Attwood Misty M, Schiöth Helgi B
Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
Front Cell Dev Biol. 2021 Jul 19;9:708754. doi: 10.3389/fcell.2021.708754. eCollection 2021.
Transmembrane proteins are involved in many essential cell processes such as signal transduction, transport, and protein trafficking, and hence many are implicated in different disease pathways. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. This analysis investigates the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). More than half of the 58 proteins identified with the 5TM architecture belong to 12 families with two or more members. Interestingly, more than half the proteins in the dataset function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this dataset in large contrast with other TM groups. The three major 5TM families, which comprise nearly 30% of the dataset, include the tweety family, the sideroflexin family and the Yip1 domain (YIPF) family. We also analyzed the evolutionary origin of these three families. The YIPF family appears to be the most ancient with presence in bacteria and archaea, while the tweety and sideroflexin families are first found in eukaryotes. We found no evidence of common decent for these three families. About 30% of the 5TM proteins have prominent expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumor types. Nearly 10% of the 5TMs are still not fully characterized and further investigation of their functional activities and expression is warranted. This study provides the first comprehensive analysis of proteins with the 5TM architecture, providing details of their unique characteristics.
跨膜蛋白参与许多重要的细胞过程，如信号转导、运输和蛋白质转运，因此许多跨膜蛋白与不同的疾病途径有关。此外，由于蛋白质的结构和功能相互关联，研究一组具有相同三级结构（即相同数量跨膜区域）的蛋白质，可能有助于了解它们的功能作用以及作为治疗靶点的潜力。本分析研究了此前未被研究过的具有五个跨膜区域（5TM）的蛋白质组。在鉴定出的具有5TM结构的58种蛋白质中，超过一半属于12个家族，每个家族有两个或更多成员。有趣的是，数据集中超过一半的蛋白质通过细胞成分的移动或系留参与定位活动，超过三分之一的蛋白质参与运输活动，特别是在线粒体中。令人惊讶的是，与其他跨膜蛋白组形成鲜明对比的是，该数据集中未发现受体活性。三个主要的5TM家族，占数据集近30%，包括翠鸟家族、铁转运黄素蛋白家族和Yip1结构域（YIPF）家族。我们还分析了这三个家族的进化起源。YIPF家族似乎是最古老的，存在于细菌和古细菌中，而翠鸟家族和铁转运黄素蛋白家族最早发现于真核生物中。我们没有发现这三个家族有共同祖先的证据。约30%的5TM蛋白质在大脑、肝脏或睾丸中有显著表达。重要的是，这些蛋白质中有60%被鉴定为癌症预后标志物，与各种肿瘤类型的临床结果相关。近10%的5TM蛋白质仍未完全表征，有必要进一步研究它们的功能活动和表达情况。本研究首次对具有5TM结构的蛋白质进行了全面分析，详细介绍了它们的独特特征。
