Shamay Meir, Barak Orr, Shaul Yosef
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Genomics. 2002 Apr;79(4):523-9. doi: 10.1006/geno.2002.6717.
The PHD/LAP (plant homology domain/leukemia associated protein) finger motif is characteristically defined by a histidine and seven cysteines that are spatially arranged in a C4HC3 consensus sequence. This unique zinc finger, found primarily in a wide variety of chromatin-associated proteins, is considered to mediate protein-protein interactions. We have isolated a novel human PHD-finger protein, HBXAP (for hepatitis B virus x associated protein). HBXAP has three alternatively spliced isoforms. We also identified the Drosophila melanogaster HBXAP ortholog, gene CG8677. Based on alignment of four different proteins, we found a novel conserved domain in HBXAP that we designated the HBXAP conserved domain (XCD). We show that HBXAP represses transcription when recruited to DNA via the DNA binding of GAL4. Furthermore, the PHD finger alone suffices to repress transcription, thus attributing a functional role to this domain. The gene HBXAP is localized to the long arm of human chromosome 11 between q13.4 and q14.1. This region is amplified and rearranged in many tumors, suggesting a role for HBXAP in tumorigenesis similar to that of other PHD-containing proteins.
PHD/LAP（植物同源结构域/白血病相关蛋白）指基序的特征是由一个组氨酸和七个半胱氨酸组成，它们在空间上排列成C4HC3共有序列。这种独特的锌指主要存在于多种与染色质相关的蛋白质中，被认为可介导蛋白质-蛋白质相互作用。我们分离出了一种新型人类PHD指蛋白，即HBXAP（乙型肝炎病毒X相关蛋白）。HBXAP有三种可变剪接异构体。我们还鉴定出了果蝇HBXAP的直系同源基因，即基因CG8677。基于四种不同蛋白质的比对，我们在HBXAP中发现了一个新的保守结构域，我们将其命名为HBXAP保守结构域（XCD）。我们发现，当通过GAL4的DNA结合被招募到DNA上时，HBXAP会抑制转录。此外，单独的PHD指就足以抑制转录，因此赋予了该结构域一种功能作用。基因HBXAP定位于人类11号染色体长臂的q13.4和q14.1之间。该区域在许多肿瘤中发生扩增和重排，表明HBXAP在肿瘤发生中发挥的作用与其他含PHD的蛋白质类似。
