The human MIP-1 beta chemokine is encoded by two paralogous genes, ACT-2 and LAG-1

Human macrophage inflammatory protein-1 beta (MIP-1 beta) is an M-r 8,000 a cidic protein that is upregulated upon stimulation in monocytes, T cells, a nd other lymphocytes. This protein belongs to the CC chemokine subfamily an d directs the migration of specific subsets of leukocytes. The first molecu lar clone was isolated in 1988, and ever since there has been confusion reg arding the exact number of genes encoding this and closely related proteins . PCR primers were designed from two genomic GenBank entries to conduct sin gle-strand conformational polymorphism analysis, sequence analysis, and PCR -RFLP, and we conclude that previously isolated clones referred to as MIP-1 beta are derived from two genes, originally called ACT-2 and LAG-1. The tw o proteins share a common length and are identical at 89 of 92 amino acids. The first two amino acid differences, V12M and L20P, occur in the signal p eptide, while the third, G70S, is in the mature protein, Within the transcr ibed region, the genes differ at 25 of 662 nucleotides. A survey of the NCB I expressed sequence tag database reveals that both genes are expressed in a variety of tissues, and five clones representing LAG-1 transcripts are al ternatively spliced, with the 115-bp exon 2 omitted. Database searches for putative orthologues in other species revealed that the rabbit protein is a bout 80% similar to the two human proteins, while those of rat and mouse ar e 70-75% similar. Comparative sequence analysis of the human and animal pro teins indicates substantially higher rates of protein evolution in the two rodents compared to human and rabbit.