Detail Information for IndEnz0002018475
IED ID IndEnz0002018475
Enzyme Type ID protease018475
Protein Name Dipeptidyl peptidase 8
DP8
EC 3.4.14.5
Dipeptidyl peptidase VIII
DPP VIII
Gene Name Dpp8
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 MKIPSGRCNMAAAMETEQLGVEIFETAECEEGNGESQDRPKLEPFYVERYSWSQLKKLLADTRKYHGYMMAKAPHDFMFVKRTDPDGPHSDRVYYLAMSGENRENTLFYSEIPKTINRAAVLMLSWKPLLDLFQATLDYGMYSREEELLRERKRIGTVGIAAYDYHPGSGTFLFQAGSGIYHIKDGGPHGFTQQPLRPNLVETSCPNIRMDPKLCPADPDWIAFIHSNDIWISNLVTREERRITYVHNELANMEEDPRSAGVATFVLQEEFDRYSGYWWCPQAERTPSGGKILRILYEENDESEVEIIHVTSPMLETRRADSFRYPKTGTANPKVTFKMSEIVVDAAGGIIDVIDKELVQPFEILFEGVEYIARAGWTPEGKHAWSILLDRSQTHLQIVLISPELFIPVEDDAMDRQRLIESVPDSVTPLIIYEETTDIWINIHDIFHVFPQTHEDEIEFIFASECKTGFRHLYKITSILKESKYKRSSGGLPAPSDFKCPIKEEITITSGEWEVLGRHGSNIWVDEARKLVYFEGTKDSPLEHHLYVTSYANPGEVVRLTDRGYSHSCCLSRHCDFFISKYSNQKNPHCVSLYKLSSPEDDPVHKTKEFWATILDSAGPLPDYTPPEIFSFESTTGFTLYGMLYKPHDLQPGKKYPTVLFIYGGPQVQLVNNRFKGVKYFRLNTLASLGYVVVVIDNRGSCHRGLKFEGAFKYKMGQIEIDDQVEGLQYLASQYDFIDLDRVGIHGWSYGGYLSLMALMQRSDIFRVAIAGAPVTLWIFYDTGYTERYMGHPDQNEQGYYLGSVAMQAEKFPSEPNRLLLLHGFLDENVHFAHTSILLSFLVRAGKPYDLQIYPQERHSIRVPESGEHYELHLLHYLQENLGSRIAALKVI
Enzyme Length 892
Uniprot Accession Number Q80YA7
Absorption
Active Site ACT_SITE 749; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:Q6V1X1; ACT_SITE 827; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:Q6V1X1; ACT_SITE 859; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:Q6V1X1
Activity Regulation ACTIVITY REGULATION: Inhibited by zinc (By similarity). Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate (By similarity). Specifically inhibited by isoindoline derivatives (By similarity). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29396289). {ECO:0000250|UniProtKB:Q6V1X1, ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29396289}.
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:0000250|UniProtKB:Q6V1X1};
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 (By similarity). 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 DPP8, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity). {ECO:0000250|UniProtKB:Q6V1X1, ECO:0000250|UniProtKB:Q86TI2, ECO:0000269|PubMed:27820798, ECO:0000269|PubMed:29396289}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (3); Chain (1); Sequence conflict (1)
Keywords Aminopeptidase;Cytoplasm;Hydrolase;Protease;Reference proteome;Serine protease
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6V1X1}.
Modified Residue
Post Translational Modification
Signal Peptide
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID 11217851; 12466851; 12520002; 14610273; 19581630; 21267068; 23704821; 28887018; 29693275; 30718379;
Motif
Gene Encoded By
Mass 102,186
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda