Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
bradykinin + H2O
Arg + des-Arg-bradykinin
bradykinin + H2O
des-Arg-bradykinin + Arg
i.e. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
-
?
bradykinin + H2O
L-Arg + des-Arg-bradykinin
-
-
-
-
?
des-Arg9-bradykinin + H2O
?
-
-
-
-
?
K(Dnp)PPGFSPK(Abz)NH2 + H2O
?
-
-
-
-
?
K(Dnp)PPGK(Abz)NH2 + H2O
?
-
-
-
-
?
K(Dnp)PPK(Abz)NH2 + H2O
?
-
-
-
-
?
L-Arg-L-Pro-L-Pro + H2O
L-Arg + L-Pro-L-Pro
-
-
-
-
?
L-prolyl-peptide + H2O
L-proline + peptide
-
X-prolyl aminopeptidase catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides
-
-
?
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
-
-
?
substance P + H2O
L-Arg + PKPQQFFGLM
-
-
-
?
additional information
?
-
bradykinin + H2O
Arg + des-Arg-bradykinin
-
-
-
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
hydrolysis of the N-terminal Arg1-Pro bond
-
?
bradykinin + H2O
Arg + des-Arg-bradykinin
-
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
-
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
?
-
no activity with Gly-Pro-hydroxyPro
-
?
additional information
?
-
-
no activity with Gly-Pro-hydroxyPro
-
?
additional information
?
-
a proline-specific APaseP
-
-
?
additional information
?
-
-
a proline-specific APaseP
-
-
?
additional information
?
-
aminopeptidase P targets Xaa-Proline peptides for cleavage. Roles of active site residues Tyr527 and Arg535, both residues make significant contributions to the catalytic efficiency, overview
-
-
?
additional information
?
-
-
aminopeptidase P targets Xaa-Proline peptides for cleavage. Roles of active site residues Tyr527 and Arg535, both residues make significant contributions to the catalytic efficiency, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Fe2+
in a metal:protein ratio of 0.07:1
NaCl
activates the wild-type enzyme at 160 mM, inhibits the enzyme mutant R353A at 160 mM
Zn2+
in a metal:protein ratio of 0.11:1
Mn2+
required for activity
Mn2+
-
required, maximal activity at 0.05 mM
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+
-
the enzyme is double Mn2+-dependent for its activity
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+
activates, required, Km values for Mn2+ are 0.0022 mM for the wild-type enzyme, 0.004 mM for mutant Y527F, and 0.0018 mM for mutant R535A. Kinetic analysis of MnCl2 activation of wild-type, Y527F and R535A hcAMPPs
additional information
a metalloprotease
additional information
-
a metalloprotease
additional information
XPNPEP1 is a metallopeptidase
additional information
XPNPEP1 is a metallopeptidase
additional information
-
XPNPEP1 is a metallopeptidase
additional information
XPNPEP2 is a metallopeptidase
additional information
XPNPEP2 is a metallopeptidase
additional information
-
XPNPEP2 is a metallopeptidase
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Alzheimer Disease
Generation of Alzheimer disease-associated amyloid ?42/43 peptide by ?-secretase can be inhibited directly by modulation of membrane thickness.
Alzheimer Disease
Targeting Cannabinoid Receptor Activation and BACE-1 Activity Counteracts TgAPP Mice Memory Impairment and Alzheimer's Disease Lymphoblast Alterations.
Angioedema
A functional XPNPEP2 promoter haplotype leads to reduced plasma aminopeptidase P and increased risk of ACE inhibitor-induced angioedema.
Angioedema
A variant in XPNPEP2 is associated with angioedema induced by angiotensin I-converting enzyme inhibitors.
Angioedema
Diagnosis and treatment of bradykinin-mediated angioedema: outcomes from an angioedema expert consensus meeting.
Angioedema
Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema.
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.
Carcinoma
Proteome profiling of clear cell renal cell carcinoma in von Hippel-Lindau patients highlights upregulation of Xaa-Pro aminopeptidase-1, an anti-proliferative and anti-migratory exoprotease.
Carcinoma, Renal Cell
Proteome profiling of clear cell renal cell carcinoma in von Hippel-Lindau patients highlights upregulation of Xaa-Pro aminopeptidase-1, an anti-proliferative and anti-migratory exoprotease.
Cervical Intraepithelial Neoplasia
XPNPEP2 is overexpressed in cervical cancer and promotes cervical cancer metastasis.
Ciliopathies
Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.
Ciliopathies
Lights on for aminopeptidases in cystic kidney disease.
Cough
PNPT1 and PCGF3 variants associated with angiotensin-converting enzyme inhibitor-induced cough: a nested case-control genome-wide study.
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.
Lymphatic Metastasis
XPNPEP2 is associated with lymph node metastasis in prostate cancer patients.
Lymphatic Metastasis
XPNPEP2 is overexpressed in cervical cancer and promotes cervical cancer metastasis.
Lymphoma
ECAPP chemotherapy for lymphoma.
Microcephaly
Developmental retardation, microcephaly, and peptiduria in mice without aminopeptidase P1.
Neoplasm Metastasis
XPNPEP2 is associated with lymph node metastasis in prostate cancer patients.
Neoplasm Metastasis
XPNPEP2 is overexpressed in cervical cancer and promotes cervical cancer metastasis.
Neoplasms
Identification of DEGs and transcription factors involved in H. pylori-associated inflammation and their relevance with gastric cancer.
Neoplasms
XPNPEP2 is associated with lymph node metastasis in prostate cancer patients.
Neoplasms
XPNPEP2 is overexpressed in cervical cancer and promotes cervical cancer metastasis.
Neoplasms
XPNPEP3 is a novel transcriptional target of canonical Wnt/?-catenin signaling.
Primary Ovarian Insufficiency
Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene.
Prostatic Neoplasms
XPNPEP2 is associated with lymph node metastasis in prostate cancer patients.
Stroke
Recurrent ischemic stroke in patients with atrial fibrillation ablation and prior stroke: A study based on etiological classification.
Trichomonas Infections
The 50kDa metalloproteinase TvMP50 is a zinc-mediated Trichomonas vaginalis virulence factor.
Trichomonas Infections
TvMP50 is an immunogenic metalloproteinase during male trichomoniasis.
Uterine Cervical Neoplasms
XPNPEP2 is overexpressed in cervical cancer and promotes cervical cancer metastasis.
xaa-pro aminopeptidase deficiency
Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency.
xaa-pro aminopeptidase deficiency
Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.056
des-Arg9-bradykinin
-
pH 7.4, 37°C
0.018
K(Dnp)PPGFSPK(Abz)NH2
-
-
0.02
K(Dnp)PPGK(Abz)NH2
-
-
0.019
K(Dnp)PPK(Abz)NH2
-
-
0.308 - 0.837
L-Arg-L-Pro-L-Pro
0.1
Lys(epsilon-dinitrophenol)-Pro-Pro-NH-CH3-CH2-NH-2-aminobenzoyl
-
-
0.077
Substance P
pH 8.2, 37°C, recombinant wild-type enzyme
additional information
additional information
-
0.075
bradykinin
-
pH 7.4, 37°C
0.078
bradykinin
-
wild type enzyme in 100 mM Tris-HCl (pH 8.0) and 100 mM NaCl at 37°C
0.101
bradykinin
pH 8.2, 37°C, recombinant wild-type enzyme
0.144
bradykinin
pH 7.5, 37°C, recombinant mutant R535A, with 1.0 mM guanidine hydrochloride
0.163
bradykinin
pH 7.5, 37°C, recombinant mutant R535A, with 10 mM guanidine hydrochloride
0.17
bradykinin
pH 7.5, 37°C, recombinant wild-type enzyme
0.2
bradykinin
pH 7.5, 37°C, recombinant mutant Y527F
0.327
bradykinin
pH 7.5, 37°C, recombinant mutant R535A, with 0.1 mM guanidine hydrochloride
0.35
bradykinin
pH 7.5, 37°C, recombinant mutant R535A
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
0.837
L-Arg-L-Pro-L-Pro
-
pH 7.4, 37°C
additional information
additional information
Michaelis-Menten steady-state kinetics. Kinetic parameters for R535A hcAMPP measured in the presence and absence of guanidine hydrochloride, overview
-
additional information
additional information
-
Michaelis-Menten steady-state kinetics. Kinetic parameters for R535A hcAMPP measured in the presence and absence of guanidine hydrochloride, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
?
x * 72000, recombinant enzyme, SDS-PAGE
dimer
2 * 71000, recombinant enzyme, SDS-PAGE
homodimer
-
2 * 70000, X-ray crystallography
additional information
interaction of the subunits can not be disrupted by 2-mercaptoethanol, 1 M NaCl, 1% Triton X-100, and 4 mM CHAPS
additional information
-
interaction of the subunits can not be disrupted by 2-mercaptoethanol, 1 M NaCl, 1% Triton X-100, and 4 mM CHAPS
additional information
the reported X-ray structure of hcAMPP depicts a homodimer with each subunit containing an N-terminal domain, a middle domain, and a C-terminal catalytic domain, two active site divalent metal ions. Dimerization is mediated by the N-terminal domain and Trp477, and conservation of the key active site residues including Asp415, Asp426, His489, Glu523, Glu537, His395, His485, and His498
additional information
-
the reported X-ray structure of hcAMPP depicts a homodimer with each subunit containing an N-terminal domain, a middle domain, and a C-terminal catalytic domain, two active site divalent metal ions. Dimerization is mediated by the N-terminal domain and Trp477, and conservation of the key active site residues including Asp415, Asp426, His489, Glu523, Glu537, His395, His485, and His498
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
E41A
-
the mutant maintains 91% of the wild type activity and demonstrates that the acidic residue, which is considered as a stabilizing factor in the protonation of catalytic residue His498, plays only a marginal role in catalysis
R535A
site-directed mutagenesis, the mutant enzyme shows reduced kcat and Km compared to the wild-type enzyme. The respective levels of activity restoration are determined to be 86%, 31%, 16%, and 10% for guanidine hydrochloride, methylguanidine, aminoguanidine and N-ethyl-guanidine
W477E
-
the mutant, designed to block dimer formation, shows only 6% of the wild type activity
Y527F
site-directed mutagenesis, the mutant enzyme shows reduced kcat and Km compared to the wild-type enzyme
additional information
design of an aminopeptidase P (APaseP) targeting tissue-specific construct conjugated to a homing peptide for selective binding to human breast-derived cancer cells. Homing peptides are short amino acid sequences derived from phage display libraries that have the unique property of localizing to specific organs. The molecular construct allows for tissue-specific drug delivery, by binding to APaseP in the vascular endothelium. The breast homing peptide is a cyclic nine-amino-acid peptide with the sequence CPGPEGAGC, referred to as PEGA. The PEGA peptide and similar peptide conjugates distribute to human breast tissue xenograft specifically and evaluate the interaction with the membrane-bound proline-specific APaseP by binding studies. In vivo localization of the breast tissue specific conjugate in a breast cancer xenograft mouse model, established by implanting enzyme-expressing human breast adenocarcinoma cell line MCF-7 in nude mice with estrogen supplementation
additional information
-
design of an aminopeptidase P (APaseP) targeting tissue-specific construct conjugated to a homing peptide for selective binding to human breast-derived cancer cells. Homing peptides are short amino acid sequences derived from phage display libraries that have the unique property of localizing to specific organs. The molecular construct allows for tissue-specific drug delivery, by binding to APaseP in the vascular endothelium. The breast homing peptide is a cyclic nine-amino-acid peptide with the sequence CPGPEGAGC, referred to as PEGA. The PEGA peptide and similar peptide conjugates distribute to human breast tissue xenograft specifically and evaluate the interaction with the membrane-bound proline-specific APaseP by binding studies. In vivo localization of the breast tissue specific conjugate in a breast cancer xenograft mouse model, established by implanting enzyme-expressing human breast adenocarcinoma cell line MCF-7 in nude mice with estrogen supplementation
additional information
downregulation of XPNPEP1 in 786-O cells by stable transduction with small-hairpin (sh)RNAs
additional information
downregulation of XPNPEP1 in 786-O cells by stable transduction with small-hairpin (sh)RNAs
additional information
-
downregulation of XPNPEP1 in 786-O cells by stable transduction with small-hairpin (sh)RNAs
additional information
kinetic analysis of MnCl2 activation of wild-type, Y527F and R535A hcAMPPs
additional information
-
kinetic analysis of MnCl2 activation of wild-type, Y527F and R535A hcAMPPs
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Hooper, N.M.; Turner, A.J.
Ectoenzymes of the kidney microvillar membrane. Aminopeptidase P is anchored by a glycosyl-phosphatidylinositol moiety
FEBS Lett.
229
340-344
1988
Homo sapiens, Sus scrofa
brenda
Holtzman, E.J.; Pillay, G.; Rosenthal, T.; Yaron, A.
Aminopeptidase P activity in rat organs and human serum
Anal. Biochem.
162
476-481
1987
Homo sapiens, Rattus norvegicus
brenda
Fleminger, G.; Carmel, A.; Goldenberg, D.; Yaron, A.
Fluorogenic substrates for bacterial aminopeptidase P and its analogs detected in human serum and calf lung
Eur. J. Biochem.
125
609-615
1982
Bos taurus, Escherichia coli, Homo sapiens
brenda
Cottrell, G.S.; Hooper, N.M.; Turner, A.J.
Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme
Biochemistry
39
15121-15128
2000
Homo sapiens (Q9NQW7), Homo sapiens
brenda
Kim, K.S.; Kumar, S.; Simmons, W.H.; Brown, N.J.
Inhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans
J. Pharmacol. Exp. Ther.
292
295-298
2000
Homo sapiens
brenda
Adam, A.; Cugno, M.; Molinaro, G.; Perez, M.; Lepage, Y.; Agostoni, A.
Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors
Lancet
359
2088-2089
2002
Homo sapiens
brenda
Molinaro, G.; Carmona, A.K.; Juliano, M.A.; Juliano, L.; Malitskaya, E.; Yessine, M.A.; Chagnon, M.; Lepage, Y.; Simmons, W.H.; Boileau, G.; Adam, A.
Human recombinant membrane-bound aminopeptidase P: production of a soluble form and characterization using novel, internally quenched fluorescent substrates
Biochem. J.
385
389-397
2005
Homo sapiens
brenda
Duan, Q.L.; Binkley, K.; Rouleau, G.A.
Genetic analysis of Factor XII and bradykinin catabolic enzymes in a family with estrogen-dependent inherited angioedema
J. Allergy Clin. Immunol.
123
906-910
2009
Homo sapiens
brenda
Li, X.; Lou, Z.; Li, X.; Zhou, W.; Ma, M.; Cao, Y.; Geng, Y.; Bartlam, M.; Zhang, X.C.; Rao, Z.
Structure of human cytosolic X-prolyl aminopeptidase: a double Mn(II)-dependent dimeric enzyme with a novel three-domain subunit
J. Biol. Chem.
283
22858-22866
2008
Homo sapiens
brenda
La Corte, A.L.; Carter, A.M.; Turner, A.J.; Grant, P.J.; Hooper, N.M.
The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill
J. Renin Angiotensin Aldosterone Syst.
9
221-225
2008
Homo sapiens
brenda
Doria, C.; Elia, E.S.; Kang, Y.; Adam, A.; Desormeaux, A.; Ramirez, C.; Frank, A.; di Francesco, F.; Herman, J.H.
Acute hypotensive transfusion reaction during liver transplantation in a patient on angiotensin converting enzyme inhibitors from low aminopeptidase P activity
Liver Transpl.
14
684-687
2008
Homo sapiens
brenda
Ragheb, D.; Bompiani, K.; Dalal, S.; Klemba, M.
Evidence for catalytic roles for Plasmodium falciparum aminopeptidase P in the food vacuole and cytosol
J. Biol. Chem.
284
24806-24815
2009
Homo sapiens, Plasmodium falciparum
brenda
OToole, J.F.; Liu, Y.; Davis, E.E.; Westlake, C.J.; Attanasio, M.; Otto, E.A.; Seelow, D.; Nurnberg, G.; Becker, C.; Nuutinen, M.; Kaerppae, M.; Ignatius, J.; Uusimaa, J.; Pakanen, S.; Jaakkola, E.; van den Heuvel, L.P.; Fehrenbach, H.; Wiggins, R.; Goyal, M.; Zhou, W.; Wolf, M.T.; Wise, E.; Helou, J.; A, A.l.
Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy
J. Clin. Invest.
120
791-802
2010
Danio rerio, Escherichia coli, Homo sapiens (Q9NQH7), Homo sapiens
brenda
Wu, S.; Liu, S.; Sim, S.; Pedersen, L.G.
Weakly antiferromagentic coupling via superexchange interaction between Mn(II)-Mn(II) atoms: A QM/MM study of the active site of human cytosolic X-propyl aminopeptidase P
J. Phys. Chem. Lett.
3
2293-2297
2012
Homo sapiens
brenda
Cordova, A.; Woodrick, J.; Grindrod, S.; Zhang, L.; Saygideger-Kont, Y.; Wang, K.; DeVito, S.; Daniele, S.G.; Paige, M.; Brown, M.L.
Aminopeptidase P mediated targeting for breast tissue specific conjugate delivery
Bioconjug. Chem.
27
1981-1990
2016
Homo sapiens (O43895), Homo sapiens
brenda
Drendel, V.; Heckelmann, B.; Chen, C.Y.; Weisser, J.; Espadas, G.; Schell, C.; Sabido, E.; Werner, M.; Jilg, C.A.; Schilling, O.
Proteome profiling of clear cell renal cell carcinoma in von Hippel-Lindau patients highlights upregulation of Xaa-Pro aminopeptidase-1, an anti-proliferative and anti-migratory exoprotease
Oncotarget
8
100066-100078
2017
Homo sapiens (O43895), Homo sapiens (Q9NQW7), Homo sapiens
brenda
Chang, H.C.; Kung, C.C.; Chang, T.T.; Jao, S.C.; Hsu, Y.T.; Li, W.S.
Investigation of the proton relay system operative in human cystosolic aminopeptidase P
PLoS ONE
13
e0190816
2018
Homo sapiens (Q9NQW7), Homo sapiens
brenda