Comparative genomic analysis of slc39a12/ZIP12: insight into a zinc transporter required for vertebrate nervous system development.
Comparative genomic analysis of slc39a12/ZIP12: insight into a zinc transporter required for vertebrate nervous system development.
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DOI：
10.1371/journal.pone.0111535
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chowanadisai W
中科院分区：
文献类型：
--
作者：
Chowanadisai W
由基因 slc39a12 编码的锌转运蛋白 ZIP12 先前已被证明对小鼠 Neuro-2a 神经母细胞瘤细胞和原代小鼠神经元的神经元分化很重要，并且对于热带爪蟾胚胎发生过程中的神经形成是必需的。然而，人们对该基因的生化特性、细胞调节或生理作用知之甚少。 ZIP12 是一种对神经系统功能和发育很重要的锌转运蛋白的假设指导了比较遗传学方法来揭示 ZIP12 在各种基因组中的存在，并鉴定与 ZIP12 相关的保守序列和表达模式。 slc39a12 的直向同源物检测是通过与人 ZIP12 的氨基酸序列与人旁系同源物 ZIP4 进行比较以及基因组之间保守的局部同线性进行相互 BLAST 命中来进行的。 ZIP12 存在于几乎所有被检查的脊椎动物的基因组中，从人类和其他哺乳动物到大多数硬骨鱼。然而，斑马鱼基因组中似乎不存在 ZIP12。在其他无脊椎动物脊索动物和后口动物中，ZIP12 与 ZIP4 的区分不成功或不确定。由于包含或排除保守外显子而导致的剪接变异存在于人类、大鼠和牛中，并且可能具有生物学意义。 ZIP12 还拥有许多通常与细胞内运输相关的推定二亮氨酸和酪氨酸基序，这些基序可能通过 ZIP12 在细胞内的定位来控制细胞锌的摄取活性。这些发现强调了 ZIP12 在生化、细胞和生理水平上的多个方面，可能具有生物学意义。 ZIP12 似乎在脊椎动物神经系统发育中具有保守的锌摄取转运蛋白功能。因此，ZIP12 的作用可能与报道的许多动物模型和人类中因缺锌引起的先天性畸形有关。
The zinc transporter ZIP12, which is encoded by the gene slc39a12, has previously been shown to be important for neuronal differentiation in mouse Neuro-2a neuroblastoma cells and primary mouse neurons and necessary for neurulation during Xenopus tropicalis embryogenesis. However, relatively little is known about the biochemical properties, cellular regulation, or the physiological role of this gene. The hypothesis that ZIP12 is a zinc transporter important for nervous system function and development guided a comparative genetics approach to uncover the presence of ZIP12 in various genomes and identify conserved sequences and expression patterns associated with ZIP12. Ortholog detection of slc39a12 was conducted with reciprocal BLAST hits with the amino acid sequence of human ZIP12 in comparison to the human paralog ZIP4 and conserved local synteny between genomes. ZIP12 is present in the genomes of almost all vertebrates examined, from humans and other mammals to most teleost fish. However, ZIP12 appears to be absent from the zebrafish genome. The discrimination of ZIP12 compared to ZIP4 was unsuccessful or inconclusive in other invertebrate chordates and deuterostomes. Splice variation, due to the inclusion or exclusion of a conserved exon, is present in humans, rats, and cows and likely has biological significance. ZIP12 also possesses many putative di-leucine and tyrosine motifs often associated with intracellular trafficking, which may control cellular zinc uptake activity through the localization of ZIP12 within the cell. These findings highlight multiple aspects of ZIP12 at the biochemical, cellular, and physiological levels with likely biological significance. ZIP12 appears to have conserved function as a zinc uptake transporter in vertebrate nervous system development. Consequently, the role of ZIP12 may be an important link to reported congenital malformations in numerous animal models and humans that are caused by zinc deficiency.
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影响因子：
5.6
作者：
Ehsani, Sepehr;Salehzadeh, Ashkan;Schmitt-Ulms, Gerold
通讯作者：
Schmitt-Ulms, Gerold
DOI：
10.1073/pnas.1222142110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Chowanadisai, Winyoo;Graham, David M.;Messerli, Mark A.
通讯作者：
Messerli, Mark A.
影响因子：
3.5
作者：
Dufner-Beattie, Jodi;Weaver, Benjamin P.;Andrews, Glen K.
通讯作者：
Andrews, Glen K.
影响因子：
14.9
作者：
Bowes JB;Snyder KA;Segerdell E;Gibb R;Jarabek C;Noumen E;Pollet N;Vize PD
通讯作者：
Vize PD
影响因子：
14.9
作者：
Dereeper A;Guignon V;Blanc G;Audic S;Buffet S;Chevenet F;Dufayard JF;Guindon S;Lefort V;Lescot M;Claverie JM;Gascuel O
通讯作者：
Gascuel O