KLHDC2
Description
The KLHDC2 (kelch domain containing 2) is a protein-coding gene located on chromosome 14.
KLHDC2 is a substrate-recognition component of the Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex within the DesCEND (destruction via C-end degrons) pathway. This complex specifically 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 a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(KLHDC2) complex recognizes proteins with a diglycine (Gly-Gly) at the C-terminus, resulting in their ubiquitination and degradation. This complex mediates the degradation of truncated SELENOK and SELENOS selenoproteins produced by failed UGA/Sec decoding, which end with a diglycine. Additionally, the CRL2(KLHDC2) complex targets proteolytically cleaved proteins ending with Gly-Gly, such as the N-terminal fragment of USP1. Furthermore, KLHDC2 may act as an indirect repressor of CREB3-mediated transcription by interfering with CREB3-DNA-binding.
KLHDC2 is also known as HCLP-1, HCLP1, LCP.
Associated Diseases
- intellectual developmental disorder with speech delay and axonal peripheral neuropathy
- X-linked parkinsonism-spasticity syndrome
- corneal-cerebellar syndrome
- spinocerebellar ataxia type 15/16
- X-linked endothelial corneal dystrophy
- spinocerebellar ataxia type 20
- torsion dystonia 2
- X-linked dystonia-parkinsonism
- granular corneal dystrophy type I
- infantile-onset generalized dyskinesia with orofacial involvement
- spinocerebellar ataxia type 12
- dystonia 23
- X-linked non progressive cerebellar ataxia
