Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Narashino 275-0022, Japan.
Int J Oncol. 2004 Oct;25(4):1201-6.
ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. Here, we characterized human ARHGAP10 gene by using bioinformatics. Complete coding sequence of ARHGAP10 isoform A was determined by assembling nucleotide position 1-725 of FLJ41791 cDNA (AK123785.1) and 5'-truncated IMAGE4310652 cDNA (BC011920.2). Nucleotide position 240-2600 of ARHGAP10 isoform A was identical to GRAF2 cDNA (AB050785.1). Complete coding sequence of ARHGAP10 isoform B was derived from FLJ41791 cDNA. ARHGAP10 isoform A, consisting of exons 1-23, encoded full-length protein (786 aa). ARHGAP10 isoform B, consisting of exons 1-5 and intron 5, encoded C-terminally truncated protein (163 aa). ARHGAP10 gene was found encoding two isoforms due to alternative splicing. ARHGAP10 mRNA was expressed in chondrosarcoma, breast cancer, kidney tumors, and brain tumors. ARHGAP10 and ARHGAP26 (GRAF), showing 57.9% total amino-acid identity, shared the common-domain structure with BAR, PH, RhoGAP and SH3 domains. ARHGAP10-NR3C2 locus at human chromosome 4q31.23 and ARHGAP26-NR3C1 locus at human chromosome 5q31 were paralogous regions (paralogons) within the human genome. ARHGAP gene family was found consisting of at least 32 members, including ARHGAP1, ARHGAP2 (CHN1), ARHGAP3, (CHN2), ARHGAP4, ARHGAP5, ARHGAP6 (STARD8), ARHGAP7 (STARD12 or DLC1), ARHGAP8, ARHGAP9, ARHGAP10, ARHGAP12, ARHGAP13 (SRGAP1), ARHGAP14 (SRGAP2), ARHGAP15, ARHGAP17 (RICH1), ARHGAP18, ARHGAP19, ARHGAP20, ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP26, STRAD13 (DLC2), HA-1, GMIP, PARG1, PIK3R1, PIK3R2, RACGAP1, and FNBP2. Genetic alterations of ARHGAP family genes lead to carcinogenesis through the dysregulation of Rho/Rac/Cdc42-like GTPases.
ARHGAP家族基因编码具有RhoGAP结构域的Rho/Rac/Cdc42样GTP酶激活蛋白。在此，我们运用生物信息学方法对人类ARHGAP10基因进行了特征分析。通过组装FLJ41791 cDNA（AK123785.1）的核苷酸位置1至725和5'端截短的IMAGE4310652 cDNA（BC011920.2），确定了ARHGAP10同工型A的完整编码序列。ARHGAP10同工型A的核苷酸位置240至2600与GRAF2 cDNA（AB050785.1）相同。ARHGAP10同工型B的完整编码序列源自FLJ41791 cDNA。由外显子1至23组成的ARHGAP10同工型A编码全长蛋白（786个氨基酸）。由外显子1至5和内含子5组成的ARHGAP10同工型B编码C端截短的蛋白（163个氨基酸）。由于选择性剪接，发现ARHGAP10基因编码两种同工型。ARHGAP10 mRNA在软骨肉瘤、乳腺癌、肾肿瘤和脑肿瘤中表达。ARHGAP10和ARHGAP26（GRAF）的总氨基酸同一性为57.9%，它们与BAR、PH、RhoGAP和SH3结构域共享共同的结构域结构。人类染色体4q31.23上的ARHGAP10 - NR3C2基因座和人类染色体5q31上的ARHGAP26 - NR3C1基因座是人类基因组中的旁系同源区域（旁系同源群）。发现ARHGAP基因家族至少由32个成员组成，包括ARHGAP1、ARHGAP2（CHN1）、ARHGAP3（CHN2）、ARHGAP4、ARHGAP5、ARHGAP6（STARD8）、ARHGAP7（STARD12或DLC1）、ARHGAP8、ARHGAP9、ARHGAP10、ARHGAP12、ARHGAP13（SRGAP1）、ARHGAP14（SRGAP2）、ARHGAP15、ARHGAP17（RICH1）、ARHGAP18、ARHGAP19、ARHGAP20、ARHGAP21、ARHGAP22、ARHGAP23、ARHGAP24、ARHGAP25、ARHGAP26、STRAD13（DLC2）、HA - 1、GMIP、PARG1、PIK3R1、PIK3R2、RACGAP1和FNBP2。ARHGAP家族基因的遗传改变通过Rho/Rac/Cdc42样GTP酶的失调导致癌症发生。
