The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins.
We have identified and further characterized a Caenorhabditis elegans gene, CEZF, that encodes a protein with substantial homology to the zinc finger and leucine zipper motifs of the human gene products AF10, MLLT6, and BR140. The first part of the zinc finger region of CEZF has strong similarity to the corresponding regions of AF10 (66%) and MLLT6 (64%) at the cDNA level. As this region is structurally different from previously described zinc finger motifs, sequence homology searches were done. Twenty-five other proteins with a similar motif were identified. Because the functional domain of this motif is potentially disrupted in leukemia-associated chromosomal translocations, we propose the name of leukemia-associated protein (LAP) finger. On the basis of these comparisons, the LAP domain consensus sequence is Cys1-Xaa1-2-Cys2-Xaa9-21-Cys3-Xaa2-4 -Cys4-Xaa4-5-His5-Xaa2-Cys6-Xaa12-46 - Cys7-Xaa2-Cys8, where subscripted numbers represent the number of amino acid residues. We review the evidence that this motif binds zinc, is the important DNA-binding domain in this group of regulatory proteins, and may be involved in leukemogenesis.
Saha
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Department of Medical Oncology, Medical College of St. Bartholomew's Hospital, London, United Kingdom.
Chaplin
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Gregorini
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Ayton
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Young
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D003545:Cysteine / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011487:Protein Conformation; D011519:Proto-Oncogenes; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; C096107:CEZF protein, C elegans; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C092513:MLLT10 protein, human; C096106:MLLT6 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D003545:Cysteine