Sequence of rat alpha 1-macroglobulin, a broad-range proteinase inhibitor from the alpha-macroglobulin-complement family.
The alpha-macroglobulin-complement family of plasma proteins includes at least three different alpha-macroglobulins in rats, alpha 2-macroglobulin (alpha 2M), alpha 1 inhibitor III (alpha 1I3), and alpha 1-macroglobulin (alpha 1M). These high molecular weight polypeptides (Mr 160,000 to 200,000) are broad-range proteinase inhibitors. They utilize an internal thiolester function to trap proteinases that cleave their bait regions. The amino acid sequences of alpha 2M and two variants of alpha 1I3 are known. The isolation of alpha 1M cDNA clones and the determination of their cDNA and derived amino acid sequences are reported here. Alpha 1M shares 57.2% and 53.0% overall amino acid sequence identity with alpha 2M and alpha 1I3, respectively, but differs significantly from both in its bait region, suggesting that each inhibitor addresses a different spectrum of proteinases. The disulfide bridge structure of alpha 1M was deduced from its sequence and showed extensive similarities with the experimentally determined structures of other alpha-macroglobulins, suggesting similar overall tertiary structures. Alpha 1M mRNA was detected in 13 different rat tissues tested, whereas alpha 2M and alpha 1I3 mRNAs showed a far more restricted tissue distribution. While alpha 2M and alpha 1I3 mRNA and protein concentrations are significantly altered during acute and chronic inflammations, alpha 1M plasma concentrations are changed only twofold. Thus, in contrast with alpha 2M and alpha 1I3, the functions provided by alpha 1M may be ubiquitously and constitutively required in a broad range of tissues.
Eggertsen
G
G
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Hudson
G
G
Shiels
B
B
Reed
D
D
Fey
G H
GH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004220:Disulfides / Q000032:analysis; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000097:blood / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D014018:Tissue Distribution / Q000235:genetics; D000511:alpha-Macroglobulins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*
D004220:Disulfides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D000511:alpha-Macroglobulins