Abstract
We have determined the sequence coding for human alpha 1-acid glycoprotein from two independently isolated cDNA clones and a genomic clone. The aminoacid sequences deduced from the three clones, deriving from three different individuals, are identical. Southern blot analysis on human DNA indicates that there are at least two genes coding for alpha 1-AGP. We propose that alpha 1-AGP found in plasma is a mixture of the products of these two different genes. This is the simpler explanation for the heterogeneity in the aminoacid composition in purified alpha 1-AGP observed by Schmid et al. (1). DNA sequence comparison with cDNA clones coding for human alpha 1-antitrypsin and haptoglobin shows a conserved sequence within the 5' untranslated region which may play a role in the acute phase response.
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- Baumann H., Firestone G. L., Burgess T. L., Gross K. W., Yamamoto K. R., Held W. A. Dexamethasone regulation of alpha 1-acid glycoprotein and other acute phase reactants in rat liver and hepatoma cells. J Biol Chem. 1983 Jan 10;258(1):563–570. [PubMed] [Google Scholar]
- Baumann H., Held W. A., Berger F. G. The acute phase response of mouse liver. Genetic analysis of the major acute phase reactants. J Biol Chem. 1984 Jan 10;259(1):566–573. [PubMed] [Google Scholar]
- Bensi G., Raugei G., Klefenz H., Cortese R. Structure and expression of the human haptoglobin locus. EMBO J. 1985 Jan;4(1):119–126. doi: 10.1002/j.1460-2075.1985.tb02325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
- Cortese R., Harland R., Melton D. Transcription of tRNA genes in vivo: single-stranded compared to double-stranded templates. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4147–4151. doi: 10.1073/pnas.77.7.4147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cortese R., Melton D., Tranquilla T., Smith J. D. Cloning of nematode tRNA genes and their expression in the frog oocyte. Nucleic Acids Res. 1978 Dec;5(12):4593–4611. [PMC free article] [PubMed] [Google Scholar]
- Dente L., Cesareni G., Cortese R. pEMBL: a new family of single stranded plasmids. Nucleic Acids Res. 1983 Mar 25;11(6):1645–1655. doi: 10.1093/nar/11.6.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emura J., Ikenaka T., Collins J. H., Schmid K. The constant and variable regions of the carboxyl-terminal CNBr fragment of alpha-acid glycoprotein. J Biol Chem. 1971 Dec 25;246(24):7821–7823. [PubMed] [Google Scholar]
- Friedman M. J. Control of malaria virulence by alpha 1-acid glycoprotein (orosomucoid), an acute-phase (inflammatory) reactant. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5421–5424. doi: 10.1073/pnas.80.17.5421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
- Greengard O. Enzymic differentiation in mammalian tissues. Essays Biochem. 1971;7:159–205. [PubMed] [Google Scholar]
- Ikenaka T., Ishiguro M., Emura J., Kaufmann H., Isemura S., Bauer W., Schmid K. Isolation and partial characterization of the cyanogen bromide fragments of 1 -acid glycoprotein and the elucidation of the amino acid sequence of the carboxyl-terminal cyanogen bromide fragment. Biochemistry. 1972 Sep 26;11(20):3817–3829. doi: 10.1021/bi00770a022. [DOI] [PubMed] [Google Scholar]
- Ikenaka T., Ishiguro M., Isemura S., Kaufmann H., Bauer W., Schmid K. The amino acid sequence of the carboxyl-terminal CNBr-fragment of alpha-1-acid glycoprotein. Biochem Biophys Res Commun. 1971 Mar 19;42(6):1142–1147. doi: 10.1016/0006-291x(71)90024-6. [DOI] [PubMed] [Google Scholar]
- Johnson A. M., Schmid K., Alper C. A. Inheritance of human alpha-1-acid glycoprotein (orosomucoid) variants. J Clin Invest. 1969 Dec;48(12):2293–2299. doi: 10.1172/JCI106195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. doi: 10.1111/j.1749-6632.1982.tb22124.x. [DOI] [PubMed] [Google Scholar]
- Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
- Morrow J. F., Stearman R. S., Peltzman C. G., Potter D. A. Induction of hepatic synthesis of serum amyloid A protein and actin. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4718–4722. doi: 10.1073/pnas.78.8.4718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raugei G., Bensi G., Colantuoni V., Romano V., Santoro C., Costanzo F., Cortese R. Sequence of human haptoglobin cDNA: evidence that the alpha and beta subunits are coded by the same mRNA. Nucleic Acids Res. 1983 Sep 10;11(17):5811–5819. doi: 10.1093/nar/11.17.5811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reid K. B., Bentley D. R., Wood K. J. Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):345–354. doi: 10.1098/rstb.1984.0095. [DOI] [PubMed] [Google Scholar]
- Ricca G. A., Hamilton R. W., McLean J. W., Conn A., Kalinyak J. E., Taylor J. M. Rat alpha 1-acid glycoprotein mRNA. Cloning of double-stranded cDNA and kinetics of induction of mRNA levels following acute inflammation. J Biol Chem. 1981 Oct 25;256(20):10362–10368. [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmid K., Ishiguro M., Emura J., Isemura S., Kaufmann H., Motoyama T. The amino acid sequences of two large glycopeptides derived from the carbohydrate-carrying region of alpha 1-acid glycoprotein. Biochem Biophys Res Commun. 1971 Jan 22;42(2):280–286. doi: 10.1016/0006-291x(71)90099-4. [DOI] [PubMed] [Google Scholar]
- Schmid K., Kaufmann H., Isemura S., Bauer F., Emura J., Motoyama T., Ishiguro M., Nanno S. Structure of 1 -acid glycoprotein. The complete amino acid sequence, multiple amino acid substitutions, and homology with the immunoglobulins. Biochemistry. 1973 Jul 3;12(14):2711–2724. doi: 10.1021/bi00738a026. [DOI] [PubMed] [Google Scholar]
- Stanley K. K., Luzio J. P. Construction of a new family of high efficiency bacterial expression vectors: identification of cDNA clones coding for human liver proteins. EMBO J. 1984 Jun;3(6):1429–1434. doi: 10.1002/j.1460-2075.1984.tb01988.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tokita K., Burke J. F., Yoshizaki H., Fischer S., Schmid K. The constancy of the alpha-1-acid glycoprotein variants of normal adults under conditions of severe stress. J Clin Invest. 1966 Oct;45(10):1624–1630. doi: 10.1172/JCI105469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vannice J. L., Ringold G. M., McLean J. W., Taylor J. M. Induction of the acute-phase reactant, alpha 1-acid glycoprotein, by glucocorticoids in rat hepatoma cells. DNA. 1983;2(3):205–212. doi: 10.1089/dna.1983.2.205. [DOI] [PubMed] [Google Scholar]
- Vannice J. L., Taylor J. M., Ringold G. M. Glucocorticoid-mediated induction of alpha 1-acid glycoprotein: evidence for hormone-regulated RNA processing. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4241–4245. doi: 10.1073/pnas.81.14.4241. [DOI] [PMC free article] [PubMed] [Google Scholar]