Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha beta-subunit junction region of prohaptoglobin.

The biosynthesis of rat haptoglobin, a hetrotetrameric glycoprotein (alpha 2 beta 2), requires the post-translational cleavage of its glycosylated primary translation product (prohaptoglobin) into alpha- and beta-subunits (Hanley, J. M., Haugen, T. H., and Heath, E. C. (1983) J. Biol. Chem. 258, 7858-7869). To elucidate the site(s) at which proteolytic cleavage occurs in prohaptoglobin, we have isolated a recombinant plasmid whose cDNA insert encodes for the carboxyl terminus of the alpha-subunit, the alpha beta-subunit junction, and the beta-subunit region, and also the entire 3'-untranslated region (142 base pairs) and poly(A) tail (55 base pairs) of the mRNA. A single arginine residue was found at the alpha beta-subunit junction region -Val-Gln-Arg-Ile-Ile-Gly-Gly-of prohaptoglobin. The sequence homology of this region with serine protease precursors suggests that post-translational processing of prohaptoglobin involves cleavage of the Arg-Ile bond and extraction of the Arg residue. The rat beta-subunit shows a high degree (approximately 80%) of sequence homology with its human counterpart although it possesses only two of the four N-glycosylation sites present in human haptoglobin beta-subunit.