Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Narashino 275-0022, Japan.
Int J Mol Med. 2003 Jun;11(6):791-7.
Parallel analyses of DNA copy number and mRNA expression level by using microarray measurements have been successfully applied for genome-wide screening of proto-oncogenes and tumor suppressor genes. The uncharacterized KIAA0456 cDNA was reported amplified and overexpressed in human breast cancer cell lines UACC812 and ZR-75-1. Here, we characterized the gene corresponding to KIAA0456 cDNA by using bioinformatics. KIAA0456 cDNA was found derived from the FNBP2 gene, consisting of 22 exons. FNBP2 gene was linked to IKBKE and NORE1 genes on human chromosome 1q32.1. FNBP2 mRNA was expressed in melanoma, germ cell tumors, chondrosarcoma and retinoblastoma. ARHGAP13/SRGAP1, ARHGAP14/SRGAP2 and ARHGAP4 cDNAs were homologous to FNBP2/KIAA0456 cDNA. KIAA1304 cDNA was a splicing variant derived from the ARHGAP13 gene, and the nucleotide sequence of representative ARHGAP13 cDNA was determined by assembling EST BU520980 and KIAA1304 cDNA. FNBP2 (1071 aa), ARHGAP13 (1062 aa), ARHGAP14 (1099 aa) and ARHGAP4 (946 aa) constitute the FNBP2 family characterized by FCH, RhoGAP and SH3 domains. The region corresponding to codon 227-345 of FNBP2 was conserved among FNBP2 family proteins as well as FNBP1 and TRIP10 proteins. Because FNBP2 and FNBP1 are formin-binding proteins, the region corresponding to codon 227-345 of FNBP2 was designated FNBP2-FNBP1 homologous (FBH) domain. FNBP2 family proteins consist of FCH, FBH, RhoGAP and SH3 domains, while FNBP1 family proteins (FNBP1 and TRIP10) consist of FCH, FBH and SH3 domains. This is the first report on comprehensive characterization of FNBP2 gene as well as on identification of the FBH domain.
通过使用微阵列测量对DNA拷贝数和mRNA表达水平进行平行分析，已成功应用于原癌基因和肿瘤抑制基因的全基因组筛选。未表征的KIAA0456 cDNA在人乳腺癌细胞系UACC812和ZR-75-1中被报道发生扩增和过表达。在此，我们通过生物信息学对与KIAA0456 cDNA对应的基因进行了表征。发现KIAA0456 cDNA源自FNBP2基因，由22个外显子组成。FNBP2基因与人1号染色体1q32.1上的IKBKE和NORE1基因相连。FNBP2 mRNA在黑色素瘤、生殖细胞肿瘤、软骨肉瘤和成视网膜细胞瘤中表达。ARHGAP13/SRGAP1、ARHGAP14/SRGAP2和ARHGAP4 cDNA与FNBP2/KIAA0456 cDNA同源。KIAA1304 cDNA是源自ARHGAP13基因的剪接变体，代表性ARHGAP13 cDNA的核苷酸序列通过组装EST BU520980和KIAA1304 cDNA确定。FNBP2（1071个氨基酸）、ARHGAP13（1062个氨基酸）、ARHGAP14（1099个氨基酸）和ARHGAP4（946个氨基酸）构成了以FCH、RhoGAP和SH3结构域为特征的FNBP2家族。FNBP2家族蛋白中对应于FNBP2第227至345密码子的区域在FNBP2家族蛋白以及FNBP1和TRIP10蛋白中保守。由于FNBP2和FNBP1是formin结合蛋白，FNBP2中对应于第227至345密码子的区域被命名为FNBP2 - FNBP1同源（FBH）结构域。FNBP2家族蛋白由FCH、FBH、RhoGAP和SH3结构域组成，而FNBP1家族蛋白（FNBP1和TRIP10）由FCH、FBH和SH3结构域组成。这是关于FNBP2基因全面表征以及FBH结构域鉴定的首次报道。
