Recombinant Human Kelch domain-containing protein 3 (KLHDC3)

Function

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 (PubMed:29775578, PubMed:29779948). 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 (PubMed:29775578, PubMed:29779948). 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 (PubMed:29775578, PubMed:29779948). 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 (PubMed:26138980). May be involved in meiotic recombination process (PubMed:12606021)

Subcellular Location

Cytoplasm

Subunit

Component of a CRL2(KLHDC3) complex, also named ECS(KLHDC3) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter KLHDC3 (PubMed:29775578, PubMed:29779948). May form oligomers as a KLHDC3-ELOB-ELOC complex; this interaction is likely autoinhibitory for the E3 ligase complex (PubMed:36805027)

Pathway

Protein modification; protein ubiquitination

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• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mungall A.J. et al. The DNA sequence and analysis of human chromosome 6. — Nature (2003)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Lin H.C. et al. SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding. — Science (2015)
• Koren I. et al. The eukaryotic proteome is shaped by E3 ubiquitin ligases targeting C-terminal degrons. — Cell (2018)
• Lin H.C. et al. C-terminal end-directed protein elimination by CRL2 ubiquitin ligases. — Mol. Cell (2018)