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Q96SW2

- CRBN_HUMAN

UniProt

Q96SW2 - CRBN_HUMAN

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Protein
Protein cereblon
Gene
CRBN, AD-006
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 KCNT1.2 Publications

Pathwayi

GO - Molecular functioni

  1. ATP-dependent peptidase activity Source: InterPro
  2. protein binding Source: UniProtKB

GO - Biological processi

  1. negative regulation of ion transmembrane transport Source: Ensembl
  2. negative regulation of protein homooligomerization Source: Ensembl
  3. positive regulation of protein homodimerization activity Source: Ensembl
  4. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  5. protein ubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein cereblon
Gene namesi
Name:CRBN
ORF Names:AD-006
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:30185. CRBN.

Subcellular locationi

Cytoplasm. Nucleus. Membrane; Peripheral membrane protein By similarity 1 Publication

GO - Cellular componenti

  1. Cul4A-RING E3 ubiquitin ligase complex Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. membrane Source: UniProtKB-SubCell
  4. nucleolus Source: HPA
  5. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi384 – 3841Y → A: Abolishes thalidomide-binding without affecting DCX protein ligase complex activity; when associated with A-386. 1 Publication
Mutagenesisi386 – 3861W → A: Abolishes thalidomide-binding without affecting DCX protein ligase complex activity; when associated with A-384. 1 Publication

Keywords - Diseasei

Mental retardation

Organism-specific databases

MIMi607417. phenotype.
Orphaneti88616. Autosomal recessive nonsyndromic intellectual disability.
1620. Distal monosomy 3p.
PharmGKBiPA134926851.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 442442Protein cereblon
PRO_0000076160Add
BLAST

Post-translational modificationi

Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ96SW2.
PaxDbiQ96SW2.
PRIDEiQ96SW2.

PTM databases

PhosphoSiteiQ96SW2.

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in brain.2 Publications

Gene expression databases

BgeeiQ96SW2.
CleanExiHS_CRBN.
GenevestigatoriQ96SW2.

Organism-specific databases

HPAiHPA045910.

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 RBX1.1 Publication

Protein-protein interaction databases

BioGridi119360. 16 interactions.
IntActiQ96SW2. 8 interactions.
MINTiMINT-4537481.
STRINGi9606.ENSP00000231948.

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4M91X-ray1.10B229-240[»]
ProteinModelPortaliQ96SW2.
SMRiQ96SW2. Positions 80-185.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini80 – 317238Lon
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni339 – 442104Thalidomide-binding
Add
BLAST

Sequence similaritiesi

Belongs to the CRBN family.
Contains 1 Lon domain.

Phylogenomic databases

eggNOGiNOG313031.
HOGENOMiHOG000067866.
HOVERGENiHBG054571.
InParanoidiQ96SW2.
KOiK11793.
OMAiCQDTEIT.
PhylomeDBiQ96SW2.
TreeFamiTF106115.

Family and domain databases

InterProiIPR003111. Pept_S16_N.
IPR015947. PUA-like_domain.
[Graphical view]
PfamiPF02190. LON. 1 hit.
[Graphical view]
SMARTiSM00464. LON. 1 hit.
[Graphical view]
SUPFAMiSSF88697. SSF88697. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q96SW2-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MAGEGDQQDA AHNMGNHLPL LPAESEEEDE MEVEDQDSKE AKKPNIINFD    50
TSLPTSHTYL GADMEEFHGR TLHDDDSCQV IPVLPQVMMI LIPGQTLPLQ 100
LFHPQEVSMV RNLIQKDRTF AVLAYSNVQE REAQFGTTAE IYAYREEQDF 150
GIEIVKVKAI GRQRFKVLEL RTQSDGIQQA KVQILPECVL PSTMSAVQLE 200
SLNKCQIFPS KPVSREDQCS YKWWQKYQKR KFHCANLTSW PRWLYSLYDA 250
ETLMDRIKKQ LREWDENLKD DSLPSNPIDF SYRVAACLPI DDVLRIQLLK 300
IGSAIQRLRC ELDIMNKCTS LCCKQCQETE ITTKNEIFSL SLCGPMAAYV 350
NPHGYVHETL TVYKACNLNL IGRPSTEHSW FPGYAWTVAQ CKICASHIGW 400
KFTATKKDMS PQKFWGLTRS ALLPTIPDTE DEISPDKVIL CL 442
Length:442
Mass (Da):50,546
Last modified:December 1, 2001 - v1
Checksum:i90DF77D98A8BEAA8
GO
Isoform 2 (identifier: Q96SW2-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     23-23: Missing.

Note: No experimental confirmation available.

Show »
Length:441
Mass (Da):50,475
Checksum:i28B44733BBB461C1
GO

Sequence cautioni

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: Frameshift at position 347.
The sequence BAG35471.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei23 – 231Missing in isoform 2.
VSP_015209

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti229 – 2291K → R in AAH67811. 1 Publication
Sequence conflicti237 – 2371L → P in BAG35471. 1 Publication
Sequence conflicti292 – 2921D → G in BAG35471. 1 Publication
Sequence conflicti330 – 3301E → G in BAG35471. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSiCCDS2562.1. [Q96SW2-1]
CCDS54547.1. [Q96SW2-2]
RefSeqiNP_001166953.1. NM_001173482.1. [Q96SW2-2]
NP_057386.2. NM_016302.3. [Q96SW2-1]
UniGeneiHs.18925.

Genome annotation databases

EnsembliENST00000231948; ENSP00000231948; ENSG00000113851. [Q96SW2-1]
ENST00000432408; ENSP00000412499; ENSG00000113851. [Q96SW2-2]
GeneIDi51185.
KEGGihsa:51185.
UCSCiuc003bpq.3. human. [Q96SW2-1]
uc003bpr.3. human. [Q96SW2-2]

Polymorphism databases

DMDMi73918916.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Protein Spotlight

A short story - Issue 117 of May 2010

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 ]
UniGenei Hs.18925.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4M91 X-ray 1.10 B 229-240 [» ]
ProteinModelPortali Q96SW2.
SMRi Q96SW2. Positions 80-185.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 119360. 16 interactions.
IntActi Q96SW2. 8 interactions.
MINTi MINT-4537481.
STRINGi 9606.ENSP00000231948.

PTM databases

PhosphoSitei Q96SW2.

Polymorphism databases

DMDMi 73918916.

Proteomic databases

MaxQBi Q96SW2.
PaxDbi Q96SW2.
PRIDEi Q96SW2.

Protocols and materials databases

DNASUi 51185.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000231948 ; ENSP00000231948 ; ENSG00000113851 . [Q96SW2-1 ]
ENST00000432408 ; ENSP00000412499 ; ENSG00000113851 . [Q96SW2-2 ]
GeneIDi 51185.
KEGGi hsa:51185.
UCSCi uc003bpq.3. human. [Q96SW2-1 ]
uc003bpr.3. human. [Q96SW2-2 ]

Organism-specific databases

CTDi 51185.
GeneCardsi GC03M003166.
HGNCi HGNC:30185. CRBN.
HPAi HPA045910.
MIMi 607417. phenotype.
609262. gene.
neXtProti NX_Q96SW2.
Orphaneti 88616. Autosomal recessive nonsyndromic intellectual disability.
1620. Distal monosomy 3p.
PharmGKBi PA134926851.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG313031.
HOGENOMi HOG000067866.
HOVERGENi HBG054571.
InParanoidi Q96SW2.
KOi K11793.
OMAi CQDTEIT.
PhylomeDBi Q96SW2.
TreeFami TF106115.

Enzyme and pathway databases

UniPathwayi UPA00143 .

Miscellaneous databases

GeneWikii Cereblon.
GenomeRNAii 51185.
NextBioi 54159.
PROi Q96SW2.
SOURCEi Search...

Gene expression databases

Bgeei Q96SW2.
CleanExi HS_CRBN.
Genevestigatori Q96SW2.

Family and domain databases

InterProi IPR003111. Pept_S16_N.
IPR015947. PUA-like_domain.
[Graphical view ]
Pfami PF02190. LON. 1 hit.
[Graphical view ]
SMARTi SM00464. LON. 1 hit.
[Graphical view ]
SUPFAMi SSF88697. SSF88697. 2 hits.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-442.
    Tissue: Adrenal gland.
  5. 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.

Entry informationi

Entry nameiCRBN_HUMAN
AccessioniPrimary (citable) accession number: Q96SW2
Secondary accession number(s): B2R6H4
, C9IZA9, C9JAH6, Q6AI62, Q6NVZ0, Q9UHW4
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

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 (1 Publication).

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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