The murine Spi-2 proteinase inhibitor locus: a multigene family with a hypervariable reactive site domain

EMBO J. 1991 Feb;10(2):255-61. doi: 10.1002/j.1460-2075.1991.tb07945.x.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cloning, Molecular
  • Cosmids
  • Exons
  • Gene Library
  • Genetic Variation*
  • Humans
  • Introns
  • Mice
  • Molecular Sequence Data
  • Multigene Family*
  • Oligonucleotide Probes
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid
  • Serine Proteinase Inhibitors / metabolism*
  • alpha 1-Antichymotrypsin / genetics

Substances

  • Oligonucleotide Probes
  • Serine Proteinase Inhibitors
  • alpha 1-Antichymotrypsin

Associated data

  • GENBANK/S60920
  • GENBANK/X56216
  • GENBANK/X56217
  • GENBANK/X56816
  • GENBANK/X56817
  • GENBANK/X56818
  • GENBANK/X56819
  • GENBANK/X56820
  • GENBANK/X56821
  • GENBANK/X56822