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. 1983 Oct;80(19):5875–5879. doi: 10.1073/pnas.80.19.5875

Identification and characterization of human haptoglobin cDNA.

F Yang, J L Brune, W D Baldwin, D R Barnett, B H Bowman
PMCID: PMC390178  PMID: 6310599

Abstract

Recombinant plasmids containing human cDNA encoding haptoglobin, a plasma protein that binds free hemoglobin, have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. Four cDNA clones containing inserts have been obtained that span 1,218 nucleotides of the haptoglobin coding sequence, including the 3' end of the haptoglobin cDNA. The cDNA sequence included a leader sequence followed by alpha 2-chain and beta-chain sequences. A heretofore unseen arginine residue was deduced between the human alpha- and beta-chain sequences. This is a probable site of limited proteolysis leading to the formation of the alpha and beta polypeptides in mature haptoglobin. A comparison of the haptoglobin alpha-beta-junction region and the heavy-light-chain junction of tissue-type plasminogen activator strengthens the evolutionary homology found in haptoglobin and the serine proteases. The Hp alpha 2 gene, which was shown earlier to be a partial duplication produced by unequal crossing-over between Hp alpha 1 genes, has been impossible to align by protein characterization. The cDNA sequence establishes the alignment of Hp alpha 2FS in the Hp alpha 2 gene studied here.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alvarado-Urbina G., Sathe G. M., Liu W. C., Gillen M. F., Duck P. D., Bender R., Ogilvie K. K. Automated synthesis of gene fragments. Science. 1981 Oct 16;214(4518):270–274. doi: 10.1126/science.6169150. [DOI] [PubMed] [Google Scholar]
  2. Barnett D. R., Lee T. H., Bowman B. H. Amino-acid sequence of the carboxyl terminal octapeptide of human haptoglobin beta chain. Nature. 1970 Mar 7;225(5236):938–939. doi: 10.1038/225938a0. [DOI] [PubMed] [Google Scholar]
  3. Black J. A., Dixon G. H. Amino-acid sequence of alpha chains of human haptoglobins. Nature. 1968 May 25;218(5143):736–741. doi: 10.1038/218736a0. [DOI] [PubMed] [Google Scholar]
  4. Blair D. G., Sherratt D. J., Clewell D. B., Helinski D. R. Isolation of supercoiled colicinogenic factor E 1 DNA sensitive to ribonuclease and alkali. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2518–2522. doi: 10.1073/pnas.69.9.2518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blobel G. Intracellular protein topogenesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496–1500. doi: 10.1073/pnas.77.3.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chow V., Murray R. K., Dixon J. D., Kurosky A. Biosynthesis of rabbit haptoglobin: chemical evidence for a single chain precursor. FEBS Lett. 1983 Mar 21;153(2):275–279. doi: 10.1016/0014-5793(83)80623-1. [DOI] [PubMed] [Google Scholar]
  7. Clewell D. B., Helinski D. R. Effect of growth conditions on the formation of the relaxation complex of supercoiled ColE1 deoxyribonucleic acid and protein in Escherichia coli. J Bacteriol. 1972 Jun;110(3):1135–1146. doi: 10.1128/jb.110.3.1135-1146.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davie E. W., Fujikawa K., Kurachi K., Kisiel W. The role of serine proteases in the blood coagulation cascade. Adv Enzymol Relat Areas Mol Biol. 1979;48:277–318. doi: 10.1002/9780470122938.ch6. [DOI] [PubMed] [Google Scholar]
  9. Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
  10. Doolittle R. F. Similar amino acid sequences: chance or common ancestry? Science. 1981 Oct 9;214(4517):149–159. doi: 10.1126/science.7280687. [DOI] [PubMed] [Google Scholar]
  11. Fuller G. M., Rasco M. A., McCombs M. L., Barnett D. R., Bowman B. H. Subunit composition of haptoglobin 2-2 polymers. Biochemistry. 1973 Jan 16;12(2):253–258. doi: 10.1021/bi00726a012. [DOI] [PubMed] [Google Scholar]
  12. Grunstein M., Hogness D. S. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. doi: 10.1073/pnas.72.10.3961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haugen T. H., Hanley J. M., Heath E. C. Haptoglobin. A novel mode of biosynthesis of a liver secretory glycoprotein. J Biol Chem. 1981 Feb 10;256(3):1055–1057. [PubMed] [Google Scholar]
  14. Hugli T. E., Müller-Eberhard H. J. Anaphylatoxins: C3a and C5a. Adv Immunol. 1978;26:1–53. doi: 10.1016/s0065-2776(08)60228-x. [DOI] [PubMed] [Google Scholar]
  15. Javid J. Haptoglobin 2-1 Bellevue, a haptoglobin beta-chain mutant. Proc Natl Acad Sci U S A. 1967 Apr;57(4):920–924. doi: 10.1073/pnas.57.4.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kurosky A., Barnett D. R., Lee T. H., Touchstone B., Hay R. E., Arnott M. S., Bowman B. H., Fitch W. M. Covalent structure of human haptoglobin: a serine protease homolog. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3388–3392. doi: 10.1073/pnas.77.6.3388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  18. Pennica D., Holmes W. E., Kohr W. J., Harkins R. N., Vehar G. A., Ward C. A., Bennett W. F., Yelverton E., Seeburg P. H., Heyneker H. L. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature. 1983 Jan 20;301(5897):214–221. doi: 10.1038/301214a0. [DOI] [PubMed] [Google Scholar]
  19. Robson E. B., Polani P. E., Dart S. J., Jacobs P. A., Renwick J. H. Probable assignment of the alpha locus of haptoglobin to chromome 16 in man. Nature. 1969 Sep 13;223(5211):1163–1165. doi: 10.1038/2231163a0. [DOI] [PubMed] [Google Scholar]
  20. SMITHIES O., CONNELL G. E., DIXON G. H. Chromosomal rearrangements and the evolution of haptoglobin genes. Nature. 1962 Oct 20;196:232–236. doi: 10.1038/196232a0. [DOI] [PubMed] [Google Scholar]
  21. SMITHIES O., WALKER N. F. Genetic control of some serum proteins in normal humans. Nature. 1955 Dec 31;176(4496):1265–1266. doi: 10.1038/1761265a0. [DOI] [PubMed] [Google Scholar]
  22. Tu C. P., Cohen S. N. 3'-end labeling of DNA with [alpha-32P]cordycepin-5'-triphosphate. Gene. 1980 Jul;10(2):177–183. doi: 10.1016/0378-1119(80)90135-3. [DOI] [PubMed] [Google Scholar]
  23. Wallace R. B., Johnson M. J., Hirose T., Miyake T., Kawashima E. H., Itakura K. The use of synthetic oligonucleotides as hybridization probes. II. Hybridization of oligonucleotides of mixed sequence to rabbit beta-globin DNA. Nucleic Acids Res. 1981 Feb 25;9(4):879–894. doi: 10.1093/nar/9.4.879. [DOI] [PMC free article] [PubMed] [Google Scholar]

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