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Information on EC 3.4.11.14 - cytosol alanyl aminopeptidase and Organism(s) Homo sapiens
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3.4.11.14 cytosol alanyl aminopeptidaseSpecify your search results
Word Map
- 3.4.11.14
- aminopeptidases
- bestatin
- amastatin
- beta-naphthylamides
- actinonin
-
enkephalin-degrading
-
tau-induced
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides and arylamides
Synonyms
puromycin-sensitive aminopeptidase, mp100, nucleomorphin, microsomal alanyl aminopeptidase, psa/npepps, npepps, alanyl-ap, aap-s, soluble alanyl aminopeptidase, puromycin-sensitive neuron-aminopeptidase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AAP-S
-
-
-
-
alanyl aminopeptidase
-
-
-
-
aminopeptidase, cytosol alanyl
-
-
-
-
Aminopolypeptidase
-
-
-
-
aminotripeptidase
-
-
-
-
cytyosol aminopeptidase III
-
-
-
-
puromycin-sensitive aminopeptidase
soluble alanyl aminopeptidase
-
-
-
-
tripeptidase
-
-
-
-
tripeptide aminopeptidase
-
-
-
-
puromycin-sensitive aminopeptidase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
243859-94-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ala-2-naphthylamide + H2O
Ala + 2-naphthylamine
-
-
-
-
?
Gly-2-naphthylamide + H2O
Gly + 2-naphthylamine
-
13.7% of the activity with Ala-2-naphthylamide
-
-
?
KKE-(5-[(2-aminoethyl) amino]-naphthalene-1-sulfonic acid)-Q9K-((4'-dimethylaminoazobenzene-4'-sulfonyl))-K + H2O
?
-
-
-
-
?
Ser-2-naphthylamide + H2O
Ser + 2-naphthylamine
-
6.0% of the activity with Ala-2-naphthylamide
-
-
?
Thr-2-naphthylamide + H2O
Thr + 2-naphthylamine
-
5.7% of the activity with Ala-2-naphthylamide
-
-
?
Trp-2-naphthylamide + H2O
Trp + 2-naphthylamine
-
19.2% of the activity with Ala-2-naphthylamide
-
-
?
additional information
?
-
-
there are two active centre ionizable groups with pKa values of approximately 6.0 and 7.5 which are involved in substrate binding or inhibitory amino acid binding
-
-
?
Arg-2-naphthylamide + H2O
Arg + 2-naphthylamine
-
28% of the activity with Ala-2-naphthylamide
-
-
?
Leu-2-naphthylamide + H2O
Leu + 2-naphthylamine
-
36.4% of the activity with Ala-2-naphthylamide
-
-
?
Lys-2-naphthylamide + H2O
Lys + 2-naphthylamine
-
13.4% of the activity with Ala-2-naphthylamide
-
-
?
Met-2-naphthylamide + H2O
Met + 2-naphthylamine
-
57.5% of the activity with Ala-2-naphthylamide
-
-
?
Phe-2-naphthylamide + H2O
Phe + 2-naphthylamine
-
62.8% of the activity with Ala-2-naphthylamide
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Zinc
Co2+
-
2.4fold activation, Co2+ binds loosely in a noncompetitive manner
Zinc
-
the enzyme contains 1 mol of zinc per 113500 g of protein, the zinc is firmly bound
Zinc
-
1 mol Zn2+ for 113500 g protein, firmly bound, not removed by chelating agents
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Leu
-
noncompetitive with Ala-2-naphthylamide, mixed type inhibition with Leu-Leu-Leu, competitive inhibition with Ala-Ala-Ala
NaCl
-
hydrolysis of Ala-4-nitropanilide, competitive inhibition at pH 6.6, inhibition is noncompetitive at pH 5.8, inhibition is mixed type at pH 6.2
additional information
-
there are two active centre ionizable groups with pKa values of approximately 6.0 and 7.5 which are involved in substrate binding or inhibitory amino acid binding
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.27
Ala-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
0.25
Leu-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
2.2
Lys-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
0.8
Met-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
0.47
Pro-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
0.21
Val-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
89
Lys-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
30
Met-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
1.43
Val-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
3.8
Ala-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
20.83
Ala-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
3.5
Leu-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
19.83
Leu-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
16.9
Pro-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
23.17
Pro-p-nitroanilide
-
with 1 mM dithiothreitol, in 10 mM Tris-HCl, pH 7.4, at 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00007
bestatin
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00008
PAQ-22
Homo sapiens
-
non-competitive, pH not specified in the publication, temperature not specified in the publication
0.0006
puromycin
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0025
puromycin aminonucleoside
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
increase of enzymic activity in the prefrontal cortex of heroin abusers while other peptidases remain unaltered
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
downregulation of enzyme expression suppresses the proliferation, migration and invasion of PC-3 cells and decreases the secretion and expression of matrix metalloproteinase-9
malfunction
-
decrease in activity increases the aggregation and toxicity of expanded huntingtin exon 1, overexpression reduces aggregates and toxicity of mutant huntingtin exon 1
physiological function
-
elevation of activity in vivo effectively blocks accumulation of soluble hyperphosphorylated TAU protein and slows down the progression of neurodegeneration in the mammalian system
physiological function
-
regulates directly Cu,Zn-superoxide dismutase 1 (SOD1) protein abundance and clearance via proteolysis
physiological function
-
suppresses accumulation of mutant huntingtin aggregates and toxicity in vivo, decreases aggregate number in cellular models of neurodegenerative diseases, enhances macroautophagy
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). PSA_HUMAN
919
0
103276
Swiss-Prot
Mitochondrion (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
contains 17.5% carbohydrate - 4.3% glucosamine, 4.1% sialic acid, 9% hexoses
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
when the enzyme is treated at 60°C with EDTA the inhibition is no longer reversible and there is a concomitant loss of zinc
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Starnes, W.L.; Szechinski, J.; Behal, F.J.
Human-liver alanine aminopeptidase. A kinin-converting enzyme sensitive to beta-lactam antibiotics
Eur. J. Biochem.
124
363-370
1982
Homo sapiens
Garner, C.W.; Behal, F.J.
Hydrophobic binding sites of human liver alanine aminopeptidase
Arch. Biochem. Biophys.
182
667-673
1977
Homo sapiens
Little, G.H.; Starnes, W.L.; Behal, F.J.
Human liver aminopeptidase
Methods Enzymol.
45
495-503
1976
Homo sapiens
Garner, C.W.; Behal, F.J.
Effect of pH on substrate and inhibitor kinetic constants of human liver alanine aminopeptidase. Evidence for two ionizable active center groups
Biochemistry
14
5084-5088
1975
Homo sapiens
Garner, C.W.; Behal, F.J.
Human liver alanine aminopeptidase. Inhibition by amino acids
Biochemistry
14
3208-3212
1975
Homo sapiens
Starnes, W.L.; Behal, F.J.
A human liver aminopeptidase. The amino acid and carbohydrate content, and some physical properties of a sialic acid containing glycoprotein
Biochemistry
13
3221-3227
1974
Homo sapiens
Garner, C.W.; Behal, F.J.
Human liver aminopeptidase. Role of metal ions in mechanism of action
Biochemistry
13
3227-3233
1974
Homo sapiens
Kao, Y.J.; Starnes, W.L.; Behal, F.J.
Human kidney alanine aminopeptidase: physical and kinetic properties of a sialic acid containing glycoprotein
Biochemistry
17
2990-2994
1978
Homo sapiens
Larrinaga, G.; Callado, L.F.; Agirregoitia, N.; Varona, A.; Gil, J.
Subcellular distribution of membrane-bound aminopeptidases in the human and rat brain
Neurosci. Lett.
383
136-140
2005
Homo sapiens, Rattus norvegicus
Larrinaga, G.; Gil, J.; Meana, J.J.; Ruiz, F.; Callado, L.F.; Irazusta, J.
Aminopeptidase activity in the postmortem brain of human heroin addicts
Neurochem. Int.
46
213-219
2005
Homo sapiens
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
Sengupta, S.; Horowitz, P.M.; Karsten, S.L.; Jackson, G.R.; Geschwind, D.H.; Fu, Y.; Berry, R.W.; Binder, L.I.
Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro
Biochemistry
45
15111-15119
2006
Homo sapiens
Bhutani, N.; Venkatraman, P.; Goldberg, A.L.
Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation
EMBO J.
26
1385-1396
2007
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
Karsten, S.L.; Sang, T.K.; Gehman, L.T.; Chatterjee, S.; Liu, J.; Lawless, G.M.; Sengupta, S.; Berry, R.W.; Pomakian, J.; Oh, H.S.; Schulz, C.; Hui, K.S.; Wiedau-Pazos, M.; Vinters, H.V.; Binder, L.I.; Geschwind, D.H.; Jackson, G.R.
A genomic screen for modifiers of tauopathy identifies puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration
Neuron
51
549-560
2006
Homo sapiens
Lee, S.H.; Kim, H.G.
Cobalt chloride-induced downregulation of puromycin-sensitive aminopeptidase suppresses the migration and invasion of PC-3 cells
J. Microbiol. Biotechnol.
19
530-536
2009
Homo sapiens
Yanagi, K.; Tanaka, T.; Kato, K.; Sadik, G.; Morihara, T.; Kudo, T.; Takeda, M.
Involvement of puromycin-sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) mutant tau
Psychogeriatrics
9
157-166
2009
Homo sapiens
Menzies, F.M.; Hourez, R.; Imarisio, S.; Raspe, M.; Sadiq, O.; Chandraratna, D.; OKane, C.; Rock, K.L.; Reits, E.; Goldberg, A.L.; Rubinsztein, D.C.
Puromycin-sensitive aminopeptidase protects against aggregation-prone proteins via autophagy
Hum. Mol. Genet.
19
4573-4586
2010
Homo sapiens
Kudo, L.C.; Parfenova, L.; Ren, G.; Vi, N.; Hui, M.; Ma, Z.; Lau, K.; Gray, M.; Bardag-Gorce, F.; Wiedau-Pazos, M.; Hui, K.S.; Karsten, S.L.
Puromycin-sensitive aminopeptidase (PSA/NPEPPS) impedes development of neuropathology in hPSA/TAU(P301L) double-transgenic mice
Hum. Mol. Genet.
20
1820-1833
2011
Homo sapiens
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