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Aliases for CRBN Gene

Aliases for CRBN Gene

  • Cereblon 2 3
  • MRT2 3 6
  • Mental Retardation, Non-Syndromic, Autosomal Recessive, 2A 2
  • Protein Cereblon 3
  • Protein X 0001 3
  • MRT2A 3

External Ids for CRBN Gene

Previous Symbols for CRBN Gene

  • MRT2A

Summaries for CRBN Gene

Entrez Gene Summary for CRBN Gene

  • This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic mental retardation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

GeneCards Summary for CRBN Gene

CRBN (Cereblon) is a Protein Coding gene. Diseases associated with CRBN include mental retardation, autosomal recessive 2 and distal monosomy 3p. GO annotations related to this gene include ATP-dependent peptidase activity.

UniProtKB/Swiss-Prot for CRBN Gene

  • 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. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. Binding of pomalidomide and other thalidomide-related drugs changes the substrate specificity of the human protein, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3.

Gene Wiki entry for CRBN Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CRBN Gene

Genomics for CRBN Gene

Genomic Location for CRBN Gene

Start:
3,148,992 bp from pter
End:
3,179,717 bp from pter
Size:
30,726 bases
Orientation:
Minus strand

Genomic View for CRBN Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for CRBN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CRBN Gene

Regulatory Elements for CRBN Gene

Proteins for CRBN Gene

  • Protein details for CRBN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96SW2-CRBN_HUMAN
    Recommended name:
    Protein cereblon
    Protein Accession:
    Q96SW2
    Secondary Accessions:
    • B2R6H4
    • C9IZA9
    • C9JAH6
    • Q6AI62
    • Q6NVZ0
    • Q9UHW4

    Protein attributes for CRBN Gene

    Size:
    442 amino acids
    Molecular mass:
    50546 Da
    Quaternary structure:
    • 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).
    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. Recently, thalidomide use has increased for the treatment of multiple myeloma and erythema nodosum leprosum, a painful complication of leprosy. Thalidomide binding 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 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.
    SequenceCaution:
    • Sequence=AAF17211.1; Type=Frameshift; Positions=347, 397, 401; Evidence={ECO:0000305}; Sequence=BAG35471.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAG35471.1; Type=Frameshift; Positions=347; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CRBN Gene

    Alternative splice isoforms for CRBN Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CRBN Gene

Proteomics data for CRBN Gene at MOPED

Post-translational modifications for CRBN Gene

  • Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys43, Lys166, and Lys300

Other Protein References for CRBN Gene

No data available for DME Specific Peptides for CRBN Gene

Domains for CRBN Gene

Protein Domains for CRBN Gene

InterPro:
ProtoNet:

UniProtKB/Swiss-Prot:

CRBN_HUMAN
Domain:
  • The thalidomide binding 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.:
    • Q96SW2
  • Contains 1 Lon domain.:
    • Q96SW2
Family:
  • Belongs to the CRBN family.:
    • Q96SW2
genes like me logo Genes that share domains with CRBN: view

No data available for Gene Families for CRBN Gene

Function for CRBN Gene

Molecular function for CRBN Gene

UniProtKB/Swiss-Prot 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. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. Binding of pomalidomide and other thalidomide-related drugs changes the substrate specificity of the human protein, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3.

Gene Ontology (GO) - Molecular Function for CRBN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004176 ATP-dependent peptidase activity IEA --
GO:0005515 protein binding IPI 20223979
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with CRBN: view

Phenotypes for CRBN Gene

genes like me logo Genes that share phenotypes with CRBN: view

Animal Models for CRBN Gene

MGI Knock Outs for CRBN:

miRNA for CRBN Gene

miRTarBase miRNAs that target CRBN

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for CRBN Gene

Localization for CRBN Gene

Subcellular locations from UniProtKB/Swiss-Prot for CRBN Gene

Cytoplasm. Nucleus. Membrane; Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CRBN Gene COMPARTMENTS Subcellular localization image for CRBN gene
Compartment Confidence
nucleus 5
cytosol 2
extracellular 1

Gene Ontology (GO) - Cellular Components for CRBN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 20223979
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IDA 20223979
GO:0016020 membrane IEA --
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex IDA 20223979
genes like me logo Genes that share ontologies with CRBN: view

Pathways for CRBN Gene

SuperPathways for CRBN Gene

No Data Available

UniProtKB/Swiss-Prot Q96SW2-CRBN_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for CRBN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006200 obsolete ATP catabolic process --
GO:0006508 proteolysis --
GO:0016567 protein ubiquitination IMP 20223979
GO:0032463 negative regulation of protein homooligomerization IEA --
GO:0034766 negative regulation of ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with CRBN: view

No data available for Pathways by source for CRBN Gene

Transcripts for CRBN Gene

Unigene Clusters for CRBN Gene

Cereblon:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for CRBN Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d ^ 4a · 4b · 4c ^ 5a · 5b ^ 6a · 6b · 6c · 6d ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b
SP1: - - - - - - -
SP2: - - - - - - -
SP3: -
SP4: -
SP5: - - -
SP6: - - - -
SP7: - - -
SP8: - - -
SP9: - - - -
SP10:
SP11: - - - - -
SP12: - -
SP13: - - - -
SP14:
SP15: -

Relevant External Links for CRBN Gene

GeneLoc Exon Structure for
CRBN
ECgene alternative splicing isoforms for
CRBN

Expression for CRBN Gene

mRNA expression in normal human tissues for CRBN Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for CRBN Gene

SOURCE GeneReport for Unigene cluster for CRBN Gene Hs.18925

mRNA Expression by UniProt/SwissProt for CRBN Gene

Q96SW2-CRBN_HUMAN
Tissue specificity: Widely expressed. Highly expressed in brain.
genes like me logo Genes that share expressions with CRBN: view

Orthologs for CRBN Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CRBN Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CRBN 36
  • 97.51 (n)
  • 97.28 (a)
CRBN 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia CRBN 36
  • 89.34 (n)
  • 93.88 (a)
CRBN 37
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CRBN 36
  • 92.37 (n)
  • 95.46 (a)
CRBN 37
  • 80 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Crbn 36
  • 88.89 (n)
  • 94.1 (a)
Crbn 16
Crbn 37
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CRBN 37
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CRBN 37
  • 87 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Crbn 36
  • 90.33 (n)
  • 95.46 (a)
chicken
(Gallus gallus)
Aves CRBN 36
  • 81.4 (n)
  • 86.42 (a)
CRBN 37
  • 83 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CRBN 37
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia crbn 36
  • 68.65 (n)
  • 72.15 (a)
Str.19548 36
zebrafish
(Danio rerio)
Actinopterygii crbn 36
  • 68.09 (n)
  • 72.34 (a)
crbn 37
  • 68 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005299 36
  • 43.96 (n)
  • 31.87 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG3925 37
  • 20 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea M18.6 37
  • 22 (a)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons AT2G25740 36
  • 49.28 (n)
  • 34.05 (a)
rice
(Oryza sativa)
Liliopsida Os01g0743600 36
  • 49.28 (n)
  • 39.13 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.157 36
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 35 (a)
OneToOne
Species with no ortholog for CRBN:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CRBN Gene

ENSEMBL:
Gene Tree for CRBN (if available)
TreeFam:
Gene Tree for CRBN (if available)

Paralogs for CRBN Gene

Pseudogenes.org Pseudogenes for CRBN Gene

genes like me logo Genes that share paralogs with CRBN: view

No data available for Paralogs for CRBN Gene

Variants for CRBN Gene

Sequence variations from dbSNP and Humsavar for CRBN Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type MAF
rs1497 -- 3,150,129(+) CCCTA(G/T)AGTAG utr-variant-3-prime
rs1499 -- 3,150,149(+) TTCAA(A/G)TTAAT utr-variant-3-prime
rs4183 -- 3,150,840(+) TTAGA(-/TAAC)ATAAC utr-variant-3-prime
rs698204 -- 3,163,748(-) TCTTC(C/G)GCACC intron-variant
rs698206 -- 3,163,120(-) CTCCA(A/G)GTGAC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for CRBN Gene

Variant ID Type Subtype PubMed ID
esv2422274 CNV Duplication 17116639
esv2751994 CNV Gain 17911159
nsv521796 CNV Loss 19592680
nsv876405 CNV Gain 21882294
nsv834604 CNV Gain 17160897
nsv3676 CNV Insertion 18451855

Relevant External Links for CRBN Gene

HapMap Linkage Disequilibrium report
CRBN
Human Gene Mutation Database (HGMD)
CRBN

Disorders for CRBN Gene

(1) OMIM Diseases for CRBN Gene (609262)

UniProtKB/Swiss-Prot

CRBN_HUMAN
  • Mental retardation, autosomal recessive 2A (MRT2A) [MIM:607417]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs. MRT2A patients display mild mental retardation 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. {ECO:0000269 PubMed:15557513}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(1) University of Copenhagen DISEASES for CRBN Gene

Relevant External Links for CRBN

Genetic Association Database (GAD)
CRBN
genes like me logo Genes that share disorders with CRBN: view

Publications for CRBN Gene

  1. A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation. (PMID: 15557513) Higgins J.J. … Rooney J.P. (Neurology 2004) 2 3 4 23
  2. Primary function analysis of human mental retardation related gene CRBN. (PMID: 17380424) Xin W. … Qihan W. (Mol. Biol. Rep. 2008) 3 4 23
  3. Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation. (PMID: 18414909) Higgins J.J. … Rajadhyaksha A.M. (Neurogenetics 2008) 3 4
  4. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). (PMID: 24328678) Gandhi A.K. … Chopra R. (Br. J. Haematol. 2014) 3 4
  5. Identification of a primary target of thalidomide teratogenicity. (PMID: 20223979) Ito T. … Handa H. (Science 2010) 3 4

Products for CRBN Gene

Sources for CRBN Gene

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