Mucosal addressin cell adhesion molecule-1(MAdCAM-1) is an ~60kD type 1 transmembrane glycoprotein. It is an endothelial cell adhesion molecule that belongs to the immunoglobulin (Ig) superfamily of proteins. Human MAdCAM-1 is synthesized as a 382aa precursor that contains an 18aa signal sequence, a 299aa extracellular domain (ECD), a 21aa transmembrane segment, and a 44aa cytoplasmic tail. Within the ECD there is one potential site for N-linked glycosylation. The ECD comprises two Ig-like domains of 90aa and 119aa, respectively, each possessing invariant cysteine residues that stabilize the Ig loop. There is also a Ser-Thr-Pro-rich (71%) mucin-like 48aa domain that is aa206-317 formed by six tandem repeats of an 8aa sequence having the general consensus DTTSPEP/SP. This mucin domain contains 19 potential sites for O-linked glycosylation. A splicing variant in which a single Ala residue is substituted for aa223-334 in isoform 1 produces a second isoform. Human mature MAdCAM-1 shares only 44% aa sequence identity with mature mouse MAdCAM-1. The integrin A(4) B(7), which is expressed on lymphocytes, functions as the MAdCAM-1 receptor. The Ig domains of MAdCAM-1 are critical to A(4) B(7) binding, and the mucin domain has activity in L-Selectin binding. MAdCAM-1 expression is up-regulated by TNF-A and IL-1B. MAdCAM-1 is expressed on the surface of high endothelial venules (HEV) in the gut and in Peyer's patches, on endothelial cells of the mesenteric lymph nodes, lamina propria of the small and large intestine, and the mammary gland during lactation, and on brain endothelial cells. MAdCAM-1 has also been reported to be expressed in the liver portal region in autoimmune hepatitis, and in bone marrow following allogenic (genetically non-identical) hematopoietic stem cell transplantation, where it recruits donor T cells, which may lead to graft versus host disease. MAdCAM-1 functions as a homing receptor, and plays a central role in leukocyte migration into HEVs and Peyer's patch. In addition to its normal role in lymphocyte trafficking to mucosal tissue, MAdCAM-1 expression is also dramatically increased in chronic inflammatory and disease states, including inflammatory bowel disease (Crohn's disease and ulcerative colitis), sclerosing cholangitis, and diabetes, and may play an important role in these conditions.