Structure and evolution of the cytotoxic cell proteinase genes CCP3, CCP4 and CCP5.

A family of serine proteinases is believed to be important in cell-mediated cytotoxicity. Presented here are the genomic sequences for three murine members of this cytotoxic cell proteinase (CCP) family: the CCP3, CCP4 and CCP5 genes. All three of these genes have introns inserted at the same codon sites and the same exon distribution of the active site residues. These characteristics are also shared with the CCP1 and CCP2 genes, the charter members of the CCP gene family. Phylogenetic analysis using intron and exon sequences suggests that all five genes arose by various duplication events. This analysis also indicates that the recently described HuCCPX and CCP2 genes originated from recombination events between genes of different lineages. A phylogenetic and Southern analysis of the recombinant HuCCPX gene suggests that the human genome contains an additional CCP gene that has yet to be described. Finally, evidence is presented suggesting that the cDNA clone originally describing the CCP5 gene was derived from an alternately spliced transcript.