SEPHS1: Its evolution, function and roles in development and diseases.
SEPHS1: Its evolution, function and roles in development and diseases.
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DOI：
10.1016/j.abb.2022.109426
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发表时间：
2022-11-15
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
硒磷酸合成酶(Sephs)最初是在原核生物中发现的，是一种以无机硒和三磷酸腺苷为底物催化硒磷合成的酶。然而，与原核生物相反，SEPHS1和SEPHS2在许多真核生物中存在。原核生物Sephs，也称为SELD，在催化区含有半胱氨酸(Cys)或硒半胱氨酸(Sec)。在真核生物中，只有SEPHS2进行硒磷酸合成，并在活性部位含有SEC。然而，SEPHS1的催化位置含有SEC或Cys以外的氨基酸。SEPHSs的系统发育分析表明，祖先Sephs同时含有硒磷酸合成和另一种未知活性，而SEPHS1失去了硒磷酸合成活性。SEPHS1的三维结构表明，其同源二聚体不能形成亚硒酸盐，但保留了产生ADP和无机磷的ATPase活性。SEPHS1最重要的功能是参与细胞氧化还原动态平衡的调节。SEPHS1基因缺失导致氧化还原动态平衡相关基因表达紊乱。根据细胞或组织类型的不同，不同类型的活性氧物种(ROS)会因Sephs缺乏而积累。ROS的积累会引起多种效应，如生长迟缓、细胞凋亡、DNA损伤和胚胎死亡。小鼠胚胎中SEPHS1缺陷会影响视黄酸信号和其他相关的信号通路，这取决于胚胎阶段，直到胚胎在E11.5死亡。SEPHS1基因异常与多种疾病的发病机制有关，包括癌症、克罗恩病和骨关节炎。
Selenophosphate synthetase (SEPHS) was originally discovered in prokaryotes as an enzyme that catalyzes selenophosphate synthesis using inorganic selenium and ATP as substrates. However, in contrast to prokaryotes, two paralogs, SEPHS1 and SEPHS2, occur in many eukaryotes. Prokaryotic SEPHS, also known as SelD, contains either cysteine (Cys) or selenocysteine (Sec) in the catalytic domain. In eukaryotes, only SEPHS2 carries out selenophosphate synthesis and contains Sec at the active site. However, SEPHS1 contains amino acids other than Sec or Cys at the catalytic position. Phylogenetic analysis of SEPHSs reveals that the ancestral SEPHS contains both selenophosphate synthesis and another unknown activity, and that SEPHS1 lost the selenophosphate synthesis activity. The three-dimensional structure of SEPHS1 suggests that its homodimer is unable to form selenophosphate, but retains ATPase activity to produce ADP and inorganic phosphate. The most prominent function of SEPHS1 is that it is implicated in the regulation of cellular redox homeostasis. Deficiency of SEPHS1 leads to the disturbance in the expression of genes involved in redox homeostasis. Different types of reactive oxygen species (ROS) are accumulated in response to SEPHS deficiency depending on cell or tissue types. The accumulation of ROS causes pleiotropic effects such as growth retardation, apoptosis, DNA damage, and embryonic lethality. SEPHS1 deficiency in mouse embryos affects retinoic signaling and other related signaling pathways depending on the embryonal stage until the embryo dies at E11.5. Dysregulated SEPHS1 is associated with the pathogenesis of various diseases including cancer, Crohn’s disease, and osteoarthritis.
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影响因子：
3.5
作者：
Jeong, DW;Kim, TS;Kim, IY
通讯作者：
Kim, IY
影响因子：
3.2
作者：
COX, JC;EDWARDS, ES;DEMOSS, JA
通讯作者：
DEMOSS, JA
来自新西兰奥克兰的病例对照人群中的硒，硒蛋白基因和克罗恩病。
影响因子：
5.9
作者：
Gentschew L;Bishop KS;Han DY;Morgan AR;Fraser AG;Lam WJ;Karunasinghe N;Campbell B;Ferguson LR
通讯作者：
Ferguson LR
DOI：
10.1016/j.bbrc.2010.05.055
发表时间：
2010-06-18
影响因子：
3.1
作者：
Kim, Jin Young;Lee, Kwang Hee;Shim, Myoung Sup;Shin, Hyein;Xu, Xue-Ming;Carlson, Bradley A.;Hatfield, Dolph L.;Lee, Byeong Jae
通讯作者：
Lee, Byeong Jae
影响因子：
4.8
作者：
Dou, Qianhui;Turanov, Anton A.;Mariotti, Marco;Hwang, Jae Yeon;Wang, Huafeng;Lee, Sang -Goo;Paulo, Joao A.;Yim, Sun Hee;Gygi, Stephen P.;Chung, Jean-Ju;Gladyshev, Vadim N.
通讯作者：
Gladyshev, Vadim N.