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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Zinc Fingers

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Disease relevance of Zinc Fingers


Psychiatry related information on Zinc Fingers


High impact information on Zinc Fingers

  • The Ikaros gene, which encodes a family of hemopoietic-specific zinc finger proteins, is described as a central regulator of lymphocyte differentiation [8].
  • Human mutations in TBX5, a gene encoding a T-box transcription factor, and SALL4, a gene encoding a zinc-finger transcription factor, cause similar upper limb and heart defects [9].
  • The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface [10].
  • We show that yeast ESCRT-I links directly to ESCRT-II, through a tight interaction of Vps28 (ESCRT-I) with the yeast-specific zinc-finger insertion within the GLUE domain of Vps36 (ESCRT-II) [11].
  • Here we show that loss of him-8 function causes profound X chromosome-specific defects in homolog pairing and synapsis. him-8 encodes a C2H2 zinc-finger protein that is expressed during meiosis and concentrates at a site on the X chromosome known as the meiotic pairing center (PC) [12].

Chemical compound and disease context of Zinc Fingers


Biological context of Zinc Fingers

  • The t(11;22)(p13;q12) chromosomal translocation that defines DSRT produces a chimaeric protein containing the potential transactivation domain of the Ewing-sarcoma protein (EWS) fused to zinc fingers 2-4 of the Wilms tumour suppressor and transcriptional repressor WT1 (refs 2,3) [18].
  • At the chromosome 8 breakpoint we identify a novel gene, MOZ, which encodes a 2,004-amino-acid protein characterized by two C4HC3 zinc fingers and a single C2HC zinc finger in conjunction with a putative acetyltransferase signature [19].
  • OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways [20].
  • Nucleotide sequence analysis of a Zfy-2 cDNA suggests that it encodes a 783 amino acid protein with two domains: the amino-terminal portion is highly acidic, with 25% of its residues being glutamic or aspartic acid, while the carboxy-terminal domain contains 13 zinc fingers [21].
  • We here demonstrate that the t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel, developmentally regulated zinc finger gene at 8q12, and the constitutively expressed gene for beta-catenin (CTNNB1), a protein interface functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis [22].

Anatomical context of Zinc Fingers


Associations of Zinc Fingers with chemical compounds

  • This domain contains a cysteine-rich zinc finger, and mutation of either of two cysteines abolishes binding to both sites [28].
  • These include the presence of four zinc finger domains and a region rich in proline and glutamine [29].
  • Significantly, the bmi-1 gene, which is expressed in diverse normal cells, encodes a Cys/His metal-binding motif (C3HC4) that resembles those in several DNA-binding proteins and defines a new category of zinc finger gene [30].
  • The mutant expresses normal levels of prespore-cell transcripts but fails to produce the spore transcript spiA. stkA encodes a predicted 99 kDa protein (STKA) with two putative C4 zinc fingers, one of which is a GATA-type finger, indicating that it may be a transcription factor [31].
  • Further replacement of five amino acids in the stem of the second zinc finger transforms the specificity to that of the thyroid hormone receptor [32].

Gene context of Zinc Fingers

  • This disorder is inherited as an autosomal dominant trait and has been mapped to 7p13 (S. Kang et al. Autosomal dominant Pallister-Hall syndrome maps to 7p13. Am. J. Hum. Genet. 59, A81 (1996)), co-localizing the PHS locus and the GLI3 zinc finger transcription factor gene [33].
  • Zfpm2 interacts specifically with the N-terminal zinc finger of Gata4 and represses Gata4-dependent transcription [34].
  • Peg3 mRNA is a 9 kb transcript encoding an unusual zinc finger protein with eleven widely spaced C2H2 type motifs and two groups of amino acid repeats [35].
  • Zfp148 belongs to a large family of C2H2-type zinc-finger transcription factors [36].
  • From this chromosomal region we have positionally cloned ZIC3, a gene encoding a putative zinc-finger transcription factor [37].

Analytical, diagnostic and therapeutic context of Zinc Fingers


  1. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Pelletier, J., Bruening, W., Kashtan, C.E., Mauer, S.M., Manivel, J.C., Striegel, J.E., Houghton, D.C., Junien, C., Habib, R., Fouser, L. Cell (1991) [Pubmed]
  2. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Person, R.E., Li, F.Q., Duan, Z., Benson, K.F., Wechsler, J., Papadaki, H.A., Eliopoulos, G., Kaufman, C., Bertolone, S.J., Nakamoto, B., Papayannopoulou, T., Grimes, H.L., Horwitz, M. Nat. Genet. (2003) [Pubmed]
  3. Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein. Rice, W.G., Turpin, J.A., Huang, M., Clanton, D., Buckheit, R.W., Covell, D.G., Wallqvist, A., McDonnell, N.B., DeGuzman, R.N., Summers, M.F., Zalkow, L., Bader, J.P., Haugwitz, R.D., Sausville, E.A. Nat. Med. (1997) [Pubmed]
  4. Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Boyer, T.G., Martin, M.E., Lees, E., Ricciardi, R.P., Berk, A.J. Nature (1999) [Pubmed]
  5. Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Rauscher, F.J., Morris, J.F., Tournay, O.E., Cook, D.M., Curran, T. Science (1990) [Pubmed]
  6. Mutations in the ZNF41 gene are associated with cognitive deficits: identification of a new candidate for X-linked mental retardation. Shoichet, S.A., Hoffmann, K., Menzel, C., Trautmann, U., Moser, B., Hoeltzenbein, M., Echenne, B., Partington, M., Van Bokhoven, H., Moraine, C., Fryns, J.P., Chelly, J., Rott, H.D., Ropers, H.H., Kalscheuer, V.M. Am. J. Hum. Genet. (2003) [Pubmed]
  7. The ZDHHC8 gene did not associate with bipolar disorder or schizophrenia. Otani, K., Ujike, H., Tanaka, Y., Morita, Y., Kishimoto, M., Morio, A., Uchida, N., Nomura, A., Kuroda, S. Neurosci. Lett. (2005) [Pubmed]
  8. The role of the Ikaros gene in lymphocyte development and homeostasis. Georgopoulos, K., Winandy, S., Avitahl, N. Annu. Rev. Immunol. (1997) [Pubmed]
  9. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Koshiba-Takeuchi, K., Takeuchi, J.K., Arruda, E.P., Kathiriya, I.S., Mo, R., Hui, C.C., Srivastava, D., Bruneau, B.G. Nat. Genet. (2006) [Pubmed]
  10. Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin. Penengo, L., Mapelli, M., Murachelli, A.G., Confalonieri, S., Magri, L., Musacchio, A., Di Fiore, P.P., Polo, S., Schneider, T.R. Cell (2006) [Pubmed]
  11. ESCRT-I Core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes. Teo, H., Gill, D.J., Sun, J., Perisic, O., Veprintsev, D.B., Vallis, Y., Emr, S.D., Williams, R.L. Cell (2006) [Pubmed]
  12. HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis. Phillips, C.M., Wong, C., Bhalla, N., Carlton, P.M., Weiser, P., Meneely, P.M., Dernburg, A.F. Cell (2005) [Pubmed]
  13. Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8. Sugahara, M., Mikawa, T., Kumasaka, T., Yamamoto, M., Kato, R., Fukuyama, K., Inoue, Y., Kuramitsu, S. EMBO J. (2000) [Pubmed]
  14. PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Chen, J., Deangelo, D.J., Kutok, J.L., Williams, I.R., Lee, B.H., Wadleigh, M., Duclos, N., Cohen, S., Adelsperger, J., Okabe, R., Coburn, A., Galinsky, I., Huntly, B., Cohen, P.S., Meyer, T., Fabbro, D., Roesel, J., Banerji, L., Griffin, J.D., Xiao, S., Fletcher, J.A., Stone, R.M., Gilliland, D.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  15. Expression of REX-1, a gene containing zinc finger motifs, is rapidly reduced by retinoic acid in F9 teratocarcinoma cells. Hosler, B.A., LaRosa, G.J., Grippo, J.F., Gudas, L.J. Mol. Cell. Biol. (1989) [Pubmed]
  16. An essential interaction between distinct domains of HIV-1 integrase mediates assembly of the active multimer. Ellison, V., Gerton, J., Vincent, K.A., Brown, P.O. J. Biol. Chem. (1995) [Pubmed]
  17. Specific binding sites in the alcR and alcA promoters of the ethanol regulon for the CREA repressor mediating carbon catabolite repression in Aspergillus nidulans. Kulmburg, P., Mathieu, M., Dowzer, C., Kelly, J., Felenbok, B. Mol. Microbiol. (1993) [Pubmed]
  18. The EWS-WT1 translocation product induces PDGFA in desmoplastic small round-cell tumour. Lee, S.B., Kolquist, K.A., Nichols, K., Englert, C., Maheswaran, S., Ladanyi, M., Gerald, W.L., Haber, D.A. Nat. Genet. (1997) [Pubmed]
  19. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Borrow, J., Stanton, V.P., Andresen, J.M., Becher, R., Behm, F.G., Chaganti, R.S., Civin, C.I., Disteche, C., Dubé, I., Frischauf, A.M., Horsman, D., Mitelman, F., Volinia, S., Watmore, A.E., Housman, D.E. Nat. Genet. (1996) [Pubmed]
  20. OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Hata, A., Seoane, J., Lagna, G., Montalvo, E., Hemmati-Brivanlou, A., Massagué, J. Cell (2000) [Pubmed]
  21. The sex-determining region of the mouse Y chromosome encodes a protein with a highly acidic domain and 13 zinc fingers. Mardon, G., Page, D.C. Cell (1989) [Pubmed]
  22. Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations. Kas, K., Voz, M.L., Röijer, E., Aström, A.K., Meyen, E., Stenman, G., Van de Ven, W.J. Nat. Genet. (1997) [Pubmed]
  23. Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Schneider-Maunoury, S., Topilko, P., Seitandou, T., Levi, G., Cohen-Tannoudji, M., Pournin, S., Babinet, C., Charnay, P. Cell (1993) [Pubmed]
  24. Drosophila CBP is required for dorsal-dependent twist gene expression. Akimaru, H., Hou, D.X., Ishii, S. Nat. Genet. (1997) [Pubmed]
  25. Yeast RAD14 and human xeroderma pigmentosum group A DNA-repair genes encode homologous proteins. Bankmann, M., Prakash, L., Prakash, S. Nature (1992) [Pubmed]
  26. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Georgopoulos, K., Moore, D.D., Derfler, B. Science (1992) [Pubmed]
  27. The ARF1 GTPase-activating protein: zinc finger motif and Golgi complex localization. Cukierman, E., Huber, I., Rotman, M., Cassel, D. Science (1995) [Pubmed]
  28. Functional dissection and sequence of yeast HAP1 activator. Pfeifer, K., Kim, K.S., Kogan, S., Guarente, L. Cell (1989) [Pubmed]
  29. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Call, K.M., Glaser, T., Ito, C.Y., Buckler, A.J., Pelletier, J., Haber, D.A., Rose, E.A., Kral, A., Yeger, H., Lewis, W.H. Cell (1990) [Pubmed]
  30. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Haupt, Y., Alexander, W.S., Barri, G., Klinken, S.P., Adams, J.M. Cell (1991) [Pubmed]
  31. Identification of the cell fate gene stalky in Dictyostelium. Chang, W.T., Newell, P.C., Gross, J.D. Cell (1996) [Pubmed]
  32. Determinants of target gene specificity for steroid/thyroid hormone receptors. Umesono, K., Evans, R.M. Cell (1989) [Pubmed]
  33. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Kang, S., Graham, J.M., Olney, A.H., Biesecker, L.G. Nat. Genet. (1997) [Pubmed]
  34. A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2. Svensson, E.C., Huggins, G.S., Lin, H., Clendenin, C., Jiang, F., Tufts, R., Dardik, F.B., Leiden, J.M. Nat. Genet. (2000) [Pubmed]
  35. Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein. Kuroiwa, Y., Kaneko-Ishino, T., Kagitani, F., Kohda, T., Li, L.L., Tada, M., Suzuki, R., Yokoyama, M., Shiroishi, T., Wakana, S., Barton, S.C., Ishino, F., Surani, M.A. Nat. Genet. (1996) [Pubmed]
  36. Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells during mouse embryogenesis. Takeuchi, A., Mishina, Y., Miyaishi, O., Kojima, E., Hasegawa, T., Isobe, K. Nat. Genet. (2003) [Pubmed]
  37. X-linked situs abnormalities result from mutations in ZIC3. Gebbia, M., Ferrero, G.B., Pilia, G., Bassi, M.T., Aylsworth, A., Penman-Splitt, M., Bird, L.M., Bamforth, J.S., Burn, J., Schlessinger, D., Nelson, D.L., Casey, B. Nat. Genet. (1997) [Pubmed]
  38. A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Sukhatme, V.P., Cao, X.M., Chang, L.C., Tsai-Morris, C.H., Stamenkovich, D., Ferreira, P.C., Cohen, D.R., Edwards, S.A., Shows, T.B., Curran, T. Cell (1988) [Pubmed]
  39. Molecular cloning of matrin F/G: A DNA binding protein of the nuclear matrix that contains putative zinc finger motifs. Hakes, D.J., Berezney, R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  40. Gastric DNA-binding proteins recognize upstream sequence motifs of parietal cell-specific genes. Tamura, S., Wang, X.H., Maeda, M., Futai, M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  41. Altered expression of the WT1 wilms tumor suppressor gene in human breast cancer. Silberstein, G.B., Van Horn, K., Strickland, P., Roberts, C.T., Daniel, C.W. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  42. Alanine scanning site-directed mutagenesis of the zinc fingers of transcription factor ADR1: residues that contact DNA and that transactivate. Thukral, S.K., Morrison, M.L., Young, E.T. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
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