The tripartite motif (TRIM) gene family is a highly conserved group of E3 ubiquitin ligase proteins that can establish substrate specificity for the ubiquitin-proteasome complex and also have proteasome-independent functions. While several family members were studied previously, it is relatively recent that over 80 genes, based on sequence homology, were grouped to establish the TRIM gene family. Functional studies of various TRIM genes linked these proteins to modulation of inflammatory responses showing that they can contribute to a wide variety of disease states including cardiovascular, neurological and musculoskeletal diseases, as well as various forms of cancer. Given the fundamental role of the ubiquitin-proteasome complex in protein turnover and the importance of this regulation in most aspects of cellular physiology, it is not surprising that TRIM proteins display a wide spectrum of functions in a variety of cellular processes. This broad range of function and the highly conserved primary amino acid sequence of family members, particularly in the canonical TRIM E3 ubiquitin ligase domain, complicates the development of therapeutics that specifically target these proteins. A more comprehensive understanding of the structure and function of TRIM proteins will help guide therapeutic development for a number of different diseases. This review summarizes the structural organization of TRIM proteins, their domain architecture, common and unique post-translational modifications within the family, and potential binding partners and targets. Further discussion is provided on efforts to target TRIM proteins as therapeutic agents and how our increasing understanding of the nature of TRIM proteins can guide discovery of other therapeutics in the future.

三方基序（TRIM）基因家族是一组高度保守的E3泛素连接酶蛋白，可以为泛素-蛋白酶体复合物建立底物特异性，并具有不依赖蛋白酶体的功能。虽然先前已经研究了几个家族成员，但是相对较近的是，基于序列同源性将80多个基因分组以建立TRIM基因家族。各种TRIM基因的功能研究将这些蛋白质与炎症反应的调节联系起来，表明它们可以导致多种疾病，包括心血管疾病，神经疾病和肌肉骨骼疾病，以及各种形式的癌症。鉴于遍在蛋白-蛋白酶体复合物在蛋白质更新中的基本作用以及该调节在细胞生理学大多数方面的重要性，毫不奇怪，TRIM蛋白在各种细胞过程中显示出广泛的功能。这种广泛的功能范围和家族成员的高度保守的一级氨基酸序列，特别是在规范的TRIM E3泛素连接酶结构域中，使专门针对这些蛋白质的治疗剂的开发变得复杂。对TRIM蛋白的结构和功能的更全面的了解将有助于指导许多不同疾病的治疗发展。这篇综述总结了TRIM蛋白的结构组织，其结构域结构，该家族内常见且独特的翻译后修饰以及潜在的结合伴侣和靶标。