Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1996 Oct 1;319(Pt 1):81–89. doi: 10.1042/bj3190081

The gene G13 in the class III region of the human MHC encodes a potential DNA-binding protein.

A Khanna 1, R D Campbell 1
PMCID: PMC1217738  PMID: 8870652

Abstract

G13 is a single-copy gene lying approx. 75 kb centromeric of the complement gene cluster in the class III region of the human MHC. The gene spans approx. 17 kb of DNA and has been shown to encode mRNA of approx. 2.7 kb that is present in cell lines representing lymphoid and non-lymphoid tissues, indicating that it is ubiquitously expressed. The complete nucleotide sequence of the 2.7 kb mRNA has been derived from cDNA and genomic clones. The longest open reading frame obtained for G13 codes for a 703 amino acid protein of approx. 77 kDa in molecular mass. Comparison of the putative G13 amino acid sequence with the protein databases revealed significant similarities with DNA-binding proteins of the leucine zipper class, including a human cAMP response element binding protein. G13 contains a bZIP motif, a region rich in basic amino acids adjacent to a coiled-coil leucine zipper domain, common to this class of proteins that is known to be involved in dimerization and DNA binding. Antibodies raised against a fragment encoding the C-terminal half of the putative G13 protein recognized a major polypeptide of approx. 86 kDa and a minor polypeptide of approx. 78 kDa on immunoblotting of U937 cell extracts; this has been confirmed by immunoprecipitation experiments. Even though it contained at least one potential bipartite nuclear localization signal, the G13 protein was present both in the cytoplasm and the nucleus of the fibroblast cells. Thus G13 might be a novel DNA-binding protein that is perhaps translocated to the nucleus in a regulated manner.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Abderrahim H., Sambucy J. L., Iris F., Ougen P., Billault A., Chumakov I. M., Dausset J., Cohen D., Le Paslier D. Cloning the human major histocompatibility complex in YACs. Genomics. 1994 Oct;23(3):520–527. doi: 10.1006/geno.1994.1538. [DOI] [PubMed] [Google Scholar]
  2. Aguado B., Campbell R. D. The novel gene G17, located in the human major histocompatibility complex, encodes PBX2, a homeodomain-containing protein. Genomics. 1995 Feb 10;25(3):650–659. doi: 10.1016/0888-7543(95)80007-9. [DOI] [PubMed] [Google Scholar]
  3. Barton G. J. Protein multiple sequence alignment and flexible pattern matching. Methods Enzymol. 1990;183:403–428. doi: 10.1016/0076-6879(90)83027-7. [DOI] [PubMed] [Google Scholar]
  4. Barton G. J., Sternberg M. J. Flexible protein sequence patterns. A sensitive method to detect weak structural similarities. J Mol Biol. 1990 Mar 20;212(2):389–402. doi: 10.1016/0022-2836(90)90133-7. [DOI] [PubMed] [Google Scholar]
  5. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brindle P. K., Montminy M. R. The CREB family of transcription activators. Curr Opin Genet Dev. 1992 Apr;2(2):199–204. doi: 10.1016/s0959-437x(05)80274-6. [DOI] [PubMed] [Google Scholar]
  8. Campbell R. D., Milner C. M. MHC genes in autoimmunity. Curr Opin Immunol. 1993 Dec;5(6):887–893. doi: 10.1016/0952-7915(93)90101-w. [DOI] [PubMed] [Google Scholar]
  9. Campbell R. D., Trowsdale J. Map of the human MHC. Immunol Today. 1993 Jul;14(7):349–352. doi: 10.1016/0167-5699(93)90234-C. [DOI] [PubMed] [Google Scholar]
  10. Chida K., Vogt P. K. Nuclear translocation of viral Jun but not of cellular Jun is cell cycle dependent. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4290–4294. doi: 10.1073/pnas.89.10.4290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  13. Davis L. I. Control of nucleocytoplasmic transport. Curr Opin Cell Biol. 1992 Jun;4(3):424–429. doi: 10.1016/0955-0674(92)90007-y. [DOI] [PubMed] [Google Scholar]
  14. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dingwall C., Laskey R. A. Nuclear targeting sequences--a consensus? Trends Biochem Sci. 1991 Dec;16(12):478–481. doi: 10.1016/0968-0004(91)90184-w. [DOI] [PubMed] [Google Scholar]
  16. Dunham I., Sargent C. A., Dawkins R. L., Campbell R. D. An analysis of variation in the long-range genomic organization of the human major histocompatibility complex class II region by pulsed-field gel electrophoresis. Genomics. 1989 Nov;5(4):787–796. doi: 10.1016/0888-7543(89)90120-1. [DOI] [PubMed] [Google Scholar]
  17. Ellenberger T. E., Brandl C. J., Struhl K., Harrison S. C. The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein-DNA complex. Cell. 1992 Dec 24;71(7):1223–1237. doi: 10.1016/s0092-8674(05)80070-4. [DOI] [PubMed] [Google Scholar]
  18. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  19. Fukagawa T., Sugaya K., Matsumoto K., Okumura K., Ando A., Inoko H., Ikemura T. A boundary of long-range G + C% mosaic domains in the human MHC locus: pseudoautosomal boundary-like sequence exists near the boundary. Genomics. 1995 Jan 1;25(1):184–191. doi: 10.1016/0888-7543(95)80124-5. [DOI] [PubMed] [Google Scholar]
  20. Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
  21. Gierasch L. M. Signal sequences. Biochemistry. 1989 Feb 7;28(3):923–930. doi: 10.1021/bi00429a001. [DOI] [PubMed] [Google Scholar]
  22. Hurst H. C. Transcription factors. 1: bZIP proteins. Protein Profile. 1994;1(2):123–168. [PubMed] [Google Scholar]
  23. Karin M., Smeal T. Control of transcription factors by signal transduction pathways: the beginning of the end. Trends Biochem Sci. 1992 Oct;17(10):418–422. doi: 10.1016/0968-0004(92)90012-x. [DOI] [PubMed] [Google Scholar]
  24. Kendall E., Sargent C. A., Campbell R. D. Human major histocompatibility complex contains a new cluster of genes between the HLA-D and complement C4 loci. Nucleic Acids Res. 1990 Dec 25;18(24):7251–7257. doi: 10.1093/nar/18.24.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  26. Lee K. A. Transcriptional regulation by cAMP. Curr Opin Cell Biol. 1991 Dec;3(6):953–959. doi: 10.1016/0955-0674(91)90113-d. [DOI] [PubMed] [Google Scholar]
  27. Lovering R., Hanson I. M., Borden K. L., Martin S., O'Reilly N. J., Evan G. I., Rahman D., Pappin D. J., Trowsdale J., Freemont P. S. Identification and preliminary characterization of a protein motif related to the zinc finger. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2112–2116. doi: 10.1073/pnas.90.6.2112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McKnight S. L. Molecular zippers in gene regulation. Sci Am. 1991 Apr;264(4):54–64. doi: 10.1038/scientificamerican0491-54. [DOI] [PubMed] [Google Scholar]
  29. Mermod N., O'Neill E. A., Kelly T. J., Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. doi: 10.1016/0092-8674(89)90108-6. [DOI] [PubMed] [Google Scholar]
  30. Metz R., Ziff E. cAMP stimulates the C/EBP-related transcription factor rNFIL-6 to trans-locate to the nucleus and induce c-fos transcription. Genes Dev. 1991 Oct;5(10):1754–1766. doi: 10.1101/gad.5.10.1754. [DOI] [PubMed] [Google Scholar]
  31. Min J., Shukla H., Kozono H., Bronson S. K., Weissman S. M., Chaplin D. D. A novel Creb family gene telomeric of HLA-DRA in the HLA complex. Genomics. 1995 Nov 20;30(2):149–156. doi: 10.1006/geno.1995.9891. [DOI] [PubMed] [Google Scholar]
  32. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pearson W. R., Miller W. Dynamic programming algorithms for biological sequence comparison. Methods Enzymol. 1992;210:575–601. doi: 10.1016/0076-6879(92)10029-d. [DOI] [PubMed] [Google Scholar]
  34. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  35. Roux P., Blanchard J. M., Fernandez A., Lamb N., Jeanteur P., Piechaczyk M. Nuclear localization of c-Fos, but not v-Fos proteins, is controlled by extracellular signals. Cell. 1990 Oct 19;63(2):341–351. doi: 10.1016/0092-8674(90)90167-d. [DOI] [PubMed] [Google Scholar]
  36. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  37. Sargent C. A., Dunham I., Trowsdale J., Campbell R. D. Human major histocompatibility complex contains genes for the major heat shock protein HSP70. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1968–1972. doi: 10.1073/pnas.86.6.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Scott M. P., Tamkun J. W., Hartzell G. W., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. doi: 10.1016/0304-419x(89)90033-4. [DOI] [PubMed] [Google Scholar]
  39. Silver P. A. How proteins enter the nucleus. Cell. 1991 Feb 8;64(3):489–497. doi: 10.1016/0092-8674(91)90233-o. [DOI] [PubMed] [Google Scholar]
  40. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  41. Spies T., Blanck G., Bresnahan M., Sands J., Strominger J. L. A new cluster of genes within the human major histocompatibility complex. Science. 1989 Jan 13;243(4888):214–217. doi: 10.1126/science.2911734. [DOI] [PubMed] [Google Scholar]
  42. Staden R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res. 1982 May 11;10(9):2951–2961. doi: 10.1093/nar/10.9.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tabor S., Richardson C. C. DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767–4771. doi: 10.1073/pnas.84.14.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Takeda J., Seino S., Bell G. I. Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Res. 1992 Sep 11;20(17):4613–4620. doi: 10.1093/nar/20.17.4613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Trowsdale J., Powis S. H. The MHC: relationship between linkage and function. Curr Opin Genet Dev. 1992 Jun;2(3):492–497. doi: 10.1016/s0959-437x(05)80163-7. [DOI] [PubMed] [Google Scholar]
  46. Vieira J., Messing J. Production of single-stranded plasmid DNA. Methods Enzymol. 1987;153:3–11. doi: 10.1016/0076-6879(87)53044-0. [DOI] [PubMed] [Google Scholar]
  47. Vinson C. R., Garcia K. C. Molecular model for DNA recognition by the family of basic-helix-loop-helix-zipper proteins. New Biol. 1992 Apr;4(4):396–403. [PubMed] [Google Scholar]
  48. Waeber G., Habener J. F. Nuclear translocation and DNA recognition signals colocalized within the bZIP domain of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB. Mol Endocrinol. 1991 Oct;5(10):1431–1438. doi: 10.1210/mend-5-10-1431. [DOI] [PubMed] [Google Scholar]
  49. Ziff E. B. Transcription factors: a new family gathers at the cAMP response site. Trends Genet. 1990 Mar;6(3):69–72. doi: 10.1016/0168-9525(90)90081-g. [DOI] [PubMed] [Google Scholar]
  50. von Heijne G. Transcending the impenetrable: how proteins come to terms with membranes. Biochim Biophys Acta. 1988 Jun 9;947(2):307–333. doi: 10.1016/0304-4157(88)90013-5. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES