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Conserved domains on  [gi|2462561173|ref|XP_054174942|]
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apoptosis regulator Bcl-2 isoform X3 [Homo sapiens]

Protein Classification

bcl-2 family protein( domain architecture ID 11489818)

bcl-2 family protein similar to Homo sapiens apoptosis regulators, Bcl-2 and BAX

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
bcl-2 TIGR00865
apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the ...
 1-195 8.53e-94

apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the apoptosis regulator, Bcl-X, and its homologues. Bcl-X is a dominant regulator of programmed cell death in mammalian cells. The long form (Bcl-X(L)) displays cell death repressor activity, but the short isoform (Bcl-X(S)) and the b-isoform (Bcl-Xb) promote cell death. Bcl-X(L), Bcl-X(S) and Bcl-Xb are three isoforms derived by alternative RNA splicing. Bcl-X(S) forms heterodimers with Bcl-2. Homologues of Bcl-X include the Bax (rat; 192 aas; spQ63690) and Bak (mouse; 208 aas; spO08734) proteins which also influence apoptosis. Using isolated mitochondria, recombinant Bax and Bak have been shown to induce Dy loss, swelling and cytochrome c release. All of these changes are dependent on Ca2+ and are prevented by cyclosporin A and bongkrekic acid, both of which are known to close permeability transition pores (megachannels). Coimmimoprecipitation studies revealed that Bax and Bak interact with VDAC to form permeability transition pores. Thus, even though they can form channels in artificial membranes at acidic pH, proapoptotic Bcl-2 family proteins (including Bax and Bak) probably induce the mitochondrial permeability transition and cytochrome c release by interacting with permeability transition pores, the most important component for pore fomation of which is VDAC. [Regulatory functions, Other]


:

Pssm-ID: 273308 [Multi-domain]  Cd Length: 213  Bit Score: 272.08  E-value: 8.53e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173   1 MAHAgrtgydNREIVMKYIHYKLSQRGYEWDAGDvgaappgaapapgifssQPGHTPHPAASRDPVARTSPLQTPAAPGA 80
Cdd:TIGR00865   1 MAGS------NRELVMKFISYKLSQRGGSWTAGE-----------------QIMKNGAPLLHGFIQHRAGPMTGETPSEG 57

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173  81 AAgpaLSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVE 160
Cdd:TIGR00865  58 PP---QDPPPSAVHQALRRAGDEFERRYRRAFSDMTSQLHITPFTARQSFFQVAAELFRDGVNWGRIVAFFSFGGALCVE 134

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2462561173 161 SVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGW 195
Cdd:TIGR00865 135 SVNKEMSELVSRIAGWMTEYLNEHLHPWIQENGGW 169
 
Name Accession Description Interval E-value
bcl-2 TIGR00865
apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the ...
 1-195 8.53e-94

apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the apoptosis regulator, Bcl-X, and its homologues. Bcl-X is a dominant regulator of programmed cell death in mammalian cells. The long form (Bcl-X(L)) displays cell death repressor activity, but the short isoform (Bcl-X(S)) and the b-isoform (Bcl-Xb) promote cell death. Bcl-X(L), Bcl-X(S) and Bcl-Xb are three isoforms derived by alternative RNA splicing. Bcl-X(S) forms heterodimers with Bcl-2. Homologues of Bcl-X include the Bax (rat; 192 aas; spQ63690) and Bak (mouse; 208 aas; spO08734) proteins which also influence apoptosis. Using isolated mitochondria, recombinant Bax and Bak have been shown to induce Dy loss, swelling and cytochrome c release. All of these changes are dependent on Ca2+ and are prevented by cyclosporin A and bongkrekic acid, both of which are known to close permeability transition pores (megachannels). Coimmimoprecipitation studies revealed that Bax and Bak interact with VDAC to form permeability transition pores. Thus, even though they can form channels in artificial membranes at acidic pH, proapoptotic Bcl-2 family proteins (including Bax and Bak) probably induce the mitochondrial permeability transition and cytochrome c release by interacting with permeability transition pores, the most important component for pore fomation of which is VDAC. [Regulatory functions, Other]


Pssm-ID: 273308 [Multi-domain]  Cd Length: 213  Bit Score: 272.08  E-value: 8.53e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173   1 MAHAgrtgydNREIVMKYIHYKLSQRGYEWDAGDvgaappgaapapgifssQPGHTPHPAASRDPVARTSPLQTPAAPGA 80
Cdd:TIGR00865   1 MAGS------NRELVMKFISYKLSQRGGSWTAGE-----------------QIMKNGAPLLHGFIQHRAGPMTGETPSEG 57

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173  81 AAgpaLSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVE 160
Cdd:TIGR00865  58 PP---QDPPPSAVHQALRRAGDEFERRYRRAFSDMTSQLHITPFTARQSFFQVAAELFRDGVNWGRIVAFFSFGGALCVE 134

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2462561173 161 SVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGW 195
Cdd:TIGR00865 135 SVNKEMSELVSRIAGWMTEYLNEHLHPWIQENGGW 169
Bcl-2_like cd06845
Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This ...
 86-195 1.76e-47

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.


Pssm-ID: 132900 [Multi-domain]  Cd Length: 144  Bit Score: 152.10  E-value: 1.76e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173  86 LSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRD-GVNWGRIVAFFEFGGVMCVESVNR 164
Cdd:cd06845    28 SGSPPSEVAETLRRVGDELEEKHRRLFENMCRQLNISPDNAYEVFQEVARELFEDgGINWGRIVALFAFGGRLAVKCVEQ 107

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462561173 165 EMSPLVDNIALWMTEYLNRHLHTWIQDNGGW 195
Cdd:cd06845   108 GLPELVRSIAEWTSDFLEENLADWIQENGGW 138
BCL smart00337
BCL (B-Cell lymphoma); contains BH1, BH2 regions; (BH1, BH2, (BH3 (one helix only)) and not ...
 97-195 1.00e-43

BCL (B-Cell lymphoma); contains BH1, BH2 regions; (BH1, BH2, (BH3 (one helix only)) and not BH4(one helix only)). Involved in apoptosis regulation


Pssm-ID: 214626  Cd Length: 100  Bit Score: 141.31  E-value: 1.00e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173   97 LRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDG-VNWGRIVAFFEFGGVMCVESVNREMSPLVDNIAL 175
Cdd:smart00337   1 LRRVGDELNKRYERAFSSFSAQLHVTPGTAIELFGEVATELFSDGnINWGRVVALLSFGGALAVKLVQKEDPDLVSRLAS 80

                           90       100
                   ....*....|....*....|
gi 2462561173  176 WMTEYLNRHLHTWIQDNGGW 195
Cdd:smart00337  81 WLSEFLRETLRSWIRENGGW 100
Bcl-2 pfam00452
Apoptosis regulator proteins, Bcl-2 family;
97-195 3.99e-39

Apoptosis regulator proteins, Bcl-2 family;


Pssm-ID: 459816  Cd Length: 101  Bit Score: 129.69  E-value: 3.99e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173  97 LRQAGDDFSRRYRRDFAEMSSQLHLTP-FTARGRFATVVEELFRDG-VNWGRIVAFFEFGGVMCVESVNREMSPLVDNIA 174
Cdd:pfam00452   1 LRRLGDELERKHPELFQNMLNQLLLTPeDTAYELFREVADELFSDGvINWGRVVALFAFAGALAVKLVRQGHPELVRRLA 80

                          90       100
                  ....*....|....*....|.
gi 2462561173 175 LWMTEYLNRHLHTWIQDNGGW 195
Cdd:pfam00452  81 EWLVDYLEERLADWIIQQGGW 101
 
Name Accession Description Interval E-value
bcl-2 TIGR00865
apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the ...
 1-195 8.53e-94

apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the apoptosis regulator, Bcl-X, and its homologues. Bcl-X is a dominant regulator of programmed cell death in mammalian cells. The long form (Bcl-X(L)) displays cell death repressor activity, but the short isoform (Bcl-X(S)) and the b-isoform (Bcl-Xb) promote cell death. Bcl-X(L), Bcl-X(S) and Bcl-Xb are three isoforms derived by alternative RNA splicing. Bcl-X(S) forms heterodimers with Bcl-2. Homologues of Bcl-X include the Bax (rat; 192 aas; spQ63690) and Bak (mouse; 208 aas; spO08734) proteins which also influence apoptosis. Using isolated mitochondria, recombinant Bax and Bak have been shown to induce Dy loss, swelling and cytochrome c release. All of these changes are dependent on Ca2+ and are prevented by cyclosporin A and bongkrekic acid, both of which are known to close permeability transition pores (megachannels). Coimmimoprecipitation studies revealed that Bax and Bak interact with VDAC to form permeability transition pores. Thus, even though they can form channels in artificial membranes at acidic pH, proapoptotic Bcl-2 family proteins (including Bax and Bak) probably induce the mitochondrial permeability transition and cytochrome c release by interacting with permeability transition pores, the most important component for pore fomation of which is VDAC. [Regulatory functions, Other]


Pssm-ID: 273308 [Multi-domain]  Cd Length: 213  Bit Score: 272.08  E-value: 8.53e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173   1 MAHAgrtgydNREIVMKYIHYKLSQRGYEWDAGDvgaappgaapapgifssQPGHTPHPAASRDPVARTSPLQTPAAPGA 80
Cdd:TIGR00865   1 MAGS------NRELVMKFISYKLSQRGGSWTAGE-----------------QIMKNGAPLLHGFIQHRAGPMTGETPSEG 57

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173  81 AAgpaLSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVE 160
Cdd:TIGR00865  58 PP---QDPPPSAVHQALRRAGDEFERRYRRAFSDMTSQLHITPFTARQSFFQVAAELFRDGVNWGRIVAFFSFGGALCVE 134

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2462561173 161 SVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGW 195
Cdd:TIGR00865 135 SVNKEMSELVSRIAGWMTEYLNEHLHPWIQENGGW 169
Bcl-2_like cd06845
Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This ...
 86-195 1.76e-47

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.


Pssm-ID: 132900 [Multi-domain]  Cd Length: 144  Bit Score: 152.10  E-value: 1.76e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173  86 LSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRD-GVNWGRIVAFFEFGGVMCVESVNR 164
Cdd:cd06845    28 SGSPPSEVAETLRRVGDELEEKHRRLFENMCRQLNISPDNAYEVFQEVARELFEDgGINWGRIVALFAFGGRLAVKCVEQ 107

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462561173 165 EMSPLVDNIALWMTEYLNRHLHTWIQDNGGW 195
Cdd:cd06845   108 GLPELVRSIAEWTSDFLEENLADWIQENGGW 138
BCL smart00337
BCL (B-Cell lymphoma); contains BH1, BH2 regions; (BH1, BH2, (BH3 (one helix only)) and not ...
 97-195 1.00e-43

BCL (B-Cell lymphoma); contains BH1, BH2 regions; (BH1, BH2, (BH3 (one helix only)) and not BH4(one helix only)). Involved in apoptosis regulation


Pssm-ID: 214626  Cd Length: 100  Bit Score: 141.31  E-value: 1.00e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173   97 LRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDG-VNWGRIVAFFEFGGVMCVESVNREMSPLVDNIAL 175
Cdd:smart00337   1 LRRVGDELNKRYERAFSSFSAQLHVTPGTAIELFGEVATELFSDGnINWGRVVALLSFGGALAVKLVQKEDPDLVSRLAS 80

                           90       100
                   ....*....|....*....|
gi 2462561173  176 WMTEYLNRHLHTWIQDNGGW 195
Cdd:smart00337  81 WLSEFLRETLRSWIRENGGW 100
Bcl-2 pfam00452
Apoptosis regulator proteins, Bcl-2 family;
97-195 3.99e-39

Apoptosis regulator proteins, Bcl-2 family;


Pssm-ID: 459816  Cd Length: 101  Bit Score: 129.69  E-value: 3.99e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462561173  97 LRQAGDDFSRRYRRDFAEMSSQLHLTP-FTARGRFATVVEELFRDG-VNWGRIVAFFEFGGVMCVESVNREMSPLVDNIA 174
Cdd:pfam00452   1 LRRLGDELERKHPELFQNMLNQLLLTPeDTAYELFREVADELFSDGvINWGRVVALFAFAGALAVKLVRQGHPELVRRLA 80

                          90       100
                  ....*....|....*....|.
gi 2462561173 175 LWMTEYLNRHLHTWIQDNGGW 195
Cdd:pfam00452  81 EWLVDYLEERLADWIIQQGGW 101
BH4 smart00265
BH4 Bcl-2 homology region 4;
7-33 2.42e-10

BH4 Bcl-2 homology region 4;


Pssm-ID: 128561  Cd Length: 27  Bit Score: 53.43  E-value: 2.42e-10
                           10        20
                   ....*....|....*....|....*..
gi 2462561173    7 TGYDNREIVMKYIHYKLSQRGYEWDAG 33
Cdd:smart00265   1 SRLDNRELVVDYVTYKLSQNGYEWDAG 27
BH4 pfam02180
Bcl-2 homology region 4;
8-32 5.01e-09

Bcl-2 homology region 4;


Pssm-ID: 426639  Cd Length: 25  Bit Score: 49.87  E-value: 5.01e-09
                          10        20
                  ....*....|....*....|....*
gi 2462561173   8 GYDNREIVMKYIHYKLSQRGYEWDA 32
Cdd:pfam02180   1 RLDNRELVVDYVSYKLSQRGYEWEH 25
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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