Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases

Abstract

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.