Katoh Yuriko, Katoh Masaru
M&M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Oncol. 2004 Dec;25(6):1875-80.
Signals of Hedgehog family proteins (SHH, IHH and DHH) are transduced through Patched family receptors (PTCH1 and PTCH2) and Smoothened (SMO) to GLI family transcription factors (GLI1, GLI2 and GLI3). SHH plays a key role in development and progression of pancreatic cancer, gastric cancer, basal cell carcinoma, and brain tumors. Drosophila Costal-2 (Cos2) is implicated in the Hedgehog pathway through the interaction with Smoothened (Smo), Cubitus interruptus (Ci), Fused (Fu), and microtubule; however, mammalian ortholog of Drosophila Cos2 remained to be identified. Here we identified and characterized human ortholog of Drosophila Cos2 by using bioinformatics. Full-length Drosophila Cos2 was most homologous to human KIF27, followed by mouse Kif7, and other KIF family members. KIF27 gene at human chromosome 9q22.1 and KIF7 gene at human chromosome 15q26.1 were paralogs within the human genome. Phylogenetic analysis revealed that KIF27, Kif7, KIF4A, KIF4B and KIF21A constitute the KIF27 subfamily among mammalian Kinesin family. Drosophila Cos2 protein consists of Kinesin motor (KISc) domain, Ci-binding domain, and Smo-binding domain. KIF27 itself shared the common domain structure with Drosophila Cos2, while other members of KIF27 subfamily shared partial domain structure with Drosophila Cos2. These facts indicate that KIF27 is one of mammalian orthologs for Drosophila Cos2.
刺猬家族蛋白(SHH、IHH和DHH)的信号通过patched家族受体(PTCH1和PTCH2)和平滑蛋白(SMO)转导至GLI家族转录因子(GLI1、GLI2和GLI3)。SHH在胰腺癌、胃癌、基底细胞癌和脑肿瘤的发生发展中起关键作用。果蝇的Costal-2(Cos2)通过与平滑蛋白(Smo)、间断翅脉(Ci)、融合蛋白(Fu)和微管相互作用参与刺猬信号通路;然而,果蝇Cos2的哺乳动物直系同源物仍有待确定。在此,我们通过生物信息学鉴定并表征了果蝇Cos2的人类直系同源物。全长果蝇Cos2与人类KIF27的同源性最高,其次是小鼠Kif7和其他KIF家族成员。人类染色体9q22.1上的KIF27基因和人类染色体15q26.1上的KIF7基因是人类基因组中的旁系同源物。系统发育分析表明,KIF27、Kif7、KIF4A、KIF4B和KIF21A在哺乳动物驱动蛋白家族中构成KIF27亚家族。果蝇Cos2蛋白由驱动蛋白运动结构域(KISc)、Ci结合结构域和Smo结合结构域组成。KIF27自身与果蝇Cos2具有共同的结构域结构,而KIF27亚家族的其他成员与果蝇Cos2具有部分结构域结构。这些事实表明,KIF27是果蝇Cos2的哺乳动物直系同源物之一。