UniProtKB - Q96SW2 (CRBN_HUMAN)
Protein cereblon
CRBN
Functioni
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 or ILF2 (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).
By similarityCurated6 PublicationsMiscellaneous
Caution
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication1 PublicationView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 323 | ZincCombined sources1 Publication | 1 | |
Metal bindingi | 326 | ZincCombined sources1 Publication | 1 | |
Binding sitei | 378 | ThalidomideCombined sources1 Publication | 1 | |
Binding sitei | 380 | ThalidomideCombined sources1 Publication | 1 | |
Binding sitei | 386 | ThalidomideCombined sources1 Publication | 1 | |
Metal bindingi | 391 | ZincCombined sources1 Publication | 1 | |
Metal bindingi | 394 | ZincCombined sources1 Publication | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- transmembrane transporter binding Source: Ensembl
GO - Biological processi
- locomotory exploration behavior Source: Ensembl
- negative regulation of large conductance calcium-activated potassium channel activity Source: Ensembl
- negative regulation of protein-containing complex assembly Source: Ensembl
- positive regulation of protein-containing complex assembly Source: Ensembl
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
- protein ubiquitination Source: UniProtKB
Keywordsi
Biological process | Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q96SW2 |
Reactomei | R-HSA-9679191, Potential therapeutics for SARS |
SignaLinki | Q96SW2 |
SIGNORi | Q96SW2 |
UniPathwayi | UPA00143 |
Protein family/group databases
TCDBi | 8.A.162.1.1, the cereblon (crbn) family |
Names & Taxonomyi
Protein namesi | Recommended name: Protein cereblon |
Gene namesi | Name:CRBN ORF Names:AD-006 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:30185, CRBN |
MIMi | 609262, gene |
neXtProti | NX_Q96SW2 |
VEuPathDBi | HostDB:ENSG00000113851 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Nucleus
- Nucleus 1 Publication
Other locations
- Membrane By similarity; Peripheral membrane protein By similarity
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleus Source: UniProtKB
Other locations
- Cul4A-RING E3 ubiquitin ligase complex Source: UniProtKB
- cytoplasm Source: UniProtKB
- membrane Source: UniProtKB-SubCell
- perinuclear region of cytoplasm Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Mental retardation, autosomal recessive 2A (MRT2A)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079409 | 391 | C → R in MRT2A. 1 PublicationCorresponds to variant dbSNP:rs797045036EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 384 | Y → A: Abolishes thalidomide-binding without affecting DCX protein ligase complex activity; when associated with A-386. 1 Publication | 1 | |
Mutagenesisi | 386 | W → A: Abolishes thalidomide-binding without affecting DCX protein ligase complex activity; when associated with A-384. Abolishes pomalidomide-induced change in substrate specificity and abolishes pomalidomide-induced decrease in cell viability that is brought about by increased degradation of MYC, IRF4 and IKZF3. 2 Publications | 1 | |
Mutagenesisi | 419 – 442 | Missing : Fails to rescue increased BK channel activity and decreased probability of neurotransmission in a mouse hippocampal neuron model. 1 PublicationAdd BLAST | 24 |
Keywords - Diseasei
Disease variant, Mental retardationOrganism-specific databases
DisGeNETi | 51185 |
MalaCardsi | CRBN |
MIMi | 607417, phenotype |
OpenTargetsi | ENSG00000113851 |
Orphaneti | 88616, Autosomal recessive non-syndromic intellectual disability |
PharmGKBi | PA134926851 |
Miscellaneous databases
Pharosi | Q96SW2, Tclin |
Chemistry databases
ChEMBLi | CHEMBL3763008 |
DrugBanki | DB00480, Lenalidomide DB08910, Pomalidomide DB01041, Thalidomide |
DrugCentrali | Q96SW2 |
GuidetoPHARMACOLOGYi | 3086 |
Genetic variation databases
BioMutai | CRBN |
DMDMi | 73918916 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076160 | 1 – 442 | Protein cereblonAdd BLAST | 442 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 25 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q96SW2 |
jPOSTi | Q96SW2 |
MassIVEi | Q96SW2 |
MaxQBi | Q96SW2 |
PaxDbi | Q96SW2 |
PeptideAtlasi | Q96SW2 |
PRIDEi | Q96SW2 |
ProteomicsDBi | 78157 [Q96SW2-1] 78158 [Q96SW2-2] |
PTM databases
iPTMneti | Q96SW2 |
PhosphoSitePlusi | Q96SW2 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000113851, Expressed in corpus callosum and 237 other tissues |
ExpressionAtlasi | Q96SW2, baseline and differential |
Genevisiblei | Q96SW2, HS |
Organism-specific databases
HPAi | ENSG00000113851, Low tissue specificity |
Interactioni
Subunit structurei
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).
By similarity5 PublicationsBinary interactionsi
Q96SW2
Isoform 2 [Q96SW2-2]
With | #Exp. | IntAct |
---|---|---|
DDB1 [Q16531] | 7 | EBI-10693561,EBI-350322 |
IKZF1 - isoform Ik7 [Q13422-7] | 2 | EBI-10693561,EBI-11522367 |
GO - Molecular functioni
- transmembrane transporter binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 119360, 185 interactors |
CORUMi | Q96SW2 |
DIPi | DIP-53521N |
IntActi | Q96SW2, 41 interactors |
MINTi | Q96SW2 |
STRINGi | 9606.ENSP00000231948 |
Chemistry databases
BindingDBi | Q96SW2 |
Miscellaneous databases
RNActi | Q96SW2, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q96SW2 |
SMRi | Q96SW2 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 81 – 317 | Lon N-terminalPROSITE-ProRule annotationAdd BLAST | 237 | |
Domaini | 318 – 426 | CULTPROSITE-ProRule annotationAdd BLAST | 109 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 45 | DisorderedSequence analysisAdd BLAST | 45 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1400, Eukaryota |
GeneTreei | ENSGT00390000016404 |
HOGENOMi | CLU_025648_1_1_1 |
InParanoidi | Q96SW2 |
OMAi | AYQMYDS |
PhylomeDBi | Q96SW2 |
TreeFami | TF106115 |
Family and domain databases
CDDi | cd15777, CRBN_C_like, 1 hit |
Gene3Di | 2.30.130.40, 1 hit |
InterProi | View protein in InterPro IPR034750, CULT IPR003111, Lon_prtase_N IPR046336, Lon_prtase_N_sf IPR015947, PUA-like_sf IPR004910, Yippee/Mis18/Cereblon |
Pfami | View protein in Pfam PF02190, LON_substr_bdg, 1 hit PF03226, Yippee-Mis18, 1 hit |
SMARTi | View protein in SMART SM00464, LON, 1 hit |
SUPFAMi | SSF88697, SSF88697, 1 hit |
PROSITEi | View protein in PROSITE PS51788, CULT, 1 hit PS51787, LON_N, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAGEGDQQDA AHNMGNHLPL LPAESEEEDE MEVEDQDSKE AKKPNIINFD
60 70 80 90 100
TSLPTSHTYL GADMEEFHGR TLHDDDSCQV IPVLPQVMMI LIPGQTLPLQ
110 120 130 140 150
LFHPQEVSMV RNLIQKDRTF AVLAYSNVQE REAQFGTTAE IYAYREEQDF
160 170 180 190 200
GIEIVKVKAI GRQRFKVLEL RTQSDGIQQA KVQILPECVL PSTMSAVQLE
210 220 230 240 250
SLNKCQIFPS KPVSREDQCS YKWWQKYQKR KFHCANLTSW PRWLYSLYDA
260 270 280 290 300
ETLMDRIKKQ LREWDENLKD DSLPSNPIDF SYRVAACLPI DDVLRIQLLK
310 320 330 340 350
IGSAIQRLRC ELDIMNKCTS LCCKQCQETE ITTKNEIFSL SLCGPMAAYV
360 370 380 390 400
NPHGYVHETL TVYKACNLNL IGRPSTEHSW FPGYAWTVAQ CKICASHIGW
410 420 430 440
KFTATKKDMS PQKFWGLTRS ALLPTIPDTE DEISPDKVIL CL
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketJ3QT87 | J3QT87_HUMAN | Protein cereblon | CRBN | 394 | Annotation score: | ||
A0A1W2PPJ5 | A0A1W2PPJ5_HUMAN | Protein cereblon | CRBN | 490 | Annotation score: | ||
J3QT51 | J3QT51_HUMAN | Protein cereblon | CRBN | 228 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 229 | K → R in AAH67811 (PubMed:16641997).Curated | 1 | |
Sequence conflicti | 237 | L → P in BAG35471 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 292 | D → G in BAG35471 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 330 | E → G in BAG35471 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079409 | 391 | C → R in MRT2A. 1 PublicationCorresponds to variant dbSNP:rs797045036EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015209 | 23 | Missing in isoform 2. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK027507 mRNA Translation: BAB55162.1 AK312577 mRNA Translation: BAG35471.1 Sequence problems. AC024060 Genomic DNA No translation available. BC017419 mRNA Translation: AAH17419.1 BC067811 mRNA Translation: AAH67811.1 AF117230 mRNA Translation: AAF17211.1 Frameshift. CR627060 mRNA Translation: CAH10361.1 |
CCDSi | CCDS2562.1 [Q96SW2-1] CCDS54547.1 [Q96SW2-2] |
RefSeqi | NP_001166953.1, NM_001173482.1 [Q96SW2-2] NP_057386.2, NM_016302.3 [Q96SW2-1] |
Genome annotation databases
Ensembli | ENST00000231948.9; ENSP00000231948.4; ENSG00000113851.16 ENST00000432408.6; ENSP00000412499.2; ENSG00000113851.16 [Q96SW2-2] |
GeneIDi | 51185 |
KEGGi | hsa:51185 |
MANE-Selecti | ENST00000231948.9; ENSP00000231948.4; NM_016302.4; NP_057386.2 |
UCSCi | uc003bpq.4, human [Q96SW2-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Protein Spotlight A short story - Issue 117 of May 2010 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK027507 mRNA Translation: BAB55162.1 AK312577 mRNA Translation: BAG35471.1 Sequence problems. AC024060 Genomic DNA No translation available. BC017419 mRNA Translation: AAH17419.1 BC067811 mRNA Translation: AAH67811.1 AF117230 mRNA Translation: AAF17211.1 Frameshift. CR627060 mRNA Translation: CAH10361.1 |
CCDSi | CCDS2562.1 [Q96SW2-1] CCDS54547.1 [Q96SW2-2] |
RefSeqi | NP_001166953.1, NM_001173482.1 [Q96SW2-2] NP_057386.2, NM_016302.3 [Q96SW2-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4M91 | X-ray | 1.10 | B | 229-240 | [»] | |
4TZ4 | X-ray | 3.01 | C | 48-428 | [»] | |
5FQD | X-ray | 2.45 | B/E | 41-442 | [»] | |
5HXB | X-ray | 3.60 | C/Z | 40-442 | [»] | |
5V3O | X-ray | 3.20 | C | 40-442 | [»] | |
6BN7 | X-ray | 3.50 | B | 1-442 | [»] | |
6BN8 | X-ray | 3.99 | B | 1-442 | [»] | |
6BN9 | X-ray | 4.38 | B | 1-442 | [»] | |
6BNB | X-ray | 6.34 | B | 1-442 | [»] | |
6BOY | X-ray | 3.33 | B | 1-442 | [»] | |
6H0F | X-ray | 3.25 | B/E/H/K | 41-442 | [»] | |
6H0G | X-ray | 4.25 | B/E | 41-397 | [»] | |
6UML | X-ray | 3.58 | C | 40-442 | [»] | |
6XK9 | X-ray | 3.64 | C/Z | 40-442 | [»] | |
7BQU | X-ray | 1.90 | A | 318-426 | [»] | |
7BQV | X-ray | 1.80 | A | 318-426 | [»] | |
7LPS | X-ray | 3.78 | B/E/H/K | 47-436 | [»] | |
AlphaFoldDBi | Q96SW2 | |||||
SMRi | Q96SW2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 119360, 185 interactors |
CORUMi | Q96SW2 |
DIPi | DIP-53521N |
IntActi | Q96SW2, 41 interactors |
MINTi | Q96SW2 |
STRINGi | 9606.ENSP00000231948 |
Chemistry databases
BindingDBi | Q96SW2 |
ChEMBLi | CHEMBL3763008 |
DrugBanki | DB00480, Lenalidomide DB08910, Pomalidomide DB01041, Thalidomide |
DrugCentrali | Q96SW2 |
GuidetoPHARMACOLOGYi | 3086 |
Protein family/group databases
TCDBi | 8.A.162.1.1, the cereblon (crbn) family |
PTM databases
iPTMneti | Q96SW2 |
PhosphoSitePlusi | Q96SW2 |
Genetic variation databases
BioMutai | CRBN |
DMDMi | 73918916 |
Proteomic databases
EPDi | Q96SW2 |
jPOSTi | Q96SW2 |
MassIVEi | Q96SW2 |
MaxQBi | Q96SW2 |
PaxDbi | Q96SW2 |
PeptideAtlasi | Q96SW2 |
PRIDEi | Q96SW2 |
ProteomicsDBi | 78157 [Q96SW2-1] 78158 [Q96SW2-2] |
Protocols and materials databases
Antibodypediai | 25089, 152 antibodies from 29 providers |
DNASUi | 51185 |
Genome annotation databases
Ensembli | ENST00000231948.9; ENSP00000231948.4; ENSG00000113851.16 ENST00000432408.6; ENSP00000412499.2; ENSG00000113851.16 [Q96SW2-2] |
GeneIDi | 51185 |
KEGGi | hsa:51185 |
MANE-Selecti | ENST00000231948.9; ENSP00000231948.4; NM_016302.4; NP_057386.2 |
UCSCi | uc003bpq.4, human [Q96SW2-1] |
Organism-specific databases
CTDi | 51185 |
DisGeNETi | 51185 |
GeneCardsi | CRBN |
HGNCi | HGNC:30185, CRBN |
HPAi | ENSG00000113851, Low tissue specificity |
MalaCardsi | CRBN |
MIMi | 607417, phenotype 609262, gene |
neXtProti | NX_Q96SW2 |
OpenTargetsi | ENSG00000113851 |
Orphaneti | 88616, Autosomal recessive non-syndromic intellectual disability |
PharmGKBi | PA134926851 |
VEuPathDBi | HostDB:ENSG00000113851 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1400, Eukaryota |
GeneTreei | ENSGT00390000016404 |
HOGENOMi | CLU_025648_1_1_1 |
InParanoidi | Q96SW2 |
OMAi | AYQMYDS |
PhylomeDBi | Q96SW2 |
TreeFami | TF106115 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
PathwayCommonsi | Q96SW2 |
Reactomei | R-HSA-9679191, Potential therapeutics for SARS |
SignaLinki | Q96SW2 |
SIGNORi | Q96SW2 |
Miscellaneous databases
BioGRID-ORCSi | 51185, 33 hits in 1120 CRISPR screens |
ChiTaRSi | CRBN, human |
GeneWikii | Cereblon |
GenomeRNAii | 51185 |
Pharosi | Q96SW2, Tclin |
PROi | PR:Q96SW2 |
RNActi | Q96SW2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000113851, Expressed in corpus callosum and 237 other tissues |
ExpressionAtlasi | Q96SW2, baseline and differential |
Genevisiblei | Q96SW2, HS |
Family and domain databases
CDDi | cd15777, CRBN_C_like, 1 hit |
Gene3Di | 2.30.130.40, 1 hit |
InterProi | View protein in InterPro IPR034750, CULT IPR003111, Lon_prtase_N IPR046336, Lon_prtase_N_sf IPR015947, PUA-like_sf IPR004910, Yippee/Mis18/Cereblon |
Pfami | View protein in Pfam PF02190, LON_substr_bdg, 1 hit PF03226, Yippee-Mis18, 1 hit |
SMARTi | View protein in SMART SM00464, LON, 1 hit |
SUPFAMi | SSF88697, SSF88697, 1 hit |
PROSITEi | View protein in PROSITE PS51788, CULT, 1 hit PS51787, LON_N, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CRBN_HUMAN | |
Accessioni | Q96SW2Primary (citable) accession number: Q96SW2 Secondary accession number(s): B2R6H4 Q9UHW4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 30, 2005 |
Last sequence update: | December 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 170 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries