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Domain

The CULT domain binds thalidomide and related drugs, such as pomalidomide and lenalidomide. Drug binding leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, while no such change is observed in rodents.

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).

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Protein modification; protein ubiquitination.

Post-translational modifications

Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex.

Sequence similarities

Belongs to the CRBN family.

Tissue specificity

Widely expressed. Highly expressed in brain.

Cellular localization

  • Cytoplasm
  • Nucleus
  • Membrane
  • Peripheral membrane protein

Alternative names

AD-006, CRBN, Protein cereblon

Target type

Proteins

Primary research area

Immuno-oncology

Molecular weight

50546Da

We found 10 products in 3 categories

Primary Antibodies

Target

Reactive species

Proteins & Peptides

Cell Lines & Lysates

Target

Cell type

Species or organism