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Kelch domain-containing protein 1 (KLHDC1)
- Target
- KLHDC1
- Molecular classification
- E3 ubiquitin ligase substrate adaptor (CRL5/Kelch-family), Adapter protein, Kelch domain family
01
Overview
Kelch domain-containing protein 1 (KLHDC1) is a member of the Kelch superfamily, specifically the KLHDC subfamily, which acts as a substrate-recognition component of a Cullin5-RING (CRL5) E3 ubiquitin ligase complex. KLHDC1 mediates ubiquitination and subsequent proteasomal degradation of proteins carrying specific C-terminal degron motifs (C-degrons), such as truncated forms of selenoprotein SELENOS produced during failed translation termination. This process is crucial for cellular protein quality control and prevents accumulation of potentially toxic truncated proteins in the cytosol. KLHDC1 interacts with proteins such as SELENOS and Cul5, but not with Cul2, distinguishing it from related family members like KLHDC2 that interact with Cul2. The physiological and pathophysiological roles of KLHDC1 are not fully understood, and it is not currently a therapeutic target or disease biomarker.
- Other names
- Kelch domain containing 1KLDC1MSTP025MST025kelch domain-containing protein 1
02
Mechanism of action
Not applicable—no known drugs target KLHDC1
03
Biological functions
Ubiquitin-dependent protein catabolic processRecognition of C-end degrons (DesCEND pathway)Proteasomal degradation of truncated or misfolded proteinsInteraction with Cullin5–RING E3 ligase complex
04
Disease associations
Other: Potential involvement in cellular protein quality controlNo strong or direct link established to specific diseases, but disease associations include *Amme complex* (a rare X-linked syndromic disorder)
05
Safety considerations
None known; functionally unexplored in therapy
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