| IED ID | IndEnz0002016754 |
| Enzyme Type ID | protease016754 |
| 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 | Rattus norvegicus (Rat) |
| 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 Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MYLLPLPAAARVALRRLGVRGLWDRGLSTADMTKGLVLGIYSKDKDDDVPQFTSAGENFNKLVSGRLREMLNISGPPLKAGKTRTFYGLHQDFPSVVVVGLGKRSAGVDDQENWHEGKENIRAAVAAGCRQVQDLELPSVEVDPCGDAQAAAEGAVLGLYEYDDLKQKKKVAVSAKLHGSGDLEAWEKGVLFASGQNLARQLMESPANEMTPTRFAEVIEKNLKSASSKTEVHIRTKSWIEEQEMGSFLSVAKGSEEPPVFLEIHYTGSPNATEAPLVFVGKGITFDSGGISIKASANMDLMRADMGGAATICSAIVSAAKLNLPINIIGLAPLCENMPSGKANKPGDVVRARNGKTIQVDNTDAEGRLILADALCYAHTFNPKVIINAATLTGAMDVALGSGATGVFTNSSWLWNKLFEASVETGDRVWRMPLFEHYTRQVIDCQLADVNNLGKYRSAGACTAAAFLREFVTHTKWAHLDIAGVMTNKDEIPYLRKGMSGRPTRTLIEFLLRFSKDSS |
| Enzyme Length | 519 |
| Uniprot Accession Number | Q68FS4 |
| Absorption | |
| Active Site | ACT_SITE 294; /evidence=ECO:0000250|UniProtKB:P00727; ACT_SITE 368; /evidence=ECO:0000250|UniProtKB:P00727 |
| Activity Regulation | ACTIVITY REGULATION: Bimane-S-cysteinylglycine-hydrolyzing activity is inhibited by o-phenanthroline or bestatin, and is activated by the addition of zinc chloride. {ECO:0000269|PubMed:12675513}. |
| Binding Site | BINDING 282; /note=Substrate; /evidence=ECO:0000250|UniProtKB:P00727; BINDING 287; /note=Substrate; /evidence=ECO:0000250|UniProtKB:P00727; BINDING 292; /note=Substrate; /evidence=ECO:0000250|UniProtKB:P00727; BINDING 294; /note=Substrate; /evidence=ECO:0000250|UniProtKB:P00727; BINDING 305; /note=Substrate; /evidence=ECO:0000250|UniProtKB:P00727; BINDING 364; /note=Substrate; /evidence=ECO:0000250|UniProtKB:P00727 |
| 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:12675513}; 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:12675513};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60445; Evidence={ECO:0000305|PubMed:12675513}; 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:12675513};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28784; Evidence={ECO:0000305|PubMed:12675513}; 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:0000269|PubMed:6108111};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62569; Evidence={ECO:0000305|PubMed:6108111}; 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:6108111, PubMed:12675513). 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 (By similarity). For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates (By similarity). 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:12675513). {ECO:0000250|UniProtKB:P00727, ECO:0000269|PubMed:12675513, ECO:0000269|PubMed:6108111}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Binding site (6); Chain (1); Metal binding (13); Modified residue (15) |
| Keywords | Acetylation;Alternative initiation;Aminopeptidase;Cytoplasm;Direct protein sequencing;Hydrolase;Magnesium;Manganese;Metal-binding;Phosphoprotein;Protease;Reference proteome;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12675513}. |
| Modified Residue | MOD_RES 42; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 45; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q9CPY7; MOD_RES 54; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; 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 221; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:P28838; MOD_RES 221; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:Q9CPY7; 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 | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 19474315; |
| Motif | |
| Gene Encoded By | |
| Mass | 56,150 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: Vmax=1.6 umol/min/mg enzyme for peptidase activity with S-benzyl-cysteine-p-nitroanilide {ECO:0000269|PubMed:6108111}; Vmax=11.9 umol/min/mg enzyme for peptidase activity with Leucine-p-nitroanilide {ECO:0000269|PubMed:6108111}; Vmax=9.4 umol/min/mg enzyme for peptidase activity with Alanine-p-nitroanilide {ECO:0000269|PubMed:6108111}; |
| Metal Binding | METAL 202; /note=Zinc 3; via carbonyl oxygen; structural; /evidence=ECO:0000250|UniProtKB:P00727; METAL 203; /note=Zinc 3; via carbonyl oxygen; structural; /evidence=ECO:0000250|UniProtKB:P00727; METAL 282; /note=Zinc 2; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 287; /note=Magnesium; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 287; /note=Zinc 1; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 287; /note=Zinc 2; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 303; /note=Zinc 3; via carbonyl oxygen; structural; /evidence=ECO:0000250|UniProtKB:P00727; METAL 305; /note=Zinc 2; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 364; /note=Magnesium; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 364; /note=Zinc 1; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 366; /note=Magnesium; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 366; /note=Zinc 1; catalytic; /evidence=ECO:0000250|UniProtKB:P00727; METAL 366; /note=Zinc 2; catalytic; /evidence=ECO:0000250|UniProtKB:P00727 |
| Rhea ID | RHEA:60444; RHEA:60445; RHEA:28783; RHEA:28784; RHEA:62568; RHEA:62569 |
| Cross Reference Brenda | 3.4.13.23; |