Isolation of two cDNAs encoding novel alpha 1-antichymotrypsin-like proteins in a murine chondrocytic cell line.
We have isolated two novel serpin-encoding sequences from EB22, a chondrocytic cell line derived from a mouse teratocarcinoma. Both sequences fall within the Spi-2 sub-family, and are related to the gene encoding human alpha 1-antichymotrypsin (ACT), a major acute-phase reactant. Considerable amplification of the Spi-2 gene family in the mouse has occurred, hindering the identification of a functional equivalent of the human gene. However, one of the sequences described here, EB22/4, exhibits several features which indicate that it may represent the physiological rodent equivalent of ACT. The sequence is expressed in the liver, as expected, and is induced several-fold during the acute-phase response. The P1 amino acid residue, which is primarily responsible for inhibitor specificity, is Met rather than the human Leu, most probably a functionally conservative substitution. Analysis of the orthologous sequence in related rodents demonstrates conservation of the predicted reactive centre-encoded specificity. The second isolated cDNA, EB22/3, encodes an unexpected Cys residue at the P1 position in the reactive centre, and represents a novel sub-class of the Spi-2 serine proteinase inhibitor (serpin)-encoding gene family. At least one of the sequences appears to be expressed at sites of skeletal deposition during the later stages of mouse foetal development, indicating a role for serpins during development.
Inglis
J D
JD
MRC Human Genetics Unit, Western General Hospital, Edinburgh, Scotland, U.K.
Lee
M
M
Davidson
D R
DR
Hill
R E
RE
D000209:Acute-Phase Proteins / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002356:Cartilage / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice / Q000235:genetics* / Q000254:growth & development; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D015843:Serpins / Q000235:genetics*; D013724:Teratoma / Q000235:genetics; D014407:Tumor Cells, Cultured; D000514:alpha 1-Antichymotrypsin / Q000235:genetics
D000209:Acute-Phase Proteins; D015843:Serpins; D000514:alpha 1-Antichymotrypsin