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. 1999 Jul;8(7):1557–1561. doi: 10.1110/ps.8.7.1557

TRIADs: a new class of proteins with a novel cysteine-rich signature.

B A van der Reijden 1, C A Erpelinck-Verschueren 1, B Löwenberg 1, J H Jansen 1
PMCID: PMC2144383  PMID: 10422847

Abstract

Triad1 was recently identified as a nuclear RING finger protein, which is up-regulated during retinoic acid induced granulocytic differentiation of acute leukemia cells. Here we show that a cysteine-rich domain (C6HC), present in Triad1, is conserved in at least 24 proteins encoded by various eukaryotes. The C6HC consensus pattern C-x(4)-C-x(14-30)-C-x(1-4)-C-x(4)-C-x(2)-C-x(4)-H-x(4)-C defines this structure as the fourth family member of the zinc-binding RING, LIM, and LAP/PHD fingers. Strikingly, in 22 of 24 proteins the C6HC domain is flanked by two RING finger structures. We have termed the novel C6HC motif DRIL (double RING finger linked). The strong conservation of the larger tripartite TRIAD (two RING fingers and DRIL) structure indicates that the three subdomains are functionally linked and identifies a novel class of proteins.

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Selected References

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

  1. Aasland R., Gibson T. J., Stewart A. F. The PHD finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem Sci. 1995 Feb;20(2):56–59. doi: 10.1016/s0968-0004(00)88957-4. [DOI] [PubMed] [Google Scholar]
  2. Dawid I. B., Breen J. J., Toyama R. LIM domains: multiple roles as adapters and functional modifiers in protein interactions. Trends Genet. 1998 Apr;14(4):156–162. doi: 10.1016/s0168-9525(98)01424-3. [DOI] [PubMed] [Google Scholar]
  3. Freemont P. S. The RING finger. A novel protein sequence motif related to the zinc finger. Ann N Y Acad Sci. 1993 Jun 11;684:174–192. doi: 10.1111/j.1749-6632.1993.tb32280.x. [DOI] [PubMed] [Google Scholar]
  4. Giles R. H., Peters D. J., Breuning M. H. Conjunction dysfunction: CBP/p300 in human disease. Trends Genet. 1998 May;14(5):178–183. doi: 10.1016/s0168-9525(98)01438-3. [DOI] [PubMed] [Google Scholar]
  5. Hofmann K., Bucher P., Falquet L., Bairoch A. The PROSITE database, its status in 1999. Nucleic Acids Res. 1999 Jan 1;27(1):215–219. doi: 10.1093/nar/27.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605–608. doi: 10.1038/33416. [DOI] [PubMed] [Google Scholar]
  7. Lupas A. Predicting coiled-coil regions in proteins. Curr Opin Struct Biol. 1997 Jun;7(3):388–393. doi: 10.1016/s0959-440x(97)80056-5. [DOI] [PubMed] [Google Scholar]
  8. Mackay J. P., Crossley M. Zinc fingers are sticking together. Trends Biochem Sci. 1998 Jan;23(1):1–4. doi: 10.1016/s0968-0004(97)01168-7. [DOI] [PubMed] [Google Scholar]
  9. Miller J., McLachlan A. D., Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985 Jun;4(6):1609–1614. doi: 10.1002/j.1460-2075.1985.tb03825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Reddy B. A., Etkin L. D., Freemont P. S. A novel zinc finger coiled-coil domain in a family of nuclear proteins. Trends Biochem Sci. 1992 Sep;17(9):344–345. doi: 10.1016/0968-0004(92)90308-v. [DOI] [PubMed] [Google Scholar]
  11. Saha V., Chaplin T., Gregorini A., Ayton P., Young B. D. The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9737–9741. doi: 10.1073/pnas.92.21.9737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Saurin A. J., Borden K. L., Boddy M. N., Freemont P. S. Does this have a familiar RING? Trends Biochem Sci. 1996 Jun;21(6):208–214. [PubMed] [Google Scholar]
  13. Schmeichel K. L., Beckerle M. C. The LIM domain is a modular protein-binding interface. Cell. 1994 Oct 21;79(2):211–219. doi: 10.1016/0092-8674(94)90191-0. [DOI] [PubMed] [Google Scholar]
  14. Schwabe J. W., Klug A. Zinc mining for protein domains. Nat Struct Biol. 1994 Jun;1(6):345–349. doi: 10.1038/nsb0694-345. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Tokunaga C., Kuroda S., Tatematsu K., Nakagawa N., Ono Y., Kikkawa U. Molecular cloning and characterization of a novel protein kinase C-interacting protein with structural motifs related to RBCC family proteins. Biochem Biophys Res Commun. 1998 Mar 17;244(2):353–359. doi: 10.1006/bbrc.1998.8270. [DOI] [PubMed] [Google Scholar]

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