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 . Acts also 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 such as brain natriuretic peptide 32 (, ). Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline .
(Microbial infection) Acts as a receptor for human coronavirus MERS-CoV-2.
Subcellular locations: Secreted
Detected in the serum and the seminal fluid.
Subcellular locations: Cell membrane, Apical cell membrane, Cell projection, Invadopodium membrane, Cell projection, Lamellipodium membrane, Cell junction, Membrane raft
Translocated to the apical membrane through the concerted action of N- and O-Glycans and its association with lipid microdomains containing cholesterol and sphingolipids . Redistributed to membrane rafts in T-cell in an interleukin-12-dependent activation . Its interaction with CAV1 is necessary for its translocation to membrane rafts . Colocalized with PTPRC in membrane rafts . Colocalized with FAP in invadopodia and lamellipodia of migratory activated endothelial cells in collagenous matrix. Colocalized with FAP on endothelial cells of capillary-like microvessels but not large vessels within invasive breast ductal carcinoma . Colocalized with ADA at the cell junction in lymphocyte-epithelial cell adhesion . Colocalized with IGF2R in internalized cytoplasmic vesicles adjacent to the cell surface .
Expressed specifically in lymphatic vessels but not in blood vessels in the skin, small intestine, esophagus, ovary, breast and prostate glands. Not detected in lymphatic vessels in the lung, kidney, uterus, liver and stomach (at protein level). Expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells. Expressed at very low levels in the colon.