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. 2000 Aug;9(8):1594–1600. doi: 10.1110/ps.9.8.1594

The L6 membrane proteins--a new four-transmembrane superfamily.

M D Wright 1, J Ni 1, G B Rudy 1
PMCID: PMC2144728  PMID: 10975581

Abstract

L6, IL-TMP, and TM4SF5 are cell surface proteins predicted to have four transmembrane domains. Previous sequence analysis led to their assignment as members of the tetraspanin superfamily. In this paper, we identify a new sequence (L6D) that is strikingly similar to L6, IL-TMP, and TM4SF5. Analyses of these four sequences indicate that they are not significantly related to genuine tetraspanins, but instead constitute their own L6 superfamily.

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Selected References

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  1. Adams M. D., Kerlavage A. R., Fleischmann R. D., Fuldner R. A., Bult C. J., Lee N. H., Kirkness E. F., Weinstock K. G., Gocayne J. D., White O. Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature. 1995 Sep 28;377(6547 Suppl):3–174. [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Amiot M. Identification and analysis of cDNA clones encoding CD53. A pan-leukocyte antigen related to membrane transport proteins. J Immunol. 1990 Dec 15;145(12):4322–4325. [PubMed] [Google Scholar]
  4. Bascom R. A., Manara S., Collins L., Molday R. S., Kalnins V. I., McInnes R. R. Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies. Neuron. 1992 Jun;8(6):1171–1184. doi: 10.1016/0896-6273(92)90137-3. [DOI] [PubMed] [Google Scholar]
  5. Boucheix C., Benoit P., Frachet P., Billard M., Worthington R. E., Gagnon J., Uzan G. Molecular cloning of the CD9 antigen. A new family of cell surface proteins. J Biol Chem. 1991 Jan 5;266(1):117–122. [PubMed] [Google Scholar]
  6. Classon B. J., Williams A. F., Willis A. C., Seed B., Stamenkovic I. The primary structure of the human leukocyte antigen CD37, a species homologue of the rat MRC OX-44 antigen. J Exp Med. 1990 Sep 1;172(3):1007–1007. doi: 10.1084/jem.172.3.1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dayhoff M. O., Barker W. C., Hunt L. T. Establishing homologies in protein sequences. Methods Enzymol. 1983;91:524–545. doi: 10.1016/s0076-6879(83)91049-2. [DOI] [PubMed] [Google Scholar]
  8. Edwards C. P., Farr A. G., Marken J. S., Nelson A., Bajorath J., Hellström K. E., Hellström I., Aruffo A. Cloning of the murine counterpart of the tumor-associated antigen H-L6: epitope mapping of the human and murine L6 antigens. Biochemistry. 1995 Oct 3;34(39):12653–12660. doi: 10.1021/bi00039a022. [DOI] [PubMed] [Google Scholar]
  9. Emi N., Kitaori K., Seto M., Ueda R., Saito H., Takahashi T. Isolation of a novel cDNA clone showing marked similarity to ME491/CD63 superfamily. Immunogenetics. 1993;37(3):193–198. doi: 10.1007/BF00191884. [DOI] [PubMed] [Google Scholar]
  10. Farrar G. J., Kenna P., Jordan S. A., Kumar-Singh R., Humphries M. M., Sharp E. M., Sheils D. M., Humphries P. A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa. Nature. 1991 Dec 12;354(6353):478–480. doi: 10.1038/354478a0. [DOI] [PubMed] [Google Scholar]
  11. Fishman G. I., Spray D. C., Leinwand L. A. Molecular characterization and functional expression of the human cardiac gap junction channel. J Cell Biol. 1990 Aug;111(2):589–598. doi: 10.1083/jcb.111.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fitter S., Tetaz T. J., Berndt M. C., Ashman L. K. Molecular cloning of cDNA encoding a novel platelet-endothelial cell tetra-span antigen, PETA-3. Blood. 1995 Aug 15;86(4):1348–1355. [PubMed] [Google Scholar]
  13. Garkavij M., Tennvall J., Strand S. E., Norrgren K., Lindgren L., Nilsson R., Sjögren H. O. Enhanced radioimmunotargeting of 125I-labeled L6-biotin monoclonal antibody (MAb) by combining preload of cold L6 MAb and subsequent immunoadsorption in rats. Cancer Res. 1995 Dec 1;55(23 Suppl):5874s–5880s. [PubMed] [Google Scholar]
  14. Gaugitsch H. W., Hofer E., Huber N. E., Schnabl E., Baumruker T. A new superfamily of lymphoid and melanoma cell proteins with extensive homology to Schistosoma mansoni antigen Sm23. Eur J Immunol. 1991 Feb;21(2):377–383. doi: 10.1002/eji.1830210219. [DOI] [PubMed] [Google Scholar]
  15. Hellström I., Beaumier P. L., Hellström K. E. Antitumor effects of L6, an IgG2a antibody that reacts with most human carcinomas. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7059–7063. doi: 10.1073/pnas.83.18.7059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hellström I., Horn D., Linsley P., Brown J. P., Brankovan V., Hellström K. E. Monoclonal mouse antibodies raised against human lung carcinoma. Cancer Res. 1986 Aug;46(8):3917–3923. [PubMed] [Google Scholar]
  17. Hemler M. E., Mannion B. A., Berditchevski F. Association of TM4SF proteins with integrins: relevance to cancer. Biochim Biophys Acta. 1996 Jun 7;1287(2-3):67–71. doi: 10.1016/0304-419x(96)00007-8. [DOI] [PubMed] [Google Scholar]
  18. Henikoff S., Henikoff J. G. Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915–10919. doi: 10.1073/pnas.89.22.10915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Higgins D. G., Bleasby A. J., Fuchs R. CLUSTAL V: improved software for multiple sequence alignment. Comput Appl Biosci. 1992 Apr;8(2):189–191. doi: 10.1093/bioinformatics/8.2.189. [DOI] [PubMed] [Google Scholar]
  20. Hotta H., Miyamoto H., Hara I., Takahashi N., Homma M. Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences. Biochem Biophys Res Commun. 1992 May 29;185(1):436–442. doi: 10.1016/s0006-291x(05)81004-6. [DOI] [PubMed] [Google Scholar]
  21. Hotta H., Ross A. H., Huebner K., Isobe M., Wendeborn S., Chao M. V., Ricciardi R. P., Tsujimoto Y., Croce C. M., Koprowski H. Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression. Cancer Res. 1988 Jun 1;48(11):2955–2962. [PubMed] [Google Scholar]
  22. Jankowski S. A., Mitchell D. S., Smith S. H., Trent J. M., Meltzer P. S. SAS, a gene amplified in human sarcomas, encodes a new member of the transmembrane 4 superfamily of proteins. Oncogene. 1994 Apr;9(4):1205–1211. [PubMed] [Google Scholar]
  23. Levy S., Nguyen V. Q., Andria M. L., Takahashi S. Structure and membrane topology of TAPA-1. J Biol Chem. 1991 Aug 5;266(22):14597–14602. [PubMed] [Google Scholar]
  24. Maecker H. T., Todd S. C., Levy S. The tetraspanin superfamily: molecular facilitators. FASEB J. 1997 May;11(6):428–442. [PubMed] [Google Scholar]
  25. Marken J. S., Schieven G. L., Hellström I., Hellström K. E., Aruffo A. Cloning and expression of the tumor-associated antigen L6. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3503–3507. doi: 10.1073/pnas.89.8.3503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Müller-Pillasch F., Wallrapp C., Lacher U., Friess H., Büchler M., Adler G., Gress T. M. Identification of a new tumour-associated antigen TM4SF5 and its expression in human cancer. Gene. 1998 Feb 16;208(1):25–30. doi: 10.1016/s0378-1119(97)00633-1. [DOI] [PubMed] [Google Scholar]
  27. Noda M., Furutani Y., Takahashi H., Toyosato M., Tanabe T., Shimizu S., Kikyotani S., Kayano T., Hirose T., Inayama S. Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor. 1983 Oct 27-Nov 2Nature. 305(5937):818–823. doi: 10.1038/305818a0. [DOI] [PubMed] [Google Scholar]
  28. Oligino L. D., Percy A. J., Harn D. A. Purification and immunochemical characterization of a 22 kilodalton surface antigen from Schistosoma mansoni. Mol Biochem Parasitol. 1988 Mar;28(2):95–103. doi: 10.1016/0166-6851(88)90056-4. [DOI] [PubMed] [Google Scholar]
  29. Oren R., Takahashi S., Doss C., Levy R., Levy S. TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol. 1990 Aug;10(8):4007–4015. doi: 10.1128/mcb.10.8.4007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Page R. D. TreeView: an application to display phylogenetic trees on personal computers. Comput Appl Biosci. 1996 Aug;12(4):357–358. doi: 10.1093/bioinformatics/12.4.357. [DOI] [PubMed] [Google Scholar]
  31. Richman C. M., DeNardo S. J., O'Grady L. F., DeNardo G. L. Radioimmunotherapy for breast cancer using escalating fractionated doses of 131I-labeled chimeric L6 antibody with peripheral blood progenitor cell transfusions. Cancer Res. 1995 Dec 1;55(23 Suppl):5916s–5920s. [PubMed] [Google Scholar]
  32. Saitou N., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
  33. Szala S., Kasai Y., Steplewski Z., Rodeck U., Koprowski H., Linnenbach A. J. Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6833–6837. doi: 10.1073/pnas.87.17.6833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tedder T. F., Streuli M., Schlossman S. F., Saito H. Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen of human B lymphocytes. Proc Natl Acad Sci U S A. 1988 Jan;85(1):208–212. doi: 10.1073/pnas.85.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tomlinson M. G., Williams A. F., Wright M. D. Epitope mapping of anti-rat CD53 monoclonal antibodies. Implications for the membrane orientation of the Transmembrane 4 Superfamily. Eur J Immunol. 1993 Jan;23(1):136–140. doi: 10.1002/eji.1830230122. [DOI] [PubMed] [Google Scholar]
  37. Travis G. H., Brennan M. B., Danielson P. E., Kozak C. A., Sutcliffe J. G. Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). Nature. 1989 Mar 2;338(6210):70–73. doi: 10.1038/338070a0. [DOI] [PubMed] [Google Scholar]
  38. Wice B. M., Gordon J. I. A tetraspan membrane glycoprotein produced in the human intestinal epithelium and liver that can regulate cell density-dependent proliferation. J Biol Chem. 1995 Sep 15;270(37):21907–21918. doi: 10.1074/jbc.270.37.21907. [DOI] [PubMed] [Google Scholar]
  39. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  40. Wright M. D., Henkle K. J., Mitchell G. F. An immunogenic Mr 23,000 integral membrane protein of Schistosoma mansoni worms that closely resembles a human tumor-associated antigen. J Immunol. 1990 Apr 15;144(8):3195–3200. [PubMed] [Google Scholar]
  41. Wright M. D., Tomlinson M. G. The ins and outs of the transmembrane 4 superfamily. Immunol Today. 1994 Dec;15(12):588–594. doi: 10.1016/0167-5699(94)90222-4. [DOI] [PubMed] [Google Scholar]
  42. Yu J., Lin J. H., Wu X. R., Sun T. T. Uroplakins Ia and Ib, two major differentiation products of bladder epithelium, belong to a family of four transmembrane domain (4TM) proteins. J Cell Biol. 1994 Apr;125(1):171–182. doi: 10.1083/jcb.125.1.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zhang J. T., Nicholson B. J. Sequence and tissue distribution of a second protein of hepatic gap junctions, Cx26, as deduced from its cDNA. J Cell Biol. 1989 Dec;109(6 Pt 2):3391–3401. doi: 10.1083/jcb.109.6.3391. [DOI] [PMC free article] [PubMed] [Google Scholar]

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