| IED ID | IndEnz0002016745 |
| Enzyme Type ID | protease016745 |
| Protein Name |
Cytosol aminopeptidase EC 3.4.11.1 Cysteinylglycine-S-conjugate dipeptidase EC 3.4.13.23 Leucine aminopeptidase 3 LAP-3 Leucyl aminopeptidase LAP Peptidase S Proline aminopeptidase EC 3.4.11.5 Prolyl aminopeptidase |
| Gene Name | LAP3 |
| Organism | Bos taurus (Bovine) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Laurasiatheria Artiodactyla Ruminantia Pecora Bovidae Bovinae Bos (oxen cattle) Bos taurus (Bovine) |
| Enzyme Sequence | MFLLPLPAAARVAVRHLSVKRLWAPGPAAADMTKGLVLGIYSKEKEEDEPQFTSAGENFNKLVSGKLREILNISGPPLKAGKTRTFYGLHEDFPSVVVVGLGKKTAGIDEQENWHEGKENIRAAVAAGCRQIQDLEIPSVEVDPCGDAQAAAEGAVLGLYEYDDLKQKRKVVVSAKLHGSEDQEAWQRGVLFASGQNLARRLMETPANEMTPTKFAEIVEENLKSASIKTDVFIRPKSWIEEQEMGSFLSVAKGSEEPPVFLEIHYKGSPNASEPPLVFVGKGITFDSGGISIKAAANMDLMRADMGGAATICSAIVSAAKLDLPINIVGLAPLCENMPSGKANKPGDVVRARNGKTIQVDNTDAEGRLILADALCYAHTFNPKVIINAATLTGAMDIALGSGATGVFTNSSWLWNKLFEASIETGDRVWRMPLFEHYTRQVIDCQLADVNNIGKYRSAGACTAAAFLKEFVTHPKWAHLDIAGVMTNKDEVPYLRKGMAGRPTRTLIEFLFRFSQDSA |
| Enzyme Length | 519 |
| Uniprot Accession Number | P00727 |
| Absorption | |
| Active Site | ACT_SITE 294; /evidence=ECO:0000269|PubMed:7578088; ACT_SITE 368; /evidence=ECO:0000269|PubMed:7578088 |
| Activity Regulation | ACTIVITY REGULATION: Zofenoprilat inhibits Cys-Gly hydrolysis activity. {ECO:0000269|PubMed:16519517}. |
| Binding Site | BINDING 282; /note="Substrate"; /evidence="ECO:0000269|PubMed:7578088, ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LAN, ECO:0007744|PDB:1LCP"; BINDING 287; /note="Substrate"; /evidence="ECO:0000269|PubMed:7578088, ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LAN, ECO:0007744|PDB:1LCP"; BINDING 292; /note="Substrate"; /evidence="ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LCP"; BINDING 294; /note="Substrate"; /evidence="ECO:0000269|PubMed:7578088, ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LAN, ECO:0007744|PDB:1LCP"; BINDING 305; /note="Substrate"; /evidence="ECO:0000269|PubMed:7578088, ECO:0007744|PDB:1LAN"; BINDING 364; /note="Substrate"; /evidence="ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LCP" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolyzed, but rates on arylamides are exceedingly low.; EC=3.4.11.1; Evidence={ECO:0000269|PubMed:14583094}; CATALYTIC ACTIVITY: Reaction=an S-substituted L-cysteinylglycine + H2O = an S-substituted L-cysteine + glycine; Xref=Rhea:RHEA:60444, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305, ChEBI:CHEBI:58717, ChEBI:CHEBI:143103; EC=3.4.13.23; Evidence={ECO:0000269|PubMed:14583094};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60445; Evidence={ECO:0000305|PubMed:14583094}; CATALYTIC ACTIVITY: Reaction=H2O + L-cysteinylglycine = glycine + L-cysteine; Xref=Rhea:RHEA:28783, ChEBI:CHEBI:15377, ChEBI:CHEBI:35235, ChEBI:CHEBI:57305, ChEBI:CHEBI:61694; Evidence={ECO:0000269|PubMed:14583094};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28784; Evidence={ECO:0000305|PubMed:14583094}; CATALYTIC ACTIVITY: Reaction=H2O + S-benzyl-L-cysteinylglycine = glycine + S-benzyl-L-cysteine; Xref=Rhea:RHEA:62568, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305, ChEBI:CHEBI:145802, ChEBI:CHEBI:145803; Evidence={ECO:0000250|UniProtKB:Q68FS4};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62569; Evidence={ECO:0000250|UniProtKB:Q68FS4}; CATALYTIC ACTIVITY: Reaction=Release of N-terminal proline from a peptide.; EC=3.4.11.5; Evidence={ECO:0000250|UniProtKB:P28839}; |
| DNA Binding | |
| EC Number | 3.4.11.1; 3.4.13.23; 3.4.11.5 |
| Enzyme Function | FUNCTION: Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides (PubMed:14583094, PubMed:16519517). The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme (PubMed:16519517). For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates (PubMed:16519517). Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status (PubMed:14583094). {ECO:0000269|PubMed:14583094, ECO:0000269|PubMed:16519517}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (2); Beta strand (23); Binding site (6); Chain (1); Erroneous initiation (1); Helix (17); Initiator methionine (1); Metal binding (14); Modified residue (13); Sequence conflict (5); Turn (4) |
| Keywords | 3D-structure;Acetylation;Alternative initiation;Aminopeptidase;Cobalt;Cytoplasm;Dipeptidase;Direct protein sequencing;Hydrolase;Magnesium;Manganese;Metal-binding;Phosphoprotein;Protease;Reference proteome;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q68FS4}. |
| Modified Residue | MOD_RES 42; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q68FS4; MOD_RES 45; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 54; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q68FS4; MOD_RES 61; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 103; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 180; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 194; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P28838; MOD_RES 238; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P28838; MOD_RES 455; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 455; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 476; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 489; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 489; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:Q9CPY7 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (9) |
| Cross Reference PDB | 1BLL; 1BPM; 1BPN; 1LAM; 1LAN; 1LAP; 1LCP; 2EWB; 2J9A; |
| Mapped Pubmed ID | 21110109; 21918843; 22304649; |
| Motif | |
| Gene Encoded By | |
| Mass | 56,289 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.42 mM for Cys-Gly (at pH 6.9 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=2.3 mM for Leu-Gly (at pH 6.9 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=2.8 mM for Met-Gly (at pH 6.9 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=0.57 mM for Cys-Gly (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=2.5 mM for Leu-Gly (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=1.5 mM for Met-Gly (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=5.2 mM for Ser-Gly (at pH 7.4 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=0.59 mM for Cys-Gly (at pH 8.3 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=1.5 mM for Leu-Gly (at pH 8.3 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=1.3 mM for Met-Gly (at pH 8.3 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; KM=5.0 mM for Ser-Gly (at pH 8.3 and 25 degrees Celsius) {ECO:0000269|PubMed:14583094}; Note=kcat is 3400 min(-1) for Cys-Gly hydrolysis activity (at pH 6.9 and 25 degrees Celsius). kcat is 11500 min(-1) for Leu-Gly hydrolysis activity (at pH 6.9 and 25 degrees Celsius). kcat is 8150 min(-1) for Met-Gly hydrolysis activity (at pH 6.9 and 25 degrees Celsius) (PubMed:14583094). kcat is 6000 min(-1) for Cys-Gly hydrolysis activity (at pH 7.4 and 25 degrees Celsius). kcat is 24000 min(-1) for Leu-Gly hydrolysis activity (at pH 7.4 and 25 degrees Celsius). kcat is 28100 min(-1) for Met-Gly hydrolysis activity (at pH 7.4 and 25 degrees Celsius). kcat is 1000 min(-1) for Ser-Gly hydrolysis activity (at pH 7.4 and 25 degrees Celsius) (PubMed:14583094). kcat is 7100 min(-1) for Cys-Gly hydrolysis activity (at pH 8.3 and 25 degrees Celsius). kcat is 40500 min(-1) for Leu-Gly hydrolysis activity (at pH 8.3 and 25 degrees Celsius). kcat is 59300 min(-1) for Met-Gly hydrolysis activity (at pH 8.3 and 25 degrees Celsius). kcat is 2500 min(-1) for Ser-Gly hydrolysis activity (at pH 8.3 and 25 degrees Celsius) (PubMed:14583094). {ECO:0000269|PubMed:14583094}; |
| Metal Binding | METAL 202; /note="Zinc 3; via carbonyl oxygen; structural"; /evidence="ECO:0000305|PubMed:7619821, ECO:0007744|PDB:1LCP"; METAL 203; /note="Zinc 3; via carbonyl oxygen; structural"; /evidence="ECO:0000305|PubMed:7619821, ECO:0007744|PDB:1LCP"; METAL 205; /note="Zinc 3; via carbonyl oxygen; structural"; /evidence="ECO:0000305|PubMed:7619821, ECO:0007744|PDB:1LCP"; METAL 282; /note="Zinc 2; catalytic"; /evidence="ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:17157838, ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A"; METAL 287; /note="Magnesium; catalytic"; /evidence="ECO:0000269|PubMed:8506345, ECO:0007744|PDB:1BPM"; METAL 287; /note="Zinc 1; catalytic"; /evidence="ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A"; METAL 287; /note="Zinc 2; catalytic"; /evidence="ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:17157838, ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A"; METAL 303; /note="Zinc 3; via carbonyl oxygen; structural"; /evidence="ECO:0000305|PubMed:7619821, ECO:0007744|PDB:1LCP"; METAL 305; /note="Zinc 2; catalytic"; /evidence="ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:17157838, ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A"; METAL 364; /note="Magnesium; catalytic"; /evidence="ECO:0000269|PubMed:8506345, ECO:0007744|PDB:1BPM"; METAL 364; /note="Zinc 1; catalytic"; /evidence="ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A"; METAL 366; /note="Magnesium; catalytic"; /evidence="ECO:0000269|PubMed:8506345, ECO:0007744|PDB:1BPM"; METAL 366; /note="Zinc 1; catalytic"; /evidence="ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A"; METAL 366; /note="Zinc 2; catalytic"; /evidence="ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, ECO:0007744|PDB:1BPM, ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A" |
| Rhea ID | RHEA:60444; RHEA:60445; RHEA:28783; RHEA:28784; RHEA:62568; RHEA:62569 |
| Cross Reference Brenda | 3.4.11.1; |