CRBN_PONAB
ID CRBN_PONAB Reviewed; 429 AA.
AC Q5R6Y2;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Protein cereblon;
GN Name=CRBN;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC Interacts with ILF2 (By similarity). {ECO:0000250|UniProtKB:Q56AP7,
CC ECO:0000250|UniProtKB:Q96SW2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96SW2}. Nucleus
CC {ECO:0000250|UniProtKB:Q96SW2}. Membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}.
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; CR860344; CAH92478.1; -; mRNA.
DR RefSeq; NP_001127555.1; NM_001134083.1.
DR AlphaFoldDB; Q5R6Y2; -.
DR SMR; Q5R6Y2; -.
DR STRING; 9601.ENSPPYP00000015323; -.
DR GeneID; 100174633; -.
DR KEGG; pon:100174633; -.
DR CTD; 51185; -.
DR eggNOG; KOG1400; Eukaryota.
DR InParanoid; Q5R6Y2; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Unplaced.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Cytoplasm; Membrane; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc.
FT CHAIN 1..429
FT /note="Protein cereblon"
FT /id="PRO_0000076162"
FT DOMAIN 68..304
FT /note="Lon N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01123"
FT DOMAIN 305..413
FT /note="CULT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 365
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 367
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 373
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96SW2"
SQ SEQUENCE 429 AA; 49245 MW; B7A9BC272EE5CB1C CRC64;
MGNHLPLLPA ESEEEDEMEV EDQDSKEAKK PNIINFDTSL PTSHTYLGAD MEEFHGRTLH
DDDSCQVIPV LPQVMMILIP GQTLPLQLFH PQEVSMVRNL IQKDRTFAVL AYSNIQEREA
QFGTTAEIYA YREEQDFGIE IVKVKAIGRQ RFKVLELRTQ SDGIQQAKVQ ILPECVLPST
MSAVQLESLN KCQIFPPKPV SREDQCSYKW WQKYQKRKFH CANLTSWPRW LYSLYDAETL
MDRIKKQLRE WDENLKDDSL PSNPIDFSYR VAACLPIDDV LRIQLLKIGS AIQRLRCELD
IMNKCTSLCC KQCQETEITT KNEIFSLSLC GPMAAYVNPH GYVHETLTVY KACNLNLIGR
PSTEHSWFPG YAWTVAQCKI CASHIGWKFT ATKKDMSPQK FWGLTRSALL PTIPDTEDEL
SPDKVILCL
