The murine Spi-2 proteinase inhibitor locus: a multigene family with a hypervariable reactive site domain.
We have isolated 10 closely linked members of a proteinase inhibitor multigene family from the inbred mouse strain 129. These sequences, termed the Serine Proteinase Inhibitor 2 (Spi-2) genes, appear to have been derived from a common ancestor represented in man by the single copy alpha 1-antichymotrypsin gene. The genes are clustered on two cloned genomic DNA segments spanning 220 kb, and have at least partially retained the intragenic structure of the ancestral Spi-2 gene. Sequence analysis from the final coding exon indicates that most of the mouse genes may be competent to encode functional proteins, some with a predictable inhibitory spectrum, and several representing novel inhibitor types. An oligonucleotide probe designed to one reactive centre sequence enabled the isolation of the cognate expressed transcript from a liver cDNA library. However, whether expressed or not, the reactive centre regions of all the sequences have diverged at a rapid rate relative to structurally defined flanking sequences. The divergence is also appreciably greater than that occurring in an adjacent non-coding sequence. This phenomenon has established novel potential inhibitory specificities, while maintaining a functional inhibitor structure.
Inglis
J D
JD
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Hill
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D003360:Cosmids; D005091:Exons; D015723:Gene Library; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000235:genetics
D015345:Oligonucleotide Probes; D015842:Serine Proteinase Inhibitors; D000514:alpha 1-Antichymotrypsin