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.
Links
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Statistics
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PSSM-Id: 132900
Aligned: 86 rows
Threshold Bit Score: 75.8324
Created: 8-Jan-2008
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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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
  • Structure:1YSW: Human Bcl-2 binds the inhibitor ABT-737, a BH3-only mimetic, contacts at 4A
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                                                           ## ##    #  ##               
2YV6_A         8 DTEEVFRSYVFYRHQqeqeaegvaapadpexvtlplqpsstxGQVGRQLAIIGDDINr-rYDSEFQTxlqhlqptaenaY 86  human
1G5J_A         8 SNRELVVDFLSYKLSqkgyswsqfsdve--enrteapegtesEAVKQALREAGDEFEl-rYRRAFSDltsqlhitpgtaY 84  human
2A5Y_A        32 DIEGFVVDYFTHRIRqngmewfg-----------apglpsgvQPEHEMMRVMGTIFEk-kHAENFETfseqllavprisF 99  nematode
1TY4_A        12 DIEGFVVDYFTHRIRqngxewfg-----------apglpcgvQPEHEXXRVXGTIFEk-kHAENFETfceqllavprisF 79  nematode
ABS84173      18 SYVGEKLRKKGLKIRgyegee----------------lkppvIEIAKTLQRVGDELEs-aNTDFFKNmcdqlqitpstaY 80  Hydra vulgaris
XP_001634697   4 DFIGYKLRQNNIFLEgfnm--------------------espTKASKHLRIVADELIa-dNSELFHSmcdqlhltpistY 62  starlet sea ane...
P41957        81 DYFTYRIAQNGLDWYdapal------------------pdgvQKEHEMMRSLGTIFEk-rHMEMFENfseqllavpkisF 141 Caenorhabditis ...
CAF74919      44 SYIVNLLRREGLNHIadqfap----------------vgstrANGYQLIERIVCQLEderSQQFIDIlrglei-dqqnlR 106 Suberites domun...
EEA75220     435 DYVFYKLNKKGLPWPnapp-------------------lpppTDAHRLMRELGDKFEe-rYREQFDEmgdqlhltpdtaY 494 Florida lancelet
XP_001897456 274 TIQSYVTDYIQYRVHlhnvycpr-----------lpeipvsdDYRFELIRAVALIFEk-kHAEELTNmvttlclngrltF 341 agent of lympha...

Feature 1        ##  ##  ##            # ## ##   #   #                                           
2YV6_A        87 EYFTKIATSLFes-------gINWGRVVALLGFGYRLALHVYQhg--ltGFLGQVTRFVVDFXLHHciARWIAQR-GGWV 156 human
1G5J_A        85 QSFEQVVNELFrd-------gVNWGRIVAFFSFGGALCVESVDke--mqVLVSRIAAWMATYLNDHl-EPWIQEN-GGWD 153 human
2A5Y_A       100 SLYQDVVRTVGnaqt--dqspMSYGRLIGLISFGGFVAAKMMEsve-lqGQVRNLFVYTSLFIKTRi-RNNWKEHnRSWD 175 nematode
1TY4_A        80 SPYQDVVRTVGnaqt--dqcpXSYGRLIGLISFGGFVAAKXXEsve-lqGQVRNLFVYTSLFIKTRi-RNNWKEHnRSWD 155 nematode
ABS84173      81 PTFQSIADEIFvs-------gKNWGRVVAFLTFGGNFAVHCALradmgeEYVDRVVNWISKYMAVNl-DYWINQQ-GGWD 151 Hydra vulgaris
XP_001634697  63 PTFVGIANEIFqs-------gKNWGRVVAFLAFGATLAVYCAQree-lhELVNDIVEWVSRYMDQNl-SCWIREN-GGWV 132 starlet sea ane...
P41957       142 SLYQEVVQTVGnssn--tpcpMSYGRLIGLISFGGMVAAKMMEsae-lqGQVRNLLMYTSLFIKTRirQSWKEHN-RSWA 217 Caenorhabditis ...
CAF74919     107 ITYQTIVGEIFnd-------gVHWGRIVAFLVFSGHLAVHCARsng-leNRVRDVVEWTEAEMRLRv-HQWVEDR-GGWE 176 Suberites domun...
EEA75220     495 QKYHNVVAELFre-------gVRWGRLVALVAFTGACTVTAVEre--mpQFVDRYVDWTVQYIDNNl-AQWLQEN-GGWE 563 Florida lancelet
XP_001897456 342 QRYVEVVECFAhndddesnkqLSYGRLVALIAFAGLVAMKLCDlq--lfTEVSMIAPYTSKFLHKRivLTWPQDR-RSWE 418 agent of lympha...

Feature 1            #
2YV6_A       157 AALNL 161 human
1G5J_A       154 TFVEL 158 human
2A5Y_A       176 DFMTL 180 nematode
1TY4_A       156 DFXTL 160 nematode
ABS84173     152 GFLIF 156 Hydra vulgaris
XP_001634697 133 RFQQV 137 starlet sea anemone
P41957       218 DFMKL 222 Caenorhabditis briggsae
CAF74919     177 AFIQH 181 Suberites domuncula
EEA75220     564 GFEDF 568 Florida lancelet
XP_001897456 419 DFFDR 423 agent of lymphatic filariasis

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