CRBN_RAT
ID CRBN_RAT Reviewed; 445 AA.
AC Q56AP7; A1L110; Q499S7;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Protein cereblon;
GN Name=Crbn;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH KCNT1,
RP AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=16045448; DOI=10.1111/j.1471-4159.2005.03344.x;
RA Jo S., Lee K.-H., Song S., Jung Y.-K., Park C.-S.;
RT "Identification and functional characterization of cereblon as a binding
RT protein for large-conductance calcium-activated potassium channel in rat
RT brain.";
RL J. Neurochem. 94:1212-1224(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3
CC protein ligase complex that mediates the ubiquitination and subsequent
CC proteasomal degradation of target proteins, such as MEIS2 or ILF2.
CC Normal degradation of key regulatory proteins is required for normal
CC limb outgrowth and expression of the fibroblast growth factor FGF8.
CC Maintains presynaptic glutamate release and consequently cognitive
CC functions, such as memory and learning, by negatively regulating large-
CC conductance calcium-activated potassium (BK) channels in excitatory
CC neurons. Likely to function by regulating the assembly and neuronal
CC surface expression of BK channels via its interaction with KCNT1 (By
CC similarity). May also be involved in regulating anxiety-like behaviors
CC via a BK channel-independent mechanism (By similarity).
CC {ECO:0000250|UniProtKB:Q8C7D2, ECO:0000250|UniProtKB:Q96SW2,
CC ECO:0000305}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q96SW2}.
CC -!- SUBUNIT: Component of a DCX (DDB1-CUL4-X-box) protein ligase complex,
CC at least composed of CRBN, CUL4A, DDB1 and RBX1. Interacts directly
CC with DDB1 (By similarity). Interacts with KCNT1.
CC {ECO:0000250|UniProtKB:Q96SW2, ECO:0000269|PubMed:16045448}.
CC -!- INTERACTION:
CC Q56AP7; O54822: ClC-2; NbExp=2; IntAct=EBI-8552884, EBI-8552809;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16045448}. Nucleus
CC {ECO:0000250|UniProtKB:Q96SW2}. Membrane {ECO:0000269|PubMed:16045448};
CC Peripheral membrane protein {ECO:0000269|PubMed:16045448}.
CC -!- TISSUE SPECIFICITY: Detected in heart, brain, liver, kidney and testis
CC (at protein level). Ubiquitous. {ECO:0000269|PubMed:16045448}.
CC -!- PTM: Ubiquitinated, ubiquitination is mediated by its own DCX protein
CC ligase complex. {ECO:0000250|UniProtKB:Q96SW2}.
CC -!- SIMILARITY: Belongs to the CRBN family. {ECO:0000305}.
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DR EMBL; AY973953; AAX73356.1; -; mRNA.
DR EMBL; BC099779; AAH99779.1; -; mRNA.
DR EMBL; BC127455; AAI27456.1; -; mRNA.
DR RefSeq; NP_001015003.1; NM_001015003.2.
DR AlphaFoldDB; Q56AP7; -.
DR SMR; Q56AP7; -.
DR BioGRID; 255596; 1.
DR IntAct; Q56AP7; 1.
DR MINT; Q56AP7; -.
DR STRING; 10116.ENSRNOP00000008873; -.
DR iPTMnet; Q56AP7; -.
DR PhosphoSitePlus; Q56AP7; -.
DR PaxDb; Q56AP7; -.
DR PRIDE; Q56AP7; -.
DR Ensembl; ENSRNOT00000008873; ENSRNOP00000008873; ENSRNOG00000006534.
DR GeneID; 297498; -.
DR KEGG; rno:297498; -.
DR UCSC; RGD:1310533; rat.
DR CTD; 51185; -.
DR RGD; 1310533; Crbn.
DR eggNOG; KOG1400; Eukaryota.
DR GeneTree; ENSGT00390000016404; -.
DR HOGENOM; CLU_025648_1_1_1; -.
DR InParanoid; Q56AP7; -.
DR OMA; DNMGNHL; -.
DR OrthoDB; 1069900at2759; -.
DR PhylomeDB; Q56AP7; -.
DR TreeFam; TF106115; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q56AP7; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000006534; Expressed in cerebellum and 18 other tissues.
DR Genevisible; Q56AP7; RN.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR GO; GO:0035641; P:locomotory exploration behavior; ISO:RGD.
DR GO; GO:0034766; P:negative regulation of ion transmembrane transport; IDA:RGD.
DR GO; GO:1902607; P:negative regulation of large conductance calcium-activated potassium channel activity; ISO:RGD.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:RGD.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR CDD; cd15777; CRBN_C_like; 1.
DR Gene3D; 2.30.130.40; -; 1.
DR InterPro; IPR034750; CULT.
DR InterPro; IPR003111; Lon_prtase_N.
DR InterPro; IPR046336; Lon_prtase_N_sf.
DR InterPro; IPR015947; PUA-like_sf.
DR InterPro; IPR004910; Yippee/Mis18/Cereblon.
DR Pfam; PF02190; LON_substr_bdg; 1.
DR Pfam; PF03226; Yippee-Mis18; 1.
DR SMART; SM00464; LON; 1.
DR SUPFAM; SSF88697; SSF88697; 1.
DR PROSITE; PS51788; CULT; 1.
DR PROSITE; PS51787; LON_N; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Membrane; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc.
FT CHAIN 1..445
FT /note="Protein cereblon"
FT /id="PRO_0000076163"
FT DOMAIN 84..320
FT /note="Lon N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01123"
FT DOMAIN 321..429
FT /note="CULT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 326
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 381
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 383
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 389
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 397
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 445 AA; 50877 MW; 554FC62FE8A73503 CRC64;
MAGEGDHQDA AHNMGNHLPL LPADSEDEDD EIEMEVEDQD SKEARKPNII NFDTSLPTSH
TYLGADMEEF HGRTLHDDDS CQVIPVLPEV MMILIPGQTL PLQLSHPQEV SMVRNLIQKD
RTFAVLAYSN VQEREAQFGT TAEIYAYREE QEFGIEVVKV KAIGRQRFKV LELRTQSDGI
QQAKVQILPE CVLPSTMSAV QLESLNKCQI FPSKPISWED QYSCKWWQKY QKRKFHCANL
TSWPRWLYSL YDAETLMDRI KKQLREWDEN LKEDSLPANP IDFSYRVAAC LPIDDVLRIQ
LLKIGSAIQR LRCELDIMNK CTSLCCKQCQ ETEITTKNEI FSLSLCGPMA AYVNPHGYVH
ETLTVYKASN LNLIGRPSTV HSWFPGYAWT IAQCKICASH IGWKFTATKK DMSPQKFWGL
TRSALLPTIP ETEDEISPDK VILCL
