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Information on EC 3.4.11.3 - cystinyl aminopeptidase and Organism(s) Homo sapiens
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3.4.11.3 cystinyl aminopeptidaseSpecify your search results
Word Map
- 3.4.11.3
- envelope
- pregnancy
- cd4
- epitope
- lymphocyte
- angiotensin
- vaccinia
- viruses
- women
- aminopeptidases
-
hiv-1-infected
-
humoral
- t-cells
- virion
-
simian
- macaque
-
hiv-specific
-
immunodominant
- nef
- seroconversion
- chimpanzee
-
anti-hiv-1
-
seronegative
- insipidus
-
syncytium
-
prime-boost
- furin
-
vaccinees
-
seropositive
-
vaccine-induced
-
glut4-containing
-
hiv-seronegative
- desmopressin
- shiv
-
ddavp
-
hiv-1iiib
-
anti-cd4
-
intrarectal
-
sivmac239
- medicine
-
alum
-
seroconverted
-
1-infected
-
non-neutralizing
- diagnostics
-
oligosaccharyltransferase
-
virus-neutralizing
-
cross-neutralizing
- pharmacology
-
coreceptors
-
cross-presentation
-
nephrogenic
-
radioimmunoprecipitation
The taxonomic range for the selected organisms is: Homo sapiens
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 amino acid, Cys-/-Xaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl arylamides exceed that for the cystinyl derivative, however
Synonyms
gp160, oxytocinase, p-lap, insulin-regulated aminopeptidase, vasopressinase, at4 receptor, cystine aminopeptidase, placental leucine aminopeptidase, otase, lnpep, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-Aminoacyl-peptide hydrolase
-
-
-
-
aminopeptidase, cystyl
-
-
-
-
CAP-I
-
-
-
-
CAP-II
-
-
-
-
cysteine aminopeptidase
-
-
-
-
cystine aminopeptidase
Cystinyl aminopeptidase
cystyl aminopeptidase
-
-
-
-
GP160
-
-
-
-
insulin-regulated aminopeptidase
Insulin-regulated membrane aminopeptidase
-
-
-
-
Insulin-responsive aminopeptidase
-
-
-
-
IRAP
L-cystine aminopeptidase
-
-
-
-
OTase
-
-
-
-
oxytocin peptidase
-
-
-
-
oxytocinase
P-LAP
Placental leucine aminopeptidase
placental leucine aminopeptidase/oxytocinase/insulin-regulated membrane aminopeptidase
-
-
vasopressinase
vasopresssinase
-
-
-
-
Vesicle protein of 165 kDa
-
-
-
-
Vp165
-
-
-
-
yscXVI
-
-
-
-
cystine aminopeptidase
-
-
-
-
Cystinyl aminopeptidase
-
-
-
-
IRAP
-
-
-
-
oxytocinase
-
-
-
-
P-LAP
-
-
-
-
Placental leucine aminopeptidase
-
-
-
-
Placental leucine aminopeptidase
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
9031-41-8
-
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
alpha-L-Asp1-Val5-angiotensin II + H2O
beta-Asp1-Val5-angiotensin II
-
transformation to beta form
-
ir
Arg-4-methylcoumaryl-7-amide + H2O
Arg + 7-amino-4-methylcoumarin
-
-
-
?
L-arginine-7-amido-4-methylcoumarin + H2O
L-arginine + 7-amino-4-methylcoumarin
-
-
-
?
L-benzyl-L-cysteine-p-nitroanilide + H2O
L-benzyl-L-cysteine + p-nitroaniline
-
-
-
-
?
L-leucine-7-amido-4-methylcoumarin + H2O
L-leucine + 7-amino-4-methylcoumarin
-
-
-
?
LGGGGGL + H2O
L-Leu + GGGGGL
hydrolysis of poly-glycine peptides, overview
-
-
?
Lys-4-methylcoumaryl-7-amide + H2O
Lys + 7-amino-4-methylcoumarin
-
-
-
?
Met-4-methylcoumaryl-7-amide + H2O
Met + 7-amino-4-methylcoumarin
-
-
-
?
Peptides + H2O
?
-
enzyme plays a role in general metabolism of peptides during pregnancy
-
-
?
S-benzyl-Cys-4-methylcoumaryl-7-amide + H2O
S-benzyl-Cys + 7-amino-4-methylcoumarin
-
-
-
?
S-benzyl-cysteine-4-methylcoumarin 7-amide + H2O
S-benzyl-cysteine + 7-amino-4-methylcoumarin
-
-
-
-
?
S-benzyl-L-cysteine-p-nitroanilide + H2O
S-benzyl-L-cysteine + p-nitroaniline
-
-
-
-
?
angiotensin III + H2O
?
-
P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as oxytocin and vasopressin
-
-
?
angiotensin III + H2O
?
-
the enzyme plays a role in blood pressure regulation via hydrolyzing vasopressin and angiotensin III
-
-
?
Leu-4-methylcoumaryl-7-amide + H2O
Leu + 7-amino-4-methylcoumarin
-
-
-
?
oxytocin + H2O
?
-
in the placenta the enzyme is thought to play a role in the prevention of premature labour and maintenance of an adequate blood flow to the uterus
-
-
?
oxytocin + H2O
?
-
P-LAP in HUVEC cells regulates effects of oxytocin with resolution
-
-
?
oxytocin + H2O
?
-
cleavage sites: Cys-/-Tyr-/-Ile-/-Gln-/-Asn-/-Cys-Pro-Leu-Gly-NH2
-
-
?
oxytocin + H2O
?
-
cleavage sites: Cys-/-Tyr-/-Phe-/-Gln-Asn-Cys-Pro-Arg-Gly-NH2
-
-
?
oxytocin + H2O
acyclic peptide + H2O
-
-
tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-(S-cysteine)cysteinyl-prolyl-leucyl-glycinamide, first product
?
oxytocin + H2O
acyclic peptide + H2O
-
cleavage of bond between N-terminal cysteine and adjacent tyrosine
-
-
?
Vasopressin + H2O
?
-
P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as oxytocin and vasopressin
-
-
?
Vasopressin + H2O
?
-
the enzyme plays a role in blood pressure regulation via hydrolyzing vasopressin and angiotensin III
-
-
?
additional information
?
-
-
peptides having proline as the second amino acid residue
-
-
?
additional information
?
-
-
peptides having proline as the second amino acid residue
-
-
?
additional information
?
-
-
peptides having proline as the second amino acid residue
-
-
?
additional information
?
-
-
not: L-Asp-beta-naphthylamide, L-Glu-beta-naphthylamide
-
-
?
additional information
?
-
-
hydrolyses neutral, aromatic, basic and acidic N-terminal amino acids from peptides
-
-
?
additional information
?
-
-
N-terminal aspartic acid bound via its beta-carboxyl group in a peptide bond
-
-
?
additional information
?
-
-
N-terminal aspartic acid bound via its beta-carboxyl group in a peptide bond
-
-
?
additional information
?
-
-
in individuals with type 2 diabetes the insulin-stimulated translocation of IRAP to the cell-surface of muscle and fat cells is impaired. This defect may lead to decreased cleavage and consequently increased action of peptide hormones that are substrates for IRAP. Impaiered IRAP action may thus play a role in the development of complications in type 2 diabetes
-
-
?
additional information
?
-
-
involvement of the enzyme in memory processing. AT4 ligands, upon binding to the catalytic site of insulin-regulated aminopeptidase, enhance spatial learning, facilitate memory retention and retrieval and reverse amnesia
-
-
?
additional information
?
-
-
vasopressinase cannot degrade 1-deamino-8D-arginine vasopressin
-
-
?
additional information
?
-
no activity with 1-deamino-8-D-arginine vasopressin
-
-
?
additional information
?
-
-
no activity with 1-deamino-8-D-arginine vasopressin
-
-
?
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
Peptides + H2O
?
-
enzyme plays a role in general metabolism of peptides during pregnancy
-
-
?
angiotensin III + H2O
?
-
P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as oxytocin and vasopressin
-
-
?
angiotensin III + H2O
?
-
the enzyme plays a role in blood pressure regulation via hydrolyzing vasopressin and angiotensin III
-
-
?
oxytocin + H2O
?
-
in the placenta the enzyme is thought to play a role in the prevention of premature labour and maintenance of an adequate blood flow to the uterus
-
-
?
oxytocin + H2O
?
-
P-LAP in HUVEC cells regulates effects of oxytocin with resolution
-
-
?
Vasopressin + H2O
?
-
P-LAP/OTase may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as oxytocin and vasopressin
-
-
?
Vasopressin + H2O
?
-
the enzyme plays a role in blood pressure regulation via hydrolyzing vasopressin and angiotensin III
-
-
?
additional information
?
-
-
in individuals with type 2 diabetes the insulin-stimulated translocation of IRAP to the cell-surface of muscle and fat cells is impaired. This defect may lead to decreased cleavage and consequently increased action of peptide hormones that are substrates for IRAP. Impaiered IRAP action may thus play a role in the development of complications in type 2 diabetes
-
-
?
additional information
?
-
no activity with 1-deamino-8-D-arginine vasopressin
-
-
?
additional information
?
-
-
no activity with 1-deamino-8-D-arginine vasopressin
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Zinc
Zn2+
Zinc
-
contains the characteristic Zn2+-coordination sequence element, HEXXH-(18-64X)-E
Zinc
-
enzyme contains 1 mol of zinc per mol of enzyme, contains the consensus HEXXH(X)18E motif of zinc-metallopeptidase proteins
Zn2+
insulin-regulated aminopeptidase (IRAP) is a membrane-bound zinc metallopeptidase
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]phenyl)acetic acid
-
-
(2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]phenyl)acetic acid
-
-
(2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]phenyl)acetic acid
-
-
(2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-leucyl)amino]methyl]phenyl)acetic acid
-
-
(2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]phenyl)acetic acid
-
-
(2-[[(N-[[3-amino-5-(4-hydroxybenzyl)phenyl]carbonyl]-L-isoleucyl)amino]methyl]phenyl)acetic acid
-
-
1,2-Acyclic oxytocin
-
slight inhibition of oxytocin degradation, marked inhibition of cystine di-beta-naphthylamide degradation
2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]benzoic acid
-
-
2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]benzoic acid
-
-
2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]benzoic acid
-
-
2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-leucyl)amino]methyl]benzoic acid
-
-
2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]benzoic acid
-
-
4-bromo-2,6-difluoro-N-[3-(1H-tetrazol-5-yl)phenyl]benzene-1-sulfonamide
-
4-bromo-5-chloro-N-methyl-N-[3-(1H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide
-
4-bromo-5-chloro-N-[3-(1-methyl-1H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide
-
7-chloro-N-[3-(1H-tetrazol-5-yl)phenyl]-2,1,3-benzoxadiazole-4-sulfonamide
-
benzyl N-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tryptophanate
-
benzyl N-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-valinate
-
benzyl N-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tryptophanate
-
benzyl N-[3-amino-4-([(2S)-2-amino-4-[4-(benzyloxy)phenyl]butanoyl]amino)benzoyl]-L-tryptophanate
-
benzyl N-[3-amino-4-[(O-benzyl-L-tyrosyl)amino]benzoyl]-L-tryptophanate
-
benzyl N-[4-amino-3-[(O-benzyl-L-tyrosyl)amino]benzoyl]-L-tryptophanate
-
cyclohexylmethyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
ethyl 2,7-diamino-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
ethyl 2-acetamido-7-hydroxy-4-(3-quinolinyl)-4H-chromene-3-carboxylate
HFI-437
ethyl 2-amino-4-(2,4-dichloropyridin-3-yl)-7-hydroxy-4H-chromene-3-carboxylate
-
-
ethyl 2-amino-4-(5,8-dihydroquinolin-2-yl)-7-hydroxy-4H-chromene-3-carboxylate
-
-
ethyl 2-amino-4-[4-(dimethylamino)phenyl]-7-hydroxy-4H-chromene-3-carboxylate
-
-
ethyl 2-amino-6-bromo-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
ethyl 2-amino-7-(dimethylamino)-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
ethyl 2-amino-7-(formyloxy)-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
ethyl 2-amino-7-hydroxy-4-(1,3-thiazol-2-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
ethyl 2-amino-7-hydroxy-4-(thiophen-2-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
ethyl 2-amino-7-hydroxy-4-[4-(pyridin-2-yl)phenyl]-4H-chromene-3-carboxylate
-
-
ethyl 2-amino-7-methoxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
50% inhibition at 100 microM
L-Arg-vasopressin
-
Ki-value for wild-type, mutants G428E, G428D, G428Q above 0.03 mM
L-Val-L-Tyr-L-Ile-2-aminomethylphenylacetic acid
-
inhibits both IRAP and aminopeptidase N and induces proliferation of stem cells at low concentrations
L-Val-L-Tyr-L-Ile-L-Cys-L-Pro-L-Cys
-
cyclic disulfide, angiotensin IV analog, considerably more stable than angiotensin IV toward enzymatic degradation
methyl 4-amino-3-([(2S)-2-amino-4-[4-(benzyloxy)phenyl]butanoyl]amino)benzoate
-
methyl 4-amino-3-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoate
-
methyl N-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tyrosinate
-
methyl N-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tyrosinate
-
methyl N2-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-argininate
-
methyl N2-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-lysinate
-
methyl N2-(4-amino-3-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoyl)-L-lysinate
-
methyl N2-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-lysinate
-
methyl N2-[4-amino-3-([(2S)-2-amino-4-[4-(benzyloxy)phenyl]butanoyl]amino)benzoyl]-L-lysinate
-
N-(3-(1H-tetrazol-5-yl)phenyl)-2,5-bis(trifluoromethyl)-benzenesulfonamide
-
N-(3-(1H-tetrazol-5-yl)phenyl)-2-fluoro-5-(trifluoromethyl)benzenesulfonamide
-
N-(3-(1H-tetrazol-5-yl)phenyl)-3,5-bis(trifluoromethyl)-benzenesulfonamide
-
N-(3-(1H-tetrazol-5-yl)phenyl)-3-fluoro-4-(trifluoromethyl)benzenesulfonamide
-
N-(3-(1H-tetrazol-5-yl)phenyl)-3-methyl-4-(trifluoromethyl)benzenesulfonamide
-
N-(3-(1H-tetrazol-5-yl)phenyl)-4-methyl-3-(trifluoromethyl)benzenesulfonamide
-
N-(3-amino-4-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoyl)-L-tryptophan
-
N-(4-amino-3-[[(2R)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoyl)-L-tryptophan
-
N-hexanoyl-L-Tyr-L-Ile
a dipeptide derivative from Ang IV, a strong cognitive enhancer and enzyme inhibitor
N-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine
-
-
N2-(2- 8[(1-amino-3-phenylpropyl)(hydroxy)phosphoryl]methyl]-4-methylpentanoyl)-L-lysyl-L-histidyl-L-histidyl-L-alanyl-L-phenylalanyl-L-seryl-L-phenylalanyl-L-lysine
i.e. DG025, an antigenic peptide precursor analogue, enzyme binding structure determination and analysis. The canonical orientation of the two N-terminal residues of DG025 is defined by the transition state nature of the ligand and the hydrophobic and aromatic interactions of the hPhe residue in the S1 specificity pocket of the enzyme (and in particular with Phe544). The remaining of the peptide extends toward the base of the cavity, where it is sandwiched between domains II and IV
N2-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-ornithine
-
[(5R)-6-amino-5-benzyl-2-(2,2-diphenylethyl)-3,6-dioxohexyl][(1R)-1-amino-3-phenylpropyl]phosphinic acid
i.e. DG026, a phosphinic pseudotripeptide that acts as very potent inhibitor of IRAP. DG026 is able to selectively downregulate IRAP-dependent cross-presentation by dendritic cells but leave ERAP1-dependent cross-presentation unaffected. Enzyme binding structure determination and analysis, overview
[2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromen-3-yl](phenyl)methanone
-
50% inhibition at 100 microM
[2-[([[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]amino)methyl]phenyl]acetic acid
-
-
[2-[([[3-amino-5-(4-hydroxybenzyl)phenyl]carbonyl]amino)methyl]phenyl]acetic acid
-
-
L-Val-L-Tyr-L-Ile-L-His-L-Pro-L-Phe
-
i.e. angiotensin IV, adopts a gamma-turn in the C-terminal of its bioactive conformation
additional information
-
inhibitory potency in decreasing order: angiotensin IV, angiotensin III, divalinal/angiotensin IV, LVV-hemorphin 7, angiotensin 4-8, angiotensin III
-
additional information
inhibition of insulin-regulated aminopeptidase (IRAP) by aryl sulfonamides, structural basis, docking and moelling, molecular dynamics simulations, overview. The fluorinated series exhibit high metabolic stability in microsomes and encompasses compounds with submicromolar affinity. The binding modes are thoroughly examined by molecular dynamics (MD)-related methods for binding affinity estimation for the whole series of aryl sulfonamides
-
additional information
-
inhibition of insulin-regulated aminopeptidase (IRAP) by aryl sulfonamides, structural basis, docking and moelling, molecular dynamics simulations, overview. The fluorinated series exhibit high metabolic stability in microsomes and encompasses compounds with submicromolar affinity. The binding modes are thoroughly examined by molecular dynamics (MD)-related methods for binding affinity estimation for the whole series of aryl sulfonamides
-
additional information
virtual screening from three-dimensional structure models for transition state analogue inhibitors of IRAP based on quantum mechanically derived reaction coordinates, overview. Transition state and high energy intermediate mimetics have the potential to be very potent enzyme inhibitors. Method development and evaluation
-
additional information
enzyme IRAP undergoes a conformational change upon inhibitor binding, docking study. Analysis of structural determinants for inhibitor selectivity, overview. Significant affinity is generated by structural elements common to all homologous enzymes: the active-site Zn(II) atom, the catalytic Tyr549 and Glu465, N-terminus recognition by Glu295, Glu431, and Glu487, and the S1 specificity residue Phe544
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0033
(2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]phenyl)acetic acid
-
-
0.0074
(2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]phenyl)acetic acid
-
-
0.0014
(2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]phenyl)acetic acid
-
-
0.0039
(2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-leucyl)amino]methyl]phenyl)acetic acid
-
-
0.0013
(2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]phenyl)acetic acid
-
-
97
(2-[[(N-[[3-amino-5-(4-hydroxybenzyl)phenyl]carbonyl]-L-isoleucyl)amino]methyl]phenyl)acetic acid
-
-
0.05
2-amino-4-(3,4-dimethoxyphenyl)-7-hydroxy-4H-chromene-3-carbonitrile
-
pH 7.4, 37°C
0.1
2-amino-4-(3,5-dimethoxyphenyl)-7-hydroxy-4H-chromene-3-carbonitrile
-
value above, pH 7.4, 37°C
0.1
2-amino-4-[4-(dimethylamino)phenyl]-7-hydroxy-4H-chromene-3-carbonitrile
-
value above, pH 7.4, 37°C
0.1
2-amino-7-hydroxy-4-(3,4,5-trimethoxyphenyl)-4H-chromene-3-carbonitrile
-
value above, pH 7.4, 37°C
0.1
2-amino-7-hydroxy-4-(3-methoxyphenyl)-4H-chromene-3-carbonitrile
-
value above, pH 7.4, 37°C
0.1
2-amino-7-hydroxy-4-(4-methoxyphenyl)-4H-chromene-3-carbonitrile
-
value above, pH 7.4, 37°C
0.1
2-amino-7-hydroxy-4-(pyridin-4-yl)-4H-chromene-3-carbonitrile
-
value above, pH 7.4, 37°C
0.004
2-methoxyethyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0063
2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]benzoic acid
-
-
0.012
2-[[(1-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-prolyl)amino]methyl]benzoic acid
-
-
0.0018
2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]benzoic acid
-
-
0.0037
2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-norleucylamino)phenyl]carbonyl]-L-leucyl)amino]methyl]benzoic acid
-
-
0.0013
2-[[(N-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-isoleucyl)amino]methyl]benzoic acid
-
-
0.00006
angiotensin IV
-
in 50 mM Tris-HCl (pH 7.4), 140 mM NaCl, 0.1% (w/v) bovine serum albumin, and 0.1 mM phenylmethylsulfonyl fluoride, at 37°C
0.0017
benzyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0026
butyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.00048
ethyl 2-(acetylamino)-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.00003
ethyl 2-(acetylamino)-7-hydroxy-4-(quinolin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.014
ethyl 2-amino-4-(2,4-dichloropyridin-3-yl)-7-hydroxy-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.1
ethyl 2-amino-4-(2-cyanophenyl)-7-hydroxy-4H-chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.0062
ethyl 2-amino-4-(3,4-dimethoxyphenyl)-7-hydroxy-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.035
ethyl 2-amino-4-(3-chlorophenyl)-7-hydroxy-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0032
ethyl 2-amino-4-(3-cyanophenyl)-7-hydroxy-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.1
ethyl 2-amino-4-(4-bromophenyl)-7-hydroxy-4H-chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.1
ethyl 2-amino-4-(4-chlorophenyl)-7-hydroxy-4H-chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.011
ethyl 2-amino-4-(4-cyanophenyl)-7-hydroxy-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.003
ethyl 2-amino-4-(5,8-dihydroquinolin-2-yl)-7-hydroxy-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.1
ethyl 2-amino-4-(pyridin-3-yl)-4H-benzo[g]chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.1
ethyl 2-amino-4-(pyridin-3-yl)-4H-benzo[h]chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.0053
ethyl 2-amino-4-[4-(dimethylamino)phenyl]-7-hydroxy-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0056
ethyl 2-amino-6-chloro-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.042
ethyl 2-amino-7-hydroxy-4-(2-nitrophenyl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.1
ethyl 2-amino-7-hydroxy-4-(4-methylphenyl)-4H-chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.0077
ethyl 2-amino-7-hydroxy-4-(4-nitrophenyl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0029
ethyl 2-amino-7-hydroxy-4-(pyridin-2-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0018
ethyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0037
ethyl 2-amino-7-hydroxy-4-(pyridin-4-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.00036
ethyl 2-amino-7-hydroxy-4-(quinolin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0009
ethyl 2-amino-7-hydroxy-4-(quinolin-4-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.1
ethyl 2-amino-7-hydroxy-4-phenyl-4H-chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.1
ethyl 2-amino-7-hydroxy-4-[4-(pyridin-2-yl)phenyl]-4H-chromene-3-carboxylate
-
value above, pH 7.4, 37°C
0.0098
ethyl 2-amino-8-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0049
methyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0012
N-[[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine
-
-
0.0016
propyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
0.0119
tert-butyl 2-amino-7-hydroxy-4-(pyridin-3-yl)-4H-chromene-3-carboxylate
-
pH 7.4, 37°C
16
[2-[([[3-(4-hydroxybenzyl)-5-(L-valylamino)phenyl]carbonyl]amino)methyl]phenyl]acetic acid
-
-
35
[2-[([[3-amino-5-(4-hydroxybenzyl)phenyl]carbonyl]amino)methyl]phenyl]acetic acid
-
-
additional information
additional information
inhibition kinetics and thermodynamics
-
additional information
additional information
-
inhibition kinetics and thermodynamics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.034
4-amino-3-(L-arginylamino)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.01
4-amino-3-(L-tyrosylamino)benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.01
4-amino-3-[(O-benzyl-L-tyrosyl)amino]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0024
benzyl N-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.014
benzyl N-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-valinate
Homo sapiens
pH and temperature not specified in the publication
0.0013
benzyl N-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.0037
benzyl N-[3-amino-4-(L-leucylamino)benzoyl]-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.000438
benzyl N-[3-amino-4-(L-norleucylamino)benzoyl]-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.0039
benzyl N-[3-amino-4-(L-norleucylamino)benzoyl]-L-valinate
Homo sapiens
pH and temperature not specified in the publication
0.0034
benzyl N-[3-amino-4-([(2S)-2-amino-4-[4-(benzyloxy)phenyl]butanoyl]amino)benzoyl]-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.0038
benzyl N-[3-amino-4-[(O-benzyl-L-tyrosyl)amino]benzoyl]-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.001
benzyl N-[4-amino-3-(D-norleucylamino)benzoyl]-L-valinate
Homo sapiens
pH and temperature not specified in the publication
0.000105
benzyl N-[4-amino-3-(L-norleucylamino)benzoyl]-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.0071
benzyl N-[4-amino-3-(L-tyrosylamino)benzoyl]-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.012
benzyl N-[4-amino-3-(L-tyrosylamino)benzoyl]-L-valinate
Homo sapiens
pH and temperature not specified in the publication
0.000933
benzyl N-[4-amino-3-[(O-benzyl-L-tyrosyl)amino]benzoyl]-L-tryptophanate
Homo sapiens
pH and temperature not specified in the publication
0.0396
methyl 3-amino-4-(L-arginylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.0033
methyl 3-amino-4-(L-norleucylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.0083
methyl 3-amino-4-(L-tyrosylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.0017
methyl 3-amino-4-[(O-benzyl-L-tyrosyl)amino]benzoate
Homo sapiens
pH and temperature not specified in the publication
0.031
methyl 3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoate
Homo sapiens
pH and temperature not specified in the publication
0.014
methyl 4-amino-3-(L-arginylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.0072
methyl 4-amino-3-(L-norleucylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.057
methyl 4-amino-3-(L-tyrosylamino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.0021
methyl 4-amino-3-([(2S)-2-amino-4-[4-(benzyloxy)phenyl]butanoyl]amino)benzoate
Homo sapiens
pH and temperature not specified in the publication
0.01
methyl 4-amino-3-[(O-benzyl-L-tyrosyl)amino]benzoate
Homo sapiens
pH and temperature not specified in the publication
0.012
methyl 4-amino-3-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoate
Homo sapiens
pH and temperature not specified in the publication
0.0013
methyl N-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.0036
methyl N-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.0022
methyl N-[3-amino-4-(L-arginylamino)benzoyl]-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.0036
methyl N-[3-amino-4-(L-norleucylamino)benzoyl]-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.0037
methyl N-[3-amino-4-(L-tyrosylamino)benzoyl]-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.0029
methyl N-[3-amino-4-[(O-benzyl-L-tyrosyl)amino]benzoyl]-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.0012
methyl N-[4-amino-3-(D-norleucylamino)benzoyl]-D-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.000966
methyl N-[4-amino-3-(L-arginylamino)benzoyl]-D-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.1
methyl N-[4-amino-3-(L-tyrosylamino)benzoyl]-L-threoninate
Homo sapiens
pH and temperature not specified in the publication
0.022
methyl N-[4-amino-3-(L-tyrosylamino)benzoyl]-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
0.0025
methyl N2-(3,4-diaminobenzoyl)-L-argininate
Homo sapiens
pH and temperature not specified in the publication
0.1
methyl N2-(3,4-diaminobenzoyl)-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.0047
methyl N2-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-argininate
Homo sapiens
pH and temperature not specified in the publication
0.02
methyl N2-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.0107
methyl N2-(4-amino-3-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoyl)-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.01
methyl N2-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.0049
methyl N2-[3-amino-4-(L-arginylamino)benzoyl]-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.1
methyl N2-[3-amino-4-(L-leucylamino)benzoyl]-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.0357
methyl N2-[3-amino-4-(L-norleucylamino)benzoyl]-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.07
methyl N2-[3-amino-4-(L-tyrosylamino)benzoyl]-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.031
methyl N2-[4-amino-3-(L-norleucylamino)benzoyl]-D-argininate
Homo sapiens
pH and temperature not specified in the publication
0.1
methyl N2-[4-amino-3-(L-norleucylamino)benzoyl]-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.0057
methyl N2-[4-amino-3-([(2S)-2-amino-4-[4-(benzyloxy)phenyl]butanoyl]amino)benzoyl]-L-lysinate
Homo sapiens
pH and temperature not specified in the publication
0.1
N-(3,4-diaminobenzoyl)-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.0052
N-(3-amino-4-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoyl)-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.02
N-(3-amino-4-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-valine
Homo sapiens
pH and temperature not specified in the publication
0.0044
N-(4-amino-3-[[(2R)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]benzoyl)-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.0076
N-[3-amino-4-(L-arginylamino)benzoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.0017
N-[3-amino-4-(L-norleucylamino)benzoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.1
N-[3-amino-4-(L-norleucylamino)benzoyl]-L-valine
Homo sapiens
pH and temperature not specified in the publication
0.0013
N-[3-amino-4-(L-tyrosylamino)benzoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.1
N-[4-amino-3-(D-norleucylamino)benzoyl]-L-valine
Homo sapiens
pH and temperature not specified in the publication
0.000655
N-[4-amino-3-(L-arginylamino)benzoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.0033
N-[4-amino-3-(L-arginylamino)benzoyl]-L-valine
Homo sapiens
pH and temperature not specified in the publication
0.000296
N-[4-amino-3-(L-norleucylamino)benzoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.1
N-[4-amino-3-(L-tyrosylamino)benzoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.1
N-[4-amino-3-(L-tyrosylamino)benzoyl]-L-valine
Homo sapiens
pH and temperature not specified in the publication
0.0000077
N2-(2- 8[(1-amino-3-phenylpropyl)(hydroxy)phosphoryl]methyl]-4-methylpentanoyl)-L-lysyl-L-histidyl-L-histidyl-L-alanyl-L-phenylalanyl-L-seryl-L-phenylalanyl-L-lysine
Homo sapiens
pH 7.0, 37°C, recombinant wild-type enzyme
0.1
N2-(4-amino-3-[[(2S)-2-amino-4-phenylbutanoyl]amino]benzoyl)-L-ornithine
Homo sapiens
pH and temperature not specified in the publication
0.0041
N2-[4-amino-3-(L-leucylamino)benzoyl]-L-lysine
Homo sapiens
pH and temperature not specified in the publication
0.0038
N2-[4-amino-3-(L-phenylalanylamino)benzoyl]-L-lysine
Homo sapiens
pH and temperature not specified in the publication
0.0048
N2-[4-amino-3-(L-tyrosylamino)benzoyl]-L-lysine
Homo sapiens
pH and temperature not specified in the publication
0.0099
methyl N-(3,4-diaminobenzoyl)-L-tyrosinate
Homo sapiens
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
-
pH 7.0: about 15% of activity maximum, pH 8.0: about 10% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
trophoblastic cell. Insulin induces enzyme expression in trophoblasts
-
P-LAP is detected in all clear-cell adenocarcinomas
-
P-LAP is detected in 15 of 17 endometrioid adenocarcinomas
-
P-LAP is detected in 13 of 14 mucinous adenocarcinomas
-
P-LAP is detected in 7 of 14 borderline tumors
-
tendency towards increased P-LAP expression with advancing grade is observed in serous adenocarcinomas
-
during normal pregnancy, enzyme activity in maternal serum gradually increases to the maximum at near term
-
type III integral membrane protein, converted to a soluble form existing in maternal serum by metalloproteases
-
P-LAP is an independent prognosticator of clinical outcome in patients with endometrial carcinoma. Assessment of the P-LAP status provides clinically useful prognostic information in patients with endometrial carcinoma
-
the enzyme is suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma
-
in the placenta the enzyme is thought to play a role in the prevention of premature labour and maintenance of an adequate blood flow to the uterus
-
predominantly expressed in differentiated trophoblasts, syncytiotrophoblasts
placental trophoblasts. Vasopressinase is proportional to placental weight
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
P-LAP is translocated from the cytosol to the plasma membrane by oxytocin stimulation in vascular endothelial cells and by vasopressin in renal cells
-
GLUT4-containing; defects in the intracellular trafficking of P-LAP/IRAP-containing GLUT4 vesicle are associated with type 2 diabetes
-
GLUT4-containing. Insulin-regulated aminopeptidase is a marker protein for specialized vesicles containing the insulin-responsive glucose transporter, GLUT4. The enzyme is thought to be involved in the tethering of GLUT4 vesicles to intracellular compartments
-
GLUT4-containing; the enzyme colocalizes with GLUT4 in specific intracellular vesicles
-
membrane-bound placental enzyme is released into maternal blood flow via proteolytic cleavage by metalloproteases and metalloproteinases
-
the soluble form present in maternal serum is converted from the membrane-bound form in placenta by an enzyme with metalloprotease activity by posttranslational proteolytic cleavage between Phe154 and Ala155. P-LAP is translocated from the cytosol to the plasma membrane by oxytocin stimulation in vascular endothelial cells and by vasopressin in renal cells
-
type III integral membrane protein, converted to a soluble form existing in maternal serum by metalloproteases
-
comparison of enzyme activity in membranes of COS-7 cells, HEK-293 cells, SK-N-MC cells, CHO-K1 cells and MDBK cells. Comparatively, CHO-K1 cells display the highest level of enzyme. In all cell types, the enzyme predominates over aminopeptidase N
insulin-regulated aminopeptidase (IRAP) is a membrane-bound zinc metallopeptidase
-
enzyme is enriched in low density microsome, and exhibits lower levels in high density microsomes. Co-localization with the vesicular marker VAMP2
-
-
insulin induces a translocation of the enzyme from GLUT4 vesicles to plasma membrane by increasing the recycling rate
-
translocated with GLUT4 to the plasma membrane unedr insulin stimulation
-
the soluble form present in maternal serum is converted from the membrane-bound form in placenta by an enzyme with metalloprotease activity
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
IRAP is a member of the oxytocinase subfamily of M1 aminopeptidases characterised by the presence of two key sequence motifs, the HEXXH zinc-binding and GXMEN substrate recognition sequences
malfunction
metabolism
physiological function
additional information
malfunction
diabetes insipidus (DI) is a rare complication of pregnancy occurring in pregnancy, it is associated with excessive vasopressinase activity, secreted by placental trophoblasts, which increases the rate of degradation of anti-diuretic hormone. It is responsive to synthetic desmopressin 1-deamino-8-D-arginine vasopressin as this form is not degraded by placental vasopressinase. Vasopressinase-induced diabetes insipidus is associated with pre-eclampsia
malfunction
peptide inhibitor DG026 is able to selectively downregulate IRAP-dependent cross-presentation by dendritic cells but leave ERAP1-dependent cross-presentation unaffected
metabolism
diabetes insipidus can manifest during pregnancy, induced by increased vasopressinase activity secreted by placental trophoblasts and usually manifests in the third trimester
metabolism
insulin-regulated aminopeptidase (IRAP) has many important regulatory functions
physiological function
aminopeptidases generate antigenic peptides influence immunodominance and adaptive cytotoxic immune responses. These enzymes efficiently process a vast number of different long peptide substrates. Insulin-regulated aminopeptidase prepares antigenic epitopes for crosspresentation in dendritic cells
physiological function
placental vasopressinase, expressed in placental trophoblasts, degrades endogenous anti-diuretic hormone (ADH) but not 1-deamino-8-D-arginine vasopressin (dDAVP), the synthetic form with a modified N-terminal, thereby allowing the resolution of symptoms with dDAVP administration
additional information
analysis of the structure of IRAP in an intermediate semi-close conformation, overview. Significant rearrangements of the GAMEN motif in IRAP are observed upon ligand binding, which couples to the transition between the original partially open and a new, fully closed conformation of the protein. Molecular dynamics simulations of IRAP focusing on local adaptation to the binding of a pseudopeptidic ligand
additional information
enzyme IRAP undergoes a conformational change upon inhibitor binding
additional information
modeling of peptide hydrolysis in the active site of insulin-regulated aminopeptidase (IRAP) developed using density functional theory calculations and the cluster approach
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). LCAP_HUMAN
1025
1
117349
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
280000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
the soluble form present in maternal serum is converted from the membrane-bound form in placenta by an enzyme with metalloprotease activity by posttranslational proteolytic cleavage between Phe154 and Ala155
side-chain modification
side-chain modification
-
sialic acid not necessary for enzymatic activity, essential to conformation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme free or in complex with inhibitory antigenic peptide precursor analogue N2-(2- 8[(1-amino-3-phenylpropyl)(hydroxy)phosphoryl]methyl]-4-methylpentanoyl)-L-lysyl-L-histidyl-L-histidyl-L-alanyl-L-phenylalanyl-L-seryl-L-phenylalanyl-L-lysine, sitting drop vapor diffusion, mixing of 100 nl of 10 mg/ml protein in 150 mM NaCl and 10 mM HEPES, pH 7.4, with 100 nl of crystallization solution containing 10% w/v PEG 4000, 20% v/v glycerol, 53.4 mM bicine, 46.6 mM Trizma base, pH 8.5, and 0.02 M each of sodium L-glutamate, DL-alanine, glycine, DL-lysine, and DL-serine, method optimization, X-ray diffraction structure determination and analysis at 3.31-3.37 A resolution, molecular replacement using the highly homologous ERAP1 open structure (PDB ID 3QNF) as a search model, and modelling
purified recombinant enzyme in complex with inhibitory peptide [(5R)-6-amino-5-benzyl-2-(2,2-diphenylethyl)-3,6-dioxohexyl][(1R)-1-amino-3-phenylpropyl]phosphinic acid, sitting drop vapor diffusion, mixing of 5 mg/ml protein in 150 mM NaCl, and 10 mM HEPES, pH 7.5, with 100 nl of crystallization solution containing 18.8% w/v PEG 20000, 37.6% v/v PEG monomethyl ether 500, 50.2 mM bicine, 43.8 mM Trizma base, pH 8.5, and 0.282 M of each of sodium fluoride, sodium bromide, and sodium iodide, 21°C, method optimization, X-ray diffraction structure determination and analysis at 2.53 A resolution, molecular replacement using the highly homologous aminopeptidase ERAP1 structure (PDB ID 2YD0) as a search model, and modelling
several crystal structures of enzyme IRAP in apo and ligand boudn states are available, PDB IDs 4P8Q, 4PJ6, 4Z7I, 5C97, and 5MJ6
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A429G
A6909T
naturally occuing mutation, polymorphism A609T interacts with the hinge domain III of IRAP, similarly to SNP K528R in ERAP1, which has been repeatedly validated for disease association and effects on activity. The A609T mutation leads to an almost 2fold reduction in activity compared to wild-type
G428A
-
the ratio of maximal velocity to Km-value is 90% of the value for the wild-type enzyme
G428D
-
80% of wild-type activity with L-Arg-vasopressin, no activity with L-Leu-enkephalin
G428E
-
50% of wild-type activity with L-Arg-vasopressin, no activity with L-Leu-enkephalin
G428Q
-
more than wild-type activity with L-Arg-vasopressin, less than 10% of wild-type activity with L-Leu-enkephalin
I166M
naturally occuing mutation, the I166M polymorphism is located in domain I of the enzyme at the interface with domain II and makes contact with loop 534-538 that is adjacent to the S1 pocket of the enzyme. The mutant enzyme activity is slightly reduced compared to the wild-type
M430I
-
the ratio of maximal velocity to Km-value is 6.2% of the value for the wild-type enzyme
M430K
-
the ratio of maximal velocity to Km-value is 3.3% of the value for the wild-type enzyme
additional information
A429G
-
the ratio of maximal velocity to Km-value is 75% of the value for the wild-type enzyme
additional information
-
endometrial adenocarcinoma A-MEC cells expressing the enzyme exhibit a significant growth-stimulatory effect compared with control. They have a remarkably high level of p85PI3K protein and show a higher degree of AKT phosphorylation by insulin stimulation
additional information
mapping and functional characterization of IRAP disease-associated singel-nucleotide polymorphisms, SNPs. Two coding single-nucleotide polymorphisms in IRAP have been associated with predisposition to the autoimmune diseases psoriasis and ankylosing spondylitis, namely rs2303138 coding for the A609T change and rs61752351 coding for the I166M change
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, 0.01 M potassium phosphate, pH 7.4, protein concentration 0.5 mg/ml, 6 months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Trichoplusia ni Hi5 cells by dialysis and nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene LNPEP, recombinant expression of His-tagged wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells and Trichoplusia ni Hi5 cells via the baculovirus transfection system
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
peptide inhibitor [(5R)-6-amino-5-benzyl-2-(2,2-diphenylethyl)-3,6-dioxohexyl][(1R)-1-amino-3-phenylpropyl]phosphinic acid is able to selectively downregulate IRAP-dependent cross-presentation by dendritic cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
development of stable second generation inhibitors of IRAP based on the AT4 ligands angiotensin IV or LVV-H7 may provide the opportunity for the development of therapeutics for memory loss in patients Altheimer's disease
medicine
-
P-LAP is an independent prognosticator of clinical outcome in patients with endometrial carcinoma. Assessment of the P-LAP status provides clinically useful prognostic information in patients with endometrial carcinoma
medicine
-
P-LAP is available for evaluation of avarian epithelial malignancy and also as target for molecular therapy
medicine
-
the enzyme is suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma
medicine
-
enzyme isoform IRAP is involved in increasing malignant potential of endometrial cancer mediated by insulin. Endometrial adenocarcinoma A-MEC cells expressing the enzyme exhibit a significant growth-stimulatory effect compared with control. They have a remarkably high level of p85PI3K protein and show a higher degree of AKT phosphorylation by insulin stimulation
medicine
-
marked decrease of membrane-bound cystinyl aminopeptidase activity in clear cell renal carcinoma cell, papillary renal carcinoma cell, and chromophobe renal carcinoma cell compared to surrounding non-tumor tissue. Minor and non-significant changes of enzyme activity in soluble fractions of carcinoma cells
medicine
-
plasma activities of cystinyl-, aspartyl-, and glutamyl-aminopeptidase are decreased by 39.4%, 24.9%, and 33.3%, respectively, in patients with Parkinson's disease
medicine
-
excessive activity of vasopressinase is probably responsible for gestational diabetes insipidus
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hanson, H.; Mannsfeldt, H.G.
Biochemische Beitraege zur Kenntnis der Serum-Oxytocinase
Nova Acta Leopold.
36
7-45
1971
Homo sapiens
-
Roy, A.C.; Sen, D.K.; Ratnam, S.S.
Fractionation and characterization of oxytocinases in human semen
J. Reprod. Fertil.
87
163-168
1989
Homo sapiens
Van Oudheusden, A.P.M.
Oxytocinase
Methods Enzym. Anal. , 3rd Ed. (Bergmeyer, H. U. , ed. )
5
15-20
1984
Homo sapiens
-
Roy, A.C.; Yeang, M.; Karim, S.M.M.
Inhibition of serum oxytocinase activity by prostaglandins
Prostaglandins Med.
6
577-587
1981
Homo sapiens
Sakura, H.; Lin, T.Y.; Doi, M.; Mizutani, S.; Kawashima, Y.
Purification and properties of ocytocinase, a metalloenzyme
Biochem. Int.
2
173-179
1981
Homo sapiens
-
Cornell, J.S.
Oxytocinase (L-cystine aminopeptidase) from term human placenta
Biochem. Int.
1
10-18
1980
Homo sapiens
-
Lampelo, S.; Vanha-Perttula, T.
Fractionation and characterization of cystine aminopeptidase (oxytocinase) and arylamidase of the human placenta
J. Reprod. Fertil.
56
285-296
1979
Homo sapiens
Hiwada, K.; Saeki-Yamaguchi, C.; Inaoka, Y.; Kokubu, T.
Cystine aminopeptidases from pregnancy serum and placenta
Biochem. Med.
20
296-304
1978
Homo sapiens
Ganguly, S.; Sarkar, D.; Ghosh, J.J.
Biochemical studies on oxytocinase activities of human endometrium, uterine fluid and plasma
Indian J. Med. Res.
66
43-48
1977
Homo sapiens
Sjoeholm, I.; Yman, L.
Degradation of oxytocin, lysine-vasopressin, angiotensin II and angiotensin-II-amide by oxytocinase (cystine aminopeptidase)
Acta Pharm. Suec.
4
65-76
1967
Homo sapiens
Yman, L.
Studies on human serum aminopeptidases
Acta Pharm. Suec.
7
75-86
1980
Homo sapiens
Sjoeholm, I.
Biochemical studies on oxytocin and oxytocinase
Acta Pharm. Suec.
4
81-96
1967
Homo sapiens
Appel, W.
Aminopeptidasen und Aminosaeurearylamidasen
Methods Enzym. Anal. , 3rd Ed. (Bergmeyer, H. U. , ed. )
1
987-1015
1974
Homo sapiens
-
Ferrier, B.M.; Hendrie, J.M.; Branda, L.A.
Plasma oxytocinase: the synthesis and biological properties of the first product of the degradation of oxytocin by this enzyme
Can. J. Biochem.
52
60-66
1974
Homo sapiens
Yamamoto, M.; Ishiura, S.; Sugita, H.
Chloride-activated cystine aminopeptidase: A new enzyme in human skeletal muscle
Biomed. Res.
9
11-19
1988
Homo sapiens
-
Itoh, C.; Watanabe, M.; Nagamatsu, A.; Soeda, S.; Kawarabayashi, T.; Shimeno, H.
Two molecular species of oxytocinase (L-cystine aminopeptidase) in human placenta: purification and characterization
Biol. Pharm. Bull.
20
20-24
1997
Homo sapiens
Irons, D.W.; Davison, J.M.; Baylis, P.H.
Evaluation of enzyme inhibitors of cystinyl aminopeptidase and application to the measurement of immunoreactive atrial natriuretic peptide in human pregnancy
Clin. Chim. Acta
231
185-191
1994
Homo sapiens
Matsumoto, H.; Rogi, T.; Yamashiro, K.; Kodama, S.; Tsuruoka, N.; Hattori, A.; Takio, K.; Mizutani, S.; Tsujimoto, M.
Characterization of a recombinant soluble form of human placental leucine aminopeptidase/oxytocinase expressed in Chinese hamster ovary cells
Eur. J. Biochem.
267
46-52
2000
Homo sapiens
Laustsen, P.G.; Vang, S.; Kristensen, T.
Mutational analysis of the active site of human insulin-regulated aminopeptidase
Eur. J. Biochem.
268
98-104
2001
Homo sapiens
Mitsui, T.; Nomura, S.; Itakura, A.; Mizutani, S.
Role of aminopeptidases in the blood pressure regulation
Biol. Pharm. Bull.
27
768-771
2004
Homo sapiens
Nomura, S.; Ito, T.; Yamamoto, E.; Sumigama, S.; Iwase, A.; Okada, M.; Shibata, K.; Ando, H.; Ino, K.; Kikkawa, F.; Mizutani, S.
Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy
Biochim. Biophys. Acta
1751
19-25
2005
Homo sapiens
Tsujimoto, M.; Hattori, A.
The oxytocinase subfamily of M1 aminopeptidases
Biochim. Biophys. Acta
1751
9-18
2005
Homo sapiens, Rattus norvegicus
Keller, S.R.
Role of the insulin-regulated aminopeptidase IRAP in insulin action and diabetes
Biol. Pharm. Bull.
27
761-764
2004
Homo sapiens
Albiston, A.L.; Fernando, R.; Ye, S.; Peck, G.R.; Chai, S.Y.
Alzheimer's, angiotensin IV and an aminopeptidase
Biol. Pharm. Bull.
27
765-767
2004
Homo sapiens
Shibata, K.; Kikkawa, F.; Kondo, C.; Mizokami, Y.; Kajiyama, H.; Ino, K.; Nomura, S.; Mizutani, S.
Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma
Gynecol. Oncol.
95
307-313
2004
Homo sapiens
Shibata, K.; Kajiyama, H.; Mizokami, Y.; Ino, K.; Nomura, S.; Mizutani, S.; Terauchi, M.; Kikkawa, F.
Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia
Gynecol. Oncol.
98
11-18
2005
Homo sapiens
Nomura, S.; Tsujimoto, M.; Mizutani, S.
Cystinyl aminopeptidase, oxytocinase and insulin-regulated aminopeptidase
Handbook of proteolytic enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. ) Academic Press
1
307-311
2004
Homo sapiens, Rattus norvegicus
-
Sano, M.; Itakura, A.; Ito, M.; Takeuchi, M.; Okada, M.; Kotani, T.; Mizutani, S.; Kikkawa, F.
Placental leucine aminopeptidase might regulate the effects of oxytocin with resolution in endothelial cells
Med. Sci. Monit.
11
BR195-199
2005
Homo sapiens
Shibata, K.; Kikkawa, F.; Suzuki, Y.; Mizokami, Y.; Kajiyama, H.; Ino, K.; Nomura, S.; Nagasaka, T.; Mizutani, S.
Expression of placental leucine aminopeptidase is associated with a poor outcome in endometrial endometrioid adenocarcinoma
Oncology
66
288-295
2004
Homo sapiens
Chai, S.Y.; Fernando, R.; Ye, S.; Peck, G.R.; Albiston, A.L.
Insulin-regulated aminopeptidase
Proteases in Biology and Disease (Hooper, N. M. ; Lendeckel, U. , eds. ) Springer
2
61-81
2004
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
-
Nakata, M.; Nomura, S.; Ikoma, Y.; Sumigama, S.; Shido, F.; Ito, T.; Okada, M.; Kikkawa, F.; Tsujimoto, M.; Mizutani, S.
Insulin stimulates placental leucine aminopeptidase/oxytocinase/insulin-regulated membrane aminopeptidase expression in BeWo choriocarcinoma cells
Regul. Pept.
117
187-193
2004
Homo sapiens
Banegas, I.; Barrero, F.; Duran, R.; Morales, B.; Luna, J.D.; Prieto, I.; Ramirez, M.; Alba, F.; Vives, F.
Plasma aminopeptidase activities in Parkinsons disease
Horm. Metab. Res.
38
758-760
2006
Homo sapiens
Ye, S.; Chai, S.Y.; Lew, R.A.; Albiston, A.L.
Insulin-regulated aminopeptidase: analysis of peptide substrate and inhibitor binding to the catalytic domain
Biol. Chem.
388
399-403
2007
Homo sapiens
Shibata, K.; Kajiyama, H.; Ino, K.; Nawa, A.; Nomura, S.; Mizutani, S.; Kikkawa, F.
P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling
BMC Cancer
7
15
2007
Homo sapiens
Demaegdt, H.; Lenaerts, P.J.; Swales, J.; De Backer, J.P.; Laeremans, H.; Le, M.T.; Kersemans, K.; Vogel, L.K.; Michotte, Y.; Vanderheyden, P.; Vauquelin, G.
Angiotensin AT4 receptor ligand interaction with cystinyl aminopeptidase and aminopeptidase N: [125I]angiotensin IV only binds to the cystinyl aminopeptidase apo-enzyme
Eur. J. Pharmacol.
546
19-27
2006
Bos taurus, Cricetulus griseus, Homo sapiens, Mus musculus
Fernando, R.N.; Luff, S.E.; Albiston, A.L.; Chai, S.Y.
Sub-cellular localization of insulin-regulated membrane aminopeptidase, IRAP to vesicles in neurons
J. Neurochem.
102
967-976
2007
Homo sapiens, Mus musculus
Axen, A.; Lindeberg, G.; Demaegdt, H.; Vauquelin, G.; Karlen, A.; Hallberg, M.
Cyclic insulin-regulated aminopeptidase (IRAP)/AT4 receptor ligands
J. Pept. Sci.
12
705-713
2006
Homo sapiens
Axen, A.; Andersson, H.; Lindeberg, G.; Roennholm, H.; Kortesmaa, J.; Demaegdt, H.; Vauquelin, G.; Karlen, A.; Hallberg, M.
Small potent ligands to the insulin-regulated aminopeptidase (IRAP)/AT(4) receptor
J. Pept. Sci.
13
434-444
2007
Homo sapiens
Larrinaga, G.; Lopez, J.I.; Casis, L.; Blanco, L.; Gil, J.; Agirregoitia, E.; Varona, A.
Cystinyl aminopeptidase activity is decreased in renal cell carcinomas
Regul. Pept.
144
56-61
2007
Homo sapiens
Andersson, H.; Demaegdt, H.; Vauquelin, G.; Lindeberg, G.; Karlen, A.; Hallberg, M.
Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2
Bioorg. Med. Chem.
16
6924-6935
2008
Homo sapiens
Wiser, A.; Hershko-Klement, A.; Fishman, A.; Nachasch, N.; Fejgin, M.
Gestational diabetes insipidus and intrauterine fetal death of monochorionic twins
J. Perinatol.
28
712-714
2008
Homo sapiens
Mountford, S.J.; Albiston, A.L.; Charman, W.N.; Ng, L.; Holien, J.K.; Parker, M.W.; Nicolazzo, J.A.; Thompson, P.E.; Chai, S.Y.
Synthesis, structure-activity relationships and brain uptake of a novel series of benzopyran inhibitors of insulin-regulated aminopeptidase
J. Med. Chem.
57
1368-1377
2014
Homo sapiens
Papakyriakou, A.; Zervoudi, E.; Tsoukalidou, S.; Mauvais, F.X.; Sfyroera, G.; Mastellos, D.C.; van Endert, P.; Theodorakis, E.A.; Vourloumis, D.; Stratikos, E.
3,4-diaminobenzoic acid derivatives as inhibitors of the oxytocinase subfamily of m1 aminopeptidases with immune-regulating properties
J. Med. Chem.
58
1524-1543
2015
Homo sapiens (Q9UIQ6), Homo sapiens
Vanga, S.R.; Saevmarker, J.; Ng, L.; Larhed, M.; Hallberg, M.; Aqvist, J.; Hallberg, A.; Chai, S.Y.; Gutierrez-de-Teran, H.
Structural basis of inhibition of human insulin-regulated aminopeptidase (IRAP) by aryl sulfonamides
ACS omega
3
4509-4521
2018
Homo sapiens (Q9UIQ6), Homo sapiens
Rodrigo, N.; Hocking, S.
Transient diabetes insipidus in a post-partum woman with pre-eclampsia associated with residual placental vasopressinase activity
Endocrinol. Diabetes Metab. Case Rep.
2018
18-0052
2018
Homo sapiens (Q9UIQ6), Homo sapiens
Hanson, A.L.; Morton, C.J.; Parker, M.W.; Bessette, D.; Kenna, T.J.
The genetics, structure and function of the M1 aminopeptidase oxytocinase subfamily and their therapeutic potential in immune-mediated disease
Hum. Immunol.
80
281-289
2019
Homo sapiens (Q9UIQ6)
Svensson, F.; Engen, K.; Lundbaeck, T.; Larhed, M.; Skoeld, C.
Virtual screening for transition state analogue inhibitors of IRAP based on quantum mechanically derived reaction coordinates
J. Chem. Inf. Model.
55
1984-1993
2015
Homo sapiens (Q9UIQ6)
Mpakali, A.; Saridakis, E.; Harlos, K.; Zhao, Y.; Papakyriakou, A.; Kokkala, P.; Georgiadis, D.; Stratikos, E.
Crystal structure of insulin-regulated aminopeptidase with bound substrate analogue provides insight on antigenic epitope precursor recognition and processing
J. Immunol.
195
2842-2851
2015
Homo sapiens (Q9UIQ6)
Mpakali, A.; Saridakis, E.; Harlos, K.; Zhao, Y.; Kokkala, P.; Georgiadis, D.; Giastas, P.; Papakyriakou, A.; Stratikos, E.
ligand-induced conformational change of insulin-regulated aminopeptidase insights on catalytic mechanism and active site plasticity
J. Med. Chem.
60
2963-2972
2017
Homo sapiens (Q9UIQ6)
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