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Literature summary 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

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

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.4.17.1 expressed in Pichia pastoris Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.17.1 Ascaris carboxypeptidase inhibitor
-
 Homo sapiens
3.4.17.1 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
3.4.17.1 latexin
-
 Homo sapiens
3.4.17.1 leech carboxypeptidase inhibitor
-
 Homo sapiens
3.4.17.1 potato carboxypeptidase inhibitor
-
 Homo sapiens
3.4.17.1 tick carboxypeptidase inhibitor from Rhipicephalus bursa Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.4.17.1 0.000329
-
 neurotensin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 0.00923
-
 Met-enkephalin-L-Arg-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 0.165
-
 Leu-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 0.227
-
 angiotensin I in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 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
3.4.17.1 0.55
-
 Met-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.4.17.1 soluble
-
 Homo sapiens
-
-

Organism

EC Number Organism UniProt Comment Textmining
3.4.17.1 Homo sapiens
-
-
-

Purification (Commentary)

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

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.4.17.1 1BR3.G cell
-
 Homo sapiens
-
3.4.17.1 DU-145 cell
-
 Homo sapiens
-
3.4.17.1 HEK-293T cell
-
 Homo sapiens
-
3.4.17.1 HeLa cell
-
 Homo sapiens
-
3.4.17.1 LNCaP cell
-
 Homo sapiens
-
3.4.17.1 PC-3 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.17.1 3-(2-furyl)acryloyl-L-Phe-L-Ala + H2O
-
 Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Ala
-
 ?
3.4.17.1 3-(2-furyl)acryloyl-L-Phe-L-Ile + H2O
-
 Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Ile
-
 ?
3.4.17.1 3-(2-furyl)acryloyl-L-Phe-L-Leu + H2O
-
 Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Leu
-
 ?
3.4.17.1 3-(2-furyl)acryloyl-L-Phe-L-Met + H2O
-
 Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Met
-
 ?
3.4.17.1 3-(2-furyl)acryloyl-L-Phe-L-Phe + H2O
-
 Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Phe
-
 ?
3.4.17.1 3-(2-furyl)acryloyl-L-Phe-L-Trp + H2O
-
 Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Trp
-
 ?
3.4.17.1 3-(2-furyl)acryloyl-L-Phe-L-Val + H2O
-
 Homo sapiens 3-(2-furyl)acryloyl-L-Phe + L-Val
-
 ?
3.4.17.1 angiotensin I + H2O partial cleavage of about 50% of angiotensin is found after 30 min of incubation with CPA4 Homo sapiens ?
-
 ?
3.4.17.1 beta-actin (169-177) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 big SAAS + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 carboxypeptidase A5 C-terminus + H2O requires an overnight incubation for a partial digestion by CPA4 Homo sapiens ?
-
 ?
3.4.17.1 cathepsin D (138-155) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 chromogranin A (374-388) + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 chromogranin A (374-390) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 chromogranin B + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 clathrin light chain A C-terminus + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 des-Asp1-angiotensin + H2O partially cleaved in 2 h Homo sapiens ?
-
 ?
3.4.17.1 dynorphin A8 + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 elongation factor 1 beta 2 N-terminus + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 gamma-actin + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 Leu-enkephalin + H2O partially cleaved in 2 h Homo sapiens ?
-
 ?
3.4.17.1 little SAAS + H2O small percentage of cleavage Homo sapiens ?
-
 ?
3.4.17.1 Met-enkephalin + H2O requires an overnight incubation for a partial digestion by CPA4 Homo sapiens ?
-
 ?
3.4.17.1 Met-enkephalin-L-Arg-L-Phe + H2O
-
 Homo sapiens Met-enkephalin-L-Arg + L-Phe
-
 ?
3.4.17.1 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 ?
-
 ?
3.4.17.1 additional information neither bradykinin nor des-Arg9-bradykinin or 3-(2-furyl)acryloyl-L-Phe-L-His are substrates for CPA4 Homo sapiens ?
-
 ?
3.4.17.1 neuromedin N + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 neurotensin + H2O
-
 Homo sapiens ?
-
 ?
3.4.17.1 peptidylprolyl isomerase A (118-129) + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 peptidylprolyl isomerase A (23-39) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 peptidylprolyl isomerase A (26-39) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 peptidylprolyl isomerase A (84-100) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 peptidylprolyl isomerase A (84-92) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 peroxiredoxin V N-terminus + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 procholecystokinin (46-62) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 procholecystokinin (46-63) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 proenkenphalin octapeptide + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 proenkephalin + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 propeptidyl-amidating monooxygenase + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 proteasome subunit beta type 6 (34-41) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 protein PEN + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 protein PEN-20 + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 provasopressin (151-end) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 ribosomal protein S21 C-terminus + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 secretogranin (287-316) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 secretogranin (300-316) + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 synaptosomal-associated protein C-terminus + H2O good substrate Homo sapiens ?
-
 ?
3.4.17.1 thioredoxin N-terminus + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 vacuolar ATP synthase subunit 2 C-terminus + H2O weak substrate Homo sapiens ?
-
 ?
3.4.17.1 voltage-dependent anion channel protein 1 C-terminus + H2O weak substrate Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.4.17.1 carboxypeptidase A4
-
 Homo sapiens
3.4.17.1 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]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.4.17.1 0.24
-
 neurotensin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 1.45
-
 Met-enkephalin-L-Arg-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 2.33
-
 Leu-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 3.43
-
 Met-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 8.23
-
 angiotensin I in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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
3.4.17.1 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

EC Number pH Minimum pH Maximum Comment Organism
3.4.17.1 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]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
3.4.17.1 0.0000008
-
 tick carboxypeptidase inhibitor
-
 Homo sapiens
3.4.17.1 0.0000013
-
 potato carboxypeptidase inhibitor
-
 Homo sapiens
3.4.17.1 0.000003
-
 latexin
-
 Homo sapiens
3.4.17.1 0.0000073
-
 leech carboxypeptidase inhibitor
-
 Homo sapiens
3.4.17.1 0.0000239
-
 Ascaris carboxypeptidase inhibitor
-
 Homo sapiens

General Information

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

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
3.4.17.1 6.2
-
 Met-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 14
-
 Leu-enkephalin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 36
-
 angiotensin I in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 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
3.4.17.1 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
3.4.17.1 157
-
 Met-enkephalin-L-Arg-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 338
-
 3-(2-furyl)acryloyl-L-Phe-L-Val in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 532
-
 3-(2-furyl)acryloyl-L-Phe-L-Ile in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 581
-
 3-(2-furyl)acryloyl-L-Phe-L-Met in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 693
-
 3-(2-furyl)acryloyl-L-Phe-L-Leu in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 730
-
 neurotensin in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens
3.4.17.1 797
-
 3-(2-furyl)acryloyl-L-Phe-L-Phe in 50 mM Tris-HCl, 100 mM NaCl, pH 7.5, at 37°C Homo sapiens