Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Narashino 275-0022, Japan.
Int J Mol Med. 2003 Jan;11(1):111-6.
Neuroblast undergoes asymmetrical cell division to produce the neuroblast itself and ganglion mother cell along the apical-basal axis. Inscuteable (Insc) and Partner of Inscuteable (Pins) are translocated to the apical cell cortex during asymmetrical cell division of Drosophila neuroblast. Insc is implicated in the apical-basal orientation of mitotic spindle and the basal localization of Prospero (Pros) and Numb. Here, we identified and characterized human Inscuteable (INSC) gene using bioinformatics. Human INSC gene, consisting of at least 13 exons, was located within human genome draft sequence AC090744.5 (around nucleotide position 150581-16936 in reverse orientation). Human INSC gene, closely linked to CALCB gene with an interval of about 30 kb, was assigned to human chromosome 11p15.2-p15.1. Amino-acid sequence of human INSC polypeptide (579 aa) was determined based on exon sequences of human INSC gene. C. elegans hypothetical protein F43E2.3 (NP_495539), homologous to human INSC, was designated C. elegans Insc. Central INSC homologous (ISH) domain and C-terminal PDZ-binding motif were evolutionary conserved among INSC proteins. The former part of ISH domain is implicated in Pros localization, while function of the latter part of ISH domain and C-terminal PDZ-binding motif remain to be elucidated. Human INSC mRNA was expressed in eye, kidney, fetal cochlea, parathyroid tumor, chondrosarcoma, epidermoid carcinoma, and skin tumor. Because LGN/Pins, PARD3/Par-3Bazooka, PARD6A/Par-6 and PRKCZ/aPKC genes implicated in asymmetrical cell division are evolutionarily and functionally conserved, human INSC protein might be implicated in asymmetrical cell division of human neural stem cells and other stem cells.
神经母细胞沿顶-基轴进行不对称细胞分裂，产生神经母细胞自身和神经节母细胞。在果蝇神经母细胞的不对称细胞分裂过程中，无柄蛋白（Insc）和无柄蛋白的伙伴（Pins）会转移至顶端细胞皮层。Insc与有丝分裂纺锤体的顶-基方向以及Prospero（Pros）和Numb的基部定位有关。在此，我们利用生物信息学鉴定并表征了人类无柄蛋白（INSC）基因。人类INSC基因至少由13个外显子组成，位于人类基因组草图序列AC090744.5内（反向方向的核苷酸位置约为150581-16936）。人类INSC基因与CALCB基因紧密相连，间隔约30 kb，定位于人类染色体11p15.2-p15.1。基于人类INSC基因的外显子序列确定了人类INSC多肽（579个氨基酸）的氨基酸序列。与人类INSC同源的秀丽隐杆线虫假想蛋白F43E2.3（NP_495539）被命名为秀丽隐杆线虫Insc。INSC蛋白之间，中央INSC同源（ISH）结构域和C端PDZ结合基序在进化上是保守的。ISH结构域的前半部分与Pros定位有关，而ISH结构域后半部分和C端PDZ结合基序的功能仍有待阐明。人类INSC mRNA在眼睛、肾脏、胎儿耳蜗、甲状旁腺肿瘤、软骨肉瘤、表皮样癌和皮肤肿瘤中表达。由于参与不对称细胞分裂的LGN/Pins、PARD3/Par-3Bazooka、PARD6A/Par-6和PRKCZ/aPKC基因在进化和功能上是保守的，人类INSC蛋白可能参与人类神经干细胞和其他干细胞的不对称细胞分裂。
