Human cytosolic sulphotransferase SULT1C3: genomic analysis and functional characterization of splice variant SULT1C3 and SULT1C3d.
Human cytosolic sulphotransferase SULT1C3: genomic analysis and functional characterization of splice variant SULT1C3 and SULT1C3d.
复制标题
人胞浆磺基转移酶 SULT1C3：剪接变体 SULT1C3 和 SULT1C3d 的基因组分析和功能表征。
DOI：
10.1093/jb/mvx044
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发表时间：
2017
影响因子：
2.7
通讯作者：
M.-C.
中科院分区：
文献类型：
--
作者：
Kurogi;K.;Shimohira;T.;Kouriki-Nagatomo;H.;Zhang;G.;Miller;E.R.;Sakakibara;Y.;Suiko;M.;Liu;M.-C.
胞质硫转移酶SULT1C3仍然是最不了解的人类硫转移酶。SULT1C3基因已被证明含有替代的外显子7和8，这提出了关于它们的进化起源的问题，并暗示产生了多个SULT1C3变体。研究了两个SULT1C3剪接变体SULT1C3a和SULT1C3d，以验证替代c端序列对其硫酸化活性的影响。序列同源性和基因定位分析验证了sult1c3基因的同源性。sult1c3基因似乎只存在于人类和其他灵长类动物中，但另一个外显子7b和8b与啮齿动物sult1c1基因的相应区域具有高度的同源性，这意味着它们的进化起源来自于一个已消亡的人类sult1c1基因。对纯化后的重组SULT1C3a和SULT1C3d对多种内源性和外源性化合物的硫酸化活性进行了分析。SULT1C3a对羟基氯联苯表现出较弱的活性和严格的底物特异性，而SULT1C3d对胆汁酸和甲状腺激素以及羟基氯联苯表现出更广泛的底物特异性。分子对接模拟表明，Tyr249和Met257可能在SULT1C3d识别底物过程中发挥重要作用。外显子7和8序列的选择性剪接导致SULT1C3变体的不同催化性能。
The cytosolic sulphotransferase SULT1C3 remained the most poorly understood human SULT. TheSULT1C3gene has been shown to contain alternative exons 7 and 8, raising the question concerning their evolutionary origin and implying the generation of multiple SULT1C3 variants. Two SULT1C3 splice variants, SULT1C3a and SULT1C3d, were investigated to verify the impact of alternative C-terminal sequences on their sulphating activity. Sequence homology and gene location analyses were performed to verify the orthology of theSULT1C3gene. TheSULT1C3gene appears to be present only in humans and other primates, but alternative exons 7b and 8b share high degrees of homology with corresponding regions of rodentSULT1C1genes, implying their evolutionary origin being from a defunct humanSULT1C1gene. Purified recombinant SULT1C3a and SULT1C3d were analyzed for sulphating activities toward a variety of endogenous and xenobiotic compounds. While SULT1C3a displayed weaker activities and strict substrate specificity toward hydroxyl-chlorinated biphenyls, SULT1C3d exhibited broader substrate specificity toward bile acids and thyroid hormones as well as hydroxyl-chlorinated biphenyls. Molecular docking simulation suggested that Tyr249 and Met257 may play an important role in substrate recognition by SULT1C3d. Alternative splicing of exons 7 and 8 sequences resulted in differential catalytic properties of SULT1C3 variants.