PMID:15584901

Citation	Gorrell, MD (2005) Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin. Sci. 108:277-92
Abstract	DP (dipeptidyl peptidase) IV is the archetypal member of its six-member gene family. Four members of this family, DPIV, FAP (fibroblast activation protein), DP8 and DP9, have a rare substrate specificity, hydrolysis of a prolyl bond two residues from the N-terminus. The ubiquitous DPIV glycoprotein has proved interesting in the fields of immunology, endocrinology, haematology and endothelial cell and cancer biology and DPIV has become a novel target for Type II diabetes therapy. The crystal structure shows that the soluble form of DPIV comprises two domains, an alpha/beta-hydrolase domain and an eight-blade beta-propeller domain. The propeller domain contains the ADA (adenosine deaminase) binding site, a dimerization site, antibody epitopes and two openings for substrate access to the internal active site. FAP is structurally very similar to DPIV, but FAP protein expression is largely confined to diseased and damaged tissue, notably the tissue remodelling interface in chronically injured liver. DPIV has a variety of peptide substrates, the best studied being GLP-1 (glucagon-like peptide-1), NPY (neuropeptide Y) and CXCL12. The DPIV family has roles in bone marrow mobilization. The functional interactions of DPIV and FAP with extracellular matrix confer roles for these proteins in cancer biology. DP8 and DP9 are widely distributed and indirectly implicated in immune function. The DPL (DP-like) glycoproteins that lack peptidase activity, DPL1 and DPL2, are brain-expressed potassium channel modulators. Thus the six members of the DPIV gene family exhibit diverse biological roles.
Links	PubMed Online version:10.1042/CS20040302
Keywords	Antigens, Neoplasm/physiology; Biomarkers, Tumor/physiology; Cell Physiological Phenomena; Dipeptidyl Peptidase 4/chemistry; Dipeptidyl Peptidase 4/physiology; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/physiology; Gelatinases; Humans; Liver Diseases/enzymology; Membrane Proteins; Neoplasms/enzymology; Protein Conformation; Serine Endopeptidases/physiology; Substrate Specificity; T-Lymphocytes/enzymology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DPP4	enables	GO:0004252: serine-type endopeptidase activity	ECO:0000269: experimental evidence used in manual assertion		F		Seeded From UniProt	complete

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