| IED ID | IndEnz0002011952 |
| Enzyme Type ID | protease011952 |
| Protein Name |
Xaa-Pro aminopeptidase 3 X-Pro aminopeptidase 3 EC 3.4.11.9 Aminopeptidase P3 APP3 |
| Gene Name | XPNPEP3 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MPWLLSAPKLVPAVANVRGLSGCMLCSQRRYSLQPVPERRIPNRYLGQPSPFTHPHLLRPGEVTPGLSQVEYALRRHKLMSLIQKEAQGQSGTDQTVVVLSNPTYYMSNDIPYTFHQDNNFLYLCGFQEPDSILVLQSLPGKQLPSHKAILFVPRRDPSRELWDGPRSGTDGAIALTGVDEAYTLEEFQHLLPKMKAETNMVWYDWMRPSHAQLHSDYMQPLTEAKAKSKNKVRGVQQLIQRLRLIKSPAEIERMQIAGKLTSQAFIETMFTSKAPVEEAFLYAKFEFECRARGADILAYPPVVAGGNRSNTLHYVKNNQLIKDGEMVLLDGGCESSCYVSDITRTWPVNGRFTAPQAELYEAVLEIQRDCLALCFPGTSLENIYSMMLTLIGQKLKDLGIMKNIKENNAFKAARKYCPHHVGHYLGMDVHDTPDMPRSLPLQPGMVITIEPGIYIPEDDKDAPEKFRGLGVRIEDDVVVTQDSPLILSADCPKEMNDIEQICSQAS |
| Enzyme Length | 507 |
| Uniprot Accession Number | Q9NQH7 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 300; /note="Substrate"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; BINDING 331; /note="Substrate"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; BINDING 342; /note="Substrate"; /evidence="ECO:0000269|PubMed:28476889, ECO:0000305|PubMed:25609706, ECO:0007744|PDB:5X49"; BINDING 424; /note="Substrate"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; BINDING 431; /note="Substrate"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; BINDING 451; /note="Substrate"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; BINDING 475; /note="Substrate"; /evidence="ECO:0000269|PubMed:28476889, ECO:0000305|PubMed:25609706, ECO:0007744|PDB:5X49" |
| 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:25609706, ECO:0000269|PubMed:28476889}; |
| DNA Binding | |
| EC Number | 3.4.11.9 |
| Enzyme Function | FUNCTION: Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala (PubMed:25609706, PubMed:28476889). Also shows low activity towards peptides with Ala or Ser at the P1 position (PubMed:28476889). {ECO:0000269|PubMed:25609706, ECO:0000269|PubMed:28476889}.; FUNCTION: [Isoform 1]: Promotes TNFRSF1B-mediated phosphorylation of MAPK8/JNK1 and MAPK9/JNK2, suggesting a function as an adapter protein for TNFRSF1B; the effect is independent of XPNPEP3 peptidase activity. May inhibit apoptotic cell death induced via TNF-TNFRSF1B signaling. {ECO:0000269|PubMed:25609706}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (6); Beta strand (21); Binding site (7); Chain (1); Helix (18); Metal binding (7); Mutagenesis (7); Natural variant (2); Region (1); Sequence conflict (2); Transit peptide (1); Turn (1) |
| Keywords | 3D-structure;Alternative splicing;Aminopeptidase;Cytoplasm;Disease variant;Hydrolase;Manganese;Metal-binding;Metalloprotease;Mitochondrion;Nephronophthisis;Protease;Reference proteome;Transit peptide |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion {ECO:0000269|PubMed:20179356, ECO:0000269|PubMed:25609706}. Cytoplasm {ECO:0000269|PubMed:25609706}. Note=Mainly mitochondrial. Translocates to the cytoplasm following TNFRSF1B activation. {ECO:0000269|PubMed:25609706}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:25609706}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 5X49; |
| Mapped Pubmed ID | 14743216; 17110338; 20360068; 20562859; 21068128; 25609649; 29383790; |
| Motif | |
| Gene Encoded By | |
| Mass | 57,034 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.62 mM for Met-Pro-Ala {ECO:0000269|PubMed:28476889}; KM=2.45 mM for Leu-Pro-Ala {ECO:0000269|PubMed:28476889}; KM=3.06 mM for Phe-Pro-Ala {ECO:0000269|PubMed:28476889}; KM=0.55 mM for Tyr-Pro-Ala {ECO:0000269|PubMed:28476889}; KM=4.91 mM for Tyr-Ser-Ser {ECO:0000269|PubMed:28476889}; KM=4.20 mM for Tyr-Ala-Ala {ECO:0000269|PubMed:28476889}; KM=3.74 mM for Tyr-Ser-Ser-Ala-Ala-Ala-Ala {ECO:0000269|PubMed:28476889}; |
| Metal Binding | METAL 331; /note="Manganese 2"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; METAL 342; /note="Manganese 1"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; METAL 342; /note="Manganese 2"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; METAL 424; /note="Manganese 1"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; METAL 451; /note="Manganese 1"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; METAL 475; /note="Manganese 1"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49"; METAL 475; /note="Manganese 2"; /evidence="ECO:0000269|PubMed:28476889, ECO:0007744|PDB:5X49" |
| Rhea ID | |
| Cross Reference Brenda | 3.4.11.9; |