CRBN_DROME
ID CRBN_DROME Reviewed; 585 AA.
AC Q9VH36; Q9VH35;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protein cereblon {ECO:0000303|PubMed:29530986};
DE AltName: Full=Protein ohgata {ECO:0000303|PubMed:27702999};
GN Name=ohgt {ECO:0000303|PubMed:27702999, ECO:0000312|FlyBase:FBgn0037780};
GN Synonyms=crbn {ECO:0000303|PubMed:29530986};
GN ORFNames=CG3925 {ECO:0000312|FlyBase:FBgn0037780};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, INTERACTION WITH PIC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP UBIQUITINATION, AND DISRUPTION PHENOTYPE.
RX PubMed=27702999; DOI=10.1074/jbc.m116.757823;
RA Wakabayashi S., Sawamura N., Voelzmann A., Broemer M., Asahi T., Hoch M.;
RT "Ohgata, the single Drosophila ortholog of Human Cereblon, regulates
RT insulin signaling-dependent organismic growth.";
RL J. Biol. Chem. 291:25120-25132(2016).
RN [5]
RP FUNCTION.
RX PubMed=29530986; DOI=10.1523/jneurosci.2081-17.2018;
RA Choi T.Y., Lee S.H., Kim Y.J., Bae J.R., Lee K.M., Jo Y., Kim S.J.,
RA Lee A.R., Choi S., Choi L.M., Bang S., Song M.R., Chung J., Lee K.J.,
RA Kim S.H., Park C.S., Choi S.Y.;
RT "Cereblon Maintains Synaptic and Cognitive Function by Regulating BK
RT Channel.";
RL J. Neurosci. 38:3571-3583(2018).
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 (Probable). Has an essential
CC role in mediating growth by negatively regulating insulin signaling
CC (PubMed:27702999). It also has a role in maintaining presynaptic
CC function in the neuromuscular junction synapses of third-instar larvae
CC (PubMed:29530986). {ECO:0000269|PubMed:27702999,
CC ECO:0000269|PubMed:29530986, ECO:0000305}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q96SW2}.
CC -!- SUBUNIT: Likely a component of a DCX (DDB1-CUL4-X-box) protein ligase
CC complex (By similarity). May interact with pic/DDB1 (PubMed:27702999).
CC {ECO:0000250|UniProtKB:Q96SW2, ECO:0000269|PubMed:27702999}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27702999}.
CC -!- TISSUE SPECIFICITY: Expressed in the fat body (at protein level).
CC {ECO:0000269|PubMed:27702999}.
CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:27702999}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile however, adults and larvae
CC display an increase in body size and tissue growth as a result of
CC increased cell number (PubMed:27702999). Overgrowth is due to an up-
CC regulation in insulin-like signaling both systematically and in the fat
CC body, which in turn results in the down-regulation of insulin-like
CC peptide (ILP) inhibitors, conv and ImpL2, and thus allows increased
CC activity of the ILPs (PubMed:27702999). RNAi-mediated knockdown in the
CC fat body results in an increase in pupal length, adult body weight and
CC posterior wing area (PubMed:27702999). {ECO:0000269|PubMed:27702999}.
CC -!- MISCELLANEOUS: The name 'Ohgata' means 'large' in Japanese and refers
CC to the overgrowth phenotype in mutants. {ECO:0000303|PubMed:27702999}.
CC -!- SIMILARITY: Belongs to the CRBN family. {ECO:0000305}.
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DR EMBL; AE014297; AAF54484.1; -; Genomic_DNA.
DR EMBL; AY118943; AAM50803.1; -; mRNA.
DR RefSeq; NP_649973.1; NM_141716.3.
DR AlphaFoldDB; Q9VH36; -.
DR SMR; Q9VH36; -.
DR BioGRID; 66385; 7.
DR IntAct; Q9VH36; 5.
DR STRING; 7227.FBpp0081652; -.
DR PaxDb; Q9VH36; -.
DR PRIDE; Q9VH36; -.
DR DNASU; 41230; -.
DR EnsemblMetazoa; FBtr0082174; FBpp0081652; FBgn0037780.
DR GeneID; 41230; -.
DR KEGG; dme:Dmel_CG3925; -.
DR UCSC; CG3925-RA; d. melanogaster.
DR CTD; 41230; -.
DR FlyBase; FBgn0037780; ohgt.
DR VEuPathDB; VectorBase:FBgn0037780; -.
DR eggNOG; KOG1400; Eukaryota.
DR GeneTree; ENSGT00390000016404; -.
DR HOGENOM; CLU_028769_0_0_1; -.
DR InParanoid; Q9VH36; -.
DR OMA; AYQMYDS; -.
DR OrthoDB; 1069900at2759; -.
DR PhylomeDB; Q9VH36; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 41230; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41230; -.
DR PRO; PR:Q9VH36; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037780; Expressed in oviduct (Drosophila) and 25 other tissues.
DR Genevisible; Q9VH36; DM.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1900075; P:positive regulation of neuromuscular synaptic transmission; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:FlyBase.
DR CDD; cd15777; CRBN_C_like; 1.
DR InterPro; IPR034750; CULT.
DR InterPro; IPR003111; Lon_prtase_N.
DR InterPro; IPR004910; Yippee/Mis18/Cereblon.
DR Pfam; PF03226; Yippee-Mis18; 1.
DR PROSITE; PS51788; CULT; 1.
DR PROSITE; PS51787; LON_N; 1.
PE 1: Evidence at protein level;
KW Metal-binding; Nucleus; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway; Zinc.
FT CHAIN 1..585
FT /note="Protein cereblon"
FT /id="PRO_0000393881"
FT DOMAIN 225..449
FT /note="Lon N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01123"
FT DOMAIN 450..559
FT /note="CULT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT REGION 1..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 156..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..37
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 455
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT BINDING 458
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT BINDING 524
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT BINDING 527
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
SQ SEQUENCE 585 AA; 66453 MW; 5C18190CB1B7905A CRC64;
MDEEENSEIN SVQARDEDVQ LEDQQSQGLQ DRQVDVIEQA WNNAMPDEPS PPAEDAFQDP
LATDGEGGDA LEAMVENVLQ DDTASEGSHP SSDMSLESPG SEDDSDLESL PHWMIPQNRL
RSAVDMMVSQ ARNRDGGIAA LLSGDNFLQR VRSMVFSQER RRSRTSEETS QEAAEQPVDP
PPQQPPRPPI DIGFDTNLPA EHSYFGNHLS RVPGVDYLEV GSVHHMLIFL HQHILFPGEV
LPFMIDGRMF DEDMPGLDGL IFGVSFPRLQ PPEDNPHKLY GVTCQIYERG ESGRGLVFYK
SRALQRIVIN CDDIKGSPQY IARNPTSKCF SKVKILPEYF LPEPLQTVDM GSMARFRDIP
SMRDKYRRFQ LSTTTWPSDA CQEYSFSSIV ERARQRLESQ KIDTMPKCPI QLSFWLVRNL
HLTEKMMRLT FLTDSVNTRL QLIKSTFKDE TLFFCRYCNS SLALCSDLFA MSKHGVQTQY
CNPEGYIHET NTVYRVISHA IGYSGEPSTK FSWFPGYQWH IILCKFCAQH VGWEFKAVHP
NLTPKVFFGL AGSSVRIGKA SEYSPFNGTT YVVRNMMRMI SSDME
