The human MIP-1beta chemokine is encoded by two paralogous genes, ACT-2 and LAG-1.
Human macrophage inflammatory protein-1 beta (MIP-1beta) is an Mr 8,000 acidic protein that is upregulated upon stimulation in monocytes, T cells, and other lymphocytes. This protein belongs to the CC chemokine subfamily and directs the migration of specific subsets of leukocytes. The first molecular clone was isolated in 1988, and ever since there has been confusion regarding the exact number of genes encoding this and closely related proteins. PCR primers were designed from two genomic GenBank entries to conduct single-strand conformational polymorphism analysis, sequence analysis, and PCR-RFLP, and we conclude that previously isolated clones referred to as MIP-1beta are derived from two genes, originally called ACT-2 and LAG-1. The two 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 peptide, while the third, G70S, is in the mature protein. Within the transcribed region, the genes differ at 25 of 662 nucleotides. A survey of the NCBI expressed sequence tag database reveals that both genes are expressed in a variety of tissues, and five clones representing LAG-1 transcripts are alternatively spliced, with the 115-bp exon 2 omitted. Database searches for putative orthologues in other species revealed that the rabbit protein is about 80% similar to the two human proteins, while those of rat and mouse are 70-75% similar. Comparative sequence analysis of the human and animal proteins indicates substantially higher rates of protein evolution in the two rodents compared to human and rabbit.
Modi
W S
WS
Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA. modi@ncifcrf.gov
Bergeron
J
J
Sanford
M
M
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000235:genetics*; D017931:DNA Primers; D020224:Expressed Sequence Tags; D020440:Gene Duplication; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D009626:Terminology as Topic; D014018:Tissue Distribution
C066507:CCL4 protein, human; D054407:Chemokine CCL4; D019742:Chemokines, CC; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D011506:Proteins