Q68FS4 · AMPL_RAT
- ProteinCytosol aminopeptidase
- GeneLap3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids519 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides (PubMed:12675513, PubMed:6108111).
The presence of Zn2+ 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 Mn2+, 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).
The presence of Zn2+ 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 Mn2+, 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).
Catalytic activity
- 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.
- an S-substituted L-cysteinylglycine + H2O = an S-substituted L-cysteine + glycineThis reaction proceeds in the forward direction.
- H2O + L-cysteinylglycine = glycine + L-cysteineThis reaction proceeds in the forward direction.
- H2O + S-benzyl-L-cysteinylglycine = glycine + S-benzyl-L-cysteineThis reaction proceeds in the forward direction.
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Binds two metal ions per subunit. Two metal binding sites with different affinities are located in the enzyme active site and can be occupied in vitro by different metals: site 1 is occupied by Zn2+, Mn2+, Mg2+ or Co2+, while the tight binding site 2 can be occupied by only Zn2+ or Co2+. One Zn2+ ion is tightly bound to site 2 and essential for enzyme activity in vivo, while site 1 can be occupied by different metals to give different enzymatic activities. Mn2+ is required for Cys-Gly hydrolysis activity. A third metal binding site may serve a structural role, possibly stabilizing part of the interface between the N-terminal and the catalytic domain.
Activity regulation
Bimane-S-cysteinylglycine-hydrolyzing activity is inhibited by o-phenanthroline or bestatin, and is activated by the addition of zinc chloride.
Kinetics
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
1.6 μmol/min/mg | for peptidase activity with S-benzyl-cysteine-p-nitroanilide | ||||
11.9 μmol/min/mg | for peptidase activity with Leucine-p-nitroanilide | ||||
9.4 μmol/min/mg | for peptidase activity with Alanine-p-nitroanilide |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 202 | Zn2+ 3 (UniProtKB | ChEBI); structural | ||||
Sequence: L | ||||||
Binding site | 203 | Zn2+ 3 (UniProtKB | ChEBI); structural | ||||
Sequence: M | ||||||
Binding site | 282 | substrate | ||||
Sequence: K | ||||||
Binding site | 282 | Zn2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: K | ||||||
Binding site | 287 | Mg2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 287 | substrate | ||||
Sequence: D | ||||||
Binding site | 287 | Zn2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 287 | Zn2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 292 | substrate | ||||
Sequence: S | ||||||
Active site | 294 | |||||
Sequence: K | ||||||
Binding site | 294 | substrate | ||||
Sequence: K | ||||||
Binding site | 303 | Zn2+ 3 (UniProtKB | ChEBI); structural | ||||
Sequence: R | ||||||
Binding site | 305 | substrate | ||||
Sequence: D | ||||||
Binding site | 305 | Zn2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 364 | Mg2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 364 | substrate | ||||
Sequence: D | ||||||
Binding site | 364 | Zn2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 366 | Mg2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Binding site | 366 | Zn2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Binding site | 366 | Zn2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Active site | 368 | |||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | trans-Golgi network | |
Molecular Function | carboxypeptidase activity | |
Molecular Function | manganese ion binding | |
Molecular Function | metalloaminopeptidase activity | |
Molecular Function | peptidase activity | |
Biological Process | proteolysis |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCytosol aminopeptidase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ68FS4
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000274146 | 1-519 | Cytosol aminopeptidase | |||
Sequence: MYLLPLPAAARVALRRLGVRGLWDRGLSTADMTKGLVLGIYSKDKDDDVPQFTSAGENFNKLVSGRLREMLNISGPPLKAGKTRTFYGLHQDFPSVVVVGLGKRSAGVDDQENWHEGKENIRAAVAAGCRQVQDLELPSVEVDPCGDAQAAAEGAVLGLYEYDDLKQKKKVAVSAKLHGSGDLEAWEKGVLFASGQNLARQLMESPANEMTPTRFAEVIEKNLKSASSKTEVHIRTKSWIEEQEMGSFLSVAKGSEEPPVFLEIHYTGSPNATEAPLVFVGKGITFDSGGISIKASANMDLMRADMGGAATICSAIVSAAKLNLPINIIGLAPLCENMPSGKANKPGDVVRARNGKTIQVDNTDAEGRLILADALCYAHTFNPKVIINAATLTGAMDVALGSGATGVFTNSSWLWNKLFEASVETGDRVWRMPLFEHYTRQVIDCQLADVNNLGKYRSAGACTAAAFLREFVTHTKWAHLDIAGVMTNKDEIPYLRKGMSGRPTRTLIEFLLRFSKDSS | ||||||
Modified residue | 42 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 45 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 54 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 61 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 103 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 180 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 194 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 221 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 221 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 238 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 455 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 455 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 476 | N6-succinyllysine | ||||
Sequence: K | ||||||
Modified residue | 489 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 489 | N6-succinyllysine; alternate | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative initiation.
Q68FS4-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length519
- Mass (Da)56,150
- Last updated2004-10-11 v1
- Checksum0D4DFDC93D0CFF9D
Q68FS4-2
- Name2
- Differences from canonical
- 1-31: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AG50 | A0A8I6AG50_RAT | Lap3 | 500 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_022633 | 1-31 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC079381 EMBL· GenBank· DDBJ | AAH79381.1 EMBL· GenBank· DDBJ | mRNA |