MADCAM-1 MADCAM-1 (mucosal vascular addressin cell adhesion molecule 1)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Peyer's Patch
Lymph Node
Lamina Propria
Endothelial Cell
Small intestine
Gut
Spleen
Mammary gland
Pancreas
Blood
50 / 50
70 / 70

Expression
MADCAM-1 is expressed at high levels on high endothelial venules (HEV) of Peyer's patches and mesenteric lymph nodes and on flat-walled venules within the gut lamina propria and the small intestine.  Expression is lesser in the colon and spleen and is not expressed in the thymus, prostate, ovaries, testis, heart, placenta, lung, liver, skeletal muscle, kidneys or peripheral blood leukocytes.   It is also expressed on vascular endothelium in mammary glands, pancreas and the spleen marginal sinus.  Expression is induced in vitro by TNFα and  IL-1 and MADCAM-1 has been detected on blood vessels within areas of chronic inflammation.

Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene family.

MADCAM-1 is a single-pass type-1 glycoprotein.  It contains a N-terminal extracellular domain which contains 2 Ig-like C2-type domains, a transmembrane domain and a cytoplasmic domain.  The C2-type domains are closely related to the 2 membrane-distal Ig domains of CD54 (ICAM-1) and CD106 (VCAM-1), which binds the integrins a4b1  CD49d/CD29 and a4b 7.  MADCAM-1 and CD106 are structurally related to 3 other integrin-binding molecules, CD50, CD54 and CD102.  Features shared by these molecules include an atypical disulfide between the B-C and F-G loops and an (I/L)(D/E)(S/T)XL motif, LDTSL in MADCAM-1) in the C-D loop.  The Ig domains are followed by a mucin-like region rich in Ser-, Thr-, and Pro-residues, which includes 8 copies of the octameric repeat (P/S)PDTTS(Q/P)E.  The 2 Ig domains, but not the mucin-like portions, are reasonably well-conserved between species.

MOLECULAR MASS
Cell Type Unreduced Reduced
54 - 62 kDa 58 - 66 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 7 different isoforms but the full length has not been determined..

POST-TRANSLATIONAL MODIFICATION

The serine/threonine mucin-like domain may proved possible sites for O-gylcosylation sites.  It may also serve as a backbone to present carbohydrate ligands to lymphocytes.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH MADCAM-1

MADCAM-1 binds the integrin a4b7 through its IgSF portion.  It can also bind CD62L, L-selectin, through poorly characterized sialoglycoconjugates present in the mucin-like portion of a subpopulation of MADCAM-1 molecules.  The a4b7  binding site incorporates the LDTSL motif in the C-D loop of domain 1, which also forms part of the binding site on other integrin-binding IgSF domains.

Function
MADCAM-1 is a cell adhesion endothelial molecule that interacts with leukocyte β7 integrin LPAM-1 (α4β7, L-selectin and VLA-4 (α4β1) on myleoid cells to direct leukocytes into mucosal and inflamed tissues.  It is expressed by mucosal venules and helps to direct lymphocyte traffic into mucosal tissues including the Peyer patches and intestinal lamina propria.  It binds both integrin CD62L and α4β7 through its interaction with the lymphocyte adhesion molecules, MADCAM-1 contributes to the retention of leukocytes and the re-circulation of naïve lymphocytes to Peyer's patches and mesenteric lymph nodes, and the homing of a subpopulation of activated or memory lymphocytes to the lamina propria of the gut mucosa.  MADCAM-1 is involved in the initial tethering and rolling of lymphocytes on endothelial surfaces through CD62L and a4b7 binding as well as the subsequent activation-induced arrest of these cells through a4b7 binding prior to extravasation.  There are two isoforms but isoform 2 lacks the mucin-like domain and may be specialized in integrin α4/β7 dependent adhesion strengthening, independent of L-selectin binding.

BIOACHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF MADCAM-1 IN INTACT ANIMAL: No information.

Comments
MOLECULAR INTERACTION-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF MADCAM-1: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY MADCAM-1: No information.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 8174Q13477
MouseS33601L21203
Antibodies

Revised June 25, 2008


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