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. 1989 Feb;8(2):489–495. doi: 10.1002/j.1460-2075.1989.tb03402.x

Molecular characterization of a new immunoglobulin superfamily protein with potential roles in opioid binding and cell contact.

P R Schofield 1, K C McFarland 1, J S Hayflick 1, J N Wilcox 1, T M Cho 1, S Roy 1, N M Lee 1, H H Loh 1, P H Seeburg 1
PMCID: PMC400831  PMID: 2721489

Abstract

A purified opioid-binding protein has been characterized by cDNA cloning. The cDNA sequence predicts an extracellularly located glycoprotein of 345 amino acids. This protein does not possess a membrane-spanning domain but contains a C-terminal hydrophobic sequence characteristic of membrane attachment by a phosphatidylinositol linkage. It displays homology to the immunoglobulin protein superfamily, featuring three domains that resemble disulfide-bonded constant regions. More specifically, the protein is most homologous to a subfamily of proteins which includes the neural cell adhesion molecule (NCAM) and myelin-associated glycoprotein (MAG) and one subgroup of the tyrosine kinase growth factor receptors comprising the platelet-derived growth factor receptor (PDGF R), the colony-stimulating factor 1 receptor (CSF-1 R) and the c-kit protooncogene. These sequence homologies suggest that the protein could be involved in either cell recognition and adhesion, peptidergic ligand binding or both.

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Selected References

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  1. Arquint M., Roder J., Chia L. S., Down J., Wilkinson D., Bayley H., Braun P., Dunn R. Molecular cloning and primary structure of myelin-associated glycoprotein. Proc Natl Acad Sci U S A. 1987 Jan;84(2):600–604. doi: 10.1073/pnas.84.2.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barthels D., Santoni M. J., Wille W., Ruppert C., Chaix J. C., Hirsch M. R., Fontecilla-Camps J. C., Goridis C. Isolation and nucleotide sequence of mouse NCAM cDNA that codes for a Mr 79,000 polypeptide without a membrane-spanning region. EMBO J. 1987 Apr;6(4):907–914. doi: 10.1002/j.1460-2075.1987.tb04837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  5. Bidlack J. M., Abood L. G., Osei-Gyimah P., Archer S. Purification of the opiate receptor from rat brain. Proc Natl Acad Sci U S A. 1981 Jan;78(1):636–639. doi: 10.1073/pnas.78.1.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Boothroyd J. C., Cross G. A., Hoeijmakers J. H., Borst P. A variant surface glycoprotein of Trypanosoma brucei synthesized with a C-terminal hydrophobic 'tail' absent from purified glycoprotein. Nature. 1980 Dec 11;288(5791):624–626. doi: 10.1038/288624a0. [DOI] [PubMed] [Google Scholar]
  8. Caras I. W., Davitz M. A., Rhee L., Weddell G., Martin D. W., Jr, Nussenzweig V. Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins. Nature. 1987 Feb 5;325(6104):545–549. doi: 10.1038/325545a0. [DOI] [PubMed] [Google Scholar]
  9. Chang K. J., Cuatrecasas P. Multiple opiate receptors. Enkephalins and morphine bind to receptors of different specificity. J Biol Chem. 1979 Apr 25;254(8):2610–2618. [PubMed] [Google Scholar]
  10. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  11. Cho T. M., Ge B. L., Yamato C., Smith A. P., Loh H. H. Isolation of opiate binding components by affinity chromatography and reconstitution of binding activities. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5176–5180. doi: 10.1073/pnas.80.17.5176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cho T. M., Hasegawa J., Ge B. L., Loh H. H. Purification to apparent homogeneity of a mu-type opioid receptor from rat brain. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4138–4142. doi: 10.1073/pnas.83.12.4138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cross G. A. Eukaryotic protein modification and membrane attachment via phosphatidylinositol. Cell. 1987 Jan 30;48(2):179–181. doi: 10.1016/0092-8674(87)90419-3. [DOI] [PubMed] [Google Scholar]
  14. Cunningham B. A., Hemperly J. J., Murray B. A., Prediger E. A., Brackenbury R., Edelman G. M. Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science. 1987 May 15;236(4803):799–806. doi: 10.1126/science.3576199. [DOI] [PubMed] [Google Scholar]
  15. Dixon R. A., Kobilka B. K., Strader D. J., Benovic J. L., Dohlman H. G., Frielle T., Bolanowski M. A., Bennett C. D., Rands E., Diehl R. E. Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature. 1986 May 1;321(6065):75–79. doi: 10.1038/321075a0. [DOI] [PubMed] [Google Scholar]
  16. Ferguson M. A., Low M. G., Cross G. A. Glycosyl-sn-1,2-dimyristylphosphatidylinositol is covalently linked to Trypanosoma brucei variant surface glycoprotein. J Biol Chem. 1985 Nov 25;260(27):14547–14555. [PubMed] [Google Scholar]
  17. Gioannini T. L., Howard A. D., Hiller J. M., Simon E. J. Purification of an active opioid-binding protein from bovine striatum. J Biol Chem. 1985 Dec 5;260(28):15117–15121. [PubMed] [Google Scholar]
  18. Hasegawa J., Loh H. H., Lee N. M. Lipid requirement for mu opioid receptor binding. J Neurochem. 1987 Oct;49(4):1007–1012. doi: 10.1111/j.1471-4159.1987.tb09987.x. [DOI] [PubMed] [Google Scholar]
  19. Hemperly J. J., Edelman G. M., Cunningham B. A. cDNA clones of the neural cell adhesion molecule (N-CAM) lacking a membrane-spanning region consistent with evidence for membrane attachment via a phosphatidylinositol intermediate. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9822–9826. doi: 10.1073/pnas.83.24.9822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Höllt V. Opioid peptide processing and receptor selectivity. Annu Rev Pharmacol Toxicol. 1986;26:59–77. doi: 10.1146/annurev.pa.26.040186.000423. [DOI] [PubMed] [Google Scholar]
  21. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kroczek R. A., Gunter K. C., Germain R. N., Shevach E. M. Thy-1 functions as a signal transduction molecule in T lymphocytes and transfected B lymphocytes. Nature. 1986 Jul 10;322(6075):181–184. doi: 10.1038/322181a0. [DOI] [PubMed] [Google Scholar]
  23. Kubo T., Fukuda K., Mikami A., Maeda A., Takahashi H., Mishina M., Haga T., Haga K., Ichiyama A., Kangawa K. Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature. 1986 Oct 2;323(6087):411–416. doi: 10.1038/323411a0. [DOI] [PubMed] [Google Scholar]
  24. Lai C., Brow M. A., Nave K. A., Noronha A. B., Quarles R. H., Bloom F. E., Milner R. J., Sutcliffe J. G. Two forms of 1B236/myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4337–4341. doi: 10.1073/pnas.84.12.4337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lathe R. Synthetic oligonucleotide probes deduced from amino acid sequence data. Theoretical and practical considerations. J Mol Biol. 1985 May 5;183(1):1–12. doi: 10.1016/0022-2836(85)90276-1. [DOI] [PubMed] [Google Scholar]
  26. Law P. Y., Wu J., Koehler J. E., Loh H. H. Demonstration and characterization of opiate inhibition of the striatal adenylate cyclase. J Neurochem. 1981 May;36(5):1834–1846. doi: 10.1111/j.1471-4159.1981.tb00438.x. [DOI] [PubMed] [Google Scholar]
  27. Lewis V. A., Koch T., Plutner H., Mellman I. A complementary DNA clone for a macrophage-lymphocyte Fc receptor. 1986 Nov 27-Dec 3Nature. 324(6095):372–375. doi: 10.1038/324372a0. [DOI] [PubMed] [Google Scholar]
  28. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  29. Low M. G., Kincade P. W. Phosphatidylinositol is the membrane-anchoring domain of the Thy-1 glycoprotein. Nature. 1985 Nov 7;318(6041):62–64. doi: 10.1038/318062a0. [DOI] [PubMed] [Google Scholar]
  30. Low M. G., Saltiel A. R. Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science. 1988 Jan 15;239(4837):268–275. doi: 10.1126/science.3276003. [DOI] [PubMed] [Google Scholar]
  31. Maneckjee R., Zukin R. S., Archer S., Michael J., Osei-Gyimah P. Purification and characterization of the mu opiate receptor from rat brain using affinity chromatography. Proc Natl Acad Sci U S A. 1985 Jan;82(2):594–598. doi: 10.1073/pnas.82.2.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Masu Y., Nakayama K., Tamaki H., Harada Y., Kuno M., Nakanishi S. cDNA cloning of bovine substance-K receptor through oocyte expression system. 1987 Oct 29-Nov 4Nature. 329(6142):836–838. doi: 10.1038/329836a0. [DOI] [PubMed] [Google Scholar]
  33. Messing J., Crea R., Seeburg P. H. A system for shotgun DNA sequencing. Nucleic Acids Res. 1981 Jan 24;9(2):309–321. doi: 10.1093/nar/9.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Milligan G., Streaty R. A., Gierschik P., Spiegel A. M., Klee W. A. Development of opiate receptors and GTP-binding regulatory proteins in neonatal rat brain. J Biol Chem. 1987 Jun 25;262(18):8626–8630. [PubMed] [Google Scholar]
  35. Moos M., Tacke R., Scherer H., Teplow D., Früh K., Schachner M. Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin. Nature. 1988 Aug 25;334(6184):701–703. doi: 10.1038/334701a0. [DOI] [PubMed] [Google Scholar]
  36. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  37. Oikawa S., Nakazato H., Kosaki G. Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence. Biochem Biophys Res Commun. 1987 Jan 30;142(2):511–518. doi: 10.1016/0006-291x(87)90304-4. [DOI] [PubMed] [Google Scholar]
  38. Reiser H., Oettgen H., Yeh E. T., Terhorst C., Low M. G., Benacerraf B., Rock K. L. Structural characterization of the TAP molecule: a phosphatidylinositol-linked glycoprotein distinct from the T cell receptor/T3 complex and Thy-1. Cell. 1986 Nov 7;47(3):365–370. doi: 10.1016/0092-8674(86)90593-3. [DOI] [PubMed] [Google Scholar]
  39. Roy S., Zhu Y. X., Loh H. H., Lee N. M. A monoclonal antibody that inhibits opioid binding to rat brain membranes. Biochem Biophys Res Commun. 1988 Jul 29;154(2):688–693. doi: 10.1016/0006-291x(88)90194-5. [DOI] [PubMed] [Google Scholar]
  40. Salzer J. L., Holmes W. P., Colman D. R. The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. J Cell Biol. 1987 Apr;104(4):957–965. doi: 10.1083/jcb.104.4.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Seki T., Moriuchi T., Chang H. C., Denome R., Silver J. Structural organization of the rat thy-1 gene. Nature. 1985 Feb 7;313(6002):485–487. doi: 10.1038/313485a0. [DOI] [PubMed] [Google Scholar]
  43. Selvaraj P., Rosse W. F., Silber R., Springer T. A. The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature. 1988 Jun 9;333(6173):565–567. doi: 10.1038/333565a0. [DOI] [PubMed] [Google Scholar]
  44. Simmons D., Makgoba M. W., Seed B. ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature. 1988 Feb 18;331(6157):624–627. doi: 10.1038/331624a0. [DOI] [PubMed] [Google Scholar]
  45. Simmons D., Seed B. The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature. 1988 Jun 9;333(6173):568–570. doi: 10.1038/333568a0. [DOI] [PubMed] [Google Scholar]
  46. Simonds W. F., Burke T. R., Jr, Rice K. C., Jacobson A. E., Klee W. A. Purification of the opiate receptor of NG108-15 neuroblastoma-glioma hybrid cells. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4974–4978. doi: 10.1073/pnas.82.15.4974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Stengelin S., Stamenkovic I., Seed B. Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning. EMBO J. 1988 Apr;7(4):1053–1059. doi: 10.1002/j.1460-2075.1988.tb02913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Stroynowski I., Soloski M., Low M. G., Hood L. A single gene encodes soluble and membrane-bound forms of the major histocompatibility Qa-2 antigen: anchoring of the product by a phospholipid tail. Cell. 1987 Aug 28;50(5):759–768. doi: 10.1016/0092-8674(87)90334-5. [DOI] [PubMed] [Google Scholar]
  49. Tse A. G., Barclay A. N., Watts A., Williams A. F. A glycophospholipid tail at the carboxyl terminus of the Thy-1 glycoprotein of neurons and thymocytes. Science. 1985 Nov 29;230(4729):1003–1008. doi: 10.1126/science.2865810. [DOI] [PubMed] [Google Scholar]
  50. Wood W. I., Capon D. J., Simonsen C. C., Eaton D. L., Gitschier J., Keyt B., Seeburg P. H., Smith D. H., Hollingshead P., Wion K. L. Expression of active human factor VIII from recombinant DNA clones. Nature. 1984 Nov 22;312(5992):330–337. doi: 10.1038/312330a0. [DOI] [PubMed] [Google Scholar]
  51. Yarden Y., Kuang W. J., Yang-Feng T., Coussens L., Munemitsu S., Dull T. J., Chen E., Schlessinger J., Francke U., Ullrich A. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341–3351. doi: 10.1002/j.1460-2075.1987.tb02655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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