Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:Q96SW2 CRBN
| Class:Id | ReferenceGeneProduct:225469 |
|---|---|
| _chainChangeLog | chain:1-442 added on Sat February 7 2015 |
| _displayName | UniProt:Q96SW2 CRBN |
| _timestamp | 2025-02-21 19:16:41 |
| chain | chain:1-442 |
| checksum | 90DF77D98A8BEAA8 |
| comment | 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).PATHWAY Protein modification; protein ubiquitination.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).INTERACTION Widely expressed. Highly expressed in brain.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.PTM Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Thalidomide was widely prescribed to pregnant women in the late 1950s as a sedative and as treatment against morning sickness. Thalidomide was found to be teratogenic, causing multiple birth defects. More recently, thalidomide use has increased for the treatment of multiple myeloma and erythema nodosum leprosum, a painful complication of leprosy. Binding of pomalidomide and other thalidomide-related drugs leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, and this is probably the underlying cause of the teratogenic activity of thalidomide, possibly due to abnormal regulation of the BMP and FGF8 signaling pathways (PubMed:20223979). The thalidomide-induced change in substrate specificity leads to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3, and this is probably the reason for the anti-proliferative and immunomodulatory effects of thalidomide and related drugs (PubMed:25108355). Thalidomide is also teratogenic in chicken and zebrafish, but not in mice.SIMILARITY Belongs to the CRBN family.CAUTION Although it contains a Lon N-terminal domain also found in proteases of the peptidase S16 family, it does not contain the ATP-binding and catalytic domains, suggesting that it has no protease activity.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION A short story - Issue 117 of May 2010 |
| created | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 |
| description | recommendedName: Protein cereblon |
| geneName | CRBN AD-006 |
| identifier | Q96SW2 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cytoplasm Disease variant Intellectual disability Membrane Metal-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Ubl conjugation Ubl conjugation pathway Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | CRBN |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9001098] ENSEMBL:ENSG00000113851 CRBN [Homo sapiens] |
| secondaryIdentifier | CRBN_HUMAN B2R6H4 C9IZA9 C9JAH6 Q6AI62 Q6NVZ0 Q9UHW4 |
| sequenceLength | 442 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:225470] UniProt:Q96SW2-2 CRBN [Homo sapiens] [ReferenceIsoform:413113] UniProt:Q96SW2-1 CRBN [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:8863300] CRBN [cytosol] [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:Q96SW2 CRBN (225469)
