MAM domain signature and profile

A domain of about 170 amino acids has been recognized [1] in the extracellular region of functionally diverse proteins. All these proteins have a modular, receptor-like architecture consisting of a signal peptide, followed by a large N-terminal extracellular domain, a single transmembrane region and a intracellular domain. These proteins are listed below.

• Meprin. This cell surface glycoprotein contains a zinc-metalloprotease domain capable of degrading a variety of polypeptides. Meprin is composed of two structurally related subunits (α and β) that form homo- or heterotetramers by the non-covalent association of two disulfide-linked dimers. In both subunits, the MAM domain is located after the catalytic domain.
• Neuropilin (A5 antigen), a calcium-independent cell adhesion molecule that function during the formation of certain neuronal circuits. The sequence contains 2 CUB domains (see <PDOC00908>, 2 FA58C domains (see <PDOC00988>) and a MAM domain.
• Receptor-like tyrosine protein phosphatases Mu, Kappa and PCP-2 (EC 3.1.3.48). These PTPases have an extracellular region which consists of a MAM domain followed by an Ig-like domain and four fibronectin-type III domains.
• Vertebrate enteropeptidase (EC 3.4.21.9), a type II membrane protein of the intestinal brush border, which activates trypsinogen. It consists at least of a catalytic light chain and a multidomain heavy chain which has 2 LDL receptor class A domains (see <PDOC00929>), a MAM domain, a SRCR domain (see <PDOC00348>) and a CUB domain (see <PDOC00604>).
• Apical endosomal glycoprotein from rat, a protein probably involved in the sorting and selective transport of receptors and ligands across polarized epithelia. This protein contains 6 MAM domains.
• Xenopus laevis thyroid hormone induced protein B. This protein contains 4 MAM domains.
• Pig zonadhesin, a protein that binds in a species-specific manner to the zona pellucida of the egg.

The MAM domain is likely to have an adhesive function. It contains four conserved cysteines which probably form two disulfide bridges. The pattern for MAM contains the third conserved cysteine which is located in the central part of the domain.