Kelch domain-containing protein 3 (KLHDC3)

Kelch domain-containing protein 3 (KLHDC3) is a substrate-specific adaptor for Cullin-RING E3 ligase complexes, particularly the CRL2(KLHDC3). It recognizes protein substrates with a C-terminal glycine and mediates their ubiquitination and subsequent degradation[5]. KLHDC3 belongs to a family of proteins characterized by the Kelch domain, a β-propeller structure known for protein–protein interaction and substrate recognition[2][3]. Unlike many Kelch proteins, KLHDC3 lacks BTB and BACK domains, distinguishing it structurally within the family. Originally identified for its role in targeting defective selenoproteins, KLHDC3 forms part of the cellular machinery maintaining protein homeostasis, specifically recognizing specific C-terminal degron motifs such as -RG, -KG, or -QG, facilitating turnover of aberrant proteins[3][5]. There is currently no published direct association with drug interactions or pathological biomarkers, but its functional category is crucial for cell biology and potentially relevant to disease if dysregulated.

Other names

KLHDC3Kelch-like protein 21