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Q96SW2 (CRBN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein cereblon
Gene names
Name:CRBN
ORF Names:AD-006
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length442 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of some DCX (DDB1-CUL4-X-box) E3 protein ligase complex, a complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins and is required for limb outgrowth and expression of the fibroblast growth factor FGF8. In the complex, may act as a substrate receptor. Regulates 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. Ref.8 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit 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. Ref.9

Subcellular location

Cytoplasm. Nucleus. Membrane; Peripheral membrane protein By similarity Ref.9.

Tissue specificity

Widely expressed. Highly expressed in brain. Ref.6 Ref.7

Post-translational modification

Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex. Ref.9

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Miscellaneous

Specifically binds thalidomide, a drug widely prescribed to pregnant women in the late 1950s. Thalidomide was sold as a sedative but 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 teratogenic activity may be a consequence of CRBN-binding, which inhibits the ubiquitin ligase activity of the DCX (DDB1-CUL4-X-box) protein ligase complex, possibly leading to abnormal regulation of the BMP and FGF8 signaling pathways (Ref.9).

Sequence similarities

Belongs to the CRBN family.

Contains 1 Lon domain.

Caution

Although it contains a Lon 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

The sequence AAF17211.1 differs from that shown. Reason: Frameshift at positions 347, 397 and 401.

The sequence BAG35471.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAG35471.1 differs from that shown. Reason: Frameshift at position 347.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96SW2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96SW2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     23-23: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 442442Protein cereblon
PRO_0000076160

Regions

Domain80 – 317238Lon
Region339 – 442104Thalidomide-binding

Natural variations

Alternative sequence231Missing in isoform 2.
VSP_015209

Experimental info

Mutagenesis3841Y → A: Abolishes thalidomide-binding without affecting DCX protein ligase complex activity; when associated with A-386. Ref.9
Mutagenesis3861W → A: Abolishes thalidomide-binding without affecting DCX protein ligase complex activity; when associated with A-384. Ref.9
Sequence conflict2291K → R in AAH67811. Ref.2
Sequence conflict2371L → P in BAG35471. Ref.1
Sequence conflict2921D → G in BAG35471. Ref.1
Sequence conflict3301E → G in BAG35471. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 90DF77D98A8BEAA8

FASTA44250,546
        10         20         30         40         50         60 
MAGEGDQQDA AHNMGNHLPL LPAESEEEDE MEVEDQDSKE AKKPNIINFD TSLPTSHTYL 

        70         80         90        100        110        120 
GADMEEFHGR TLHDDDSCQV IPVLPQVMMI LIPGQTLPLQ LFHPQEVSMV RNLIQKDRTF 

       130        140        150        160        170        180 
AVLAYSNVQE REAQFGTTAE IYAYREEQDF GIEIVKVKAI GRQRFKVLEL RTQSDGIQQA 

       190        200        210        220        230        240 
KVQILPECVL PSTMSAVQLE SLNKCQIFPS KPVSREDQCS YKWWQKYQKR KFHCANLTSW 

       250        260        270        280        290        300 
PRWLYSLYDA ETLMDRIKKQ LREWDENLKD DSLPSNPIDF SYRVAACLPI DDVLRIQLLK 

       310        320        330        340        350        360 
IGSAIQRLRC ELDIMNKCTS LCCKQCQETE ITTKNEIFSL SLCGPMAAYV NPHGYVHETL 

       370        380        390        400        410        420 
TVYKACNLNL IGRPSTEHSW FPGYAWTVAQ CKICASHIGW KFTATKKDMS PQKFWGLTRS 

       430        440 
ALLPTIPDTE DEISPDKVIL CL 

« Hide

Isoform 2 [UniParc].

Checksum: 28B44733BBB461C1
Show »

FASTA44150,475

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Lung.
[4]"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning."
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. expand/collapse author list , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-442.
Tissue: Adrenal gland.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-250.
Tissue: Fetal kidney.
[6]"A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation."
Higgins J.J., Pucilowska J., Lombardi R.Q., Rooney J.P.
Neurology 63:1927-1931(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MRT2A, TISSUE SPECIFICITY.
[7]"Primary function analysis of human mental retardation related gene CRBN."
Xin W., Xiaohua N., Peilin C., Xin C., Yaqiong S., Qihan W.
Mol. Biol. Rep. 35:251-256(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation."
Higgins J.J., Hao J., Kosofsky B.E., Rajadhyaksha A.M.
Neurogenetics 9:219-223(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Identification of a primary target of thalidomide teratogenicity."
Ito T., Ando H., Suzuki T., Ogura T., Hotta K., Imamura Y., Yamaguchi Y., Handa H.
Science 327:1345-1350(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A DCX COMPLEX WITH DDB1; RBX1 AND CUL4A, THALIDOMIDE-BINDING, UBIQUITINATION, MUTAGENESIS OF TYR-384 AND TRP-386.
+Additional computationally mapped references.

Web resources

Protein Spotlight

A short story - Issue 117 of May 2010

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS2562.1. [Q96SW2-1]
CCDS54547.1. [Q96SW2-2]
RefSeqNP_001166953.1. NM_001173482.1. [Q96SW2-2]
NP_057386.2. NM_016302.3. [Q96SW2-1]
UniGeneHs.18925.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4M91X-ray1.10B229-240[»]
ProteinModelPortalQ96SW2.
SMRQ96SW2. Positions 80-185.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119360. 16 interactions.
IntActQ96SW2. 8 interactions.
MINTMINT-4537481.
STRING9606.ENSP00000231948.

PTM databases

PhosphoSiteQ96SW2.

Polymorphism databases

DMDM73918916.

Proteomic databases

MaxQBQ96SW2.
PaxDbQ96SW2.
PRIDEQ96SW2.

Protocols and materials databases

DNASU51185.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000231948; ENSP00000231948; ENSG00000113851. [Q96SW2-1]
ENST00000432408; ENSP00000412499; ENSG00000113851. [Q96SW2-2]
GeneID51185.
KEGGhsa:51185.
UCSCuc003bpq.3. human. [Q96SW2-1]
uc003bpr.3. human. [Q96SW2-2]

Organism-specific databases

CTD51185.
GeneCardsGC03M003166.
HGNCHGNC:30185. CRBN.
HPAHPA045910.
MIM607417. phenotype.
609262. gene.
neXtProtNX_Q96SW2.
Orphanet88616. Autosomal recessive nonsyndromic intellectual disability.
1620. Distal monosomy 3p.
PharmGKBPA134926851.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG313031.
HOGENOMHOG000067866.
HOVERGENHBG054571.
InParanoidQ96SW2.
KOK11793.
OMACQDTEIT.
PhylomeDBQ96SW2.
TreeFamTF106115.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

BgeeQ96SW2.
CleanExHS_CRBN.
GenevestigatorQ96SW2.

Family and domain databases

InterProIPR003111. Pept_S16_N.
IPR015947. PUA-like_domain.
[Graphical view]
PfamPF02190. LON. 1 hit.
[Graphical view]
SMARTSM00464. LON. 1 hit.
[Graphical view]
SUPFAMSSF88697. SSF88697. 2 hits.
ProtoNetSearch...

Other

GeneWikiCereblon.
GenomeRNAi51185.
NextBio54159.
PROQ96SW2.
SOURCESearch...

Entry information

Entry nameCRBN_HUMAN
AccessionPrimary (citable) accession number: Q96SW2
Secondary accession number(s): B2R6H4 expand/collapse secondary AC list , C9IZA9, C9JAH6, Q6AI62, Q6NVZ0, Q9UHW4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM