更新于：2024-09-19

SAMD8

更新于：2024-09-19

基本信息

别名

Ceramide phosphoethanolamine synthase、CPE synthase、FLJ25082

+ [7]

简介

Sphingomyelin synthases synthesize sphingolipids through transfer of a phosphatidyl head group on to the primary hydroxyl of ceramide. SAMD8 is an endoplasmic reticulum (ER) transferase that has no sphingomyelin synthase activity but can convert phosphatidylethanolamine (PE) and ceramide to ceramide phosphoethanolamine (CPE) albeit with low product yield. Appears to operate as a ceramide sensor to control ceramide homeostasis in the endoplasmic reticulum rather than a converter of ceramides. Seems to be critical for the integrity of the early secretory pathway.

关联

100 项与 SAMD8 相关的临床结果

登录后查看更多信息

100 项与 SAMD8 相关的转化医学

登录后查看更多信息

0 项与 SAMD8 相关的专利（医药）

登录后查看更多信息

项与 SAMD8 相关的文献（医药）

2024-06-01·Nature Structural & Molecular Biology

Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis

Article

作者: Zhang, Qing ; Jiang, Xian-Cheng ; Zhou, Lu ; Chen, Yang ; Cao, Mi ; Cao, Yu ; Zhao, Jie ; Qin, An ; Hu, Kexin ; Yao, Deqiang ; Yang, Jintong ; Li, Shaobai ; Xia, Ying ; Shen, Yafeng ; Lu, Hongliang ; Rao, Bing

Sphingomyelin (SM) has key roles in modulating mammalian membrane properties and serves as an important pool for bioactive molecules. SM biosynthesis is mediated by the sphingomyelin synthase (SMS) family, comprising SMS1, SMS2 and SMS-related (SMSr) members. Although SMS1 and SMS2 exhibit SMS activity, SMSr possesses ceramide phosphoethanolamine synthase activity. Here we determined the cryo-electron microscopic structures of human SMSr in complexes with ceramide, diacylglycerol/phosphoethanolamine and ceramide/phosphoethanolamine (CPE). The structures revealed a hexameric arrangement with a reaction chamber located between the transmembrane helices. Within this structure, a catalytic pentad E-H/D-H-D was identified, situated at the interface between the lipophilic and hydrophilic segments of the reaction chamber. Additionally, the study unveiled the two-step synthesis process catalyzed by SMSr, involving PE-PLC (phosphatidylethanolamine-phospholipase C) hydrolysis and the subsequent transfer of the phosphoethanolamine moiety to ceramide. This research provides insights into the catalytic mechanism of SMSr and expands our understanding of sphingolipid metabolism.

2024-04-01·Journal of Biological Chemistry

Correction: Sphingomyelin synthase–related protein SMSr is a phosphatidylethanolamine phospholipase C that promotes nonalcoholic fatty liver disease

作者: He, Mulin ; Li, Zhiqiang ; Chiang, Yeun-Po ; Jiang, Xian-Cheng ; Pan, Meixia ; Han, Xianlin ; Jones, Quiana

2023-11-15·Aging

Identification of M5c regulator-medicated methylation modification patterns for prognosis and immune microenvironment in glioma

Article

作者: Xiao, Zhenyong ; Yan, Xianlei ; Li, Jinwei ; Liang, Cong ; Zhang, Yuxia ; Liu, Yamei ; Zhang, Yuxiu ; Liu, Quan

Glioma is a common intracranial tumor and is generally associated with poor prognosis. Recently, numerous studies illustrated the importance of 5-methylcytosine (m5C) RNA modification to tumorigenesis. However, the prognostic value and immune correlation of m5C in glioma remain unclear. We obtained RNA expression and clinical information from The Cancer Genome Atlas (TCGA) and The Chinese Glioma Genome Atlas (CGGA) datasets to analyze. Nonnegative matrix factorization (NMF) was used to classify patients into two subgroups and compare these patients in survival and clinicopathological characteristics. CIBERSORT and single-sample gene-set algorithm (ssGSEA) methods were used to investigate the relationship between m5C and the immune environment. The Weighted correlation network analysis (WGCNA) and univariate Cox proportional hazard model (CoxPH) were used to construct a m5C-related signature. Most of m5C RNA methylation regulators presented differential expression and prognostic values. There were obvious relationships between immune infiltration cells and m5C regulators, especially NSUN7. In the m5C-related module from WGCNA, we found SEPT3, CHI3L1, PLBD1, PHYHIPL, SAMD8, RAP1B, B3GNT5, RER1, PTPN7, SLC39A1, and MXI1 were prognostic factors for glioma, and they were used to construct the signature. The great significance of m5C-related signature in predicting the survival of patients with glioma was confirmed in the validation sets and CGGA cohort.

项与 SAMD8 相关的新闻（医药）

2024-02-27

·生物探索

Nat Struct Mol Biol | 韩晓/李锴发现M2巨噬细胞促进米色脂肪生成的潜在机制

引言鞘磷脂(Sphingomyelin, SM)在调节哺乳动物膜特性中起着关键作用，是一个重要的生物活性分子库。SM的生物合成是由鞘磷脂合成酶(sphingomyelin synthase, SMS)家族介导的，包括SMS1、SMS2和SMSr相关成员。虽然SMS1和SMS2具有SMS活性，但SMSr具有神经酰胺磷酸乙醇胺合成酶活性。2024年2月22日，上海交通大学曹禹、赵杰、姚德强及复旦大学周璐共同通讯在Nature Structural & Molecular Biology （IF 16.8）在线发表题为“Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis”的研究论文，该研究测定了与神经酰胺、二酰基甘油/磷酸乙醇胺和神经酰胺/磷酸乙醇胺(CPE)配合物的人SMSr的冷冻电镜结构。鞘脂是真核生物中一类重要的脂类，其含量影响膜组织和动力学及其周围的膜蛋白。SMs是哺乳动物鞘脂的主要形式，广泛分布于哺乳动物细胞的外质小叶中，与胆固醇等多种生物活性分子结合。与甘油磷脂形成的相对“软”的膜结构相反，在膜中加入SMs形成了一个“硬”的屏蔽状区域，防止机械应变和温度变化。被称为“脂筏”的富含SMs的微结构域存在于细胞膜上，这些微结构域形成特定的条件来调节膜蛋白的功能。例如，免疫受体，包括T细胞受体和B细胞受体，以及其他免疫信号成分，如酪氨酸激酶FYN、CD40和CD154，在受体激活后被转运到脂筏中，从而促进免疫细胞的增殖和激活。此外，SM代谢还产生和消耗多种生物活性脂质，包括中间体鞘氨醇、二酰基甘油(DAG)和神经酰胺及其衍生物鞘氨醇-1-磷酸和神经酰胺-L-磷酸。这些化合物在细胞凋亡、炎症、细胞周期和血管生成等广泛的生物学途径中发挥信号功能。hSMS催化CPE/SM合成两步反应示意图（Credit: Nature Structural & Molecular Biology）哺乳动物体内SMs的生物合成从丝氨酸和棕榈酰辅酶A在内质网(ER)内缩合生成3-酮鞘氨酸开始，最后由磷脂酰胆碱(PC)/磷脂酰乙醇胺(PE)将磷脂胆碱(PCho)/磷酸乙醇胺(PEA)转移到神经酰胺，从而生成SM或神经酰胺磷酸乙醇胺(CPE)，具体取决于反应中的含磷酸基团供体(PC或PE)。SM/CPE合成的最后一步由SMS家族催化，该家族在哺乳动物中包括三个主要成员：SMS1, SMS2和SMSr。研究表明SMS1是SM的主要产生酶，SMSr是CPE合成酶，而SMS2是同时产生SM和CPE的双功能酶。功能失调的SMSs会破坏脂质稳态，导致严重的生理后果。相比之下，缺乏SMS2的小鼠对高脂肪饮食表现出更好的耐受性，肥胖症状减轻，胰岛素敏感性增加，动脉粥样硬化减少，这表明SMS2抑制剂具有治疗潜力。虽然SMSr缺乏确实会影响细胞和循环中的测试脂质(神经酰胺、SM、胆固醇和甘油三酯)，但它可能对PE代谢有重要影响。然而，对于这些酶催化的生化过程的分子机制以及在SMS1、SMS2和SMSr中观察到的底物特异性知之甚少，这限制了人们对它们的反应和亚型特异性抑制剂的开发。该研究报告了人类SMSr (hSMSr)的冷冻电镜结构以及用于CPE合成的底物/产物。结构显示出六聚体排列，反应室位于跨膜螺旋之间。在该结构中，发现了一个催化五联体E-H / D-H-D，位于反应室亲脂段和亲水段之间的界面。此外，该研究揭示了由SMSr催化的两步合成过程，包括PE-PLC(磷脂酰乙醇胺-磷脂酶C)水解和随后将磷酸乙醇胺部分转移到神经酰胺。该研究为SMSr的催化机制提供了新的见解，并扩展了人们对鞘脂代谢的理解。原文链接https://www-nature-com.libproxy1.nus.edu.sg/articles/s41594-024-01237-2责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 癌症与神经系统的致命舞蹈