CUL5

Description

The CUL5 (cullin 5) is a protein-coding gene located on chromosome 11.

Cullin-5 is a protein that in humans is encoded by the CUL5 gene. The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin. It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor. Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5. Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules. Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation. One study have shown that Cul5 plays a role in Reelin signaling cascade, participating in the DAB1 degradation and thus ensuring the negative feedback mechanism of Reelin signaling during corticogenesis. CUL5 has been shown to interact with RBX1.

CUL5 is a core component of multiple SCF-like ECS (Elongin-Cullin 2/5- SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein, CUL5 may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. ECS(KLHDC1) complex is part of the DesCEND (destruction via C-end degrons) pathway and mediates ubiquitination and degradation of truncated SELENOS selenoprotein produced by failed UGA/Sec decoding, which ends with a glycine. As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5, CUL5 polyubiquitinates monoubiquitinated POLR2A. CUL5 may form a cell surface vasopressin receptor.

CUL5 is also known as CUL-5, VACM-1, VACM1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing