cDNA clones encoding the α chain of the murine lymphocyte-Peyer's patch adhesion molecule (LPAM), which is associated with lymphocyte homing, have been isolated by screening with the human VLA-4 (α4h) probe. Several α4 antigenic determinants were identified on COS-7 cells after transfection. From overlapping clones, ∼5 kb of contiguous nucleotide sequence have been determined, encoding a protein sequence of 1039 amino acids for the LPAM α chain (α4m). LPAM is a member of the integrin family of cell-surface heterodimers, and α4m is the murine homologue of the human α4h chain. The two proteins have a total sequence similarity of 84%, with an almost perfect conservation (31/32 amino acids) in the cytoplasmic domain. Like α4h, α4m is distinct from other integrin α chains because it has neither an I-domain nor a COOH-terminal cleavage site. The positions of the characteristic Cysteine residues are conserved, and a putative protease cleavage site is located near the middle of the protein sequence. The NH2-terminal part of the protein contains seven homologous repeats, and three of them include putative divalent cation-binding sites. These sites are among the most conserved between the α4m sequence and other α chains, and may therefore be involved in the binding of integrin α and β chains. An additional cDNA clone was isolated which shares a sequence of perfect homology with the α4m encoding cDNAs, but has a unique 3′ poly-A end. This observation correlates with the fact that three discrete murine RNA bands are observed in Northern blot experiments using α4m as a probe, whereas only two human RNA species are described for α4h, indicating a higher complexity for murine than for human sequences.
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