| IED ID | IndEnz0002006799 |
| Enzyme Type ID | protease006799 |
| Protein Name |
Dipeptidyl peptidase 8 DP8 EC 3.4.14.5 Dipeptidyl peptidase IV-related protein 1 DPRP-1 Dipeptidyl peptidase VIII DPP VIII Prolyl dipeptidase DPP8 |
| Gene Name | DPP8 DPRP1 MSTP097 MSTP135 MSTP141 |
| 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 | MWKRSEQMKIKSGKCNMAAAMETEQLGVEIFETADCEENIESQDRPKLEPFYVERYSWSQLKKLLADTRKYHGYMMAKAPHDFMFVKRNDPDGPHSDRIYYLAMSGENRENTLFYSEIPKTINRAAVLMLSWKPLLDLFQATLDYGMYSREEELLRERKRIGTVGIASYDYHQGSGTFLFQAGSGIYHVKDGGPQGFTQQPLRPNLVETSCPNIRMDPKLCPADPDWIAFIHSNDIWISNIVTREERRLTYVHNELANMEEDARSAGVATFVLQEEFDRYSGYWWCPKAETTPSGGKILRILYEENDESEVEIIHVTSPMLETRRADSFRYPKTGTANPKVTFKMSEIMIDAEGRIIDVIDKELIQPFEILFEGVEYIARAGWTPEGKYAWSILLDRSQTRLQIVLISPELFIPVEDDVMERQRLIESVPDSVTPLIIYEETTDIWINIHDIFHVFPQSHEEEIEFIFASECKTGFRHLYKITSILKESKYKRSSGGLPAPSDFKCPIKEEIAITSGEWEVLGRHGSNIQVDEVRRLVYFEGTKDSPLEHHLYVVSYVNPGEVTRLTDRGYSHSCCISQHCDFFISKYSNQKNPHCVSLYKLSSPEDDPTCKTKEFWATILDSAGPLPDYTPPEIFSFESTTGFTLYGMLYKPHDLQPGKKYPTVLFIYGGPQVQLVNNRFKGVKYFRLNTLASLGYVVVVIDNRGSCHRGLKFEGAFKYKMGQIEIDDQVEGLQYLASRYDFIDLDRVGIHGWSYGGYLSLMALMQRSDIFRVAIAGAPVTLWIFYDTGYTERYMGHPDQNEQGYYLGSVAMQAEKFPSEPNRLLLLHGFLDENVHFAHTSILLSFLVRAGKPYDLQIYPQERHSIRVPESGEHYELHLLHYLQENLGSRIAALKVI |
| Enzyme Length | 898 |
| Uniprot Accession Number | Q6V1X1 |
| Absorption | |
| Active Site | ACT_SITE 755; /note="Charge relay system"; /evidence="ECO:0000305|PubMed:12534281, ECO:0000305|PubMed:29382749"; ACT_SITE 833; /note="Charge relay system"; /evidence="ECO:0000305|PubMed:12534281, ECO:0000305|PubMed:29382749"; ACT_SITE 865; /note="Charge relay system"; /evidence="ECO:0000305|PubMed:12534281, ECO:0000305|PubMed:29382749" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by zinc. Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate. Specifically inhibited by isoindoline derivatives (PubMed:11012666, PubMed:12662155, PubMed:15664838). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29967349, PubMed:32796818). {ECO:0000250|UniProtKB:Q86TI2, ECO:0000269|PubMed:11012666, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15664838, ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29967349, ECO:0000269|PubMed:32796818}. |
| Binding Site | |
| 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:11012666, ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077, ECO:0000269|PubMed:15664838, ECO:0000269|PubMed:20536396, ECO:0000269|PubMed:29382749}; |
| 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:11012666, PubMed:12534281, PubMed:12662155, PubMed:15039077, PubMed:15664838, PubMed:20536396, PubMed:29382749). 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:29967349, PubMed:32796818). 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 (PubMed:34019797, PubMed:33731929, PubMed:33731932). The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP8, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity). {ECO:0000250|UniProtKB:Q86TI2, ECO:0000269|PubMed:11012666, ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077, ECO:0000269|PubMed:15664838, ECO:0000269|PubMed:20536396, ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29967349, ECO:0000269|PubMed:32796818, ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932, ECO:0000269|PubMed:34019797, ECO:0000305|PubMed:29382749}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.4-8.5. Little activity below pH 6.5. {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (5); Beta strand (51); Chain (1); Erroneous initiation (2); Frameshift (3); Helix (22); Mutagenesis (7); Sequence conflict (10); Turn (12) |
| Keywords | 3D-structure;Alternative splicing;Aminopeptidase;Apoptosis;Cytoplasm;Hydrolase;Protease;Reference proteome;Serine protease |
| Interact With | |
| Induction | INDUCTION: In activated T-cells. {ECO:0000269|PubMed:11012666}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11012666, ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (17) |
| Cross Reference PDB | 6EOO; 6EOP; 6EOS; 6EOT; 6HP8; 6QZW; 6TRW; 6TRX; 7A3G; 7A3I; 7A3J; 7A3K; 7A3L; 7AYQ; 7AYR; 7OR4; 7OZ7; |
| Mapped Pubmed ID | 16700509; 16704418; 17040910; 18275857; 19581630; 20043068; 20534982; 21711053; 22736146; 23519473; 23608773; 23704821; 24072711; 25464020; 30225951; 32998073; 34188616; |
| Motif | |
| Gene Encoded By | |
| Mass | 103,358 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=208 uM for Ala-Pro-AMC {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; KM=130 uM for Ala-Pro-AFC {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; KM=120 uM for H-Ala-Pro-pNa {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; KM=1420 uM for H-Ala-Ala-pNa {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; KM=310 uM for H-Arg-Pro-pNa {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; KM=2050 uM for H-Asp-Pro-pNa {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; KM=480 uM for H-Gly-Pro-pNa {ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |