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Protein

Protein cereblon

Gene

Crbn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (By similarity). 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 (By similarity).By similarityCurated

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarity
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi326 – 3261Zinc1 Publication
Metal bindingi329 – 3291Zinc1 Publication
Metal bindingi394 – 3941Zinc1 Publication
Metal bindingi397 – 3971Zinc1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein cereblon
Short name:
Protein PiL
Gene namesi
Name:Crbn
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1913277. Crbn.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Membrane By similarity; Peripheral membrane protein By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

No obvious phenotype, excepting a deficit in contextual fear learning.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 445445Protein cereblonPRO_0000076161Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei25 – 251PhosphoserineBy similarity

Post-translational modificationi

Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8C7D2.
MaxQBiQ8C7D2.
PaxDbiQ8C7D2.
PRIDEiQ8C7D2.

PTM databases

iPTMnetiQ8C7D2.
PhosphoSiteiQ8C7D2.

Expressioni

Tissue specificityi

Highly expressed in brain.1 Publication

Developmental stagei

In brain, expression is abundant in the cerebellum, with less expression in the neocortical, hippocampus and striatum in adult. Neocortical expression increases from embryonic stages to adulthood.1 Publication

Gene expression databases

BgeeiQ8C7D2.
CleanExiMM_CRBN.
ExpressionAtlasiQ8C7D2. baseline and differential.
GenevisibleiQ8C7D2. MM.

Interactioni

Subunit structurei

Component of a DCX (DDB1-CUL4-X-box) protein ligase complex, at least composed of CRBN, CUL4A, DDB1 and RBX1. Interacts directly with DDB1 (By similarity). Interacts with KCNT1 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061604.

Structurei

Secondary structure

1
445
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi323 – 3264Combined sources
Turni327 – 3293Combined sources
Beta strandi333 – 3364Combined sources
Helixi337 – 3393Combined sources
Helixi350 – 3534Combined sources
Beta strandi361 – 3666Combined sources
Beta strandi370 – 3789Combined sources
Beta strandi387 – 3948Combined sources
Turni395 – 3973Combined sources
Beta strandi400 – 40910Combined sources
Beta strandi412 – 42110Combined sources
Helixi422 – 4243Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3WX1X-ray1.93A/B322-430[»]
3WX2X-ray2.00A/B322-430[»]
4TZCX-ray1.88A/B/C/D322-428[»]
4TZUX-ray2.00A/B/C/D322-429[»]
ProteinModelPortaliQ8C7D2.
SMRiQ8C7D2. Positions 51-431.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini84 – 320237Lon N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini321 – 429109CULTPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni381 – 3899Thalidomide binding1 Publication

Domaini

The CULT domain binds thalidomide and related drugs. Thalidomide 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.1 Publication

Sequence similaritiesi

Belongs to the CRBN family.Curated
Contains 1 CULT domain.PROSITE-ProRule annotation
Contains 1 Lon N-terminal domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1400. Eukaryota.
ENOG410XQGE. LUCA.
GeneTreeiENSGT00390000016404.
HOVERGENiHBG054571.
InParanoidiQ8C7D2.
KOiK11793.
OMAiEARKPNI.
OrthoDBiEOG71VSSQ.
PhylomeDBiQ8C7D2.
TreeFamiTF106115.

Family and domain databases

InterProiIPR003111. LON_substr-bd_dom.
IPR015947. PUA-like_domain.
IPR004910. Yippee/Mis18/Cereblon.
[Graphical view]
PfamiPF02190. LON_substr_bdg. 1 hit.
PF03226. Yippee-Mis18. 1 hit.
[Graphical view]
SMARTiSM00464. LON. 1 hit.
[Graphical view]
SUPFAMiSSF88697. SSF88697. 2 hits.
PROSITEiPS51788. CULT. 1 hit.
PS51787. LON_N. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8C7D2-1) [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

        10         20         30         40         50
MAGEGDQQDA AHNMGNHLPL LPADSEDEDD EIEMEVEDQD SKEARKPNII
60 70 80 90 100
NFDTSLPTSH TYLGADMEEF HGRTLHDDDS CQVIPVLPEV LMILIPGQTL
110 120 130 140 150
PLQLSHPQEV SMVRNLIQKD RTFAVLAYSN VQEREAQFGT TAEIYAYREE
160 170 180 190 200
QEFGIEVVKV KAIGRQRFKV LELRTQSDGI QQAKVQILPE CVLPSTMSAV
210 220 230 240 250
QLESLNKCQV FPSKPISWED QYSCKWWQKY QKRKFHCANL TSWPRWLYSL
260 270 280 290 300
YDAETLMDRI KKQLREWDEN LKDDSLPENP IDFSYRVAAC LPIDDVLRIQ
310 320 330 340 350
LLKIGSAIQR LRCELDIMNK CTSLCCKQCQ ETEITTKNEI FSLSLCGPMA
360 370 380 390 400
AYVNPHGYVH ETLTVYKASN LNLIGRPSTV HSWFPGYAWT IAQCKICASH
410 420 430 440
IGWKFTATKK DMSPQKFWGL TRSALLPTIP ETEDEISPDK VILCL
Length:445
Mass (Da):50,880
Last modified:March 1, 2003 - v1
Checksum:iD66C2C3D50366E27
GO
Isoform 2 (identifier: Q8C7D2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MAGEGDQQDAAHNMGNHLPLLPA → MGNHLPLLP

Note: No experimental confirmation available.
Show »
Length:431
Mass (Da):49,484
Checksum:i61A6438B7B01C422
GO
Isoform 3 (identifier: Q8C7D2-3) [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:444
Mass (Da):50,809
Checksum:iF22B2AB53B068416
GO

Sequence cautioni

The sequence AAF35895.1 differs from that shown. Reason: Frameshift at position 27. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 101A → R in AAF35895 (Ref. 3) Curated
Sequence conflicti48 – 481N → D in AAF35895 (Ref. 3) Curated
Sequence conflicti71 – 711H → P in BAC36214 (PubMed:16141072).Curated
Sequence conflicti82 – 821Q → R in AAF35895 (Ref. 3) Curated
Sequence conflicti127 – 1271A → G in AAF35895 (Ref. 3) Curated
Sequence conflicti202 – 2021L → V in AAH86488 (PubMed:15489334).Curated
Sequence conflicti310 – 3101R → A in AAF35895 (Ref. 3) Curated
Sequence conflicti317 – 3171I → V in BAC36970 (PubMed:16141072).Curated
Sequence conflicti439 – 4391D → N in BAE35697 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2323MAGEG…PLLPA → MGNHLPLLP in isoform 2. 1 PublicationVSP_015210Add
BLAST
Alternative sequencei23 – 231Missing in isoform 3. 1 PublicationVSP_039063

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK050557 mRNA. Translation: BAC34322.1.
AK076144 mRNA. Translation: BAC36214.1.
AK077707 mRNA. Translation: BAC36970.1.
AK160219 mRNA. Translation: BAE35697.1.
BC046967 mRNA. Translation: AAH46967.1.
BC069905 mRNA. Translation: AAH69905.1.
BC086488 mRNA. Translation: AAH86488.1.
AF229032 mRNA. Translation: AAF35895.1. Frameshift.
CCDSiCCDS39583.1. [Q8C7D2-1]
CCDS39584.1. [Q8C7D2-3]
RefSeqiNP_067424.2. NM_021449.3. [Q8C7D2-3]
NP_780566.1. NM_175357.3. [Q8C7D2-1]
UniGeneiMm.290085.

Genome annotation databases

EnsembliENSMUST00000013882; ENSMUSP00000013882; ENSMUSG00000005362. [Q8C7D2-3]
ENSMUST00000113239; ENSMUSP00000108865; ENSMUSG00000005362. [Q8C7D2-1]
GeneIDi58799.
KEGGimmu:58799.
UCSCiuc009dda.2. mouse. [Q8C7D2-3]
uc009ddb.2. mouse. [Q8C7D2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK050557 mRNA. Translation: BAC34322.1.
AK076144 mRNA. Translation: BAC36214.1.
AK077707 mRNA. Translation: BAC36970.1.
AK160219 mRNA. Translation: BAE35697.1.
BC046967 mRNA. Translation: AAH46967.1.
BC069905 mRNA. Translation: AAH69905.1.
BC086488 mRNA. Translation: AAH86488.1.
AF229032 mRNA. Translation: AAF35895.1. Frameshift.
CCDSiCCDS39583.1. [Q8C7D2-1]
CCDS39584.1. [Q8C7D2-3]
RefSeqiNP_067424.2. NM_021449.3. [Q8C7D2-3]
NP_780566.1. NM_175357.3. [Q8C7D2-1]
UniGeneiMm.290085.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3WX1X-ray1.93A/B322-430[»]
3WX2X-ray2.00A/B322-430[»]
4TZCX-ray1.88A/B/C/D322-428[»]
4TZUX-ray2.00A/B/C/D322-429[»]
ProteinModelPortaliQ8C7D2.
SMRiQ8C7D2. Positions 51-431.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061604.

PTM databases

iPTMnetiQ8C7D2.
PhosphoSiteiQ8C7D2.

Proteomic databases

EPDiQ8C7D2.
MaxQBiQ8C7D2.
PaxDbiQ8C7D2.
PRIDEiQ8C7D2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000013882; ENSMUSP00000013882; ENSMUSG00000005362. [Q8C7D2-3]
ENSMUST00000113239; ENSMUSP00000108865; ENSMUSG00000005362. [Q8C7D2-1]
GeneIDi58799.
KEGGimmu:58799.
UCSCiuc009dda.2. mouse. [Q8C7D2-3]
uc009ddb.2. mouse. [Q8C7D2-1]

Organism-specific databases

CTDi51185.
MGIiMGI:1913277. Crbn.

Phylogenomic databases

eggNOGiKOG1400. Eukaryota.
ENOG410XQGE. LUCA.
GeneTreeiENSGT00390000016404.
HOVERGENiHBG054571.
InParanoidiQ8C7D2.
KOiK11793.
OMAiEARKPNI.
OrthoDBiEOG71VSSQ.
PhylomeDBiQ8C7D2.
TreeFamiTF106115.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

NextBioi314364.
PROiQ8C7D2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8C7D2.
CleanExiMM_CRBN.
ExpressionAtlasiQ8C7D2. baseline and differential.
GenevisibleiQ8C7D2. MM.

Family and domain databases

InterProiIPR003111. LON_substr-bd_dom.
IPR015947. PUA-like_domain.
IPR004910. Yippee/Mis18/Cereblon.
[Graphical view]
PfamiPF02190. LON_substr_bdg. 1 hit.
PF03226. Yippee-Mis18. 1 hit.
[Graphical view]
SMARTiSM00464. LON. 1 hit.
[Graphical view]
SUPFAMiSSF88697. SSF88697. 2 hits.
PROSITEiPS51788. CULT. 1 hit.
PS51787. LON_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
    Strain: C57BL/6J.
    Tissue: Head and Pancreas.
  2. "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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-445 (ISOFORM 1).
    Tissue: Eye.
  3. "A novel gene mutated in R197 insertional mutant mice."
    Rose J.B., van Driel I.R., Tan S.
    Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-445.
  4. "Temporal and spatial mouse brain expression of cereblon, an ionic channel regulator involved in human intelligence."
    Higgins J.J., Tal A.L., Sun X., Hauck S.C., Hao J., Kosofosky B.E., Rajadhyaksha A.M.
    J. Neurogenet. 24:18-26(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  5. "Behavioral characterization of cereblon forebrain-specific conditional null mice: a model for human non-syndromic intellectual disability."
    Rajadhyaksha A.M., Ra S., Kishinevsky S., Lee A.S., Romanienko P., DuBoff M., Yang C., Zupan B., Byrne M., Daruwalla Z.R., Mark W., Kosofsky B.E., Toth M., Higgins J.J.
    Behav. Brain Res. 226:428-434(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  6. Cited for: X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 322-430 IN COMPLEX WITH S-THALIDOMIDE AND ZINC, DOMAIN.

Entry informationi

Entry nameiCRBN_MOUSE
AccessioniPrimary (citable) accession number: Q8C7D2
Secondary accession number(s): Q3TVC2
, Q5RJV6, Q6IS49, Q80XJ1, Q8BP45, Q8C6B7, Q9JKR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: March 1, 2003
Last modified: May 11, 2016
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.