
-
-
dipeptidyl-aminopeptidase IV
-
-
-
-
dipeptidyl-peptidase IV (CD26)
-
-
-
-
dipeptidyl-peptide hydrolase
-
-
-
-
DPP IV/CD26
-
-
-
-
DPP-IV
-
-
Gly-Pro-naphthylamidase
-
-
-
-
glycoprotein GP110
-
-
-
-
glycylproline aminopeptidase
-
-
-
-
glycylproline-dipeptidyl-aminopeptidase
-
-
-
-
glycylprolyl aminopeptidase
-
-
-
-
glycylprolyl dipeptidylaminopeptidase
-
-
-
-
GP110 glycoprotein
-
-
-
-
leukocyte antigen CD26
-
-
-
-
lymphocyte, antigen CD26
-
-
-
-
Pep X
-
-
-
-
peptidase, dipeptidyl, IV
-
-
-
-
postproline dipeptidyl aminopeptidase IV
-
-
-
-
T cell triggering molecule Tp103
-
-
-
-
T-cell activation antigen CD26
-
-
-
-
THAM
-
-
-
-
Thymocyte-activating molecule
-
-
-
-
TP103
-
-
-
-
WC10
-
-
-
-
X-PDAP
-
-
-
-
X-prolyl dipeptidyl aminopeptidase
-
-
-
-
Xaa-Pro-dipeptidyl-aminopeptidase
-
-
-
-
dipeptidyl aminopeptidase IV
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of an N-terminal dipeptide, Xaa-Yaa-/-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline
cleaves dipeptides containing proline or alanine or one of several other amino acids at the penultimate position from the amino termini of substrates, contains a Ser-His-Asp catalytic triad, active site structure, the Glu-Glu motif is necessary for amino dipeptide selection
-
CAS REGISTRY NUMBER
COMMENTARY
54249-88-6
-
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-Pro-7-amido-4-methylcoumarin + H2O
Ala-Pro + 7-amino-4-methylcoumarin
-
-
-
?
gastrin releasing peptide-(1-27) + H2O
?
-
i.e. GRP-(1-27), cleaves N-terminal dipeptide VP
-
ir
gastrin releasing peptide-(3-27) + H2O
?
-
i.e. GRP-(3-27), cleaves N-terminal dipeptide LP
-
ir
GLP-1 + H2O
?
-
an incretin involved in the glucose-dependent production of insulin
-
?
glucagon-like peptide 2 + H2O
?
-
i.e. GLP-1, degradation, regulation of activity, cleaves N-terminal dipeptide HA
-
ir
glucose-dependent insulinotropic peptide + H2O
?
-
-
-
-
?
Gly-L-Pro-7-amido-4-methylcoumarin + H2O
Gly-L-Pro + 7-amino-4-methylcoumarin
-
-
-
-
?
Gly-Pro-4-methylcoumarin 7-amide + H2O
Gly-Pro + 7-amino-4-methylcoumarin
-
-
-
-
?
Gly-Pro-7-amido-4-methylcoumarin + H2O
Gly-Pro + 7-amino-4-methylcoumarin
-
-
-
-
?
growth hormone releasing hormone-(1-29) fragment + H2O
?
-
i.e. GHRH-(1-29), cleaves N-terminal dipeptide YA
-
ir
growth hormone releasing hormone-(1-44) fragment + H2O
?
-
i.e. GHRH-(1-44), cleaves N-terminal dipeptide YA
-
ir
H-Ala-L-Pro-7-amido-4-methylcoumarin + H2O
H-Ala-L-Pro + 7-amino-4-methylcoumarin
-
-
-
-
?
pituitary adenylate cyclase-activating polypeptide-(1-27) + H2O
?
-
i.e. PACAP27, cleaves N-terminal dipeptide HS
-
?
glucagon-like peptide 1 + H2O
?
-
-
-
-
?
glucagon-like peptide 1 + H2O
?
-
i.e. GLP-1, degradation, regulation of activity
-
?
glucagon-like peptide 1 + H2O
?
-
i.e. GLP-1, degradation, regulation of activity, cleaves N-terminal dipeptide HA
-
ir
glucose-dependent insulinotropic polypeptide + H2O
?
-
i.e. GIP, cleaves N-terminal dipeptide YA
-
ir
growth hormone-(1-43) fragment + H2O
?
-
cleaves N-terminal dipeptide FP
-
ir
pituitary adenylate cyclase-activating polypeptide-(1-38) + H2O
?
-
i.e. PACAP38, a critical mediator in lipid and carbohydrate metabolism
-
?
pituitary adenylate cyclase-activating polypeptide-(1-38) + H2O
?
-
i.e. PACAP38, enzyme plays a major role in the degradation of circulating PACAP38, cleaves N-terminal dipeptide HS
-
?
SDF-1/CXCL12 + H2O
?
-
CD26 may play a role in SDF-1/CXCL12 mediated functions such as chemotaxis
-
-
?
SDF-1/CXCL12 + H2O
?
-
CD26 can cleave SDF-1/CXCL12 to a chemotactically-null molecule
-
-
?
additional information
?
-
-
specifically recognized immobilized gelatin and type I collagen
-
-
?
additional information
?
-
-
Ser624, Asp702, and His734 form the catalytic triad
-
-
?
additional information
?
-
-
enzyme binds to CD45 and to adenosine deaminase
-
?
additional information
?
-
-
may play a role in cell attachment to collagen
-
-
?
additional information
?
-
-
enzyme is important for metabolic regulation
-
?
additional information
?
-
-
substrate specificity, cleavage of N-terminal dipeptide, no activity with vasoactive intestinal peptide, glucagon and secretin are poor substrates
-
?
additional information
?
-
-
DPP-IV influences pain perception via modulation of the peripheral concentration of substance P
-
-
?
additional information
?
-
-
CD26/DP IV is a nonredundant inhibitory receptor controlling T cell activation and Th1-mediated autoimmunity
-
-
?
additional information
?
-
-
DPP-4 plays a role in the control of immune function, inflammatory responses, and behavior
-
-
?
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
gastrin releasing peptide-(1-27) + H2O
?
-
i.e. GRP-(1-27), cleaves N-terminal dipeptide VP
-
ir
gastrin releasing peptide-(3-27) + H2O
?
-
i.e. GRP-(3-27), cleaves N-terminal dipeptide LP
-
ir
glucagon-like peptide 2 + H2O
?
-
i.e. GLP-1, degradation, regulation of activity, cleaves N-terminal dipeptide HA
-
ir
glucose-dependent insulinotropic peptide + H2O
?
-
-
-
-
?
glucose-dependent insulinotropic polypeptide + H2O
?
-
i.e. GIP, cleaves N-terminal dipeptide YA
-
ir
growth hormone releasing hormone-(1-29) fragment + H2O
?
-
i.e. GHRH-(1-29), cleaves N-terminal dipeptide YA
-
ir
growth hormone releasing hormone-(1-44) fragment + H2O
?
-
i.e. GHRH-(1-44), cleaves N-terminal dipeptide YA
-
ir
growth hormone-(1-43) fragment + H2O
?
-
cleaves N-terminal dipeptide FP
-
ir
pituitary adenylate cyclase-activating polypeptide-(1-27) + H2O
?
-
i.e. PACAP27, cleaves N-terminal dipeptide HS
-
?
pituitary adenylate cyclase-activating polypeptide-(1-38) + H2O
?
-
i.e. PACAP38, enzyme plays a major role in the degradation of circulating PACAP38, cleaves N-terminal dipeptide HS
-
?
SDF-1/CXCL12 + H2O
?
-
CD26 may play a role in SDF-1/CXCL12 mediated functions such as chemotaxis
-
-
?
glucagon-like peptide 1 + H2O
?
-
-
-
-
?
glucagon-like peptide 1 + H2O
?
-
i.e. GLP-1, degradation, regulation of activity, cleaves N-terminal dipeptide HA
-
ir
additional information
?
-
-
may play a role in cell attachment to collagen
-
-
?
additional information
?
-
-
enzyme is important for metabolic regulation
-
?
additional information
?
-
-
substrate specificity, cleavage of N-terminal dipeptide, no activity with vasoactive intestinal peptide, glucagon and secretin are poor substrates
-
?
additional information
?
-
-
DPP-IV influences pain perception via modulation of the peripheral concentration of substance P
-
-
?
additional information
?
-
-
CD26/DP IV is a nonredundant inhibitory receptor controlling T cell activation and Th1-mediated autoimmunity
-
-
?
additional information
?
-
-
DPP-4 plays a role in the control of immune function, inflammatory responses, and behavior
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
vildagliptin
vildagliptin improves glucose tolerance and increases the beta-cell mass by reducing beta-cell apoptosis in Insulin Receptor Substrate-2-Knockout mice fed a high-fat diet, and the reduction of beta-cell apoptosis by vildagliptin is independent of the Insulin Receptor Substrate-2 expression in the cells
(2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide
-
a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
(3R)-4-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one
-
competitive, reversible inhibitor
(3R)-4-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-methyl-1,4-diazepan-2-one
-
pharmacokinetic parameters
(R)-3-amino-4-(2,5-difluorophenyl)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)butan-1-one
-
-
3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate
ASP-8497
-
(2S,4S)-4-fluoro-1-([[4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino]acetyl)pyrrolidine-2-carbonitrile monofumarate, selective and competitive inhibitor of DPP-IV, ASP8497 is a DPP-IV inhibitor with long-acting antidiabetic effect that might be a potential agent for type 2 diabetes
MK0431
-
sitagliptin, treatment of NOD mice with daily 4 g/kg MK0431 before and after islet transplantation results in prolongation of islet graft survival
Syrrx106124
-
acutely lowers blood glucose and enhances glucose-stimulated insulin secretion in wild-type mice and in mice with targeted disruption of single incretin receptors
TP8211
-
acutely lowers blood glucose and enhances glucose-stimulated insulin secretion in wild-type mice and in mice with targeted disruption of single incretin receptors
-
[(2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro-1,2,4[triazolo]4,3-alpha]pyrazin-7(8H)-yl]-1-(2,5-difluorophenyl)butan-2-amine hydrochloride
-
selective DP IV inhibitor
additional information
-
selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge
-
3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate
-
i.e. E3024, pharmacokinetic profile
3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate
-
i.e. E3024, selective, and competitive
3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate
-
selective and competitive dipeptidyl peptidase-IV inhibitor
alogliptin
-
i.e. 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]benzonitrile monobenzoate, formerly SYR-322, potent and highly selective dipeptidyl peptidase-4 inhibitor, after 2 days alogliptin (0.002%, 0.01%, or 0.03%) dose-dependently inhibits DPP-4 activity by 28-82%
alogliptin
-
i.e. 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]benzonitrilemonobenzoate, about 80% inhibition of DPP-4 after 4-week treatment with 45.7 mg/kg/day (0.03%) alogliptin
ASP8497
-
i.e. (2S,4S)-4-fluoro-1-([[4-methyl-1-(methylsulfonyl)-piperidin-4-yl]amino]acetyl)pyrrolidine-2-carbonitrile monofumarate, potent and long-acting inhibitor of plasma DPP-IV activity, inhibitory activity lasts up to 24 h when administered at 5 mg/kg twice a day or 10 mg/kg once a day
ASP8497
-
i.e. (2S,4S)-4-fluoro-1-([[4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino]acetyl)pyrrolidine-2-carbonitrile monofumarate, potent DPP-IV inhibitor and potential agent for the treatment of type 2 diabetes
ASP8497
-
i.e. [(2S,4S)-4-fluoro-1-([4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino]acetyl)pyrrolidine-2-carbonitrile monofumarate, the combination of 1 mg/kg ASP8497 with antidiabetic drugs can be useful for correcting the postprandial hyperglycemia seen with type 2 diabetes
ASP8497
-
potent, selective, and competitive dipeptidyl peptidase-IV inhibitor with antihyperglycemic activity, i.e. (2S,4S)-4-fluoro-1-([[4-methyl-1-(methylsulfonyl)piperidin-4-yl]amino]acetyl)pyrrolidine-2-carbonitrile monofumarate
BI 1356
-
competitive inhibitor, i.e. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione, proposed trade name Ondero, BI 1356 is more than 10000fold selective for DPP-4 than DPP-8, DPP-9, aminopeptidases N and P, prolyloligopeptidase, trypsin, plasmin, and thrombin and is 90-fold more selective than for fibroblast activation protein in vitro
BI 1356
-
proposed trade name ONDERO, exhibits a prominent concentration-dependent plasma protein binding due to a saturable high affinity binding to the DPP-4 target in plasma
Lys[Z(NO2)]-pyrrolidide
-
non-specific DPIV inhibitor, 96% inhibition at 0.01 mM
saxagliptin
-
BMS-477178, (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo[3.1.0]-hexane-3-carbonitrile hydrochloride
sitagliptin
-
MK-0431, (2 R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo-[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine phosphate
sitagliptin
-
MK0431, potent inhibitor, inhibition of DPP-IV with sitagliptin (dose of 4g/kg/day over 7 days) prolongs islet graft retention in a type 1 diabetes mouse model
vildagliptin
-
acutely lowers blood glucose and enhances glucose-stimulated insulin secretion in wild-type mice and in mice with targeted disruption of single incretin receptors
vildagliptin
-
LAF237, 1-[[(3-hydroxy-1-adamantyl)-amino]acetyl]-2-cyano-(S)-pyrrolidine
vildagliptin
-
LAF237, 1-[[3-hydroxy-1-adamantyl]amino]acetyl-2-cyano-(S)-pyrrolidine
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000027
(R)-3-amino-4-(2,5-difluorophenyl)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)butan-1-one
Mus musculus
-
-
0.0001 - 0.00028
3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate
0.00000386
ASP-8497
Mus musculus
-
in 25 mM HEPES, 140 mM NaCl, 80 mM MgCl2, 0.5% BSA, pH 7, at 25°C
0.0000026
ASP8497
Mus musculus
-
median inhibition concentration, in 25 mM HEPES, 140 mM NaCl, 80 mM MgCl2, 0.5% bovine serum albumin, at pH 7.3 and 25°C
0.00000257
saxagliptin
Mus musculus
-
in 25 mM HEPES, 140 mM NaCl, 80 mM MgCl2, 0.5% BSA, pH 7, at 25°C
0.0000213
sitagliptin
Mus musculus
-
in 25 mM HEPES, 140 mM NaCl, 80 mM MgCl2, 0.5% BSA, pH 7, at 25°C
0.00000324
vildagliptin
Mus musculus
-
in 25 mM HEPES, 140 mM NaCl, 80 mM MgCl2, 0.5% BSA, pH 7, at 25°C
0.0001
3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate
Mus musculus
-
recombinant enzyme
0.00028
3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate
Mus musculus
-
plasma enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 8
-
about 40% of maximal activity at pH 4.0 and at pH 8.0, hydrolysis of Gly-Pro-4-nitroanilide, citrate buffer
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in artery DPIV represents 92% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in brain DPIV represents 22% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in colon DPIV represents 33% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in duodenum DPIV represents 89% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in heart DPIV represents 71% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in ileum DPIV represents 94% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in kidney DPIV represents 92% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in liver DPIV represents 94% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in lymph nodes DPIV represents 62% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in pancreas DPIV represents 14% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in skin DPIV represents 79% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in thymus DPIV represents 93% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in vein DPIV represents 80% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
-
679662, 679663, 696134, 697556, 697561, 697763, 697770, 697773, 699445, 699748, 699944, 699985, 700399, 700400, 700615
-
in blood plasma DPIV represents 78% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in lung DPIV represents 94% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
-
in spleen DPIV represents 73% of the total Gly-L-Pro-4-nitroanilide-hydrolyzing activity
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
inhibition of enzyme by vildagliptin improves glucose tolerance and increases the beta-cell mass by reducing beta-cell apoptosis in Insulin Receptor Substrate-2-knockout mice fed a high-fat diet, and the reduction of beta-cell apoptosis by vildagliptin is independent of the Insulin Receptor Substrate-2 expression in the cells
malfunction
-
DPP-IV knockout mice have no major differences in the leukocytes populations in spleen, thymus and blood as compared to their wild type controls
physiological function
-
dipeptidyl peptidase IV regulates T lymphocyte activation
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). DPP4_MOUSE
760
1
87437
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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knock-out mutant shows residual activity with Gly-Pro-4-nitroanilide in plasma, but not with GLP-1, mutant mice are healthy
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
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specific inhibition of the enzyme shows efficacy in the treatment of type 2 diabetes
medicine
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(2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide is a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
medicine
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a DPP-IV inhibitor (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) in combination with glybenclamide or nateglinide may be a promising option for the treatment of type 2 diabetes, and particularly, for controlling postprandial hyperglycemia in the clinic
medicine
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CD26 inhibition may represent a novel approach to increasing the efficacy and success of hematopoietic stem cell/hematopoietic progenitor cell transplantation, especially under conditions of limiting donor cell yield
medicine
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CD26 is an appropriate molecular target for renal cell carcinoma therapy. Anti-CD26 mAb treatment leads to loss of tumorigenicity. The potent antitumor effect of anti-CD26 mAb may be used in the future as novel therapeutic approaches against various CD26-positive malignancies, including renal cell carcinoma
medicine
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CD26/DP IV is a nonredundant inhibitory receptor controlling T cell activation and Th1-mediated autoimmunity, and may have important therapeutic implications for the treatment of autoimmune CNS disease
medicine
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combination of DPP IV inhibitor with low dose of thiazolidinedione can interact synergistically to represent a therapeutic advantage for the clinical treatment of type 2 diabetes without the adverse effects of haemodilution and weight gain associated with thiazolidinediones
medicine
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DPP-4 inhibition increases active glucagon-like peptide 1 levels and improves glucose tolerance and islet function with improved islet topography in mice with a beta-cellspecific overexpression of human islet amyloid peptide. These findings support the potential value of DPP-4 inhibition in the treatment of diabetes with the potential of normalizing islet function
medicine
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DPP-4 inhibitors are effective agents for achieving blood glucose control
medicine
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DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal. The combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia
medicine
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metformin decreases the plasma DPP IV activity, limiting the inactivation of exogenously administered GLP-1 and improving glycaemic control
medicine
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in a murine model of acute respiratory distress syndrome, aspirated bleomycin induces a significant increase in the number of neutrophils in the lungs after 3 d. Oropharyngeal aspiration of dipeptidyl peptidase IV inhibits the bleomycin-induced accumulation of mouse neutrophils
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bauvois, B.
A collagen-binding glycoprotein on the surface of mouse fibroblasts is identified as dipeptidyl peptidase IV
Biochem. J.
252
723-731
1988
Mus musculus
David, F.; Bernard, A.M.; Pierres, M.; Marguet, D.
Identification of serine 624, aspartic acid 702, and histidine 734 as the catalytic triad residues of mouse dipeptidyl-peptidase IV (CD26). A member of a novel family of nonclassical serine hydrolases
J. Biol. Chem.
268
17247-17252
1993
Mus musculus
Rosenblum, J.S.; Kozarich, J.W.
Prolyl peptidases: a serine protease subfamily with high potential for drug discovery
Curr. Opin. Chem. Biol.
7
496-504
2003
Homo sapiens, Mammalia, Mus musculus, Rattus norvegicus, Sus scrofa
Zhu, L.; Tamvakopoulos, C.; Xie, D.; Dragovic, J.; Shen, X.; Fenyk-Melody, J.E.; Schmidt, K.; Bagchi, A.; Griffin, P.R.; Thornberry, N.A.; Sinha Roy, R.
The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: in vivo metabolism of pituitary adenylate cyclase activating polypeptide-(1-38)
J. Biol. Chem.
278
22418-22423
2003
Mus musculus
Guieu, R.; Fenouillet, E.; Devaux, C.; Fajloun, Z.; Carrega, L.; Sabatier, J.M.; Sauze, N.; Marguet, D.
CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity
Behav. Brain Res.
166
230-235
2006
Mus musculus
Edmondson, S.D.; Mastracchio, A.; Mathvink, R.J.; He, J.; Harper, B.; Park, Y.J.; Beconi, M.; Di Salvo, J.; Eiermann, G.J.; He, H.; Leiting, B.; Leone, J.F.; Levorse, D.A.; Lyons, K.; Patel, R.A.; Patel, S.B.; Petrov, A.; Scapin, G.; Shang, J.; Roy, R.S.; Smith, A.; Wu, J.K.; Xu, S.; Zhu, B.; Thornberry, N.A.; Weber, A.E.
(2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
J. Med. Chem.
49
3614-3627
2006
Mus musculus
Kondo, T.; Nekado, T.; Sugimoto, I.; Ochi, K.; Takai, S.; Kinoshita, A.; Hatayama, A.; Yamamoto, S.; Kawabata, K.; Nakai, H.; Toda, M.
Discovery of long-acting N-(cyanomethyl)-N-alkyl-L-prolinamide inhibitors of dipeptidyl peptidase IV
Bioorg. Med. Chem.
16
190-208
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Biftu, T.; Feng, D.; Qian, X.; Liang, G.B.; Kieczykowski, G.; Eiermann, G.; He, H.; Leiting, B.; Lyons, K.; Petrov, A.; Sinha-Roy, R.; Zhang, B.; Scapin, G.; Patel, S.; Gao, Y.D.; Singh, S.; Wu, J.; Zhang, X.; Thornberry, N.A.; Weber, A.E.
(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Bioorg. Med. Chem. Lett.
17
49-52
2007
Canis lupus familiaris, Mus musculus, Rattus norvegicus
Inamoto, T.; Yamochi, T.; Ohnuma, K.; Iwata, S.; Kina, S.; Inamoto, S.; Tachibana, M.; Katsuoka, Y.; Dang, N.H.; Morimoto, C.
Anti-CD26 monoclonal antibody-mediated G1-S arrest of human renal clear cell carcinoma Caki-2 is associated with retinoblastoma substrate dephosphorylation, cyclin-dependent kinase 2 reduction, p27(kip1) enhancement, and disruption of binding to the extra
Clin. Cancer Res.
12
3470-3477
2006
Mus musculus
Drucker, D.J.
Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action
Diabetes Care
30
1335-1343
2007
Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Green, B.D.; Irwin, N.; Duffy, N.A.; Gault, V.A.; Oharte, F.P.; Flatt, P.R.
Inhibition of dipeptidyl peptidase-IV activity by metformin enhances the antidiabetic effects of glucagon-like peptide-1
Eur. J. Pharmacol.
547
192-199
2006
Mus musculus
Yasuda, N.; Nagakura, T.; Inoue, T.; Yamazaki, K.; Katsutani, N.; Takenaka, O.; Clark, R.; Matsuura, F.; Emori, E.; Yoshikawa, S.; Kira, K.; Ikuta, H.; Okada, T.; Saeki, T.; Asano, O.; Tanaka, I.
E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor
Eur. J. Pharmacol.
548
181-187
2006
Canis lupus familiaris, Homo sapiens, Mus musculus
Green, B.D.; Flatt, P.R.; Bailey, C.J.
Inhibition of dipeptidylpeptidase IV activity as a therapy of type 2 diabetes
Expert. Opin. Emerg. Drugs
11
525-539
2006
Homo sapiens, Mus musculus, Rattus norvegicus
Campbell, T.B.; Broxmeyer, H.E.
CD26 inhibition and hematopoiesis: a novel approach to enhance transplantation
Front. Biosci.
13
1795-1805
2008
Homo sapiens, Mus musculus
Preller, V.; Gerber, A.; Wrenger, S.; Togni, M.; Marguet, D.; Tadje, J.; Lendeckel, U.; Roecken, C.; Faust, J.; Neubert, K.; Schraven, B.; Martin, R.; Ansorge, S.; Brocke, S.; Reinhold, D.
TGF-beta1-mediated control of central nervous system inflammation and autoimmunity through the inhibitory receptor CD26
J. Immunol.
178
4632-4640
2007
Mus musculus
Pissurlenkar, R.R.; Shaikh, M.S.; Coutinho, E.C.
3D-QSAR studies of dipeptidyl peptidase IV inhibitors using a docking based alignment
J. Mol. Model.
13
1047-1071
2007
Mus musculus, Homo sapiens (P27487)
Yamazaki, K.; Yasuda, N.; Inoue, T.; Yamamoto, E.; Sugaya, Y.; Nagakura, T.; Shinoda, M.; Clark, R.; Saeki, T.; Tanaka, I.
Effects of the combination of a dipeptidyl peptidase IV inhibitor and an insulin secretagogue on glucose and insulin levels in mice and rats
J. Pharmacol. Exp. Ther.
320
738-746
2007
Mus musculus, Rattus norvegicus
Roy, S.; Khanna, V.; Mittra, S.; Dhar, A.; Singh, S.; Mahajan, D.C.; Priyadarsiny, P.; Davis, J.A.; Sattigeri, J.; Saini, K.S.; Bansal, V.S.
Combination of dipeptidylpeptidase IV inhibitor and low dose thiazolidinedione: preclinical efficacy and safety in db/db mice
Life Sci.
81
72-79
2007
Mus musculus
Ahren, B.; Winzell, M.S.; Wierup, N.; Sundler, F.; Burkey, B.; Hughes, T.E.
DPP-4 inhibition improves glucose tolerance and increases insulin and GLP-1 responses to gastric glucose in association with normalized islet topography in mice with beta-cell-specific overexpression of human islet amyloid polypeptide
Regul. Pept.
143
97-103
2007
Mus musculus
Matsuyama-Yokono, A.; Tahara, A.; Nakano, R.; Someya, Y.; Nagase, I.; Hayakawa, M.; Shibasaki, M.
ASP8497 is a novel selective and competitive dipeptidyl peptidase-IV inhibitor with antihyperglycemic activity
Biochem. Pharmacol.
76
98-107
2008
Canis lupus familiaris, Homo sapiens, Mus musculus, Rattus norvegicus
Ansorge, S.; Bank, U.; Heimburg, A.; Helmuth, M.; Koch, G.; Tadje, J.; Lendeckel, U.; Wolke, C.; Neubert, K.; Faust, J.; Fuchs, P.; Reinhold, D.; Thielitz, A.; Taeger, M.
Recent insights into the role of dipeptidyl aminopeptidase IV (DPIV) and aminopeptidase N (APN) families in immune functions
Clin. Chem. Lab. Med.
47
253-261
2009
Mus musculus
Kim, S.J.; Nian, C.; Doudet, D.J.; McIntosh, C.H.
Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice
Diabetes
57
1331-1339
2008
Mus musculus
Kim, S.J.; Nian, C.; Doudet, D.J.; McIntosh, C.H.
Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation
Diabetes
58
641-651
2009
Mus musculus, Mus musculus NOD/LtJ
Moritoh, Y.; Takeuchi, K.; Asakawa, T.; Kataoka, O.; Odaka, H.
Chronic administration of alogliptin, a novel, potent, and highly selective dipeptidyl peptidase-4 inhibitor, improves glycemic control and beta-cell function in obese diabetic ob/ob mice
Eur. J. Pharmacol.
588
325-332
2008
Mus musculus
Moritoh, Y.; Takeuchi, K.; Asakawa, T.; Kataoka, O.; Odaka, H.
The dipeptidyl peptidase-4 inhibitor alogliptin in combination with pioglitazone improves glycemic control, lipid profiles, and increases pancreatic insulin content in ob/ob mice
Eur. J. Pharmacol.
602
448-454
2009
Mus musculus
Tahara, A.; Matsuyama-Yokono, A.; Nakano, R.; Someya, Y.; Hayakawa, M.; Shibasaki, M.
Effects of the combination of dipeptidyl peptidase-IV inhibitor ASP8497 and antidiabetic drugs in streptozotocin-nicotinamide-induced mildly diabetic mice
Eur. J. Pharmacol.
605
170-176
2009
Mus musculus
Connolly, B.A.; Sanford, D.G.; Chiluwal, A.K.; Healey, S.E.; Peters, D.E.; Dimare, M.T.; Wu, W.; Liu, Y.; Maw, H.; Zhou, Y.; Li, Y.; Jin, Z.; Sudmeier, J.L.; Lai, J.H.; Bachovchin, W.W.
Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety
J. Med. Chem.
51
6005-6013
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Fuchs, H.; Tillement, J.P.; Urien, S.; Greischel, A.; Roth, W.
Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans
J. Pharm. Pharmacol.
61
55-62
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Thomas, L.; Eckhardt, M.; Langkopf, E.; Tadayyon, M.; Himmelsbach, F.; Mark, M.
(R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with oth
J. Pharmacol. Exp. Ther.
325
175-182
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Cheng, Q.; Law, P.K.; de Gasparo, M.; Leung, P.S.
Combination of the dipeptidyl peptidase IV inhibitor LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] with the angiotensin II type 1 receptor antagonist valsartan [N-(1-oxopentyl)-N-[[2-(1H-tetrazol-5-yl)-[1,1-biphenyl]-4-yl]methyl]-L-valine ] enhances pancreatic islet morphology and function in a mouse model of type 2 diabetes
J. Pharmacol. Exp. Ther.
327
683-691
2008
Mus musculus
Kuehlmann, U.C.; Chwieralski, C.E.; van den Brule, S.; Roecken, C.; Reinhold, D.; Welte, T.; Buehling, F.
Modulation of cytokine production and silica-induced lung fibrosis by inhibitors of aminopeptidase N and of dipeptidyl peptidase-IV-related proteases
Life Sci.
84
1-11
2009
Homo sapiens, Mus musculus
Liu, X.; Harada, N.; Yamane, S.; Kitajima, L.; Uchida, S.; Hamasaki, A.; Mukai, E.; Toyoda, K.; Yamada, C.; Yamada, Y.; Seino, Y.; Inagaki, N.
Effects of long-term dipeptidyl peptidase-IV inhibition on body composition and glucose tolerance in high fat diet-fed mice
Life Sci.
84
876-881
2009
Mus musculus
Matsuyama-Yokono, A.; Tahara, A.; Nakano, R.; Someya, Y.; Shiraki, K.; Hayakawa, M.; Shibasaki, M.
Antidiabetic effects of dipeptidyl peptidase-IV inhibitors and sulfonylureas in streptozotocin-nicotinamide-induced mildly diabetic mice
Metab. Clin. Exp.
58
379-386
2009
Mus musculus
Someya, Y.; Tahara, A.; Nakano, R.; Matsuyama-Yokono, A.; Nagase, I.; Fukunaga, Y.; Takasu, T.; Hayakawa, M.; Shibasaki, M.
Pharmacological profile of ASP8497, a novel, selective, and competitive dipeptidyl peptidase-IV inhibitor, in vitro and in vivo
Naunyn Schmiedebergs Arch. Pharmacol.
377
209-217
2008
Canis lupus familiaris, Homo sapiens, Mus musculus
Matsuyama-Yokono, A.; Tahara, A.; Nakano, R.; Someya, Y.; Hayakawa, M.; Shibasaki, M.
Chronic inhibition of dipeptidyl peptidase-IV with ASP8497 improved the HbA(1c) level, glucose intolerance, and lipid parameter level in streptozotocin-nicotinamide-induced diabetic mice
Naunyn Schmiedebergs Arch. Pharmacol.
379
191-199
2009
Mus musculus
Tahara, A.; Matsuyama-Yokono, A.; Nakano, R.; Someya, Y.; Hayakawa, M.; Shibasaki, M.
Evaluation of the antidiabetic effects of dipeptidyl peptidase-IV inhibitor ASP8497 in streptozotocin-nicotinamide-induced mildly diabetic mice
Pharmacology
83
177-187
2009
Mus musculus
Vora, K.; Porter, G.; Peng, R.; Cui, Y.; Pryor, K.; Eiermann, G.; Zaller, D.
Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses
BMC Immunol.
10
19
2009
Mus musculus
Reinhold, D.; Goihl, A.; Wrenger, S.; Reinhold, A.; Kuehlmann, U.C.; Faust, J.; Neubert, K.; Thielitz, A.; Brocke, S.; Taeger, M.; Ansorge, S.; Bank, U.
Role of dipeptidyl peptidase IV (DP IV)-like enzymes in T lymphocyte activation: investigations in DP IV/CD26-knockout mice
Clin. Chem. Lab. Med.
47
268-274
2009
Mus musculus
Sato, K.; Nakamura, A.; Shirakawa, J.; Muraoka, T.; Togashi, Y.; Shinoda, K.; Orime, K.; Kubota, N.; Kadowaki, T.; Terauchi, Y.
Impact of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance and beta-cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet
Endocrinology
153
1093-1102
2012
Mus musculus (P28843)
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