Kelch domain-containing protein 3

Definition

Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(KLHDC3) complex specifically recognizes proteins with a glycine (Gly) at the C-terminus, leading to their ubiquitination and degradation: recognizes the C-terminal -Arg-(Xaa)n-Arg-Gly, -Arg-(Xaa)n-Lys-Gly, and -Arg-(Xaa)n-Gln-Gly degrons. The CRL2(KLHDC3) complex mediates ubiquitination and degradation of truncated SELENOV and SEPHS2 selenoproteins produced by failed UGA/Sec decoding, which end with a glycine. May be involved in meiotic recombination process.

References:

[1]. Hsiu-Chuan Lin, et al. C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases. Mol Cell. 2018 May 17;70(4):602-613.e3. [Content Brief]

[2]. Itay Koren, et al. The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons. Cell. 2018 Jun 14;173(7):1622-1635.e14. [Content Brief]

[3]. Hsiu-Chuan Lin, et al. SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding. Science. 2015 Jul 3;349(6243):91-5. [Content Brief]

[4]. Yasuhide Ohinata, et al. A novel testis-specific RAG2-like protein, Peas: its expression in pachytene spermatocyte cytoplasm and meiotic chromatin. FEBS Lett. 2003 Feb 27;537(1-3):1-5. [Content Brief]

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