Pilcher Courtney, Buco Paula Armina V, Truong Jia Q, Ramsland Paul A, Smeets Monique F, Walkley Carl R, Holien Jessica K
School of Science, STEM College, RMIT University, Melbourne, Australia.
St Vincent's Institute of Medical Research, Fitzroy, Australia.
FEBS Lett. 2025 Apr;599(8):1094-1112. doi: 10.1002/1873-3468.15108. Epub 2025 Jan 30.
The Kelch protein superfamily is an evolutionary conserved family containing 63 alternate protein coding members. The superfamily is split into three subfamilies: Kelch like (KLHL), Kelch-repeat and bric-a-bracs (BTB) domain containing (KBTBD) and Kelch domain containing protein (KLHDC). The KLHDC subfamily is one of the smallest within the Kelch superfamily, containing 10 primary members. There is little known about the structures and functions of the subfamily; however, they are thought to be involved in several cellular and molecular processes. Recently, there have been significant structural and biochemical advances for KLHDC2, which has aided our understanding of other KLHDC family members. Furthermore, small molecules directly targeting KLHDC2 have been identified, which act as tools for targeted protein degradation. This review utilises this information, in conjunction with a thorough exploration of the structural aspects and potential biological functions to summarise the relationship between KLHDCs and human disease.
Kelch蛋白超家族是一个进化保守的家族，包含63个可变蛋白编码成员。该超家族分为三个亚家族：类Kelch（KLHL）、含Kelch重复序列和bric-a-brac结构域（BTB）的蛋白（KBTBD）以及含Kelch结构域的蛋白（KLHDC）。KLHDC亚家族是Kelch超家族中最小的亚家族之一，包含10个主要成员。人们对该亚家族的结构和功能了解甚少；然而，它们被认为参与了多个细胞和分子过程。最近，KLHDC2在结构和生化方面取得了重大进展，这有助于我们了解其他KLHDC家族成员。此外，已鉴定出直接靶向KLHDC2的小分子，它们可作为靶向蛋白质降解的工具。本综述利用这些信息，结合对结构方面和潜在生物学功能的深入探讨，总结KLHDC与人类疾病之间的关系。
