Kelch domain-containing protein 10 (KLHDC10)

Kelch domain-containing protein 10 (KLHDC10) is a substrate-recognition component of a CRL2 (Cullin-2-RING ligase) E3 ubiquitin ligase complex, involved in selective protein degradation through the DesCEND (destruction via C-end degrons) pathway[2][4][5]. KLHDC10 specifically recognizes short sequence motifs, typically proline-glycine or alanine-rich "CAT tails" at the extreme C-terminus of target proteins and truncated polypeptides, leading to their ubiquitination and subsequent proteasomal degradation[1][2][4][5]. Structurally, KLHDC10 contains a six-bladed β-propeller Kelch domain for substrate recognition, an N-terminal region, and a C-terminal domain mediating interactions with Cullin-2 adaptors[1][2]. It is active in the nucleoplasm and cytoplasm as part of the CRL2-KLHDC10 complex[5]. KLHDC10 helps maintain cellular proteostasis and protein quality control, especially rescuing stalled ribosomes and removing erroneous or aberrant proteins that terminate with certain C-end degrons, but its detailed biological roles and regulation remain subjects of emerging research[1][2][3][5].

Other names

KIAA0265slimscruin like at the midline homolog (Drosophila)PNAS-138PNAS-119scruin like at the midline homologKLHDC10

Ubiquitin ligase substrate recognition—targets proteins for proteasomal degradation by binding to specific C-terminal degrons (e.g., Ala-tails, Pro-Gly motifs) and directing them to the CRL2 ubiquitin ligase complex[1][2][4][5]