Description
Dipeptidyl Peptidase IV (DPPIV; also known as CD26 and adenosine deaminase (ADA) complexing protein 2) is a serine protease that releases Xaa-Pro dipeptides from the N-terminus of oligo- and polypeptides. It is a type II membrane protein consisting of a small cytoplasmic tail, a transmembrane region, and a large extracellular domain. The extracellular domain contains glycosylation sites, a cysteine-rich region, and the catalytic active site (Ser, Asp and His charge relay system). In the native state, DPPIV is present as a non-covalently linked homodimer on the surface of a variety of cell types. The soluble form is also present in human serum and other body fluids. The form purified from human serum or seminal fluid corresponds to the intact extracellular domain.
DPPIV plays an important role in many physiological and pathological processes. It interacts with ADA and CD45, providing a co-stimulating signal to the CD3/T-cell receptor complex. It cleaves many chemokines with Xaa-Pro at their N-terminus, altering their receptor specificity and biological function. It degrades many peptide hormones, such as glucagon-like peptide-1, shorting their bioactivity. DPPIV inhibitors are being developed to extend their bioactivity and currently being tested in late-stage clinical trials for the treatment of type 2 diabetes. DPPIV truncates the N-terminus of procalcitonin, a marker for systemic bacterial and fungal infections. DPPIV interacts with HIV-1 Tat protein and its binding to ADA is inhibited by HIV envelop protein gp120