CUL2 gene

CUL2 (Cullin 2) is a protein-coding gene located on chromosome 10p11.21. The encoded protein enables ubiquitin-protein ligase binding activity. It is thought to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolism and in the ubiquitination of proteins. Located in the nucleoplasm and is part of the Cul2-RING ubiquitin ligase complex.

Related signaling pathways include class I MHC-mediated antigen processing and presentation and nervous system development. An important paralog of this gene is CUL1.

Core component of several Cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS box protein) E3 ubiquitin-protein ligase complexes that mediate ubiquitination of target proteins (Kamura T et al. 2001). CUL2 may serve as a rigid scaffold in the complex and may contribute to catalysis by positioning the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the ECS complex depends on the substrate recognition component (mediates ubiquitination of hypoxia-inducible factor (HIF). A range of ECS complexes.

Diseases associated with CUL2 include squamous cell carcinoma of the pinna (Lobo D et al. 2008) and Von Hippel-Lindau syndrome.

1. Kamura T et al. (2001) Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase. J Biol Chem 276:29748-29753.
2. Kelsall IR et al.(2013) TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. EMBO J 32:2848-2860.
3. Lobo D et al. (2008) Squamous cell carcinoma of the external auditory canal. Skull Base 18:167-172.