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. 1987 Jan 26;15(2):443–463. doi: 10.1093/nar/15.2.443

The human ubiquitin gene family: structure of a gene and pseudogenes from the Ub B subfamily.

R T Baker, P G Board
PMCID: PMC340445  PMID: 3029682

Abstract

An ubiquitin cDNA clone was isolated from a human liver cDNA library. This clone contained two complete, and a portion of a third, ubiquitin coding sequences joined head to tail with no spacer peptides. Screening a human genomic library with a probe derived from the coding region of this cDNA identified a large number of cross-hybridising clones. Differential screening of these genomic clones with the 3' non-coding region of the cDNA identified three different 3'-positive clones. Sequence analysis of these three clones revealed: a gene corresponding to the cDNA containing an intron in the 5' non-coding region and coding for three direct repeats of mature ubiquitin, and two related pseudogenes which appear to have arisen by reverse transcription and insertion into the genome. However, one pseudogene contains two repeats of the ubiquitin coding sequence, while the other contains only one. Hybridisation analysis of restricted human genomic DNA suggests the presence of one other closely related gene within the genome.

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Selected References

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

  1. Bachmair A., Finley D., Varshavsky A. In vivo half-life of a protein is a function of its amino-terminal residue. Science. 1986 Oct 10;234(4773):179–186. doi: 10.1126/science.3018930. [DOI] [PubMed] [Google Scholar]
  2. Bell G. I., Pictet R. L., Rutter W. J., Cordell B., Tischer E., Goodman H. M. Sequence of the human insulin gene. Nature. 1980 Mar 6;284(5751):26–32. doi: 10.1038/284026a0. [DOI] [PubMed] [Google Scholar]
  3. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Board P. G. Genetic heterogeneity of the B subunit of coagulation factor XIII: resolution of type 2. Ann Hum Genet. 1984 Jul;48(Pt 3):223–228. doi: 10.1111/j.1469-1809.1984.tb01018.x. [DOI] [PubMed] [Google Scholar]
  6. Bond U., Schlesinger M. J. Ubiquitin is a heat shock protein in chicken embryo fibroblasts. Mol Cell Biol. 1985 May;5(5):949–956. doi: 10.1128/mcb.5.5.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Burke J. F. High-sensitivity S1 mapping with single-stranded [32P]DNA probes synthesized from bacteriophage M13mp templates. Gene. 1984 Oct;30(1-3):63–68. doi: 10.1016/0378-1119(84)90105-7. [DOI] [PubMed] [Google Scholar]
  9. Busch H., Goldknopf I. L. Ubiquitin - protein conjugates. Mol Cell Biochem. 1981 Nov 13;40(3):173–187. doi: 10.1007/BF00224611. [DOI] [PubMed] [Google Scholar]
  10. Casadaban M. J., Cohen S. N. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J Mol Biol. 1980 Apr;138(2):179–207. doi: 10.1016/0022-2836(80)90283-1. [DOI] [PubMed] [Google Scholar]
  11. Ciechanover A., Finley D., Varshavsky A. Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85. Cell. 1984 May;37(1):57–66. doi: 10.1016/0092-8674(84)90300-3. [DOI] [PubMed] [Google Scholar]
  12. Costanzo F., Colombo M., Staempfli S., Santoro C., Marone M., Frank R., Delius H., Cortese R. Structure of gene and pseudogenes of human apoferritin H. Nucleic Acids Res. 1986 Jan 24;14(2):721–736. doi: 10.1093/nar/14.2.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fitzgerald M., Shenk T. The sequence 5'-AAUAAA-3'forms parts of the recognition site for polyadenylation of late SV40 mRNAs. Cell. 1981 Apr;24(1):251–260. doi: 10.1016/0092-8674(81)90521-3. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Gallatin M., St John T. P., Siegelman M., Reichert R., Butcher E. C., Weissman I. L. Lymphocyte homing receptors. Cell. 1986 Mar 14;44(5):673–680. doi: 10.1016/0092-8674(86)90832-9. [DOI] [PubMed] [Google Scholar]
  16. Gausing K., Barkardottir R. Structure and expression of ubiquitin genes in higher plants. Eur J Biochem. 1986 Jul 1;158(1):57–62. doi: 10.1111/j.1432-1033.1986.tb09720.x. [DOI] [PubMed] [Google Scholar]
  17. Gavilanes J. G., Gonzalez de Buitrago G., Perez-Castells R., Rodriguez R. Isolation, characterization, and amino acid sequence of a ubiquitin-like protein from insect eggs. J Biol Chem. 1982 Sep 10;257(17):10267–10270. [PubMed] [Google Scholar]
  18. Giannelli F., Choo K. H., Rees D. J., Boyd Y., Rizza C. R., Brownlee G. G. Gene deletions in patients with haemophilia B and anti-factor IX antibodies. Nature. 1983 May 12;303(5913):181–182. doi: 10.1038/303181a0. [DOI] [PubMed] [Google Scholar]
  19. Graves B. J., Johnson P. F., McKnight S. L. Homologous recognition of a promoter domain common to the MSV LTR and the HSV tk gene. Cell. 1986 Feb 28;44(4):565–576. doi: 10.1016/0092-8674(86)90266-7. [DOI] [PubMed] [Google Scholar]
  20. Grunebaum L., Cazenave J. P., Camerino G., Kloepfer C., Mandel J. L., Tolstoshev P., Jaye M., De la Salle H., Lecocq J. P. Carrier detection of Hemophilia B by using a restriction site polymorphism associated with the coagulation Factor IX gene. J Clin Invest. 1984 May;73(5):1491–1495. doi: 10.1172/JCI111354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  22. Hershko A., Ciechanover A. Mechanisms of intracellular protein breakdown. Annu Rev Biochem. 1982;51:335–364. doi: 10.1146/annurev.bi.51.070182.002003. [DOI] [PubMed] [Google Scholar]
  23. Koltunow A. M., Gregg K., Rogers G. E. Intron sequences modulate feather keratin gene transcription in Xenopus oocytes. Nucleic Acids Res. 1986 Aug 26;14(16):6375–6392. doi: 10.1093/nar/14.16.6375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lehman W. Hybrid troponin reconstituted from vertebrate and arthropod subunits. Nature. 1975 May 29;255(5507):424–426. doi: 10.1038/255424a0. [DOI] [PubMed] [Google Scholar]
  25. Levinger L., Varshavsky A. Selective arrangement of ubiquitinated and D1 protein-containing nucleosomes within the Drosophila genome. Cell. 1982 Feb;28(2):375–385. doi: 10.1016/0092-8674(82)90355-5. [DOI] [PubMed] [Google Scholar]
  26. Lin H. C., Lei S. P., Wilcox G. An improved DNA sequencing strategy. Anal Biochem. 1985 May 15;147(1):114–119. doi: 10.1016/0003-2697(85)90016-8. [DOI] [PubMed] [Google Scholar]
  27. Lomedico P., Rosenthal N., Efstratidadis A., Gilbert W., Kolodner R., Tizard R. The structure and evolution of the two nonallelic rat preproinsulin genes. Cell. 1979 Oct;18(2):545–558. doi: 10.1016/0092-8674(79)90071-0. [DOI] [PubMed] [Google Scholar]
  28. Lund P. K., Moats-Staats B. M., Simmons J. G., Hoyt E., D'Ercole A. J., Martin F., Van Wyk J. J. Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor. J Biol Chem. 1985 Jun 25;260(12):7609–7613. [PubMed] [Google Scholar]
  29. Marx J. L. Ubiquitin moves to the cell surface. Science. 1986 Feb 21;231(4740):796–797. doi: 10.1126/science.3003911. [DOI] [PubMed] [Google Scholar]
  30. McCallum F. S., Maden B. E. Human 18 S ribosomal RNA sequence inferred from DNA sequence. Variations in 18 S sequences and secondary modification patterns between vertebrates. Biochem J. 1985 Dec 15;232(3):725–733. doi: 10.1042/bj2320725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. McLauchlan J., Gaffney D., Whitton J. L., Clements J. B. The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3' termini. Nucleic Acids Res. 1985 Feb 25;13(4):1347–1368. doi: 10.1093/nar/13.4.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  34. Murray N. E., Brammar W. J., Murray K. Lambdoid phages that simplify the recovery of in vitro recombinants. Mol Gen Genet. 1977 Jan 7;150(1):53–61. doi: 10.1007/BF02425325. [DOI] [PubMed] [Google Scholar]
  35. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  36. Ozkaynak E., Finley D., Varshavsky A. The yeast ubiquitin gene: head-to-tail repeats encoding a polyubiquitin precursor protein. Nature. 1984 Dec 13;312(5995):663–666. doi: 10.1038/312663a0. [DOI] [PubMed] [Google Scholar]
  37. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  38. Rackwitz H. R., Zehetner G., Frischauf A. M., Lehrach H. Rapid restriction mapping of DNA cloned in lambda phage vectors. Gene. 1984 Oct;30(1-3):195–200. doi: 10.1016/0378-1119(84)90120-3. [DOI] [PubMed] [Google Scholar]
  39. Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Remaut E., Tsao H., Fiers W. Improved plasmid vectors with a thermoinducible expression and temperature-regulated runaway replication. Gene. 1983 Apr;22(1):103–113. doi: 10.1016/0378-1119(83)90069-0. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Schlesinger D. H., Goldstein G., Niall H. D. The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells. Biochemistry. 1975 May 20;14(10):2214–2218. doi: 10.1021/bi00681a026. [DOI] [PubMed] [Google Scholar]
  44. Sharp P. A. Conversion of RNA to DNA in mammals: Alu-like elements and pseudogenes. Nature. 1983 Feb 10;301(5900):471–472. doi: 10.1038/301471a0. [DOI] [PubMed] [Google Scholar]
  45. Shinagawa M., Padmanabhan R. Comparative sequence analysis of the inverted terminal repetitions from different adenoviruses. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3831–3835. doi: 10.1073/pnas.77.7.3831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Siegelman M., Bond M. W., Gallatin W. M., St John T., Smith H. T., Fried V. A., Weissman I. L. Cell surface molecule associated with lymphocyte homing is a ubiquitinated branched-chain glycoprotein. Science. 1986 Feb 21;231(4740):823–829. doi: 10.1126/science.3003913. [DOI] [PubMed] [Google Scholar]
  47. St John T., Gallatin W. M., Siegelman M., Smith H. T., Fried V. A., Weissman I. L. Expression cloning of a lymphocyte homing receptor cDNA: ubiquitin is the reactive species. Science. 1986 Feb 21;231(4740):845–850. doi: 10.1126/science.3003914. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. Stanley K. K. Solubilization and immune-detection of beta-galactosidase hybrid proteins carrying foreign antigenic determinants. Nucleic Acids Res. 1983 Jun 25;11(12):4077–4092. doi: 10.1093/nar/11.12.4077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tinoco I., Jr, Borer P. N., Dengler B., Levin M. D., Uhlenbeck O. C., Crothers D. M., Bralla J. Improved estimation of secondary structure in ribonucleic acids. Nat New Biol. 1973 Nov 14;246(150):40–41. doi: 10.1038/newbio246040a0. [DOI] [PubMed] [Google Scholar]
  51. Urano Y., Watanabe K., Sakai M., Tamaoki T. The human albumin gene. Characterization of the 5' and 3' flanking regions and the polymorphic gene transcripts. J Biol Chem. 1986 Mar 5;261(7):3244–3251. [PubMed] [Google Scholar]
  52. Watson D. C., Levy W. B., Dixon G. H. Free ubiquitin is a non-histone protein of trout testis chromatin. Nature. 1978 Nov 9;276(5684):196–198. doi: 10.1038/276196a0. [DOI] [PubMed] [Google Scholar]
  53. White J. W., Saunders G. F. Structure of the human glucagon gene. Nucleic Acids Res. 1986 Jun 25;14(12):4719–4730. doi: 10.1093/nar/14.12.4719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Wiborg O., Pedersen M. S., Wind A., Berglund L. E., Marcker K. A., Vuust J. The human ubiquitin multigene family: some genes contain multiple directly repeated ubiquitin coding sequences. EMBO J. 1985 Mar;4(3):755–759. doi: 10.1002/j.1460-2075.1985.tb03693.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Wilkinson K. D., Cox M. J., O'Connor L. B., Shapira R. Structure and activities of a variant ubiquitin sequence from bakers' yeast. Biochemistry. 1986 Sep 9;25(18):4999–5004. doi: 10.1021/bi00366a005. [DOI] [PubMed] [Google Scholar]
  56. Yarden Y., Escobedo J. A., Kuang W. J., Yang-Feng T. L., Daniel T. O., Tremble P. M., Chen E. Y., Ando M. E., Harkins R. N., Francke U. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature. 1986 Sep 18;323(6085):226–232. doi: 10.1038/323226a0. [DOI] [PubMed] [Google Scholar]

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