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Information on EC 3.4.11.9 - Xaa-Pro aminopeptidase
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3.4.11.9 Xaa-Pro aminopeptidaseSpecify your search results
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
Synonyms
aminoacylproline aminopeptidase, aminopeptidase P, aminopeptidase P1, aminopeptidase, aminoacylproline, AMPP, AP-P, APP, APP1, APPro, DAP-P, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminoacylproline aminopeptidase
-
-
-
-
aminopeptidase P
aminopeptidase, aminoacylproline
-
-
-
-
AP-P
APP
mAmP
-
-
-
-
Membrane-bound AmP
-
-
-
-
Membrane-bound APP
-
-
-
-
proline aminopeptidase
-
-
-
-
X-Pro aminopeptidase
X-prolyl aminopeptidase 3
Xaa-Pro aminopeptidase
-
-
-
-
XPNPEP1
XPNPEP3
additional information
aminopeptidase P
-
-
-
-
AP-P
-
-
-
-
APP
-
-
-
-
X-Pro aminopeptidase
-
-
-
-
additional information
-
the enzyme belongs to the peptidase family M24
additional information
the enzyme belongs to the peptidase family M24
additional information
the enzyme belongs to the peptidase family M24
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
mechanism, cis-trans specificity
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
-
-
-
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
acive site configuration, modeling, Asp449, Asp460, His523, Glu554, and Glu568 are in volved in metal binding in the active site, His429 and His523 are involved in shuttling protons during catalysis
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
isozyme APP-2 shows a preference for Arg-Pro-Pro-, Arg-Pro-Lys-, Pro-Pro-Gly-, -Phe-Gly- in descending order
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
R404 participates in proton relay and in the hydrogen bond network
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
H243 stabilizes substrate binding, H361 stabilizes substrate binding and the gem-diol catalytic intermediate. H350 forms part of a hydrophobic binding pocket that gives the enzyme its proline specificity
-
release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide
mechanism, cis-trans specificity
Escherichia coli B / ATCC 11303
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
exopeptidase, N-terminus, amino acid
-
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CAS REGISTRY NUMBER
COMMENTARY
37288-66-7
-
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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
(4-nitro)Phe-Pro-HN-CH2-CH2-NH-o-aminobenzoyl + H2O
(4-nitro)Phe + Pro-HN-CH2-CH2-NH-o-aminobenzoyl
-
-
-
?
(4-nitro)Phe-Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl + H2O
(4-nitro)Phe + Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
-
-
-
?
bradykinin + H2O
Arg + PPGFSPFR
i.e. RPPGFSPFR, rapid hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
centrosomal protein 290 kDa/NPHP6 + H2O
?
-
ciliary proteome is screened for proteins with a proline in the second position: 3 candidate substrates centrosomal protein 290 kDa/NPHP6 (CEP290/NPHP6), Alstrom syndrome 1 (ALMS1), and leucine rich repeat containing 50 (LRRC50), known to cause cystic renal disease are shown to be cleaved by ecAPP
-
-
?
FPHFD + H2O
?
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
Gly-Pro-4-methylcoumarin 7-amide + H2O
Gly + Pro-4-methyl-7-coumarylamide
-
-
-
-
?
Gly-Pro-4-methylcoumarin 7-amide + H2O
Gly + Pro-4-methylcoumarin 7-amide
-
-
-
-
?
L-Ala-L-Pro-L-Ala-2-naphthylamide + H2O
L-Ala-L-Pro-L-Ala + 2-naphthylamine
Q8IKT5
-
-
-
?
L-Ala-L-Pro-p-nitroanilide + H2O
L-Ala-L-Pro + p-nitroaniline
-
-
-
-
?
L-Asn-L-Pro-L-Thr-L-Asn-L-Leu-L-His + H2O
L-Asn + L-Pro-L-Thr-L-Asn-L-Leu-L-His
-
-
-
-
?
L-prolyl-peptide + H2O
L-proline + peptide
-
X-prolyl aminopeptidase catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides
-
-
?
leucine rich repeat containing 50 + H2O
?
-
ciliary proteome is screened for proteins with a proline in the second position: 3 candidate substrates centrosomal protein 290 kDa/NPHP6 (CEP290/NPHP6), Alstrom syndrome 1 (ALMS1), and leucine rich repeat containing 50 (LRRC50), known to cause cystic renal disease are shown to be cleaved by ecAPP
-
-
?
Lys(epsilon-dinitrophenol)-Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl + H2O
Lys(epsilon-dinitrophenol) + Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl
N-alpha-aminobenzyloxycarbonyl-Lys-Pro-Pro-4-nitroanilide + H2O
N-alpha-aminobenzyloxycarbonyl-Lys + Pro-Pro-4-nitroaniline
-
-
?
papain + H2O
?
-
reduced and carboxymethylated, with the N-terminal sequence Ile-Pro-Glu-Tyr-Val
-
-
?
substance P + H2O
Arg + PKPQQFFGLM
i.e. RPKPQQFFGLM, hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
YPWTQ + H2O
?
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide + H2O
Abz-L-Lys + L-Pro-L-Pro-4-nitroanilide
-
-
-
-
?
Abz-L-Lys-L-Pro-L-Pro-4-nitroanilide + H2O
Abz-L-Lys + L-Pro-L-Pro-4-nitroanilide
Q2QC92
-
-
-
?
Abz-L-Lys-L-Pro-L-Pro-p-nitroanilide + H2O
Abz-L-Lys + L-Pro-L-Pro-p-nitroanilide
-
-
-
-
?
Abz-L-Lys-L-Pro-L-Pro-p-nitroanilide + H2O
Abz-L-Lys + L-Pro-L-Pro-p-nitroanilide
-
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
i.e. bradykinin
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
i.e. bradykinin
one Arg is released per mol of bradykinin in less than 5 min, the following Pro residue is released within 1 h
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
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-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
-
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O
Arg + Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
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-
-
-
?
bradykinin + H2O
?
-
potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
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i.e. RPPGFSPFR, hydrolysis of the N-terminal Arg1-Pro2 bond
i.e. PPGFSPFR
?
bradykinin + H2O
Arg + des-Arg-bradykinin
i.e. RPPGFSPFR, hydrolysis of the N-terminal Arg1-Pro2 bond
i.e. PPGFSPFR
?
bradykinin + H2O
Arg + des-Arg-bradykinin
hydrolysis of the N-terminal Arg1-Pro bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
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hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
-
hydrolysis of the N-terminal Arg1-Pro2 bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
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enzyme activity in plasma of humans with previous angio-oedema, a rare but potentially life-threatening side-effect of angiotensin-converting enzyme inhibitor treatment, is low compared to humans without this sensitivity and might be a predisposing factor for development of angio-oedema
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
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the enzyme contributes to the degradation of bradykinin in human skin, especially in case of angiotensin-converting enzyme inhibition
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
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hydrolysis of the N-terminal Arg1-Pro2 bond
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?
L-Ala-L-Pro-4-nitroanilide + H2O
L-Ala + L-Pro-4-nitroanilide
best substrate
-
-
?
L-Ala-L-Pro-4-nitroanilide + H2O
L-Ala + L-Pro-4-nitroanilide
best substrate
-
-
?
L-Ala-L-Pro-4-nitroanilide + H2O
L-Ala + L-Pro-4-nitroanilide
-
best substrate
-
-
?
Lys(epsilon-dinitrophenol)-Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl + H2O
Lys(epsilon-dinitrophenol) + Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl
-
-
-
-
?
Lys(epsilon-dinitrophenol)-Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl + H2O
Lys(epsilon-dinitrophenol) + Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl
-
-
-
-
?
substance P + H2O
Arg + des-Arg-substance P
i.e. RPKPQQFFGLM, hydrolysis of the N-terminal Arg1-Pro2 bond
i.e. PKPQQFFGLM
?
additional information
?
-
-
the enzyme favors peptides with 2 proline residues or proline analogs in position 2 and 3 of the substrate
-
-
-
additional information
?
-
-
enzyme may be important for the modulation of the biological activity of neuropeptides
-
-
-
additional information
?
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-
the enzyme is involved in the pulmonary inactivation of circulating bradykinin
-
-
-
additional information
?
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-
the enzyme may have an important role in the pulmonary degradation of the potent vasoactive peptide, bradykinin
-
-
-
additional information
?
-
-
no activity with angiotensin I, des-Arg-bradykinin, AF1, i.e. KNEFIRNRVYIHPFHL, and substance P
-
?
additional information
?
-
-
the enzyme can only hydrolyze the trans form of the X-L-Pro-peptide bond, the cis form has to isomerize before it can be cleaved
-
-
-
additional information
?
-
-
enzyme hydrolyzes the Xaa-Pro peptide bond when the first amino acid is Asn, Ala, or Met
-
-
-
additional information
?
-
-
peptides in which L-Pro is replaced by N-methyl-L-Ala or L-Ala are extremely poor substrates
-
-
-
additional information
?
-
-
ciliary proteome is screened for proteins with a proline in the second position: 3 candidate substrates centrosomal protein 290 kDa/NPHP6 (CEP290/NPHP6), Alstrom syndrome 1 (ALMS1), and leucine rich repeat containing 50 (LRRC50), known to cause cystic renal disease are shown to be cleaved by ecAPP
-
-
-
additional information
?
-
no activity with Gly-Pro-hydroxyPro
-
?
additional information
?
-
-
the enzyme removes the N-terminal amino acid from peptides only where Pro, and in one case Ala, is present in the penultimate position. No hydrolysis of dipeptides even when Pro is present in the C-terminal position or when either N-termial Pro or pyroglutamate is present preceeding a Pro residue in the penultimate position of longer peptides
-
-
-
additional information
?
-
-
aminopeptidase P appears to be an important enzyme for debittering of casein-derived peptides
-
-
-
additional information
?
-
-
the enzyme releases only amino acid X from the NH2-termini of peptides with the general structure X-Pro-Y-Z
-
-
-
additional information
?
-
Q8IKT5
specific role in the catabolism of proline-containing peptides in both the vacuole and the cytosol, enzyme is required for efficient parasite proliferation
-
-
-
additional information
?
-
-
the enzyme liberates all unblocked preferentially basic or hydrophobic ultimate amino acids from dipeptides, tripeptides and oligopeptides with N-terminal Xaa-Pro- sequences, overview
-
-
-
additional information
?
-
-
the enzyme accounts for virtually all of the pulmonary inactivation of bradykinin injected in vitro
-
-
-
additional information
?
-
-
the enzyme probably plays an important role in conjunction with other intestinal prolyl peptidases in the digestion of proline containing peptides and proteins
-
-
-
additional information
?
-
-
the enzyme plays an important role in hydrolysis of Xaa-Pro-Yaa peptides
-
-
-
additional information
?
-
-
the enzyme participates in the myocardial kinin metabolism to the same extent as angiotensin-converting enzyme, APP inhibition leads to a reduction in myocardial infarct size by the bradykinin-dependent pathway, synergistic with inhibition of angiotensin-converting enzyme, overview
-
?
additional information
?
-
-
the enzyme is involved in degradation of peptide intermediates
-
-
-
additional information
?
-
systemin, a peptide hormone-like signaling molecule from tomato plants, is no substrate
-
?
additional information
?
-
systemin, a peptide hormone-like signaling molecule from tomato plants, is no substrate
-
?
additional information
?
-
-
systemin, a peptide hormone-like signaling molecule from tomato plants, is no substrate
-
?
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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
bradykinin + H2O
?
-
potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
FPHFD + H2O
?
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
YPWTQ + H2O
?
-
globin pentapeptide sequence, potential natural substrate, efficiently hydrolyzed by PfAPP
-
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
-
enzyme activity in plasma of humans with previous angio-oedema, a rare but potentially life-threatening side-effect of angiotensin-converting enzyme inhibitor treatment, is low compared to humans without this sensitivity and might be a predisposing factor for development of angio-oedema
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
-
the enzyme contributes to the degradation of bradykinin in human skin, especially in case of angiotensin-converting enzyme inhibition
-
?
additional information
?
-
-
enzyme may be important for the modulation of the biological activity of neuropeptides
-
-
-
additional information
?
-
-
the enzyme is involved in the pulmonary inactivation of circulating bradykinin
-
-
-
additional information
?
-
-
the enzyme may have an important role in the pulmonary degradation of the potent vasoactive peptide, bradykinin
-
-
-
additional information
?
-
-
aminopeptidase P appears to be an important enzyme for debittering of casein-derived peptides
-
-
-
additional information
?
-
Q8IKT5
specific role in the catabolism of proline-containing peptides in both the vacuole and the cytosol, enzyme is required for efficient parasite proliferation
-
-
-
additional information
?
-
-
the enzyme accounts for virtually all of the pulmonary inactivation of bradykinin injected in vitro
-
-
-
additional information
?
-
-
the enzyme probably plays an important role in conjunction with other intestinal prolyl peptidases in the digestion of proline containing peptides and proteins
-
-
-
additional information
?
-
-
the enzyme plays an important role in hydrolysis of Xaa-Pro-Yaa peptides
-
-
-
additional information
?
-
-
the enzyme participates in the myocardial kinin metabolism to the same extent as angiotensin-converting enzyme, APP inhibition leads to a reduction in myocardial infarct size by the bradykinin-dependent pathway, synergistic with inhibition of angiotensin-converting enzyme, overview
-
?
additional information
?
-
-
the enzyme is involved in degradation of peptide intermediates
-
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Co2+
Cu2+
Mg2+
Mn2+
Ni2+
Zn2+
additional information
Ca2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Ca2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
Co2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Co2+
in a metal:protein ratio of 0.11:1, slightly activates the enzyme at 0.01-0.1 mM, 2.8fold activation at 1 mM in presence of 1 mM glutathione
Co2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
Cu2+
-
0.1 mM, moderate inhibitory effect; 10 mM, strong inhibitory effect
Mg2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Mn2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM with substrates substance P and bradykinin
Mn2+
-
wild-type and mutat R404A, binding of Mn2+ with a stoichiometry of 2 per monomer
Mn2+
in a metal:protein ratio of 1:1, activates the enzyme 2.80fold at 0.1 mM with substrate substance P, maximal at 0.3 mM, 4.6fold activation at 1 mM in presence of 1 mM glutathione
Mn2+
-
using the QM/MM method it is shown that XPNPEP1 employs two divalent manganese atoms (Mn(II)-Mn(II)) in the active site. The possibility of a single Mn(II) atom or other combination of divalent metal ions: Ca(II), Fe(II), Mg(II) is excluded
Mn2+
-
enhances activity, atomic absorption studies reveal the presence of Mn2+ in the protein as a co-factor
Mn2+
-
4-10 mM, activates hydrolysis of Gly-Pro-Hyp, beta-casomorphin or substance P
Zn2+
-
0.01 mM, moderate inhibitory effect; 10 mM, strong inhibitory effect
Zn2+
-
mono-zinc-containing enzyme, lacks any of the typical metal binding motifs found in other zinc metalloproteases
additional information
-
metalloenzyme, enzyme which is free of metals due to EDTA-treatment cannot be reactivated by addition of Co2+, Zn2+, or Mn2+
additional information
-
the active site contains a dinuclear metal binding site, the enzyme contains 12 metal atoms per molecule, 2 of which are Mn2+ ions
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetyl-Phe(NO2)-Pro-Pro-HN-CH2-CH2-NH-2-aminobenzoyl
-
0.5 mM, 30% inhibition of hydrolysis of (4-nitr)Phe-Pro-Pro-HN-CH2-CH2-NH-o-aminobenzoyl
cilazaprilat
-
inhibits hydrolysis of Gly-Pro-Hyp, Gly-Pro-4-methyl-7-coumarylamide, substance P, and beta-casomorphin. Weak inhibition of hydrolysis of Arg-Pro-Pro. No effect on hydrolysis of bradykinin
enaprilat
-
inhibits hydrolysis of Gly-Pro-Hyp, Gly-Pro-4-methylcoumarin 7-amide, substance P, and beta-casomorphin. Weak inhibition of hydrolysis of Arg-Pro-Pro. No effect on hydrolysis of bradykinin
L-Pro-L-Leu
-
product inhibition, a third metal binding site is formed by two conserved His-residues and L-Pro-L-Leu
4-chloromercuriphenyl sulfonic acid
-
inhibits hydrolysis of Gly-Pro-Hyp, activates hydrolysis of bradykinin
apstatin
-
binds to the active site with its N-terminal amino group coordinated to one of the two Mn(II) ions at the metal center
Ca2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Ca2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
Co2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Co2+
stimulation of enzyme activity at 0.4 mM, inhibition at 4 mM
Mg2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM
Mn2+
activates the enzyme at concentrations of 0.01-0.1 mM with substrate substance P, inhibits above 1 mM with substrates substance P and bradykinin
Pro-HN-CH2-CH2-NH-2-aminobenzoyl
-
0.01 mM, complete inhibition of hydrolysis of (4-nitro)Phe-Pro-Pro-HN-CH2-CH2-NH-2-aminobenzoyl
ramiprilat
-
inhibits hydrolysis of Gly-Pro-Hyp, Gly-Pro-4-methylcoumarin 7-amide, substance P or beta-casomorphin. Weak inhibition of hydrolysis of Arg-Pro-Pro. No effect on hydrolysis of bradykinin
additional information
-
not inhibitory: L-Ala-(N-methyl)-L-Ala-L-Ala, L-Ala-L-Ala-L-Ala
-
additional information
no significant inhibition by amastatin and enalaprilat
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-chloromercuriphenyl sulfonic acid
-
inhibits hydrolysis of Gly-Pro-Hyp, activates hydrolysis of bradykinin
glutathione
activates the enzyme in presence of Mn2+ or Co2+, and slightly in presence of Zn2+
progesterone
-
exposure of HepG2 cells to 0.001 mM progesterone results in a significant increase in the AP-P activity of cell lysates
additional information
-
women on the oral contraceptive pill have higher age-adjusted plasma AP-P compared to women not on the oral contraceptive pill or males
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Alzheimer Disease
Generation of Alzheimer disease-associated amyloid ?42/43 peptide by ?-secretase can be inhibited directly by modulation of membrane thickness.
Asthma
Eastern Carolina Asthma Prevention Program (ECAPP): An Environmental Intervention Study Among Rural and Underserved Children with Asthma in Eastern North Carolina.
Biliary Atresia
Association of X-prolyl aminopeptidase 1 rs17095355 polymorphism with biliary atresia in Thai children.
Ciliopathies
Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.
Kidney Diseases
Mitochondrial aminopeptidase deletion increases chronological lifespan and oxidative stress resistance while decreasing respiratory metabolism in S. cerevisiae.
Kidney Diseases, Cystic
Structure of the human aminopeptidase XPNPEP3 and comparison of its in vitro activity with Icp55 orthologs: Insights into diverse cellular processes.
Microcephaly
Developmental retardation, microcephaly, and peptiduria in mice without aminopeptidase P1.
xaa-pro aminopeptidase deficiency
Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.5
L-Ile-L-Pro-L-Pro
-
pH 7, temperature not specified in the publication
4.7
L-Leu-L-Pro-L-Pro
-
pH 7, temperature not specified in the publication
13.6
L-Val-L-Pro-L-Pro
-
pH 7, temperature not specified in the publication
0.087
2-aminobenzoyl-L-Lys-L-Pro-L-Pro-4-nitroanilide
-
wild-type, pH 8.1, 37°C
0.14
2-aminobenzoyl-L-Lys-L-Pro-L-Pro-4-nitroanilide
-
mutant H350A, pH 8.1, 37°C
0.078
bradykinin
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37°C
0.308
L-Arg-L-Pro-L-Pro
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
7.7
L-Arg-L-Pro-L-Pro
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37°C
3.8
bradykinin
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0603
(2R,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30°C
0.269
(2R,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30°C
0.0282
(2R,3S)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30°C
0.0789
(2R,3S)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30°C
0.027
(2S,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30°C
0.0307
(2S,3R)-3-amino-1-oxo-4-phenyl-1-(1,3-thiazolidin-3-yl)butan-2-ol
-
pH 7.4, 30°C
0.0198
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl pyrrolidide
-
pH 7.4, 30°C
0.037
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl pyrrolidide
-
pH 7.4, 30°C
0.00126
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-L-Phe-OMe
-
pH 7.4, 30°C
0.057
(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-Pro-L-Phe-OMe
-
pH 7.4, 30°C
0.014
(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-thiazolidide
-
pH 7.4, 30°C
0.11
(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-thiazolidide
-
pH 7.4, 30°C
0.0043
(2S,3R)-3-amino-5-methyl-1-oxo-1-(1,3-thiazolidin-3-yl)hexan-2-ol
-
pH 7.4, 30°C
0.0229
(2S,3R)-3-amino-5-methyl-1-oxo-1-(1,3-thiazolidin-3-yl)hexan-2-ol
-
pH 7.4, 30°C
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.016
-
humans with previous angiotensin-converting enzyme-inhibitor treatment-associated angio-oedema
0.022 - 0.023
-
humans without angiotensin-converting enzyme-inhibitor treatment-associated angio-oedema
additional information
additional information
-
the supernatant shows a specific activity of the recombinant enzyme of 117 units/mg, the cell-free extract shows a specific activity of the recombinant enzyme of 8 units/mg
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
8.5
7
-
hydrolysis of bradykinin(1-8), 0.5 mM, in both 0.1 M Hepes buffer or 0.1 M potassium phosphate buffer
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
wild type and mutant strain that lacks peptidase P
-
-
brenda
-
-
-
brenda
-
-
-
brenda
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
enriched in caveolae on the luminal surface of pulmonary vascular endothelium. Lung vascular targeting is assessed using a human/mouse chimeric monoclonal antibody (833c) against APP
brenda
additional information
Q8IKT5
enzyme is expressed through the asexual erythrocytic cycle
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
attached to the membranes via a glycosylphosphatidylinositol anchor
brenda
-
attached to the membranes via a glycosylphosphatidylinositol anchor
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
malfunction
-
suppression of zebrafish xpnpep3 phenocopied the developmental phenotypes of ciliopathy morphants, and this effect is rescued by human XPNPEP3 that is devoid of a mitochondrial localization signal, suggesting that the protein might also have mitochondrial-independent activity
malfunction
in 2 families with an nephronophthisis-like phenotype, homozygous frameshift and splice-site mutations, respectively, are detected in the X-prolyl aminopeptidase 3 gene
malfunction
-
Xpnpep1 knockout mice display severe growth retardation, microcephaly, and modest lethality. Imino-oligopeptide excretion is observed in urine samples from APP1-deficient mice
Show AA Sequence and Transmembrane Helices (3839 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Escherichia coli (strain K12)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
68000
-
x * 71000, recombinant His-tagged fusion protein, SDS-PAGE, x * 68000, W03G9.4 protein, SDS-PAGE
71000
90000
91000
105000
x * 105000, recombinant GST-fusion protein, SDS-PAGE
140000
220000
71000
-
x * 71000, recombinant His-tagged fusion protein, SDS-PAGE, x * 68000, W03G9.4 protein, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
-
arranged in 2 types of tetramers, one tetramer comprises 4 crystallographically independent subunits, while the other tetramer comprises 2 pairs of subunits related by a crystallographic 2fold axis
homodimer
tetramer
additional information
interaction of the subunits can not be disrupted by 2-mercaptoethanol, 1 M NaCl, 1% Triton X-100, and 4 mM CHAPS
?
-
x * 71000, recombinant His-tagged fusion protein, SDS-PAGE, x * 68000, W03G9.4 protein, SDS-PAGE
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
side-chain modification
glycoprotein
-
secreted enzyme mutant with translational stop codon at position 658, N-glycosylated
side-chain modification
-
the enzyme is attached to the membranes via a glycosylphosphatidylinositol anchor
side-chain modification
-
the enzyme is anchored to the membrane via a covalently attached glycosyl-phosphatidylinositol moiety
side-chain modification
-
the enzyme contains at least 17% N-linked carbohydrate
side-chain modification
-
the enzyme is attached to the membranes via a glycosylphosphatidylinositol anchor
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
8 mg/ml purified recombinant enzyme in Tris, pH 8.5, hanging drop vapour diffusion method, 0.003 ml mixed with 0.002 ml reservoir solution containing 25% PEG 4000, 0.1 M Tris-HCl, pH 8.0, 0.2 M sodium acetate, and 1 mM MnCl2, 1 month at 4°C, cryoprotectant is 2-methyl-2,4-pentanediol, X-ray diffraction structure determination and analysis at 2.4 A resolution, modeling
-
Mn(II)-form of enzyme and substituted with Mg2+, Zn2+, Ca2+, Na+ and apo-enzyme in complex with L-Val-L-Pro-L-Leu
-
mutants E383A, H361A and H243A in complex with substrate L-Val-L-Pro-L-Leu. Substrate interacts with one of the active site metal ions via its terminal amino group
-
hanging drop vapour diffusion method, using 20% (v/v) polyethylene glycol 400, 0.15 M CaCl2, and 100 mM HEPES (pH 7.5)