Schultz D C, Balasara B R, Testa J R, Godwin A K
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, 19111, USA.
Genomics. 1998 Sep 1;52(2):186-91. doi: 10.1006/geno.1998.5420.
Sequence analysis of the candidate tumor suppressor OVCA1 revealed extensive sequence identity and similarity to proteins from a diverse number of species, including the yeast diphthamide biosynthesis protein-2, dph2, which suggested that OVCA1 may be the human homologue to this yeast gene. However, searches of the translated EST database for sequences in common with dph2 and OVCA1 uncovered an EST, h52976, with significant amino acid conservation with dph2. Isolation of a cDNA clone encompassing the EST by RACE methodologies and sequence analysis indicate the identification of a previously unidentified gene that is ubiquitously expressed and maps to chromosome 1p34. Based on amino acid sequence analysis, the 489-amino-acid protein encoded by this novel gene is distinct from OVCA1 and is more closely related to the yeast dph2 gene product. Therefore, we refer to this novel gene as DPH2L2, which constitutes one member of a novel gene family that may be involved in diphthamide biosynthesis in humans.
对候选肿瘤抑制基因OVCA1的序列分析显示,它与多种物种的蛋白质具有广泛的序列同一性和相似性,包括酵母双氢氨甲酰生物合成蛋白2(dph2),这表明OVCA1可能是该酵母基因的人类同源物。然而,在翻译后的EST数据库中搜索与dph2和OVCA1共有的序列时,发现了一个EST(h52976),它与dph2具有显著的氨基酸保守性。通过RACE方法分离包含该EST的cDNA克隆并进行序列分析,结果表明鉴定出了一个以前未被识别的基因,该基因在全身表达,定位于染色体1p34。基于氨基酸序列分析,这个新基因编码的489个氨基酸的蛋白质与OVCA1不同,并且与酵母dph2基因产物的关系更为密切。因此,我们将这个新基因称为DPH2L2,它构成了一个可能参与人类双氢氨甲酰生物合成的新基因家族的一个成员。