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Literature summary for 3.4.17.1 extracted from

  • Tanco, S.; Zhang, X.; Morano, C.; Aviles, F.X.; Lorenzo, J.; Fricker, L.D.
    Characterization of the substrate specificity of human carboxypeptidase A4 and implications for a role in extracellular peptide processing (2010), J. Biol. Chem., 285, 18385-18396.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
Trypsin tryptic activation at a 1:10 (w/w) ratio for 60 min at room temperature Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Pichia pastoris Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Ascaris carboxypeptidase inhibitor
-
Homo sapiens
EDTA complete inhibition of CPA4 activity s only achieved using a 100 mM concentration of EDTA in an overnight incubation, whereas the same inhibitor concentration causes only 60% inhibition after 5 h of treatment Homo sapiens
latexin
-
Homo sapiens
leech carboxypeptidase inhibitor
-
Homo sapiens
potato carboxypeptidase inhibitor
-
Homo sapiens
tick carboxypeptidase inhibitor from Rhipicephalus bursa Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.000329
-
neurotensin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.00923
-
Met-enkephalin-L-Arg-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.0194
-
3-(2-furyl)acryloyl-L-Phe-L-Leu in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.0233
-
3-(2-furyl)acryloyl-L-Phe-L-Ile in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.04
-
3-(2-furyl)acryloyl-L-Phe-L-Met in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.0556
-
3-(2-furyl)acryloyl-L-Phe-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.0573
-
3-(2-furyl)acryloyl-L-Phe-L-Val in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.0615
-
3-(2-furyl)acryloyl-L-Phe-L-Trp in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.165
-
Leu-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.227
-
angiotensin I in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.372
-
3-(2-furyl)acryloyl-L-Phe-L-Ala in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
0.55
-
Met-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
soluble
-
Homo sapiens
-
-

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
TSK DEAE 5PW column chromatography Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
1BR3.G cell
-
Homo sapiens
-
DU-145 cell
-
Homo sapiens
-
HEK-293T cell
-
Homo sapiens
-
HeLa cell
-
Homo sapiens
-
LNCaP cell
-
Homo sapiens
-
PC-3 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-(2-furyl)acryloyl-L-Phe-L-Ala + H2O
-
Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Ala
-
?
3-(2-furyl)acryloyl-L-Phe-L-Ile + H2O
-
Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Ile
-
?
3-(2-furyl)acryloyl-L-Phe-L-Leu + H2O
-
Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Leu
-
?
3-(2-furyl)acryloyl-L-Phe-L-Met + H2O
-
Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Met
-
?
3-(2-furyl)acryloyl-L-Phe-L-Phe + H2O
-
Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Phe
-
?
3-(2-furyl)acryloyl-L-Phe-L-Trp + H2O
-
Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Trp
-
?
3-(2-furyl)acryloyl-L-Phe-L-Val + H2O
-
Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Val
-
?
angiotensin I + H2O partial cleavage of about 50% of angiotensin is found after 30 min of incubation with CPA4 Homo sapiens ?
-
?
beta-actin (169-177) + H2O weak substrate Homo sapiens ?
-
?
big SAAS + H2O good substrate Homo sapiens ?
-
?
carboxypeptidase A5 C-terminus + H2O requires an overnight incubation for a partial digestion by CPA4 Homo sapiens ?
-
?
cathepsin D (138-155) + H2O weak substrate Homo sapiens ?
-
?
chromogranin A (374-388) + H2O good substrate Homo sapiens ?
-
?
chromogranin A (374-390) + H2O weak substrate Homo sapiens ?
-
?
chromogranin B + H2O good substrate Homo sapiens ?
-
?
clathrin light chain A C-terminus + H2O weak substrate Homo sapiens ?
-
?
des-Asp1-angiotensin + H2O partially cleaved in 2 h Homo sapiens ?
-
?
dynorphin A8 + H2O weak substrate Homo sapiens ?
-
?
elongation factor 1 beta 2 N-terminus + H2O good substrate Homo sapiens ?
-
?
gamma-actin + H2O weak substrate Homo sapiens ?
-
?
Leu-enkephalin + H2O partially cleaved in 2 h Homo sapiens ?
-
?
little SAAS + H2O small percentage of cleavage Homo sapiens ?
-
?
Met-enkephalin + H2O requires an overnight incubation for a partial digestion by CPA4 Homo sapiens ?
-
?
Met-enkephalin-L-Arg-L-Phe + H2O
-
Homo sapiens Met-enkephalin-L-Arg + L-Phe
-
?
additional information CPA4 is able to cleave hydrophobic C-terminal residues with a preference for Phe, Leu, Ile, Met, Tyr, and Val. Aliphatic, aromatic, and basic residues in the P1 position have a positive influence on the cleavage specificity. In contrast, acidic residues, Pro, and Gly have a negative influence in the P1 position Homo sapiens ?
-
?
additional information neither bradykinin nor des-Arg9-bradykinin or 3-(2-furyl)acryloyl-L-Phe-L-His are substrates for CPA4 Homo sapiens ?
-
?
neuromedin N + H2O good substrate Homo sapiens ?
-
?
neurotensin + H2O
-
Homo sapiens ?
-
?
peptidylprolyl isomerase A (118-129) + H2O good substrate Homo sapiens ?
-
?
peptidylprolyl isomerase A (23-39) + H2O weak substrate Homo sapiens ?
-
?
peptidylprolyl isomerase A (26-39) + H2O weak substrate Homo sapiens ?
-
?
peptidylprolyl isomerase A (84-100) + H2O weak substrate Homo sapiens ?
-
?
peptidylprolyl isomerase A (84-92) + H2O weak substrate Homo sapiens ?
-
?
peroxiredoxin V N-terminus + H2O good substrate Homo sapiens ?
-
?
procholecystokinin (46-62) + H2O weak substrate Homo sapiens ?
-
?
procholecystokinin (46-63) + H2O weak substrate Homo sapiens ?
-
?
proenkenphalin octapeptide + H2O weak substrate Homo sapiens ?
-
?
proenkephalin + H2O good substrate Homo sapiens ?
-
?
propeptidyl-amidating monooxygenase + H2O good substrate Homo sapiens ?
-
?
proteasome subunit beta type 6 (34-41) + H2O weak substrate Homo sapiens ?
-
?
protein PEN + H2O good substrate Homo sapiens ?
-
?
protein PEN-20 + H2O good substrate Homo sapiens ?
-
?
provasopressin (151-end) + H2O weak substrate Homo sapiens ?
-
?
ribosomal protein S21 C-terminus + H2O weak substrate Homo sapiens ?
-
?
secretogranin (287-316) + H2O weak substrate Homo sapiens ?
-
?
secretogranin (300-316) + H2O weak substrate Homo sapiens ?
-
?
synaptosomal-associated protein C-terminus + H2O good substrate Homo sapiens ?
-
?
thioredoxin N-terminus + H2O weak substrate Homo sapiens ?
-
?
vacuolar ATP synthase subunit 2 C-terminus + H2O weak substrate Homo sapiens ?
-
?
voltage-dependent anion channel protein 1 C-terminus + H2O weak substrate Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
carboxypeptidase A4
-
Homo sapiens
CPA4 CPA4 is originally referred to as CPA3 but is renamed CPA4 to reflect the order in which the CPAs are discovered Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.24
-
neurotensin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
1.45
-
Met-enkephalin-L-Arg-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
2.33
-
Leu-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.43
-
Met-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
8.23
-
angiotensin I in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
12.4
-
3-(2-furyl)acryloyl-L-Phe-L-Ile in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
13.4
-
3-(2-furyl)acryloyl-L-Phe-L-Leu in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
19.4
-
3-(2-furyl)acryloyl-L-Phe-L-Val in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
23.9
-
3-(2-furyl)acryloyl-L-Phe-L-Met in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
24.3
-
3-(2-furyl)acryloyl-L-Phe-L-Ala in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
44.3
-
3-(2-furyl)acryloyl-L-Phe-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
57.3
-
3-(2-furyl)acryloyl-L-Phe-L-Trp in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens

pH Range

pH Minimum pH Maximum Comment Organism
8.5 9 the optimal pH for cleavage of 3-(2-furyl)acryloyl-L-Phe-L-Phe and 3-(2-furyl)acryloyl-L-Phe-L-Ala is in the range of 8.5-9.0 with very low activity below pH 6.0 Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0000008
-
tick carboxypeptidase inhibitor
-
Homo sapiens
0.0000013
-
potato carboxypeptidase inhibitor
-
Homo sapiens
0.000003
-
latexin
-
Homo sapiens
0.0000073
-
leech carboxypeptidase inhibitor
-
Homo sapiens
0.0000239
-
Ascaris carboxypeptidase inhibitor
-
Homo sapiens

General Information

General Information Comment Organism
physiological function CPA4 functions in neuropeptide processing and regulation in the extracellular environment Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
6.2
-
Met-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
14
-
Leu-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
36
-
angiotensin I in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
65
-
3-(2-furyl)acryloyl-L-Phe-L-Ala in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
93
-
3-(2-furyl)acryloyl-L-Phe-L-Trp in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
157
-
Met-enkephalin-L-Arg-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
338
-
3-(2-furyl)acryloyl-L-Phe-L-Val in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
532
-
3-(2-furyl)acryloyl-L-Phe-L-Ile in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
581
-
3-(2-furyl)acryloyl-L-Phe-L-Met in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
693
-
3-(2-furyl)acryloyl-L-Phe-L-Leu in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
730
-
neurotensin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
797
-
3-(2-furyl)acryloyl-L-Phe-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens