| IED ID | IndEnz0002005707 |
| Enzyme Type ID | protease005707 |
| Protein Name |
Dipeptidyl peptidase 9 DP9 EC 3.4.14.5 Dipeptidyl peptidase IX DPP IX Dipeptidyl peptidase-like protein 9 DPLP9 |
| Gene Name | Dpp9 |
| Organism | Mus musculus (Mouse) |
| 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 Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MCSGVSPVEQVAAGDMDDTAARFCVQKHSWDGLRSIIHGSRKSSGLIVSKAPHDFQFVQKPDESGPHSHRLYYLGMPYGSRENSLLYSEIPKKVRKEALLLLSWKQMLDHFQATPHHGVYSREEELLRERKRLGVFGITSYDFHSESGLFLFQASNSLFHCRDGGKNGFMVSPMKPLEIKTQCSGPRMDPKICPADPAFFSFINNSDLWVANIETGEERRLTFCHQGSAGVLDNPKSAGVATFVIQEEFDRFTGCWWCPTASWEGSEGLKTLRILYEEVDESEVEVIHVPSPALEERKTDSYRYPRTGSKNPKIALKLAELQTDHQGKIVSSCEKELVQPFSSLFPKVEYIARAGWTRDGKYAWAMFLDRPQQRLQLVLLPPALFIPAVESEAQRQAAARAVPKNVQPFVIYEEVTNVWINVHDIFHPFPQAEGQQDFCFLRANECKTGFCHLYRVTVELKTKDYDWTEPLSPTEDEFKCPIKEEVALTSGEWEVLSRHGSKIWVNEQTKLVYFQGTKDTPLEHHLYVVSYESAGEIVRLTTLGFSHSCSMSQSFDMFVSHYSSVSTPPCVHVYKLSGPDDDPLHKQPRFWASMMEAANCPPDYVPPEIFHFHTRADVQLYGMIYKPHTLQPGRKHPTVLFVYGGPQVQLVNNSFKGIKYLRLNTLASLGYAVVVIDGRGSCQRGLHFEGALKNQMGQVEIEDQVEGLQYVAEKYGFIDLSRVAIHGWSYGGFLSLMGLIHKPQVFKVAIAGAPVTVWMAYDTGYTERYMDVPENNQQGYEAGSVALHVEKLPNEPNRLLILHGFLDENVHFFHTNFLVSQLIRAGKPYQLQIYPNERHSIRCRESGEHYEVTLLHFLQEHL |
| Enzyme Length | 862 |
| Uniprot Accession Number | Q8BVG4 |
| Absorption | |
| Active Site | ACT_SITE 729; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:28887018, ECO:0000305|PubMed:24223149"; ACT_SITE 807; /note="Charge relay system"; /evidence="ECO:0000250|UniProtKB:Q6V1X1"; ACT_SITE 839; /note="Charge relay system"; /evidence="ECO:0000250|UniProtKB:Q6V1X1" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate (By similarity). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29396289). Val-boroPro inhibits activity by binding to the active site, mimicking a substrate-bound state, thereby displacing the C-terminal fragment of NLRP1, leading to activation of the NLRP1 inflammasome. In contrast, Val-boroPro does not directly displaces CARD8: it acts by promoting degradation of the N-terminal part of CARD8, leading to indirect disruption of the ternary complex (By similarity). {ECO:0000250|UniProtKB:Q86TI2, ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29396289}. |
| Binding Site | BINDING 729; /note=Val-boroPro; inhibitor; covalent; /evidence=ECO:0000250|UniProtKB:Q86TI2 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline.; EC=3.4.14.5; Evidence={ECO:0000269|PubMed:24223149}; |
| DNA Binding | |
| EC Number | 3.4.14.5 |
| Enzyme Function | FUNCTION: Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2 (PubMed:24223149). Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8 (PubMed:27820798, PubMed:29396289). Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation (By similarity). The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP9, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity). {ECO:0000250|UniProtKB:Q86TI2, ECO:0000269|PubMed:24223149, ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29396289}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (3); Binding site (1); Chain (1); Frameshift (1); Mutagenesis (1); Sequence conflict (3) |
| Keywords | Alternative splicing;Aminopeptidase;Cytoplasm;Hydrolase;Protease;Reference proteome;Serine protease |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:24223149}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12466851; 12520002; 14610273; 17967808; 18799693; 19581630; 21677750; 23704821; 24194600; 26175140; 26242871; 26930324; 27626380; 28256001; 29693275; 29709545; 30718379; 31086209; |
| Motif | |
| Gene Encoded By | |
| Mass | 98,001 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |