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Database: UniProt
Entry: Q96SW2
LinkDB: Q96SW2
Original site: Q96SW2 
ID   CRBN_HUMAN              Reviewed;         442 AA.
AC   Q96SW2; B2R6H4; C9IZA9; C9JAH6; Q6AI62; Q6NVZ0; Q9UHW4;
DT   30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   29-SEP-2021, entry version 168.
DE   RecName: Full=Protein cereblon;
GN   Name=CRBN; ORFNames=AD-006;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, and Lung;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-442.
RC   TISSUE=Adrenal gland;
RX   PubMed=10931946; DOI=10.1073/pnas.160270997;
RA   Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA   Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA   Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA   Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA   Chen M.-D., Chen J.-L.;
RT   "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT   and full-length cDNA cloning.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-250.
RC   TISSUE=Fetal kidney;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6]
RP   INVOLVEMENT IN MRT2A, AND TISSUE SPECIFICITY.
RX   PubMed=15557513; DOI=10.1212/01.wnl.0000146196.01316.a2;
RA   Higgins J.J., Pucilowska J., Lombardi R.Q., Rooney J.P.;
RT   "A mutation in a novel ATP-dependent Lon protease gene in a kindred with
RT   mild mental retardation.";
RL   Neurology 63:1927-1931(2004).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=17380424; DOI=10.1007/s11033-007-9077-3;
RA   Xin W., Xiaohua N., Peilin C., Xin C., Yaqiong S., Qihan W.;
RT   "Primary function analysis of human mental retardation related gene CRBN.";
RL   Mol. Biol. Rep. 35:251-256(2008).
RN   [8]
RP   FUNCTION.
RX   PubMed=18414909; DOI=10.1007/s10048-008-0128-2;
RA   Higgins J.J., Hao J., Kosofsky B.E., Rajadhyaksha A.M.;
RT   "Dysregulation of large-conductance Ca2+-activated K+ channel expression in
RT   nonsyndromal mental retardation due to a cereblon p.R419X mutation.";
RL   Neurogenetics 9:219-223(2008).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY,
RP   IDENTIFICATION IN A DCX COMPLEX WITH DDB1; RBX1 AND CUL4A,
RP   THALIDOMIDE-BINDING, UBIQUITINATION, AND MUTAGENESIS OF TYR-384 AND
RP   TRP-386.
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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [11]
RP   FUNCTION, AND MISCELLANEOUS.
RX   PubMed=24328678; DOI=10.1111/bjh.12708;
RA   Gandhi A.K., Kang J., Havens C.G., Conklin T., Ning Y., Wu L., Ito T.,
RA   Ando H., Waldman M.F., Thakurta A., Klippel A., Handa H., Daniel T.O.,
RA   Schafer P.H., Chopra R.;
RT   "Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells
RT   by inducing degradation of T cell repressors Ikaros and Aiolos via
RT   modulation of the E3 ubiquitin ligase complex CRL4(CRBN.).";
RL   Br. J. Haematol. 164:811-821(2014).
RN   [12]
RP   FUNCTION, INTERACTION WITH DDB1, AND UBIQUITINATION.
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).
RN   [13]
RP   FUNCTION, AND MUTAGENESIS OF 419-ARG--LEU-442.
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).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 48-428 IN COMPLEX WITH DDB1;
RP   S-LENALIDOMIDE AND ZINC, FUNCTION, INTERACTION WITH DDB1, DOMAIN,
RP   MUTAGENESIS OF TRP-386, AND MISCELLANEOUS.
RX   PubMed=25108355; DOI=10.1038/nsmb.2874;
RA   Chamberlain P.P., Lopez-Girona A., Miller K., Carmel G., Pagarigan B.,
RA   Chie-Leon B., Rychak E., Corral L.G., Ren Y.J., Wang M., Riley M.,
RA   Delker S.L., Ito T., Ando H., Mori T., Hirano Y., Handa H., Hakoshima T.,
RA   Daniel T.O., Cathers B.E.;
RT   "Structure of the human cereblon-DDB1-lenalidomide complex reveals basis
RT   for responsiveness to thalidomide analogs.";
RL   Nat. Struct. Mol. Biol. 21:803-809(2014).
RN   [15]
RP   INVOLVEMENT IN MRT2A, AND VARIANT MRT2A ARG-391.
RX   PubMed=28143899; DOI=10.1136/jmedgenet-2016-104117;
RA   Sheereen A., Alaamery M., Bawazeer S., Al Yafee Y., Massadeh S., Eyaid W.;
RT   "A missense mutation in the CRBN gene that segregates with intellectual
RT   disability and self-mutilating behaviour in a consanguineous Saudi
RT   family.";
RL   J. Med. Genet. 54:236-240(2017).
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, PubMed:24328678, PubMed:25043012, PubMed:25108355).
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 (PubMed:18414909, PubMed:29530986). Likely to function by
CC       regulating the assembly and neuronal surface expression of BK channels
CC       via its interaction with KCNT1 (PubMed:18414909). May also be involved
CC       in regulating anxiety-like behaviors via a BK channel-independent
CC       mechanism (By similarity). {ECO:0000250|UniProtKB:Q8C7D2,
CC       ECO:0000269|PubMed:18414909, ECO:0000269|PubMed:20223979,
CC       ECO:0000269|PubMed:24328678, ECO:0000269|PubMed:25043012,
CC       ECO:0000269|PubMed:25108355, ECO:0000269|PubMed:29530986, ECO:0000305}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000269|PubMed:20223979, ECO:0000305|PubMed:25108355}.
CC   -!- SUBUNIT: Interacts with KCNT1 (By similarity). Component of a DCX
CC       (DDB1-CUL4-X-box) protein ligase complex, at least composed of CRBN,
CC       CUL4A, DDB1 and RBX1. Interacts directly with DDB1 (PubMed:25043012,
CC       PubMed:25108355). Interacts (in pomalidomide-bound form) with IKZF1 and
CC       IKZF3 (PubMed:24328678). {ECO:0000250|UniProtKB:Q56AP7,
CC       ECO:0000269|PubMed:20223979, ECO:0000269|PubMed:24328678,
CC       ECO:0000269|PubMed:25043012, ECO:0000269|PubMed:25108355}.
CC   -!- INTERACTION:
CC       Q96SW2; Q96A83-2: COL26A1; NbExp=3; IntAct=EBI-2510250, EBI-21553822;
CC       Q96SW2; P48729: CSNK1A1; NbExp=3; IntAct=EBI-2510250, EBI-1383726;
CC       Q96SW2; Q16531: DDB1; NbExp=3; IntAct=EBI-2510250, EBI-350322;
CC       Q96SW2; O14901: KLF11; NbExp=3; IntAct=EBI-2510250, EBI-948266;
CC       Q96SW2; Q8IVT2: MISP; NbExp=3; IntAct=EBI-2510250, EBI-2555085;
CC       Q96SW2; Q9P286: PAK5; NbExp=4; IntAct=EBI-2510250, EBI-741896;
CC       Q96SW2; D3DTS7: PMP22; NbExp=3; IntAct=EBI-2510250, EBI-25882629;
CC       Q96SW2; Q93062: RBPMS; NbExp=3; IntAct=EBI-2510250, EBI-740322;
CC       Q96SW2-2; Q16531: DDB1; NbExp=7; IntAct=EBI-10693561, EBI-350322;
CC       Q96SW2-2; Q13422-7: IKZF1; NbExp=2; IntAct=EBI-10693561, EBI-11522367;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20223979}. Nucleus
CC       {ECO:0000269|PubMed:20223979}. Membrane {ECO:0000250}; Peripheral
CC       membrane protein {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q96SW2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96SW2-2; Sequence=VSP_015209;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in brain.
CC       {ECO:0000269|PubMed:15557513, ECO:0000269|PubMed:17380424}.
CC   -!- DOMAIN: The CULT domain binds thalidomide and related drugs, such as
CC       pomalidomide and lenalidomide. Drug binding leads to a change in
CC       substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein
CC       ligase complex, while no such change is observed in rodents.
CC       {ECO:0000269|PubMed:25108355}.
CC   -!- PTM: Ubiquitinated, ubiquitination is mediated by its own DCX protein
CC       ligase complex. {ECO:0000269|PubMed:20223979,
CC       ECO:0000269|PubMed:25043012}.
CC   -!- DISEASE: Mental retardation, autosomal recessive 2A (MRT2A)
CC       [MIM:607417]: A disorder characterized by significantly below average
CC       general intellectual functioning associated with impairments in
CC       adaptive behavior and manifested during the developmental period. Non-
CC       syndromic mental retardation patients do not manifest other clinical
CC       signs. MRT2A patients display mild mental retardation with a standard
CC       IQ ranged from 50 to 70. IQ scores are lower in males than females.
CC       Developmental milestones are mildly delayed. There are no dysmorphic or
CC       autistic features. {ECO:0000269|PubMed:15557513,
CC       ECO:0000269|PubMed:28143899}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: Thalidomide was widely prescribed to pregnant women in
CC       the late 1950s as a sedative and as treatment against morning sickness.
CC       Thalidomide was found to be teratogenic, causing multiple birth
CC       defects. Recently, thalidomide use has increased for the treatment of
CC       multiple myeloma and erythema nodosum leprosum, a painful complication
CC       of leprosy. Binding of pomalidomide and other thalidomide-related drugs
CC       leads to a change in substrate specificity of the human DCX (DDB1-CUL4-
CC       X-box) E3 protein ligase complex, and this is probably the underlying
CC       cause of the teratogenic activity of thalidomide, possibly due to
CC       abnormal regulation of the BMP and FGF8 signaling pathways
CC       (PubMed:20223979). The thalidomide-induced change in substrate
CC       specificity leads to decreased degradation of MEIS2 and other target
CC       proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3, and
CC       this is probably the reason for the anti-proliferative and
CC       immunomodulatory effects of thalidomide and related drugs
CC       (PubMed:25108355). Thalidomide is also teratogenic in chicken and
CC       zebrafish, but not in mice. {ECO:0000305|PubMed:20223979,
CC       ECO:0000305|PubMed:25108355}.
CC   -!- SIMILARITY: Belongs to the CRBN family. {ECO:0000305}.
CC   -!- CAUTION: Although it contains a Lon N-terminal domain also found in
CC       proteases of the peptidase S16 family, it does not contain the ATP-
CC       binding and catalytic domains, suggesting that it has no protease
CC       activity. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF17211.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=BAG35471.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAG35471.1; Type=Frameshift; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=A short story - Issue 117 of
CC       May 2010;
CC       URL="https://web.expasy.org/spotlight/back_issues/117";
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DR   EMBL; AK027507; BAB55162.1; -; mRNA.
DR   EMBL; AK312577; BAG35471.1; ALT_SEQ; mRNA.
DR   EMBL; AC024060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC017419; AAH17419.1; -; mRNA.
DR   EMBL; BC067811; AAH67811.1; -; mRNA.
DR   EMBL; AF117230; AAF17211.1; ALT_FRAME; mRNA.
DR   EMBL; CR627060; CAH10361.1; -; mRNA.
DR   CCDS; CCDS2562.1; -. [Q96SW2-1]
DR   CCDS; CCDS54547.1; -. [Q96SW2-2]
DR   RefSeq; NP_001166953.1; NM_001173482.1. [Q96SW2-2]
DR   RefSeq; NP_057386.2; NM_016302.3. [Q96SW2-1]
DR   PDB; 4M91; X-ray; 1.10 A; B=229-240.
DR   PDB; 4TZ4; X-ray; 3.01 A; C=48-428.
DR   PDB; 5FQD; X-ray; 2.45 A; B/E=41-442.
DR   PDB; 5HXB; X-ray; 3.60 A; C/Z=40-442.
DR   PDB; 5V3O; X-ray; 3.20 A; C=40-442.
DR   PDB; 6BN7; X-ray; 3.50 A; B=1-442.
DR   PDB; 6BN8; X-ray; 3.99 A; B=1-442.
DR   PDB; 6BN9; X-ray; 4.38 A; B=1-442.
DR   PDB; 6BNB; X-ray; 6.34 A; B=1-442.
DR   PDB; 6BOY; X-ray; 3.33 A; B=1-442.
DR   PDB; 6H0F; X-ray; 3.25 A; B/E/H/K=41-442.
DR   PDB; 6H0G; X-ray; 4.25 A; B/E=41-397.
DR   PDB; 6UML; X-ray; 3.58 A; C=40-442.
DR   PDB; 6XK9; X-ray; 3.64 A; C/Z=40-442.
DR   PDB; 7BQU; X-ray; 1.90 A; A=318-426.
DR   PDB; 7BQV; X-ray; 1.80 A; A=318-426.
DR   PDB; 7LPS; X-ray; 3.78 A; B/E/H/K=47-436.
DR   PDBsum; 4M91; -.
DR   PDBsum; 4TZ4; -.
DR   PDBsum; 5FQD; -.
DR   PDBsum; 5HXB; -.
DR   PDBsum; 5V3O; -.
DR   PDBsum; 6BN7; -.
DR   PDBsum; 6BN8; -.
DR   PDBsum; 6BN9; -.
DR   PDBsum; 6BNB; -.
DR   PDBsum; 6BOY; -.
DR   PDBsum; 6H0F; -.
DR   PDBsum; 6H0G; -.
DR   PDBsum; 6UML; -.
DR   PDBsum; 6XK9; -.
DR   PDBsum; 7BQU; -.
DR   PDBsum; 7BQV; -.
DR   PDBsum; 7LPS; -.
DR   SMR; Q96SW2; -.
DR   BioGRID; 119360; 171.
DR   CORUM; Q96SW2; -.
DR   DIP; DIP-53521N; -.
DR   IntAct; Q96SW2; 40.
DR   MINT; Q96SW2; -.
DR   STRING; 9606.ENSP00000231948; -.
DR   BindingDB; Q96SW2; -.
DR   ChEMBL; CHEMBL3763008; -.
DR   DrugBank; DB00480; Lenalidomide.
DR   DrugBank; DB08910; Pomalidomide.
DR   DrugBank; DB01041; Thalidomide.
DR   DrugCentral; Q96SW2; -.
DR   GuidetoPHARMACOLOGY; 3086; -.
DR   TCDB; 8.A.162.1.1; the cereblon (crbn) family.
DR   iPTMnet; Q96SW2; -.
DR   PhosphoSitePlus; Q96SW2; -.
DR   BioMuta; CRBN; -.
DR   DMDM; 73918916; -.
DR   EPD; Q96SW2; -.
DR   jPOST; Q96SW2; -.
DR   MassIVE; Q96SW2; -.
DR   MaxQB; Q96SW2; -.
DR   PaxDb; Q96SW2; -.
DR   PeptideAtlas; Q96SW2; -.
DR   PRIDE; Q96SW2; -.
DR   ProteomicsDB; 78157; -. [Q96SW2-1]
DR   ProteomicsDB; 78158; -. [Q96SW2-2]
DR   Antibodypedia; 25089; 151 antibodies.
DR   DNASU; 51185; -.
DR   Ensembl; ENST00000231948; ENSP00000231948; ENSG00000113851. [Q96SW2-1]
DR   Ensembl; ENST00000432408; ENSP00000412499; ENSG00000113851. [Q96SW2-2]
DR   GeneID; 51185; -.
DR   KEGG; hsa:51185; -.
DR   UCSC; uc003bpq.4; human. [Q96SW2-1]
DR   CTD; 51185; -.
DR   DisGeNET; 51185; -.
DR   GeneCards; CRBN; -.
DR   HGNC; HGNC:30185; CRBN.
DR   HPA; ENSG00000113851; Low tissue specificity.
DR   MalaCards; CRBN; -.
DR   MIM; 607417; phenotype.
DR   MIM; 609262; gene.
DR   neXtProt; NX_Q96SW2; -.
DR   OpenTargets; ENSG00000113851; -.
DR   Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR   PharmGKB; PA134926851; -.
DR   VEuPathDB; HostDB:ENSG00000113851; -.
DR   eggNOG; KOG1400; Eukaryota.
DR   GeneTree; ENSGT00390000016404; -.
DR   HOGENOM; CLU_025648_1_1_1; -.
DR   InParanoid; Q96SW2; -.
DR   OMA; AYQMYDS; -.
DR   PhylomeDB; Q96SW2; -.
DR   TreeFam; TF106115; -.
DR   PathwayCommons; Q96SW2; -.
DR   Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR   SIGNOR; Q96SW2; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 51185; 25 hits in 1057 CRISPR screens.
DR   ChiTaRS; CRBN; human.
DR   GeneWiki; Cereblon; -.
DR   GenomeRNAi; 51185; -.
DR   Pharos; Q96SW2; Tclin.
DR   PRO; PR:Q96SW2; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q96SW2; protein.
DR   Bgee; ENSG00000113851; Expressed in corpus callosum and 237 other tissues.
DR   ExpressionAtlas; Q96SW2; baseline and differential.
DR   Genevisible; Q96SW2; HS.
DR   GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl.
DR   GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR   GO; GO:1902607; P:negative regulation of large conductance calcium-activated potassium channel activity; IEA:Ensembl.
DR   GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IEA:Ensembl.
DR   GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IEA:Ensembl.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR   CDD; cd15777; CRBN_C_like; 1.
DR   InterPro; IPR034750; CULT.
DR   InterPro; IPR003111; Lon_substr-bd.
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; Alternative splicing; Cytoplasm; Disease variant; Membrane;
KW   Mental retardation; Metal-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc.
FT   CHAIN           1..442
FT                   /note="Protein cereblon"
FT                   /id="PRO_0000076160"
FT   DOMAIN          81..317
FT                   /note="Lon N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01123"
FT   DOMAIN          318..426
FT                   /note="CULT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01124"
FT   REGION          1..45
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          378..386
FT                   /note="Thalidomide binding"
FT                   /evidence="ECO:0000269|PubMed:25108355,
FT                   ECO:0007744|PDB:4TZ4"
FT   METAL           323
FT                   /note="Zinc"
FT                   /evidence="ECO:0000269|PubMed:25108355,
FT                   ECO:0007744|PDB:4TZ4"
FT   METAL           326
FT                   /note="Zinc"
FT                   /evidence="ECO:0000269|PubMed:25108355,
FT                   ECO:0007744|PDB:4TZ4"
FT   METAL           391
FT                   /note="Zinc"
FT                   /evidence="ECO:0000269|PubMed:25108355,
FT                   ECO:0007744|PDB:4TZ4"
FT   METAL           394
FT                   /note="Zinc"
FT                   /evidence="ECO:0000269|PubMed:25108355,
FT                   ECO:0007744|PDB:4TZ4"
FT   MOD_RES         25
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         23
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_015209"
FT   VARIANT         391
FT                   /note="C -> R (in MRT2A; dbSNP:rs797045036)"
FT                   /evidence="ECO:0000269|PubMed:28143899"
FT                   /id="VAR_079409"
FT   MUTAGEN         384
FT                   /note="Y->A: Abolishes thalidomide-binding without
FT                   affecting DCX protein ligase complex activity; when
FT                   associated with A-386."
FT                   /evidence="ECO:0000269|PubMed:20223979"
FT   MUTAGEN         386
FT                   /note="W->A: Abolishes thalidomide-binding without
FT                   affecting DCX protein ligase complex activity; when
FT                   associated with A-384. Abolishes pomalidomide-induced
FT                   change in substrate specificity and abolishes pomalidomide-
FT                   induced decrease in cell viability that is brought about by
FT                   increased degradation of MYC, IRF4 and IKZF3."
FT                   /evidence="ECO:0000269|PubMed:20223979,
FT                   ECO:0000269|PubMed:25108355"
FT   MUTAGEN         419..442
FT                   /note="Missing: Fails to rescue increased BK channel
FT                   activity and decreased probability of neurotransmission in
FT                   a mouse hippocampal neuron model."
FT                   /evidence="ECO:0000269|PubMed:29530986"
FT   CONFLICT        229
FT                   /note="K -> R (in Ref. 2; AAH67811)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        237
FT                   /note="L -> P (in Ref. 1; BAG35471)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        292
FT                   /note="D -> G (in Ref. 1; BAG35471)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        330
FT                   /note="E -> G (in Ref. 1; BAG35471)"
FT                   /evidence="ECO:0000305"
FT   TURN            51..53
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           54..56
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           58..60
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          78..83
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          96..101
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           104..115
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          119..127
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   TURN            128..131
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          132..149
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          152..172
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          174..176
FT                   /evidence="ECO:0007829|PDB:6H0F"
FT   STRAND          178..184
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           195..197
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           200..205
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           215..219
FT                   /evidence="ECO:0007829|PDB:6H0F"
FT   HELIX           220..231
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           233..237
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          238..240
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           242..246
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           250..262
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           269..272
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           277..286
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           292..299
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   HELIX           304..317
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          320..323
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   TURN            324..326
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          330..333
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   HELIX           334..336
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          341..343
FT                   /evidence="ECO:0007829|PDB:7BQU"
FT   STRAND          345..350
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          356..363
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          367..375
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          384..391
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   TURN            392..394
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          397..406
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          410..418
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   HELIX           419..421
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          422..424
FT                   /evidence="ECO:0007829|PDB:7BQV"
FT   STRAND          427..429
FT                   /evidence="ECO:0007829|PDB:5FQD"
FT   STRAND          432..434
FT                   /evidence="ECO:0007829|PDB:6H0F"
SQ   SEQUENCE   442 AA;  50546 MW;  90DF77D98A8BEAA8 CRC64;
     MAGEGDQQDA AHNMGNHLPL LPAESEEEDE MEVEDQDSKE AKKPNIINFD TSLPTSHTYL
     GADMEEFHGR TLHDDDSCQV IPVLPQVMMI LIPGQTLPLQ LFHPQEVSMV RNLIQKDRTF
     AVLAYSNVQE REAQFGTTAE IYAYREEQDF GIEIVKVKAI GRQRFKVLEL RTQSDGIQQA
     KVQILPECVL PSTMSAVQLE SLNKCQIFPS KPVSREDQCS YKWWQKYQKR KFHCANLTSW
     PRWLYSLYDA ETLMDRIKKQ LREWDENLKD DSLPSNPIDF SYRVAACLPI DDVLRIQLLK
     IGSAIQRLRC ELDIMNKCTS LCCKQCQETE ITTKNEIFSL SLCGPMAAYV NPHGYVHETL
     TVYKACNLNL IGRPSTEHSW FPGYAWTVAQ CKICASHIGW KFTATKKDMS PQKFWGLTRS
     ALLPTIPDTE DEISPDKVIL CL
//
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