CRBN_CHICK
ID CRBN_CHICK Reviewed; 445 AA.
AC P0CF65;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Protein cereblon;
GN Name=CRBN;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 46-321.
RA Wistow G., Peterson K., McMurtry J.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND MISCELLANEOUS.
RX PubMed=20223979; DOI=10.1126/science.1177319;
RA Ito T., Ando H., Suzuki T., Ogura T., Hotta K., Imamura Y., Yamaguchi Y.,
RA Handa H.;
RT "Identification of a primary target of thalidomide teratogenicity.";
RL Science 327:1345-1350(2010).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH DDB1;
RP S-LENALIDOMIDE; S-POMALIDOMIDE; S-THALIDOMIDE AND ZINC.
RX PubMed=25043012; DOI=10.1038/nature13527;
RA Fischer E.S., Bohm K., Lydeard J.R., Yang H., Stadler M.B., Cavadini S.,
RA Nagel J., Serluca F., Acker V., Lingaraju G.M., Tichkule R.B.,
RA Schebesta M., Forrester W.C., Schirle M., Hassiepen U., Ottl J., Hild M.,
RA Beckwith R.E., Harper J.W., Jenkins J.L., Thoma N.H.;
RT "Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with
RT thalidomide.";
RL Nature 512:49-53(2014).
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 (Probable).
CC Normal degradation of key regulatory proteins is required for normal
CC limb outgrowth and expression of the fibroblast growth factor FGF8
CC (PubMed:20223979). Maintains presynaptic glutamate release and
CC consequently cognitive functions, such as memory and learning, by
CC negatively regulating large-conductance calcium-activated potassium
CC (BK) channels in excitatory neurons. Likely to function by regulating
CC the assembly and neuronal surface expression of BK channels via its
CC interaction with KCNT1 (By similarity). May also be involved in
CC regulating anxiety-like behaviors via a BK channel-independent
CC mechanism (By similarity). {ECO:0000250|UniProtKB:Q8C7D2,
CC ECO:0000250|UniProtKB:Q96SW2, ECO:0000269|PubMed:20223979,
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 Interacts directly with DDB1 (PubMed:25043012).
CC {ECO:0000269|PubMed:25043012, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96SW2}. Nucleus
CC {ECO:0000250|UniProtKB:Q96SW2}.
CC -!- MISCELLANEOUS: Thalidomide is teratogenic in human, chicken and
CC zebrafish, but not in mice. Binding of thalidomide and related drugs
CC changes the substrate specificity of the human DCX (DDB1-CUL4-X-box) E3
CC protein ligase complex, leading to decreased degradation of endogenous
CC target proteins and increased degradation of other proteins that are
CC not normal substrates. This is probably the underlying cause of the
CC teratogenic activity of thalidomide, possibly due to abnormal
CC regulation of the BMP and FGF8 signaling pathways (PubMed:20223979).
CC {ECO:0000305|PubMed:20223979}.
CC -!- SIMILARITY: Belongs to the CRBN family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; DR425223; -; NOT_ANNOTATED_CDS; mRNA.
DR PDB; 4CI1; X-ray; 2.98 A; B=1-445.
DR PDB; 4CI2; X-ray; 2.95 A; B=1-445.
DR PDB; 4CI3; X-ray; 3.50 A; B=1-445.
DR PDBsum; 4CI1; -.
DR PDBsum; 4CI2; -.
DR PDBsum; 4CI3; -.
DR AlphaFoldDB; P0CF65; -.
DR SMR; P0CF65; -.
DR DIP; DIP-61026N; -.
DR IntAct; P0CF65; 1.
DR STRING; 9031.ENSGALP00000013451; -.
DR iPTMnet; P0CF65; -.
DR PaxDb; P0CF65; -.
DR VEuPathDB; HostDB:geneid_416106; -.
DR eggNOG; KOG1400; Eukaryota.
DR InParanoid; P0CF65; -.
DR PhylomeDB; P0CF65; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000000539; 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: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 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Metal-binding; Nucleus; Reference proteome;
KW Ubl conjugation pathway; Zinc.
FT CHAIN 1..445
FT /note="Protein cereblon"
FT /id="PRO_0000393876"
FT DOMAIN 82..319
FT /note="Lon N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01123"
FT DOMAIN 320..428
FT /note="CULT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..36
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 325
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:25043012"
FT BINDING 328
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:25043012"
FT BINDING 380
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000269|PubMed:25043012"
FT BINDING 382
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000269|PubMed:25043012"
FT BINDING 388
FT /ligand="(S)-thalidomide"
FT /ligand_id="ChEBI:CHEBI:61918"
FT /evidence="ECO:0000269|PubMed:25043012"
FT BINDING 393
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:25043012"
FT BINDING 396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:25043012"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 105..115
FT /evidence="ECO:0007829|PDB:4CI2"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:4CI2"
FT TURN 129..132
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 133..150
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 153..173
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:4CI2"
FT TURN 194..198
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:4CI1"
FT HELIX 223..233
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 235..239
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:4CI1"
FT HELIX 244..247
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 252..266
FT /evidence="ECO:0007829|PDB:4CI2"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 279..288
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 294..302
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 306..319
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:4CI2"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 332..335
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 346..352
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 358..365
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 369..377
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 386..393
FT /evidence="ECO:0007829|PDB:4CI2"
FT TURN 394..396
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 399..408
FT /evidence="ECO:0007829|PDB:4CI2"
FT STRAND 412..420
FT /evidence="ECO:0007829|PDB:4CI2"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:4CI2"
SQ SEQUENCE 445 AA; 51118 MW; A5546BAE25846CE9 CRC64;
MAAEEGGDGR RNMGNPPPPA PAESEEEDDN EMEVEDQDGK EAEKPNMINF DTSLPTSHMY
LGSDMEEFHG RTLHDDDSCQ VIPVLPHVMV MLIPGQTLPL QLFHPQEVSM VRNLIQKDRT
FAVLAYSNVR EREAHFGTTA EIYAYREEQE YGIETVKVKA IGRQRFKVLE IRTQSDGIQQ
AKVQILPERV LPSTMSAVQL QSLSRRHIFP SSKPKVWQDR AFRQWWQKYQ KRKFHCASLT
SWPPWLYSLY DAETLMERVK RQLHEWDENL KDESLPTNPI DFSYRVAACL PIDDALRIQL
LKIGSAIQRL RCELDIMNKC TSLCCKQCQD TEITTKNEIF SLSLCGPMAA YVNPHGYIHE
TLTVYKACNL NLSGRPSTEH SWFPGYAWTI AQCRICGNHM GWKFTATKKD MSPQKFWGLT
RSALLPRIPE AEDELGHDRS PLLCL
