Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Narashino 275-0022, Japan.
Int J Mol Med. 2004 Aug;14(2):333-8.
RhoGAP family proteins, encoded by ARHGAP family genes, are negative regulators of Rho family GTPases, which are implicated in actin remodeling, cell polarity control, and cell migration. Based on the homology with ARHGAP22, we identified and characterized two novel ARHGAP family genes, ARHGAP24 and ARHGAP25. FLJ33877 cDNA (AK091196.1) and aberrant DKFZp564- B1162 cDNA (NM_031305.1) were derived from human ARHGAP24 gene. Two isoforms of KIAA0053 type (D29642.1) and BM927439 type were derived from human ARHGAP25 gene due to alternative splicing (alternative promoter). Mouse 0610025G21 (NM_029270.1) and A130039I20 (AK037710.1) were representative cDNAs derived from mouse Arhgap24 and Arhgap25 genes, respectively. Exon-intron structure of ARHGAP25 gene at human chromosome 2p13 was slightly divergent from that of ARHGAP22 and ARHGAP24 genes. MGC35285, MAPK8 and C10orf64 genes linked to ARHGAP22 gene were paralogs of PTPN13, MAPK10 and WDFY3 genes linked to ARHGAP24 gene, respectively. MGC35285-ARHGAP22-MAPK8-C10orf64 locus at human chromosome 10q11 and the WDFY3-ARHGAP24-MAPK10-PTPN13 locus at human chromosome 4q21 were paralogous regions (paralogons) within the human genome. Human ARHGAP24 showed 91.8% and 48.6% total-amino-acid identity with mouse Arhgap24 and human ARHGAP22, respectively. Human ARHGAP25 showed 86.1% and 40.8% total-amino-acid identity with mouse Arhgap25 and human ARHGAP22, respectively. ARHGAP22, ARHGAP24 and ARHGAP25 were found to constitute the RhoGAP subfamily featured by Pleckstrin homology (PH) domain and C-terminal Coiled-coil domain. This is the first report on identification and characterization of the ARHGAP24 and ARHGAP25 genes.
由ARHGAP家族基因编码的RhoGAP家族蛋白是Rho家族GTP酶的负调控因子，Rho家族GTP酶与肌动蛋白重塑、细胞极性控制和细胞迁移有关。基于与ARHGAP22的同源性，我们鉴定并表征了两个新的ARHGAP家族基因，即ARHGAP24和ARHGAP25。FLJ33877 cDNA（AK091196.1）和异常的DKFZp564 - B1162 cDNA（NM_031305.1）源自人类ARHGAP24基因。由于可变剪接（可变启动子），KIAA0053型（D29642.1）和BM927439型的两种异构体源自人类ARHGAP25基因。人类染色体2p13上ARHGAP25基因的外显子 - 内含子结构与ARHGAP22和ARHGAP24基因的外显子 - 内含子结构略有不同。与ARHGAP22基因连锁的MGC35285、MAPK8和C10orf64基因分别是与ARHGAP24基因连锁的PTPN13、MAPK10和WDFY3基因的旁系同源物。人类染色体10q11上的MGC35285 - ARHGAP22 - MAPK8 - C10orf64基因座和人类染色体4q21上的WDFY3 - ARHGAP24 - MAPK10 - PTPN13基因座是人类基因组中的旁系同源区域（旁系同源段）。人类ARHGAP24与小鼠Arhgap24和人类ARHGAP22的总氨基酸同一性分别为91.8%和48.6%。人类ARHGAP25与小鼠Arhgap25和人类ARHGAP22的总氨基酸同一性分别为86.1%和40.8%。发现ARHGAP22、ARHGAP24和ARHGAP25构成了以普列克底物蛋白同源（PH）结构域和C端卷曲螺旋结构域为特征的RhoGAP亚家族。这是关于ARHGAP24和ARHGAP25基因鉴定与表征的首次报道。
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