UniProt functional annotation for P00727

UniProt code: P00727.

Organism:		Bos taurus (Bovine).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.
Function:		Cytolosic 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}.
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};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:16519517}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:16519517}; 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 Zn(2+), Mn(2+), Mg(2+) or Co(2+), while the tight binding site 2 can be occupied by only Zn(2+) or Co(2+) (PubMed:16519517). One Zn(2+) 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 (PubMed:16519517). Mn(2+) is required for Cys-Gly hydrolysis activity (PubMed:16519517). A third metal binding site may serve a structural role, possibly stabilizing part of the interface between the N-terminal and the catalytic domain (PubMed:7619821). {ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:7619821, ECO:0000303|PubMed:16519517};
Activity regulation:		Zofenoprilat inhibits Cys-Gly hydrolysis activity. {ECO:0000269|PubMed:16519517}.
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};
Subunit:		Homohexamer. {ECO:0000269|PubMed:14583094}.
Subcellular location:		Cytoplasm {ECO:0000250|UniProtKB:Q68FS4}.
Similarity:		Belongs to the peptidase M17 family. {ECO:0000305}.
Sequence caution:		Sequence=AAB28170.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.