| IED ID | IndEnz0002013489 |
| Enzyme Type ID | protease013489 |
| Protein Name |
Xaa-Pro aminopeptidase 2 EC 3.4.11.9 Membrane-bound aminopeptidase P Membrane-bound APP mAPP X-prolyl aminopeptidase 2 |
| Gene Name | Xpnpep2 |
| 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 | MAQAYWQCYPWLVLLCACAWSYPGPESLGREDVRDCSTNPPRLPVTAVNTTMRLAALRQQMEKSNLSAYIIPDTDAHMSEYIGKHDERRAWISGFTGSAGTAVVTKKKAAVWTDSRYWTQAERQMDCNWELHKEVSISSIVAWILAEVPDGENVGFDPFLFSVGSWENYDQELQDSNRHLLSITTNLVDVAWGSERPPVPSQPIYALPKEFTGSTWQEKVSAIRSYMQNHTMAPTGVLLSALDETAWLFNLRSSDIPYNPFFYSYTLLTDSSIRLFVNKSRFSLETLQYLNTNCTLPMCVQLEDYSQIRDGVKAYASGNVKILIGISYTTYGVYDVIPKEKLVTETYSPVMLIKAVKNSKEQALLKASHVRDAVAVIQYLVWLEKNVPKGTVDEFSGAEHIDQLRRNENFSSGPSFETISASGLNAALAHYSPTKELHRKLSLDEMYLVDSGGQYWDGTTDITRTVHWGTPTAFQKEAYTRVLMGNIDLSRLVFPAATSGRVVEAFARRALWEVGLNYGHGTGHGIGNFLCVHEWPVGFQYNNMAMAKGMFTSIEPGYYQDGEFGIRLEDVALVVEAKTKYPGTYLTFELVSFVPYDRNLIDVSLLSPEQLQYLNRYYQTIRENIGPELQRRQLLEEFAWLERHTEPLSASAPHTTSLASMWVASALAILSWSC |
| Enzyme Length | 674 |
| Uniprot Accession Number | Q99MA2 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by the chelating agents 1,10-phenanthroline and EDTA. Inhibited by the thiol-containing compounds 2-mercaptoethanol and dithiothreitol. Also inhibited by apstatin, captopril and p-(ch1oromercuri)benzenesulfonic acid. Weakly inhibited by D,L-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and N-[l-(R,S)-carboxy-(2-phenylethyl)]-Ala-Ala-Phe-p-aminobenzoate. Inhibited by ramiprilat and enalaprilat, in a Mn(2+)-dependent manner. Metal ions have a complex substrate- and concentration-dependent effect on activity. Activity towards Arg-Pro-Pro and Gly-Pro-Hyp is stimulated by Mn(2+) ion concentrations of 10-100 uM and then inhibited at Mn(2+) concentrations of 1-2 mM. Mn(2+) concentrations in excess of 2 mM stimulate activity towards Gly-Pro-Hyp but inhibit activity towards Arg-Pro-Pro. Zn(2+) and Co(2+) ions also inhibit activity towards Arg-Pro-Pro at high concentrations. Activity towards bradykinin is inhibited by Mn(2+) concentrations in excess of 1 mM. {ECO:0000269|PubMed:7669781}. |
| Binding Site | BINDING 116; /note=Substrate; /evidence=ECO:0000250|UniProtKB:O44750; BINDING 430; /note=Substrate; via tele nitrogen; /evidence=ECO:0000250|UniProtKB:O44750; BINDING 524; /note=Substrate; via tele nitrogen; /evidence=ECO:0000250|UniProtKB:O44750; BINDING 533; /note=Substrate; via tele nitrogen; /evidence=ECO:0000250|UniProtKB:O44750; BINDING 555; /note=Substrate; /evidence=ECO:0000250|UniProtKB:O44750 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide.; EC=3.4.11.9; Evidence={ECO:0000269|PubMed:7669781}; |
| DNA Binding | |
| EC Number | 3.4.11.9 |
| Enzyme Function | FUNCTION: Membrane-bound metalloprotease which catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro. May play a role in the metabolism of the vasodilator bradykinin. {ECO:0000269|PubMed:7669781}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Thermostable to 55 degrees Celsius. Complete loss of activity above 70-75 degrees Celsius. {ECO:0000269|PubMed:7669781}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0 for bradykinin. Active between pH 6.0-11.0. {ECO:0000269|PubMed:7669781}; |
| Pathway | |
| nucleotide Binding | |
| Features | Binding site (5); Chain (1); Glycosylation (3); Lipidation (1); Metal binding (7); Propeptide (1); Signal peptide (1) |
| Keywords | Aminopeptidase;Cell membrane;Direct protein sequencing;GPI-anchor;Glycoprotein;Hydrolase;Lipoprotein;Membrane;Metal-binding;Protease;Reference proteome;Signal;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:7669781}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:7669781}. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated. {ECO:0000269|PubMed:7669781}. |
| Signal Peptide | SIGNAL 1..22; /evidence=ECO:0000269|PubMed:7669781 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 76,080 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.35 mM for Arg-Pro-Pro (at pH 8.0) {ECO:0000269|PubMed:7669781}; KM=0.36 mM for Arg-Pro-Pro (at pH 8.0, in the presence of 4 mM Mn(2+)) {ECO:0000269|PubMed:7669781}; KM=0.32 mM for Gly-Pro-Hyp (at pH 8.0) {ECO:0000269|PubMed:7669781}; KM=2.0 mM for Gly-Pro-Hyp (at pH 8.0, in the presence of 4 mM Mn(2+)) {ECO:0000269|PubMed:7669781}; KM=0.021 mM for Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (bradykinin, at pH 6.8) {ECO:0000269|PubMed:7669781}; KM=0.039 mM for Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe (at pH 6.8) {ECO:0000269|PubMed:7669781}; KM=0.051 mM for Arg-Pro-Pro-Gly-Phe-Ser-Pro (at pH 6.8) {ECO:0000269|PubMed:7669781}; KM=0.032 mM for Arg-Pro-Pro-Gly-Phe-Ser (at pH 6.8) {ECO:0000269|PubMed:7669781}; KM=0.048 mM for Arg-Pro-Pro-Gly-Phe (at pH 6.8) {ECO:0000269|PubMed:7669781}; KM=0.030 mM for Arg-Pro-Pro-Gly (at pH 6.8) {ECO:0000269|PubMed:7669781}; KM=1.0 mM for Arg-Pro-Pro (at pH 6.8) {ECO:0000269|PubMed:7669781}; |
| Metal Binding | METAL 450; /note=Zinc 1; /evidence=ECO:0000250|UniProtKB:O44750; METAL 461; /note=Zinc 1; /evidence=ECO:0000250|UniProtKB:O44750; METAL 461; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:O44750; METAL 524; /note=Zinc 2; via tele nitrogen; /evidence=ECO:0000250|UniProtKB:O44750; METAL 555; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:O44750; METAL 569; /note=Zinc 1; /evidence=ECO:0000250|UniProtKB:O44750; METAL 569; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:O44750 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.11.9; |