DPP4N_Peptidase_S9

Family: DPP4N_Peptidase_S9

Block: X

Parent Family: Peptidase_S9

Comment

Dipeptidyl petidase IV related proteins (EC 3.4.14.5) (DPP IV) important for the activation or inactivation of extracellular endocrine paracrine and autocrine peptides. DPPIV is synonymous with CD26 (important in HIV infection). Some members lack active serine and are probably not enzymes. The prototype structure has a 8-bladed beta-propeller N-terminal domain which guide substrates to the active site and a transmembrane segment. DPP4 is a cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. The novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) binds cells through DPP4. Mutations in the DPP6 gene are linked to autosomal dominant mental retardation.(Liao et al 2013). The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting beta-subunit of neuronal K(V)4.2 channels. Structures of the complex are available (Kise et al.). DPP8 and DPP9 are cytosolic peptidases. Have dpp activity similar to dpp4. The first identified endogenous DPP9 substrate is the tumor epitope RU13442 (VPYGSFKHV). Inhibition or silencing of DPP9, but not DPP8, led to increased presentation of this antigen on MHC class I alleles to cytotoxic T-cells, linking DPP9 to the MHC class I antigen presentation pathway. Small ubiquitin-like protein modifier SUMO1 acts as an allosteric activator of DPP9. By binding to an armlike motif in DPP9; DPP9 functions as an endogenous inhibitor of NLRP1 inflammasome. DPP9 interacts with a unique autoproteolytic domain found in NLRP1 and CARD8. Dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 is able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Sitagliptin, has little effect on microbial DPP4. daurisoline-d4 (Dau-d4) is a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.