Molecular structure and characterization of a novel murine ABC transporter, Abca13
Molecular structure and characterization of a novel murine ABC transporter, Abca13
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DOI：
10.1016/s0378-1119(03)00465-7
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发表时间：
2003-03-27
期刊：
影响因子：
3.5
通讯作者：
Cannon, RE
中科院分区：
文献类型：
--
作者：
Barros, SA;Tennant, RW;Cannon, RE
我们报道了一种新的小鼠三磷酸腺苷结合盒(ABC)转运蛋白Abca13的全长基因和cDNA的分离和结构特征。该基因从小鼠肾脏中分离得到，全长6.7kb，编码2143个氨基酸组成的蛋白质，预测相对分子质量为240 kDa。Abca13基因由44个外显子组成，跨越360 kb的基因组序列。Abca13已经被定位到小鼠染色体11.a2上，揭示了人类同源基因在人类染色体7p12的同线区域高度保守。其氨基酸序列与人ABCA1(50%)、ABCA4(50%)和ABCA12(56%)同源性最高。对推测的Abca13启动子区域的分析揭示了与髓系和淋巴系细胞类型相关的潜在转录因子结合位点。小鼠颌下腺、附睾腺、卵巢和胸腺的mRNA转录水平最高；其他各种组织中的转录水平较低。在没有外显子11的小鼠肾脏中发现了一种可选的转录本。通过转录后剪接去除外显子I I会导致开放阅读框架中的框架移位，导致提前终止密码子。我们推测，外显子I的切除可能是肾脏的一种调节机制，也可能是其他组织的调节机制。小鼠ABCA13基因的分子特征为进一步研究人类ABCA13转运蛋白的功能奠定了基础。爱思唯尔科学公司出版。
We report the isolation and structural characterization of the full-length gene and cDNA for a novel mouse ATP-binding cassette (ABC) transporter, Abca13. The mRNA, isolated from mouse kidney, is 6.7 kb in size and encodes a protein consisting of 2143 amino acids with a predicted molecular weight of 240 kDa. The Abca13 gene consists of 44 exons which span 360 kb of genomic sequence. Abca13 has been mapped to mouse chromosome 11.a2, revealing the human orthologue highly conserved on a syntenic region of human chromosome 7p12. The deduced mouse Abca13 protein shows highest amino acid sequence homology to human ABCA 1 (50%), ABCA4 (50%), and ABCA 12 (56%). Analysis of the putative Abca13 promoter region revealed potential transcription factor binding sites associated with myeloid- and lymphoid-derived cell types. mRNA transcript levels were highest in mouse submaxillary gland, epididymus, ovary, and thymus; with lower levels in a variety of other tissues. An alternative transcript was discovered in mouse kidney devoid of exon 11. The removal of exon I I by post-transcriptional splicing causes a frameshift in the open reading frame and results in a premature termination codon. We hypothesize that the excision of exon I I may serve as a regulatory mechanism in kidney, and perhaps other tissues as well. The molecular characterization of the mouse Abca13 gene will establish the foundation for future functional studies of the human ABCA13 transporter. Published by Elsevier Science B.V.