Recombinant Human Protein cereblon (CRBN), partial, Biotinylated

Function

Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2, ILF2 or GLUL (PubMed:26990986, PubMed:33009960). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979, PubMed:24328678, PubMed:25043012, PubMed:25108355). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (PubMed:18414909, PubMed:29530986). Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (PubMed:18414909). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). Plays a negative role in TLR4 signaling by interacting with TRAF6 and ECSIT, leading to inhibition of ECSIT ubiquitination, an important step of the signaling (PubMed:31620128)

Subcellular Location

Cytoplasm; Nucleus; Membrane (Peripheral membrane protein)

Disease Association

Intellectual developmental disorder, autosomal recessive 2 (MRT2) : A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT2 patients display mild intellectual disability with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widely expressed. Highly expressed in brain

Subunit

Interacts with KCNT1 (By similarity). Component of a DCX (DDB1-CUL4-X-box) protein ligase complex, at least composed of CRBN, CUL4A, DDB1 and RBX1. Interacts directly with DDB1 (PubMed:25043012, PubMed:25108355). Interacts (in pomalidomide-bound form) with IKZF1 and IKZF3 (PubMed:24328678). Interacts with ILF2 (PubMed:33009960). Interacts with TRAF6 and ECSIT (PubMed:31620128)

Pathway

Protein modification; protein ubiquitination

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• Muzny D.M. et al. The DNA sequence, annotation and analysis of human chromosome 3. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Hu R.-M. et al. Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. — Proc. Natl. Acad. Sci. U.S.A. (2000)
• Bechtel S. et al. The full-ORF clone resource of the German cDNA consortium. — BMC Genomics (2007)
• Higgins J.J. et al. A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation. — Neurology (2004)
• Xin W. et al. Primary function analysis of human mental retardation related gene CRBN. — Mol. Biol. Rep. (2008)
• Higgins J.J. et al. Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation. — Neurogenetics (2008)