THE LEUKEMIA-ASSOCIATED-PROTEIN (LAP) DOMAIN, A CYSTEINE-RICH MOTIF, IS PRESENT IN A WIDE-RANGE OF PROTEINS, INCLUDING MLL, AF10, AND MLLT6 PROTEINS
THE LEUKEMIA-ASSOCIATED-PROTEIN (LAP) DOMAIN, A CYSTEINE-RICH MOTIF, IS PRESENT IN A WIDE-RANGE OF PROTEINS, INCLUDING MLL, AF10, AND MLLT6 PROTEINS
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DOI：
10.1073/pnas.92.21.9737
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发表时间：
1995-10-10
影响因子：
11.1
通讯作者：
YOUNG, BD
中科院分区：
文献类型：
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作者：
SAHA, V;CHAPLIN, T;YOUNG, BD
我们已经鉴定并进一步鉴定了秀丽线虫的一个基因CEZF，它编码的蛋白质与人类基因产物AF10、Mllt6和BR140的锌指和亮氨酸拉链基序有很大的同源性。CEZF锌指区的第一部分在基因水平上与AF10(66%)和Mllt6(%)的相应区域有很强的相似性，由于该区域在结构上不同于先前描述的锌指基序，我们进行了序列同源性搜索，发现了另外25个具有相似基序的蛋白质，由于该基序的功能结构域在白血病相关染色体易位中可能被破坏，我们建议将其命名为白血病相关蛋白(LAP)Finger。在这些比较的基础上，LAP结构域的共识序列是Cys(1)-Xaa(1-2)-Cys(2)-Xaa(9-21)-Cys(3)-Xaa(2-4)-Cys(4)-Xaa(4-5)-His(5)-Xaa(2)-Cys(6)-Xaa(12-46)-Cys(7)-Xaa(2)-Cys(8)，，其中下标数字代表氨基酸残基的数量，我们综述了该基序与锌结合的证据，是这组调控蛋白中重要的DNA结合域，可能参与白血病的发生。
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 Cys(1)-Xaa(1-2)-Cys(2)-Xaa(9-21)-Cys(3)-Xaa(2-4)-Cys(4)-Xaa(4-5)-His(5)-Xaa(2)-Cys(6)-Xaa(12-46)-Cys(7)-Xaa(2)-Cys(8), 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.