Recombinant Rat Dipeptidyl peptidase 4 (Dpp4),Partial Protein

Function

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. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Also acts as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline

Subcellular Location

Cell membrane (Single-pass type II membrane protein); Apical cell membrane (Single-pass type II membrane protein); Cell projection, invadopodium membrane (Single-pass type II membrane protein); Cell projection, lamellipodium membrane (Single-pass type II membrane protein); Cell junction; Membrane raft

Tissue Specificity

Expressed in bile ducts and other epithelial brush borders (small intestine, kidney, colon, pancreatic duct); acinar structures in salivary glands; endothelial structures and T cell areas in thymus, spleen and lymph node

Subunit

Monomer. Homodimer. Heterodimer with Seprase (FAP). Requires homodimerization for optimal dipeptidyl peptidase activity and T-cell costimulation. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Associates with collagen. Interacts with PTPRC; the interaction is enhanced in an interleukin-12-dependent manner in activated lymphocytes. Interacts (via extracellular domain) with ADA; does not inhibit its dipeptidyl peptidase activity. Interacts with CAV1 (via the N-terminus); the interaction is direct. Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction with CARD11. Interacts with IGF2R; the interaction is direct. Interacts with GPC3

• Ogata S. et al. Primary structure of rat liver dipeptidyl peptidase IV deduced from its cDNA and identification of the NH2-terminal signal sequence as the membrane-anchoring domain. — J. Biol. Chem. (1989)
• Hong W. et al. cDNA cloning for a bile canaliculus domain-specific membrane glycoprotein of rat hepatocytes. — Proc. Natl. Acad. Sci. U.S.A. (1987)
• Hong W.J. et al. Membrane orientation of rat gp110 as studied by in vitro translation. — J. Biol. Chem. (1988)
• McCaughan G.W. et al. Identification of the bile canalicular cell surface molecule GP110 as the ectopeptidase dipeptidyl peptidase IV: an analysis by tissue distribution, purification and N-terminal amino acid sequence. — Hepatology (1990)
• Iwaki-Egawa S. et al. N-terminal amino acid sequence of the 60-kDa protein of rat kidney dipeptidyl peptidase IV. — Biol. Chem. Hoppe-Seyler (1993)
• Ogata S. et al. Identification of the active site residues in dipeptidyl peptidase IV by affinity labeling and site-directed mutagenesis. — Biochemistry (1992)
• Hong W. et al. Molecular dissection of the NH2-terminal signal/anchor sequence of rat dipeptidyl peptidase IV. — J. Cell Biol. (1990)
• Longenecker K.L. et al. Crystal structures of DPP-IV (CD26) from rat kidney exhibit flexible accommodation of peptidase-selective inhibitors. — Biochemistry (2006)