2YV6,1G5J,1O0L,1YSW,1F16,2A5Y,1YSG,1G5M,2PQK,2VM6,2VOG,1TY4


Conserved Protein Domain Family
Bcl-2_like

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cd06845: Bcl-2_like 
Click on image for an interactive view with Cn3D
Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This alignment model spans what have been described as Bcl-2 homology regions BH1, BH2, BH3, and BH4. Many members of this family have an additional C-terminal transmembrane segment. Some homologous proteins, which are not included in this model, may miss either the BH4 (Bax, Bak) or the BH2 (Bcl-X(S)) region, and some appear to only share the BH3 region (Bik, Bim, Bad, Bid, Egl-1). This family is involved in the regulation of the outer mitochondrial membrane's permeability and in promoting or preventing the release of apoptogenic factors, which in turn may trigger apoptosis by activating caspases. Bcl-2 and the closely related Bcl-X(L) are anti-apoptotic key regulators of programmed cell death. They are assumed to function via heterodimeric protein-protein interactions, binding pro-apoptotic proteins such as Bad (BCL2-antagonist of cell death), Bid, and Bim, by specifically interacting with their BH3 regions. Interfering with this heterodimeric interaction via small-molecule inhibitors may prove effective in targeting various cancers. This family also includes the Caenorhabditis elegans Bcl-2 homolog CED-9, which binds to CED-4, the C. Elegans homolog of mammalian Apaf-1. Apaf-1, however, does not seem to be inhibited by Bcl-2 directly.
Statistics
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PSSM-Id: 132900
View PSSM: cd06845
Aligned: 86 rows
Threshold Bit Score: 75.8324
Threshold Setting Gi: 2493281
Created: 8-Jan-2008
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
BH3-homologyBH4BH3BH1BH2
Conserved site includes 21 residues -Click on image for an interactive view with Cn3D
Feature 1:BH3-homology region binding site
Evidence:
  • Structure:1G5J: Bcl-X(L) domain from Homo sapiens binds a peptide derived from Bad, which corresponds to the BH3 homology region, contacts at 4A
    View structure with Cn3D
  • Structure:1YSW: Human Bcl-2 binds the inhibitor ABT-737, a BH3-only mimetic, contacts at 4A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                           ## ##    #  ##               
2YV6_A         8 DTEEVFRSYVFYRHQqeqeaegvaapadpexvtlplqpsstxGQVGRQLAIIGDDINr-rYDSEFQTxlqhlqptaenaY 86
1G5J_A         8 SNRELVVDFLSYKLSqkgyswsqfsdve--enrteapegtesEAVKQALREAGDEFEl-rYRRAFSDltsqlhitpgtaY 84
2A5Y_A        32 DIEGFVVDYFTHRIRqngmewfg-----------apglpsgvQPEHEMMRVMGTIFEk-kHAENFETfseqllavprisF 99
1TY4_A        12 DIEGFVVDYFTHRIRqngxewfg-----------apglpcgvQPEHEXXRVXGTIFEk-kHAENFETfceqllavprisF 79
gi 154705494  18 SYVGEKLRKKGLKIRgyegee----------------lkppvIEIAKTLQRVGDELEs-aNTDFFKNmcdqlqitpstaY 80
gi 156388833   4 DFIGYKLRQNNIFLEgfnm--------------------espTKASKHLRIVADELIa-dNSELFHSmcdqlhltpistY 62
gi 62288024   81 DYFTYRIAQNGLDWYdapal------------------pdgvQKEHEMMRSLGTIFEk-rHMEMFENfseqllavpkisF 141
gi 55770952   44 SYIVNLLRREGLNHIadqfap----------------vgstrANGYQLIERIVCQLEderSQQFIDIlrglei-dqqnlR 106
gi 210127538 435 DYVFYKLNKKGLPWPnapp-------------------lpppTDAHRLMRELGDKFEe-rYREQFDEmgdqlhltpdtaY 494
gi 170585368 274 TIQSYVTDYIQYRVHlhnvycpr-----------lpeipvsdDYRFELIRAVALIFEk-kHAEELTNmvttlclngrltF 341
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ##  ##  ##            # ## ##   #   #                                           
2YV6_A        87 EYFTKIATSLFes-------gINWGRVVALLGFGYRLALHVYQhg--ltGFLGQVTRFVVDFXLHHciARWIAQR-GGWV 156
1G5J_A        85 QSFEQVVNELFrd-------gVNWGRIVAFFSFGGALCVESVDke--mqVLVSRIAAWMATYLNDHl-EPWIQEN-GGWD 153
2A5Y_A       100 SLYQDVVRTVGnaqt--dqspMSYGRLIGLISFGGFVAAKMMEsve-lqGQVRNLFVYTSLFIKTRi-RNNWKEHnRSWD 175
1TY4_A        80 SPYQDVVRTVGnaqt--dqcpXSYGRLIGLISFGGFVAAKXXEsve-lqGQVRNLFVYTSLFIKTRi-RNNWKEHnRSWD 155
gi 154705494  81 PTFQSIADEIFvs-------gKNWGRVVAFLTFGGNFAVHCALradmgeEYVDRVVNWISKYMAVNl-DYWINQQ-GGWD 151
gi 156388833  63 PTFVGIANEIFqs-------gKNWGRVVAFLAFGATLAVYCAQree-lhELVNDIVEWVSRYMDQNl-SCWIREN-GGWV 132
gi 62288024  142 SLYQEVVQTVGnssn--tpcpMSYGRLIGLISFGGMVAAKMMEsae-lqGQVRNLLMYTSLFIKTRirQSWKEHN-RSWA 217
gi 55770952  107 ITYQTIVGEIFnd-------gVHWGRIVAFLVFSGHLAVHCARsng-leNRVRDVVEWTEAEMRLRv-HQWVEDR-GGWE 176
gi 210127538 495 QKYHNVVAELFre-------gVRWGRLVALVAFTGACTVTAVEre--mpQFVDRYVDWTVQYIDNNl-AQWLQEN-GGWE 563
gi 170585368 342 QRYVEVVECFAhndddesnkqLSYGRLVALIAFAGLVAMKLCDlq--lfTEVSMIAPYTSKFLHKRivLTWPQDR-RSWE 418

                 ....*
Feature 1            #
2YV6_A       157 AALNL 161
1G5J_A       154 TFVEL 158
2A5Y_A       176 DFMTL 180
1TY4_A       156 DFXTL 160
gi 154705494 152 GFLIF 156
gi 156388833 133 RFQQV 137
gi 62288024  218 DFMKL 222
gi 55770952  177 AFIQH 181
gi 210127538 564 GFEDF 568
gi 170585368 419 DFFDR 423

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