Laminins are a family of heterotrimeric glycoproteins specific to basement membranes. Laminin-2, consisting of alpha 2, beta 1 and gamma 1 chains, was originally identified in the basement membranes of skeletal muscle and peripheral nerve. We have isolated and sequenced the full-length cDNA for the mouse laminin alpha 2 chain. Four overlapping clones spanning 9,330 bp encode a predicted polypeptide of 3,106 amino acids having a calculated molecular mass of 390 kDa including a 23-amino-acid signal peptide. The amino acid sequence of the alpha 2 chain shares a 45.9% identify with that of the alpha 1 chain. Similar to the structure of the alpha 1 chain, the alpha 2 chain consists of several domains beginning at the N-terminus with three globular domains alternating with three epidermal growth factor-like domains followed by two alpha-helical domains and a C-terminal globular domain. The most N-terminal globular domain is highly conserved (77.3% identity) between the alpha 2 and alpha 1 chains, whereas the alpha-helical domains have low homology (30.3% identity). Northern blot and ribonuclease protection analysis revealed expression of mRNA for the alpha 2 chain in heart, kidney, liver, skin, lung and skeletal muscle of newborn mice. such a tissue distribution suggests a role for the alpha 2 chain and, consequently, laminin-2 or -4 not only in the organization and the function of nerve and muscle tissue but possibly also in the mesenchymal components of certain tissues.