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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)DescriptionActionsGraphical viewLength
Metal bindingi326Zinc1 Publication1
Metal bindingi329Zinc1 Publication1
Metal bindingi394Zinc1 Publication1
Metal bindingi397Zinc1 Publication1

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)DescriptionActionsGraphical viewLength
ChainiPRO_00000761611 – 445Protein cereblonAdd BLAST445

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8C7D2.
PeptideAtlasiQ8C7D2.
PRIDEiQ8C7D2.

PTM databases

iPTMnetiQ8C7D2.
PhosphoSitePlusiQ8C7D2.

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

BgeeiENSMUSG00000005362.
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

1445
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi323 – 326Combined sources4
Turni327 – 329Combined sources3
Beta strandi333 – 336Combined sources4
Helixi337 – 339Combined sources3
Helixi350 – 353Combined sources4
Beta strandi361 – 366Combined sources6
Beta strandi370 – 378Combined sources9
Beta strandi387 – 394Combined sources8
Turni395 – 397Combined sources3
Beta strandi400 – 409Combined sources10
Beta strandi412 – 421Combined sources10
Helixi422 – 424Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini84 – 320Lon N-terminalPROSITE-ProRule annotationAdd BLAST237
Domaini321 – 429CULTPROSITE-ProRule annotationAdd BLAST109

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni381 – 389Thalidomide binding1 Publication9

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.
OrthoDBiEOG091G0EBG.
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 differs from that shown. Reason: Frameshift at position 27.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10A → R in AAF35895 (Ref. 3) Curated1
Sequence conflicti48N → D in AAF35895 (Ref. 3) Curated1
Sequence conflicti71H → P in BAC36214 (PubMed:16141072).Curated1
Sequence conflicti82Q → R in AAF35895 (Ref. 3) Curated1
Sequence conflicti127A → G in AAF35895 (Ref. 3) Curated1
Sequence conflicti202L → V in AAH86488 (PubMed:15489334).Curated1
Sequence conflicti310R → A in AAF35895 (Ref. 3) Curated1
Sequence conflicti317I → V in BAC36970 (PubMed:16141072).Curated1
Sequence conflicti439D → N in BAE35697 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0152101 – 23MAGEG…PLLPA → MGNHLPLLP in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_03906323Missing in isoform 3. 1 Publication1

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
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061604.

PTM databases

iPTMnetiQ8C7D2.
PhosphoSitePlusiQ8C7D2.

Proteomic databases

PaxDbiQ8C7D2.
PeptideAtlasiQ8C7D2.
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.
OrthoDBiEOG091G0EBG.
PhylomeDBiQ8C7D2.
TreeFamiTF106115.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ8C7D2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000005362.
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...

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: November 2, 2016
This is version 106 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.