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Information on EC 3.4.11.21 - aspartyl aminopeptidase
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EC Tree
3.4.11.21 aspartyl aminopeptidaseSpecify your search results
Word Map
- 3.4.11.21
- angiotensin
-
aminopeptidases
-
renin-angiotensin
- gluap
-
glutamyl
- angiotensinase
-
alanyl
- cysap
-
glutamyl-aminopeptidase
-
arylamide
- aspartyl-aminopeptidase
-
serine-carboxyl
- synthesis
- medicine
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
Synonyms
aspap, dnpep, peptidase e, acid peptidase, m18aap, aspartyl-ap, alpha-aspartyl dipeptidase, ec 3.4.11.7, soluble acid aminopeptidase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-aspartyl dipeptidase
-
-
-
-
Aminopeptidase
aminopeptidase A
-
-
-
-
angiotensinase
Asp-AP
AspAP
aspartate aminopeptidase
-
-
-
-
aspartic aminopeptidase
-
-
-
-
aspartyl aminopeptidase
aspartyl-AP
DAP
EC 3.4.11.7
glutamyl aminopeptidase
-
-
-
-
L-aspartate aminopeptidase
-
-
-
-
M18AAP
peptidase E
Yhr113w
additional information
angiotensinase
-
-
-
-
AspAP
-
considered initially an alternative name for glutamyl aminopeptidase
additional information
-
the enzyme belongs to the peptidase family M18
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
-
-
-
-
release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
the conserved residues His94, His170, and His440 are essential for activity
-
release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
the conserved residues His94, His170, and His440 are essential for activity
-
release of an N-terminal aspartate or glutamate from a peptide, with a preference for aspartate
the conserved residues His94, His170, and His440 are essential for activity
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
9074-83-3
-
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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
angiotensin II antipeptide + H2O
Glu + Gly-Val-Thr-Val-His-Pro-Val
-
i.e. Glu-Gly-Val-Thr-Val-His-Pro-Val
-
-
?
angiotensinogen 1-14 + H2O
Asp + Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, low activity
-
-
?
Asp-7-amido-4-methylcoumarin + H2O
Asp + 7-amino-4-methylcoumarin
-
-
-
-
?
Asp-Ala-Pro-2-naphthylamide + H2O
Asp + Ala-Pro-2-naphthylamide
-
preferring acidic amino acids favouring aspartyl residues, requires a free alpha-amino group
-
?
Asp-Ala-Pro-sulfamethoxazole + H2O
Asp + Ala-Pro-sulfamethoxazole
-
-
-
?
Asp-Xaa + H2O
Asp + Xaa
-
-
-
r
Asp-Xaa-Xaa + H2O
Asp + Xaa-Xaa
-
no activity on oligopeptides larger than tripeptides
-
r
Asp-Xaa-Xaa-Xaa + H2O
Asp + Xaa-Xaa-Xaa
-
neutral or hydrophobic amino acids in P1 position preferred
-
?
Glu-7-amido-4-methylcoumarin + H2O
Glu + 7-amino-4-methylcoumarin
-
-
-
-
?
L-aspartyl-beta-naphthylamide + H2O
L-aspartic acid + beta-naphthylamine
-
-
-
?
angiotensin + H2O
Asp + des-Asp-angiotensin
-
intracellular protein and peptide metabolism
-
?
angiotensin + H2O
Asp + des-Asp-angiotensin
-
metabolism of angiotensin I, angiotensin II, cholecystokinin-8 and neuropeptide, solube and membrane-bound AspAP play different functional roles in the brain
-
?
angiotensin + H2O
Asp + des-Asp-angiotensin
-
intracellular protein and peptide metabolism
-
?
angiotensin + H2O
Asp + des-Asp-angiotensin
-
intracellular protein and peptide metabolism
-
?
angiotensin I + H2O
Asp + Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu
-
-
?
angiotensin I + H2O
Asp + Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu
-
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin II + H2O
Asp + angiotensin III
-
octapeptides preferred to tetrapeptides
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin II + H2O
Asp + angiotensin III
-
aspartyl aminopeptidase and several other aminopeptidases, i.e. angiotensinases, are involved in angiotensin II and cholecystokinin, CCK, metabolism, angiotensin II is the principal effector of the renin-angiotensin-system, RAS, which induces vasoconstriction and increases sodium and water retention thereby leading to increased blood pressure
-
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe, best substrate
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe, best substrate
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
Asp 2-naphthylamide + H2O
Asp + 2-naphthylamine
-
higher affinity for Asp 2-naphthylamide than for Glu 2-naphthylamide
-
?
Asp 2-naphthylamide + H2O
Asp + 2-naphthylamine
-
attacked more rapidly than 2-naphthylamide derivates of neutral or basic amino acids
-
?
Asp-2-naphthylamide + H2O
Asp + 2-naphthylamine
-
most susceptible substrate
-
-
?
aspartyl peptides + H2O
Asp + des-Asp-angiotensin
-
catabolism of intracellular proteins, breakdown of abnormal cell proteins, supplement of nutritional sources
-
?
aspartyl peptides + H2O
Asp + des-Asp-angiotensin
-
activation and degradation of several neuropeptides, excitatory Asp and Glu implicated in pathogenesis of different neurogeneratives diseases
-
?
Glu 2-naphthylamide + H2O
Glu + 2-naphthylamine
-
attacked more rapidly than 2-naphthylamide derivatives of neutral or basic amino acids
-
-
?
N-(alpha-L-aspartyl)-4-nitroanilide + H2O
L-aspartic acid + 4-nitroaniline
-
-
-
-
?
N-(alpha-L-aspartyl)-4-nitroanilide + H2O
L-aspartic acid + 4-nitroaniline
-
-
-
-
?
N-(alpha-L-aspartyl)-4-nitroanilide + H2O
L-aspartic acid + 4-nitroaniline
-
-
-
-
?
N-(alpha-L-glutamyl)-2-naphthylamide + H2O
L-glutamic acid + 2-naphthylamine
-
-
-
-
?
N-(alpha-L-glutamyl)-2-naphthylamide + H2O
L-glutamic acid + 2-naphthylamine
-
-
-
-
?
N-(alpha-L-glutamyl)-2-naphthylamide + H2O
L-glutamic acid + 2-naphthylamine
-
-
-
-
?
N-(alpha-L-glutamyl)-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
-
-
-
-
?
N-(alpha-L-glutamyl)-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
-
-
-
-
?
N-(alpha-L-glutamyl)-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
-
-
-
-
?
additional information
?
-
-
does not hydrolyze [Asn1, Val5]-angiotensin II, less than 0.5% activity on Ala-p-nitroanilide, Pro-p-nitroanilide, Met-p-nitroanilide, Arg-p-nitroanilide, and Leu-p-nitroanilide
-
-
-
additional information
?
-
Q2U9Z9
does not hydrolyze [Asn1, Val5]-angiotensin II, less than 0.5% activity on Ala-p-nitroanilide, Pro-p-nitroanilide, Met-p-nitroanilide, Arg-p-nitroanilide, and Leu-p-nitroanilide
-
-
-
additional information
?
-
does not hydrolyze [Asn1, Val5]-angiotensin II, less than 0.5% activity on Ala-p-nitroanilide, Pro-p-nitroanilide, Met-p-nitroanilide, Arg-p-nitroanilide, and Leu-p-nitroanilide
-
-
-
additional information
?
-
-
substrate specificity, overview, the substrate chain length is important for activity, the enzyme has little or no activity towards aminoacyl-arylamines, no or little activity towards aspartyl dipeptides with a positively charged residue in the second position
-
-
-
additional information
?
-
-
substrate specificity, overview, the substrate chain length is important for activity, the enzyme has little or no activity towards aminoacyl-arylamines, no or little activity towards aspartyl dipeptides with a positively charged residue in the second position
-
-
-
additional information
?
-
-
the enzyme catalyzes the hydrolysis of N-terminal alpha-L-glutamyl and alpha-L-aspartyl residues
-
-
-
additional information
?
-
-
substrate specificity, overview, the substrate chain length is important for activity, the enzyme has little or no activity towards aminoacyl-arylamines, no or little activity towards aspartyl dipeptides with a positively charged residue in the second position
-
-
-
additional information
?
-
-
no hydrolysis is observed against Leu-7-amido-4-methylcoumarin, Phe-7-amido-4-methylcoumarin, Ala-7-amido-4-methylcoumarin, Pro-7-amido-4-methylcoumarin, Gly-7-amido-4-methylcoumarin, Val-7-amido-4-methylcoumarin, Arg-7-amido-4-methylcoumarin, and Ile-7-amido-4-methylcoumarin
-
-
-
additional information
?
-
-
the enzyme is specific for unblocked N-terminal acidic amino acid residues, no activity with N-acetyl-angiotensinogen 1-14, Tyr-bradykinin, Ile-Ser-bradykinin, and [Sar1, Ala8]-angiotensin II, overview
-
-
-
additional information
?
-
-
the enzyme is specific for unblocked N-terminal acidic amino acid residues, no activity with N-acetyl-angiotensinogen 1-14, Tyr-bradykinin, Ile-Ser-bradykinin, and [Sar1, Ala8]-angiotensin II, overview
-
-
-
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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
angiotensin II + H2O
Asp + angiotensin III
-
aspartyl aminopeptidase and several other aminopeptidases, i.e. angiotensinases, are involved in angiotensin II and cholecystokinin, CCK, metabolism, angiotensin II is the principal effector of the renin-angiotensin-system, RAS, which induces vasoconstriction and increases sodium and water retention thereby leading to increased blood pressure
-
-
?
Asp-Xaa + H2O
Asp + Xaa
-
-
-
r
angiotensin + H2O
Asp + des-Asp-angiotensin
-
intracellular protein and peptide metabolism
-
?
angiotensin + H2O
Asp + des-Asp-angiotensin
-
metabolism of angiotensin I, angiotensin II, cholecystokinin-8 and neuropeptide, solube and membrane-bound AspAP play different functional roles in the brain
-
?
angiotensin + H2O
Asp + des-Asp-angiotensin
-
intracellular protein and peptide metabolism
-
?
angiotensin + H2O
Asp + des-Asp-angiotensin
-
intracellular protein and peptide metabolism
-
?
aspartyl peptides + H2O
Asp + des-Asp-angiotensin
-
catabolism of intracellular proteins, breakdown of abnormal cell proteins, supplement of nutritional sources
-
?
aspartyl peptides + H2O
Asp + des-Asp-angiotensin
-
activation and degradation of several neuropeptides, excitatory Asp and Glu implicated in pathogenesis of different neurogeneratives diseases
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
additional information
additional information
-
activity is not enhanced by Ca2+, Fe2+, Mg2+, Mn2+, and Ni2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-[2-(acridin-9-ylamino)ethyl]benzene-1,2-diol
IC50 value for parasite growth is 0.0013 mM
NaCl
Q2U9Z9, Q2UPZ7
about 30% of activity is retained in 20% (w/v) NaCl; about 30% of activity is retained in 20% (w/v) NaCl
o-phenanthroline
-
activity is reduced to 8.3% after incubating with 20 mM o-phenanthroline
additional information
-
no inhibition by Zn2+ in contrary to glutamyl aminopeptidase, EC 3.4.11.7, no inhibition by Glu-thiol, Asp-thiol, bestatin, amastatin, and puromycin
-
additional information
-
no inhibition by Zn2+ in contrary to glutamyl aminopeptidase, EC 3.4.11.7, no inhibition by Glu-thiol, Asp-thiol, bestatin, amastatin, and puromycin
-
additional information
-
no inhibition by Zn2+ in contrary to glutamyl aminopeptidase, EC 3.4.11.7, no inhibition by Glu-thiol, Asp-thiol, bestatin, amastatin, and puromycin
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Anti-Glomerular Basement Membrane Disease
Chloride Channel ClC-5 Binds to Aspartyl Aminopeptidase to Regulate Renal Albumin Endocytosis.
Astrocytoma
Differential Effects of Doxazosin on Renin-Angiotensin-System-Regulating Aminopeptidase Activities in Neuroblastoma and Glioma Tumoral Cells.
Breast Neoplasms
Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer.
Breast Neoplasms
Renin-Angiotensin system-regulating aminopeptidase activities are modified in the pineal gland of rats with breast cancer induced by N-methyl-nitrosourea.
Chagas Disease
[Description of an acidic peptidase, insensitive to classical inhibitors, in protein extracts of Trypanosoma cruzi, from a rural area of Venezuela, where Chagas disease is endemic].
Colorectal Neoplasms
Clinical impact of aspartyl aminopeptidase expression and activity in colorectal cancer.
Coma
Crystal structure of the peptidase domain of Streptococcus ComA, a bifunctional ATP-binding cassette transporter involved in the quorum-sensing pathway.
Hyperthyroidism
Angiotensinase activity in hypothalamus and pituitary of hypothyroid, euthyroid and hyperthyroid adult male rats.
Hyperthyroidism
Atrial angiotensinase activity in hypothyroid, euthyroid, and hyperthyroid rats.
Hyperthyroidism
Thyroid Disorders Change the Pattern of Response of Angiotensinase Activities in the Hypothalamus-Pituitary-Adrenal Axis of Male Rats.
Malaria
Identification of Potent and Selective Inhibitors of the Plasmodium falciparum M18 Aspartyl Aminopeptidase (PfM18AAP) of Human Malaria via High-Throughput Screening.
Malaria
In silico prediction of anti-malarial hit molecules based on machine learning methods.
Malaria
The M18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum.
Malaria
X-ray Crystal Structure and Specificity of the Plasmodium falciparum Malaria Aminopeptidase PfM18AAP.
Malaria, Falciparum
X-ray Crystal Structure and Specificity of the Plasmodium falciparum Malaria Aminopeptidase PfM18AAP.
Neoplasms
Glutamyl- but not aspartyl-aminopeptidase activity is modified in serum of N-methyl nitrosourea-induced rat mammary tumours.
Neoplasms
The pro-oxidant buthionine sulfoximine (BSO) reduces tumor growth of implanted Lewis lung carcinoma in mice associated with increased protein carbonyl, tubulin abundance, and aminopeptidase activity.
Neuroblastoma
Differential Effects of Doxazosin on Renin-Angiotensin-System-Regulating Aminopeptidase Activities in Neuroblastoma and Glioma Tumoral Cells.
Osteoporosis, Postmenopausal
Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis.
Pancreatic Neoplasms
BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion.
Proteinuria
Chloride Channel ClC-5 Binds to Aspartyl Aminopeptidase to Regulate Renal Albumin Endocytosis.
Proteinuria
Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.94
Asp-Xaa
-
overexpressed enzyme
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.354
Asp-7-amido-4-methylcoumarin
-
at pH 7.5, in the presence of 1 mM Co2+
0.011
Glu-7-amido-4-methylcoumarin
-
at pH 7.5, in the absesence of Co2+
0.33
Glu-7-amido-4-methylcoumarin
-
at pH 7.5, in the presence of 1 mM Co2+
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00339
(S)-(+)-apomorphine
pH 7.5, temperature not specified in the publication
0.183
3-amino-3-[P-(2-carboxypropyl)phosphinyl]propionic acid
-
at pH 7.5
0.0427
4-amino-4-[P-(2-carboxypropyl)phosphinyl]butyric acid
-
at pH 7.5
0.00135
4-[2-(acridin-9-ylamino)ethyl]benzene-1,2-diol
pH 7.5, temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00013
-
normal healthy rats, soluble fraction of heart, APA; normal healthy rats, soluble fraction of lung, APA
additional information
additional information
-
enzyme activities in soluble fractions of heat, kidney, lung, and adrenal gland from PEG-treated rats, acute salt-loaded rats, water-overloaded rats, salt-loaded rats, and water-deprived rats, overview
additional information
-
angiotensin I: 100%, angiotensin II: 144%, angiotensinogen 1-14: 35%, angiotensin II antipeptide: 116%, N-acetyl-angiotensinogen 1-14: 0%, Tyr-bradykinin: 0%, Ile-Ser-bradykinin: 0%, [sar1,ala8] angiotensin II: 0%
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
additional information
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
29 and 33 months old rats show a 50% decrease of enzymatic activity
brenda
additional information
-
bilateral distribution of aminopeptidases in stress-related areas, overview
brenda
additional information
-
enzyme in visceral organs during alterations in body fluid volume and osmolality, overview
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
aspartyl aminopeptidase is a moonlight protein that has aspartyl aminopeptidase and chaperone activities
physiological function
-
a small portion localizes in the vacuole, but its vacuolar transport is accelerated by nutrient starvation, and it stably resides in the vacuole lumen, it is proposed that cytosolic enzyme is redistributed to the vacuole when yeast cells need more active vacuolar degradation
physiological function
-
aspartyl aminopeptidase interacts with ClC-5, a chloride/proton exchanger that plays an obligate role in albumin uptake by the renal proximal tubule. ClC-5 forms an endocytic complex with the albumin receptor megalin/cubilin. Aspartyl aminopeptidase and ClC-5 associate in cells. The two proteins bind directly to each other. Overexpression of wild-type aspartyl aminopeptidase increases cell-surface levels of ClC-5 and albumin uptake. Overexpression results in significant decrease in the amount of G actin, suggesting a role for aspartyl aminopeptidase in stabilizing the cytoskeleton
physiological function
-
aspartyl aminopeptidase immunoprecipitates with beta-actin and tubulin, suggesting a role in cytoskeletal maintenance. Enzyme is not present in the urine of healthy rats, however, it is readily detected in the urine in rat models of mild and heavy proteinuria. Urinary levels correlate with the severity of proteinuria
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
DNPEP_SCHPO
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
467
0
51741
Swiss-Prot
DNPEP_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
490
0
54174
Swiss-Prot
DNPEP_ASPOR
Aspergillus oryzae (strain ATCC 42149 / RIB 40)
498
0
53992
Swiss-Prot
A0A0F8D3V9_CERFI
493
0
53606
TrEMBL
M5C3F4_THACB
Thanatephorus cucumeris (strain AG1-IB / isolate 7/3/14)
417
0
45907
TrEMBL
W1QG73_OGAPD
Ogataea parapolymorpha (strain ATCC 26012 / BCRC 20466 / JCM 22074 / NRRL Y-7560 / DL-1)
481
0
53714
TrEMBL
A3LQF5_PICST
Scheffersomyces stipitis (strain ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL Y-11545)
489
0
54224
TrEMBL
A0A3G7M6F3_9PSED
429
0
46999
TrEMBL
B8MT99_TALSN
Talaromyces stipitatus (strain ATCC 10500 / CBS 375.48 / QM 6759 / NRRL 1006)
407
0
44408
TrEMBL
A0A3G7RU85_9PSED
429
0
46985
TrEMBL
A0A3G7B5N5_9PSED
429
0
46964
TrEMBL
A0A125YW18_TOXGM
Toxoplasma gondii (strain ATCC 50611 / Me49)
508
0
55897
TrEMBL
A0A3G7IKE9_9PSED
429
0
47003
TrEMBL
A0A125YW20_TOXGV
Toxoplasma gondii (strain ATCC 50861 / VEG)
508
0
55897
TrEMBL
S7UJV5_TOXGG
Toxoplasma gondii (strain ATCC 50853 / GT1)
508
0
55897
TrEMBL
B8MT98_TALSN
Talaromyces stipitatus (strain ATCC 10500 / CBS 375.48 / QM 6759 / NRRL 1006)
526
0
57427
TrEMBL
A0A086KCA6_TOXGO
508
0
55897
TrEMBL
B9W989_CANDC
Candida dubliniensis (strain CD36 / ATCC MYA-646 / CBS 7987 / NCPF 3949 / NRRL Y-17841)
494
0
55076
TrEMBL
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55000
440000
680000
-
gel filtration; native enzyme, dodecamer, determined using a Superose 6 column
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dodecamer
homooctamer
-
8 * 65000, SDS-PAGE; 8 * 70000, high performance liquid chromatography
additional information
dodecamer
-
12 * 56000, SDS-PAGE; dodecamer comprising 12 identical units
dodecamer
-
12 * 56000, SDS-PAGE; dodecamer comprising 12 identical units
-
additional information
-
peptide mass fingerprinting by MALDI-TOF MS analysis
additional information
-
peptide mass fingerprinting by MALDI-TOF MS analysis
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
in complex with zinc and substrate analogue aspartate-beta-hydroxamate, to 2.2 A resolution. Structure reveals a dodecameric machinery built by domain-swapped dimers, in agreement with electron microscopy data. For both Asp-Ala and Glu-Ala substrates, the Asp and Glu side chains fit into the P1 substrate pocket without steric constraints, while the main chain is modeled onto the hydroxamate group of aspartate-beta-hydroxamate in a position optimal for hydrolysis. The P1 substrate pocket is created by strand beta15 and the beta16-alpha12 and beta17-alpha13 loops, with the beta17-lpha13 loop lining the wall and restricting the dimensions of the pocket. This limited space disfavours bulky hydrophobic residues
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H352F
-
dramatically reduced activity, destabilization of quarternary structure and dissociation of the native 440000 Da enzyme
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50
60 - 70
AAP is not precipitated by heat treatment for 30 min at 60°C, only less than 10% of AAP protein is precipitated by heating at 70°C
50
Q2U9Z9, Q2UPZ7
the enzyme remains stabel upt to 50°C and retains about 70% activity after 20 h at 50°C, is inactivated rapidly at temperature in excess of this; the enzyme remains stable upt to 50°C and retains about 70% activity after 20 h at 50°C, is inactivated rapidly at temperature in excess of this
50
-
remarkably stable below 50°C, soon inactivated at 60°C
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PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
2000fold to homogeneity, Triton X-100 solubilized microsomal fraction, DEAE-cellulose chromatography, immunoadsorbent chromatography; proteinase solubilized microsomal fraction, DEAE-cellulose chromatography, immunoadsorbent chromatography to homogeneity
-
aspartyl aminopeptidase is purified from yeast cells, using ultracentrifugation, ammonium sulfate fractionating, and chromatography on a Bio-Gel column, on a Mono Q column, and a Superose 6 column; native enzyme to homogeneity by ultracentrifugation, ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
DEAE-Sephacel gel filtration and TSK phenyl 5-PW gel filtration
Ni-Sepharose 6 Fast Flow column chromatography; Ni-Sepharose 6 Fast Flow column chromatography
Q2U9Z9, Q2UPZ7
non-fusion protein expressed in Escherichia coli, 440fold to homogeneity
-
partial, ammonium sulfate fractionation, gel filtration, ion-exchange chromatography
-
recombinant His6-tagged enzyme from Escherichia coli by nickel affinity chromatography to homogeneity
-
soluble enzyme from brain to homogeneity by affinity chromatography, gel filtration, hydrophobic interaction and hydroxyapatite chromatography
-
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CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, expression in Escherichia coli as His6-tagged enzyme
-
expressed in Escherichia coli BL21(DE3), GFP- and hemagglutinin-tagged constructs
-
expressed in Escherichia coli; expressed in Escherichia coli
Q2U9Z9, Q2UPZ7
expression in Escherichia coli
gene YHR113W, located on chromosome VIII, DNA and amino acid sequence determination and analysis
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
solubilization of inclusion bodies by treatment with 0.6% Triton X-100, pH 10.0, 30 mM NaCl at 40°C for 20 min
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
enzyme is not present in the urine of healthy rats, however, it is readily detected in the urine in rat models of mild and heavy proteinuria. Urinary levels correlate with the severity of proteinuria
synthesis
-
dipeptide sweeteners aspartame and alitame
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Danielsen, E.M.; Noren, O.; Sjoestroem, H.; Ingram, J.; Kenny, A.J.
Proteins of the kidney microvillar membrane. Aspartate aminopeptidase: purification by immunoadsorbent chromatography and properties of the detergent- and proteinase-solubilized forms
Biochem. J.
189
591-603
1980
Sus scrofa
brenda
Ramirez-Exposito, M.J.; Martinez, J.M.; Prieto, I.; Alba, F.; Ramirez, M.
Comparative distribution of glutamyl and aspartyl aminopeptidase activities in mouse organs
Horm. Metab. Res.
32
161-163
2000
Mus musculus
brenda
Wilk, S.; Wilk, E.; Magnusson, R.P.
Purification, characterization and cloning of a cytosolic aspartyl aminopeptidase
J. Biol. Chem.
273
15961-15970
1998
Homo sapiens, Oryctolagus cuniculus, Rattus sp.
brenda
Iribar, C.; Esteban, M.J.; Martinez, J.M.; Peinado, J.M.
Decrease in cytosolic aspartyl-aminopeptidase but not in alanyl-aminopeptidase activity in the frontal cortex of the aged rat
Brain Res.
687
211-213
1995
Rattus sp.
brenda
Nathan, P.B.; Ahmad, S.I.; Griffin, M.
Identification and characterization of an aspartate-specific peptidase (peptidase E) in Escherichia coli K12
Biochem. Soc. Trans.
17
354
1989
Escherichia coli
-
brenda
Zhang, H.; Zhang, J.; Wang, X.; Yang, W.; Lu, J.
Biochemical characterization of alpha-aspartyl dipeptidase. Cloning and expression of its gene
Ann. N. Y. Acad. Sci.
864
621-625
1998
Salmonella enterica subsp. enterica serovar Typhimurium
brenda
Wilk, S.; Wilk, E.; Magnusson, R.P.
Identification of histidine residues important in the catalysis and structure of aspartyl aminopeptidase
Arch. Biochem. Biophys.
407
176-183
2002
Homo sapiens
brenda
Banegas, I.; Prieto, I.; Alba, F.; Vives, F.; Araque, A.; Segarra, A.B.; Duran, R.; de Gasparo, M.; Ramirez, M.
Angiotensinase activity is asymmetrically distributed in the amygdala, hippocampus and prefrontal cortex of the rat
Behav. Brain Res.
156
321-326
2005
Rattus norvegicus
brenda
Yokoyama, R.; Kawasaki, H.; Hirano, H.
Identification of yeast aspartyl aminopeptidase gene by purifying and characterizing its product from yeast cells
FEBS J.
273
192-198
2006
Saccharomyces cerevisiae, Saccharomyces cerevisiae B-8032
brenda
Adang, M.J.
Aminopeptidase A
Handbook of Proteolytic Enzymes (2nd Edition)
1
299-303
2004
Mus musculus
-
brenda
Simmons, W.H.
Aspartyl aminopeptidase
Handbook of Proteolytic Enzymes (2nd Edition)
1
937-939
2004
Homo sapiens, Mus musculus, Oryctolagus cuniculus
-
brenda
Gasparello-Clemente, E.; Casis, L.; Varona, A.; Gil, J.; Irazusta, J.; Silveira, P.F.
Aminopeptidases in visceral organs during alterations in body fluid volume and osmolality
Peptides
24
1367-1372
2003
Rattus norvegicus
brenda
Varona, A.; Blanco, L.; Lopez, J.I.; Gil, J.; Agirregoitia, E.; Irazusta, J.; Larrinaga, G.
Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma
Am. J. Physiol. Renal Physiol.
292
F780-F788
2007
Homo sapiens
brenda
Watanabe, J.; Tanaka, H.; Akagawa, T.; Mogi, Y.; Yamazaki, T.
Characterization of Aspergillus oryzae aspartyl aminopeptidase expressed in Escherichia coli
Biosci. Biotechnol. Biochem.
71
2557-2560
2007
Aspergillus oryzae, Aspergillus oryzae (Q2U9Z9), Aspergillus oryzae (Q2UPZ7)
brenda
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
brenda
Teuscher, F.; Lowther, J.; Skinner-Adams, T.S.; Spielmann, T.; Dixon, M.W.; Stack, C.M.; Donnelly, S.; Mucha, A.; Kafarski, P.; Vassiliou, S.; Gardiner, D.L.; Dalton, J.P.; Trenholme, K.R.
The M18 aspartyl aminopeptidase of the human malaria parasite Plasmodium falciparum
J. Biol. Chem.
282
30817-30826
2007
Plasmodium falciparum
brenda
Segarra, A.B.; Wangensteen, R.; Ramirez, M.; Banegas, I.; Hermoso, F.; Vargas, F.; Vives, F.; Duran, R.; Alba, F.; de Gasparo, M.; Prieto, I.
Atrial angiotensinase activity in hypothyroid, euthyroid, and hyperthyroid rats
J. Cardiovasc. Pharmacol.
48
117-120
2006
Rattus norvegicus
brenda
Banegas, I.; Prieto, I.; Vives, F.; Alba, F.; de Gasparo, M.; Segarra, A.B.; Hermoso, F.; Duran, R.; Ramirez, M.
Brain aminopeptidases and hypertension
J. Renin Angiotensin Aldosterone Syst.
7
129-134
2006
Rattus norvegicus
brenda
Lee, S.; Kim, J.S.; Yun, C.H.; Chae, H.Z.; Kim, K.
Aspartyl aminopeptidase of Schizosaccharomyces pombe has a molecular chaperone function
BMB Rep.
42
812-816
2009
Schizosaccharomyces pombe (O36014), Schizosaccharomyces pombe
brenda
Trenholme, K.R.; Brown, C.L.; Skinner-Adams, T.S.; Stack, C.; Lowther, J.; To, J.; Robinson, M.W.; Donnelly, S.M.; Dalton, J.P.; Gardiner, D.L.
Aminopeptidases of malaria parasites: new targets for chemotherapy
Infect. Disord. Drug Targets
10
217-225
2010
Plasmodium falciparum
brenda
Cai, W.W.; Wang, L.; Chen, Y.
Aspartyl aminopeptidase, encoded by an evolutionarily conserved syntenic gene, is colocalized with its cluster in secretory granules of pancreatic islet cells
Biosci. Biotechnol. Biochem.
74
2050-2055
2010
Mus musculus (Q9Z2W0)
brenda
Yuga, M.; Gomi, K.; Klionsky, D.J.; Shintani, T.
Aspartyl aminopeptidase is imported from the cytoplasm to the vacuole by selective autophagy in Saccharomyces cerevisiae
J. Biol. Chem.
286
13704-13713
2011
Saccharomyces cerevisiae
brenda
Lee, A.; Slattery, C.; Nikolic-Paterson, D.J.; Hryciw, D.H.; Wilk, S.; Wilk, E.; Zhang, Y.; Valova, V.A.; Robinson, P.J.; Kelly, D.J.; Poronnik, P.
Chloride channel ClC-5 binds to aspartyl aminopeptidase to regulate renal albumin endocytosis
Am. J. Physiol. Renal Physiol.
308
F784-F792
2015
Didelphis sp., Rattus norvegicus
brenda
Chaikuad, A.; Pilka, E.; De Riso, A.; Von Delft, F.; Kavanagh, K.; Venien-Bryan, C.; Oppermann, U.; Yue, W.
Structure of human aspartyl aminopeptidase complexed with substrate analogue: Insight into catalytic mechanism, substrate specificity and M18 peptidase family
BMC Struct. Biol.
12
14
2012
Homo sapiens, Homo sapiens (Q9ULA0)
brenda
Spicer, T.; Fernandez-Vega, V.; Chase, P.; Scampavia, L.; To, J.; Dalton, J.P.; Da Silva, F.L.; Skinner-Adams, T.S.; Gardiner, D.L.; Trenholme, K.R.; Brown, C.L.; Ghosh, P.; Porubsky, P.; Wang, J.L.; Whipple, D.A.; Schoenen, F.J.; Hodder, P.
Identification of potent and selective inhibitors of the Plasmodium falciparum M18 aspartyl aminopeptidase (PfM18AAP) of human malaria via high-throughput screening
J. Biomol. Screen.
19
1107-1115
2014
Plasmodium falciparum, Plasmodium falciparum (Q8I2J3)
brenda
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