3WX1,4TZ4,4CI1,6R0Q


Conserved Protein Domain Family
CRBN_C-like

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cd15777: CRBN_C-like (This model is not part of the current CDD release)
Thalidomide-binding C-terminal domain of cereblon (CRBN) and similar protein domains
Cereblon is part of an E3 ubiquitin ligase complex, together with damaged DNA-binding protein 1 (DDB1), CUL4A and ROC1. Cereblon interacts directly with DDB1, although the C-terminal domain characterized here does not contribute to that interaction. Ubiquination of cellular targets by this complex increases levels of FGF8 and FGF10, which was shown to affect the development of limbs and auditory vesicles in embryogenesis. The C-terminal domain of Cereblon was shown to contain the binding site for thalidomide and its analogs, a class of teratogenic drugs that exhibit an antiproliferative effect on myelomas. Mutations in CRBN, some of which map onto the C-terminal domain, were associated with autosomal recessive mental retardation, which may have to do with interactions between CRBN and ion channels in the brain.
Statistics
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PSSM-Id: 501547
Aligned: 154 rows
Threshold Bit Score: 65.7939
Created: 30-Oct-2024
Updated: 30-Oct-2024
Structure
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Program:
Drawing:
Aligned Rows:
 
ThalidomideZn binding site
Conserved site includes 9 residues -Click on image for an interactive view with Cn3D
Feature 1: Thalidomide binding site [chemical binding site], 9 residue positions
Conserved feature residue pattern:N [PSAN] x x [STCG] [WF] W [WF] [FY]Click to see conserved feature residue pattern help
Evidence:
  • Structure:4TZ4: The C-terminal domain of human cereblon binds lenalidomide, a thalidomide analog; contacts at 4A

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                   ###                   
3WX1_A          5 LCCKQCQEt----EITTKNEIFSLSlc------------------------gPXAAYVNPHGYVH------------ETL 44   house mouse
4TZ4_C        274 LCCKQCQEt----EITTKNEIFSLSlc------------------------gPMAAYVNPHGYVH------------ETL 313  human
XP_784157       4 MRSRDSPSfr-lvTVGTTQAVHRRNgtilg------------------kenvLIQLLKNPQGRHF------------EII 52   purple sea ur...
XP_013396276  145 IWCAECNI-----LLAKAMHLQERNvtrrkgerdss-----eriaiagvhgmRLERVSNPGEYYF------------LIV 202  Lingula anatina
XP_013396276   24 HIKCECGA-----FISHATEIINGDdsiqqgfsak-------kqyrlfgkpvKTWGFKNPSNYLH------------VIV 79   Lingula anatina
KAJ0406697     69 VRCRMCGA-----KIADKADYMELFdtakavssr---------etdvlgqvrHLHTFVNPSRVEM------------ELV 122  Pythium insid...
XP_005832298    1 MRAMTSPFa----HERRNRPVGNDQh-------------------------vQTQVLVNPHGSSF------------EVL 39   Guillardia th...
XP_021332510  237 LHCASMTSwp-pwVYSLYDSKTLMSrvkkqlh-------------ewdenlkDESLPTNPTDFSYrvaaclpiddalRLQ 302  zebrafish
OLQ01767       29 PHMSECPGegcdcPAQKQLDLSLMNlvpfqpvqad--------sflgmekyeTRGLEVNLYNFKQparlse-lqlpfKLL 99   Symbiodinium ...
OLP82234       10 YRCSTCGQ-----ELAEAASLLPASdsrvvpcsgitarscevagkttlqfstCQSFVINPFPRRF------------ELV 72   Symbiodinium ...
Feature 1                                             ###     #              # #                  
3WX1_A         45 TVYKa--------------sNLNLIGRPST-----VHSWFPGYAWTIAQCKi-CASHIGWKFTAtkkdxsPQKFWGLTRS 104  house mouse
4TZ4_C        314 TVYKa--------------cNLNLIGRPST-----EHSWFPGYAWTVAQCKi-CASHIGWKFTAtkkdmsPQKFWGLTRS 373  human
XP_784157      53 TTSAa---------------EVSKQPHLHK-----DHTWFDGYGWQIISCPq-CRSHLGWYFEPtepkktETCQEEKDKD 111  purple sea ur...
XP_013396276  203 PVSEc--------------iNYRAAGGKTS-----YYTWYKGYEWEIIYCSg-CGNHIGWKYTNrk---pSDTFYGLIRD 259  Lingula anatina
XP_013396276   80 RVKSa---------------TVDWDNQEVLd----TYPWFKGYSWSIAYCKd-CRQFLGWKFIKg-----QQYFFGLVIK 134  Lingula anatina
KAJ0406697    123 AFRK----------------VVGLEGEAFTt----TATFFDGYNWRDLRCSs-CNRHIGWKFHHda---lQKCIHDKILD 178  Pythium insid...
XP_005832298   40 RTRRv--------------vNSLIYGRRVL-----RHSWYPGFAWQCVACKg-CLAHLGWFFTPqdkegeGDPWFEDEMV 99   Guillardia th...
XP_021332510  303 LLKIgsaiqrlrceldimdrCTSLCCKQCQdteitSKNEIFRYAWTIAQCRt-CSSHMGWKFSAvkkdlsPPRFWGLTRS 381  zebrafish
OLQ01767      100 LLKTldl----------tdlHVLEVSKEQA-----QDSWFPGYEWSVLVCGrcDGRHLGWKFVPar---sGSAFYALIVE 161  Symbiodinium ...
OLP82234       73 LVEKiv------------arAASEIGPEAMl----ENSWFEGHAHRVLVCTh-CEDHIGWSYKGr----hGDTIYGLALS 131  Symbiodinium ...
Feature 1           
3WX1_A        105 AL 106  house mouse
4TZ4_C        374 AL 375  human
XP_784157     112 VC 113  purple sea urchin
XP_013396276  260 RL 261  Lingula anatina
XP_013396276  135 KL 136  Lingula anatina
KAJ0406697    179 VM 180  Pythium insidiosum
XP_005832298  100 EQ 101  Guillardia theta CCMP2712
XP_021332510  382 AL 383  zebrafish
OLQ01767      162 AV 163  Symbiodinium microadriaticum
OLP82234      132 VS 133  Symbiodinium microadriaticum

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