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Conserved domains on  [gi|315583623]
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Chain C, Induced myeloid leukemia cell differentiation protein Mcl-1

Protein Classification

Bcl-2 family protein( domain architecture ID 10160139)

Bcl-2 (B-cell lymphoma 2) family protein 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

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Bcl-2_like cd06845
Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This ...
 38-181 1.26e-44

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: 144.78  E-value: 1.26e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623  38 YRQSLEIISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVF 117
Cdd:cd06845    1 DEITRRLARDYLRYRLGEPETPNSPLPSGSPPSEVAETLRRVGDELEEKHRRLFENMCRQLNISPDNAYEVFQEVARELF 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 315583623 118 SDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVRTKRDWLVKQRGWDGFVEF 181
Cdd:cd06845   81 EDGGINWGRIVALFAFGGRLAVKCVEQGLPELVRSIAEWTSDFLEENLADWIQENGGWDGFVEF 144
RNase_A super family cl00128
RNase A family, or Pancreatic RNases family; includes vertebrate RNase homologs to the bovine ...
 5-26 1.57e-04

RNase A family, or Pancreatic RNases family; includes vertebrate RNase homologs to the bovine pancreatic ribonuclease A (RNase A). Many of these enzymes have special biological activities; for example, some stimulate the development of vascular endothelial cells, dendritic cells, and neurons, are cytotoxic/anti-tumoral and/or anti-pathogenic. RNase A is involved in endonucleolytic cleavage of 3'-phosphomononucleotides and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates. The catalytic mechanism is a transphosphorylation of P-O 5' bonds on the 3' side of pyrimidines and subsequent hydrolysis to generate 3' phosphate groups. The RNase A family proteins have a conserved catalytic triad (two histidines and one lysine); recently some family members lacking the catalytic residues have been identified. They also share three or four disulfide bonds. The most conserved disulfide bonds are close to the N and C termini and contribute most significantly to the conformational stability. 8 RNase A homologs had initially been identified in the human genome, pancreatic RNase (RNase 1), Eosinophil Derived Neurotoxin (EDN/RNASE 2), Eosinophil Cationic Protein (ECP/RNase 3), RNase 4, Angiogenin (RNase 5), RNase 6 or k6, the skin derived RNase (RNase 7) and RNase 8. These eight human genes are all located in a cluster on chromosome 14. Recent genomic analysis has extended the family to 13 sequences. However only the first eight identified human RNases, which are refered to as "canonical" RNases, contain the catalytic residues required for RNase A activity. The new genes corresponding to RNases 9-13 are also located in the same chromosome cluster and seem to be related to male-reproductive functions. RNases 9-13 have the characteristic disulfide bridge pattern but are unlikely to share RNase activity. The RNase A family most likely started off in vertebrates as a host-defense protein, and comparative analysis in mammals and birds indicates that the family may have originated from a RNase 5-like gene. This hypothesis is supported by the fact that only RNase 5-like RNases have been reported outside the mammalian class. The RNase 5 group would therefore be the most ancient form of this family, and all other members would have arisen during mammalian evolution.


The actual alignment was detected with superfamily member smart00092:

Pssm-ID: 469623  Cd Length: 123  Bit Score: 39.58  E-value: 1.57e-04
                           10        20
                   ....*....|....*....|..
gi 315583623     5 KETAAAKFERQHMDSPDLGTDD 26
Cdd:smart00092   1 KETRAQKFLRQHIDSTPSSSSS 22
 
Name Accession Description Interval E-value
Bcl-2_like cd06845
Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This ...
 38-181 1.26e-44

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: 144.78  E-value: 1.26e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623  38 YRQSLEIISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVF 117
Cdd:cd06845    1 DEITRRLARDYLRYRLGEPETPNSPLPSGSPPSEVAETLRRVGDELEEKHRRLFENMCRQLNISPDNAYEVFQEVARELF 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 315583623 118 SDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVRTKRDWLVKQRGWDGFVEF 181
Cdd:cd06845   81 EDGGINWGRIVALFAFGGRLAVKCVEQGLPELVRSIAEWTSDFLEENLADWIQENGGWDGFVEF 144
BCL smart00337
BCL (B-Cell lymphoma); contains BH1, BH2 regions; (BH1, BH2, (BH3 (one helix only)) and not ...
 76-175 4.24e-36

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: 121.66  E-value: 4.24e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623    76 LRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAE 155
Cdd:smart00337   1 LRRVGDELNKRYERAFSSFSAQLHVTPGTAIELFGEVATELFSDGNINWGRVVALLSFGGALAVKLVQKEDPDLVSRLAS 80

                           90       100
                   ....*....|....*....|
gi 315583623   156 SITDVLVRTKRDWLVKQRGW 175
Cdd:smart00337  81 WLSEFLRETLRSWIRENGGW 100
Bcl-2 pfam00452
Apoptosis regulator proteins, Bcl-2 family;
76-175 7.72e-34

Apoptosis regulator proteins, Bcl-2 family;


Pssm-ID: 459816  Cd Length: 101  Bit Score: 115.82  E-value: 7.72e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623   76 LRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKS-LSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLA 154
Cdd:pfam00452   1 LRRLGDELERKHPELFQNMLNQLLLTPEDTAYElFREVADELFSDGVINWGRVVALFAFAGALAVKLVRQGHPELVRRLA 80

                          90       100
                  ....*....|....*....|.
gi 315583623  155 ESITDVLVRTKRDWLVKQRGW 175
Cdd:pfam00452  81 EWLVDYLEERLADWIIQQGGW 101
bcl-2 TIGR00865
apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the ...
 71-182 6.42e-18

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: 77.94  E-value: 6.42e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623   71 KALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVtNWGRIVTLISFGAFVAkhLKTINQEscI 150
Cdd:TIGR00865  66 AVHQALRRAGDEFERRYRRAFSDMTSQLHITPFTARQSFFQVAAELFRDGV-NWGRIVAFFSFGGALC--VESVNKE--M 140

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 315583623  151 EPLAESI----TDVLVRTKRDWLVKQRGWDGFVEFF 182
Cdd:TIGR00865 141 SELVSRIagwmTEYLNEHLHPWIQENGGWDGFVELY 176
RNAse_Pc smart00092
Pancreatic ribonuclease;
5-26 1.57e-04

Pancreatic ribonuclease;


Pssm-ID: 128403  Cd Length: 123  Bit Score: 39.58  E-value: 1.57e-04
                           10        20
                   ....*....|....*....|..
gi 315583623     5 KETAAAKFERQHMDSPDLGTDD 26
Cdd:smart00092   1 KETRAQKFLRQHIDSTPSSSSS 22
PHA03159 PHA03159
hypothetical protein; Provisional
 91-181 7.19e-03

hypothetical protein; Provisional


Pssm-ID: 165430  Cd Length: 160  Bit Score: 35.75  E-value: 7.19e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623  91 FQGMLRKLDIKNEDDVKSLSRVmIHVFSDGVTNWGRIVTLISFGAFVakhLKTINQE-SCIEplAESITDVLVRT-KRDW 168
Cdd:PHA03159  41 FEALMPDFSICAHDRIKFTGEA-ILLTTEHNTNWGKVVAMISFSAAA---LQTIDEDyKCVA--TSMLSSYIAKSvGANW 114

                         90
                 ....*....|...
gi 315583623 169 LVKQRGWDGFVEF 181
Cdd:PHA03159 115 FIDHGGEKGLVEF 127
 
Name Accession Description Interval E-value
Bcl-2_like cd06845
Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This ...
 38-181 1.26e-44

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: 144.78  E-value: 1.26e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623  38 YRQSLEIISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVF 117
Cdd:cd06845    1 DEITRRLARDYLRYRLGEPETPNSPLPSGSPPSEVAETLRRVGDELEEKHRRLFENMCRQLNISPDNAYEVFQEVARELF 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 315583623 118 SDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVRTKRDWLVKQRGWDGFVEF 181
Cdd:cd06845   81 EDGGINWGRIVALFAFGGRLAVKCVEQGLPELVRSIAEWTSDFLEENLADWIQENGGWDGFVEF 144
BCL smart00337
BCL (B-Cell lymphoma); contains BH1, BH2 regions; (BH1, BH2, (BH3 (one helix only)) and not ...
 76-175 4.24e-36

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: 121.66  E-value: 4.24e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623    76 LRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAE 155
Cdd:smart00337   1 LRRVGDELNKRYERAFSSFSAQLHVTPGTAIELFGEVATELFSDGNINWGRVVALLSFGGALAVKLVQKEDPDLVSRLAS 80

                           90       100
                   ....*....|....*....|
gi 315583623   156 SITDVLVRTKRDWLVKQRGW 175
Cdd:smart00337  81 WLSEFLRETLRSWIRENGGW 100
Bcl-2 pfam00452
Apoptosis regulator proteins, Bcl-2 family;
76-175 7.72e-34

Apoptosis regulator proteins, Bcl-2 family;


Pssm-ID: 459816  Cd Length: 101  Bit Score: 115.82  E-value: 7.72e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623   76 LRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKS-LSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLA 154
Cdd:pfam00452   1 LRRLGDELERKHPELFQNMLNQLLLTPEDTAYElFREVADELFSDGVINWGRVVALFAFAGALAVKLVRQGHPELVRRLA 80

                          90       100
                  ....*....|....*....|.
gi 315583623  155 ESITDVLVRTKRDWLVKQRGW 175
Cdd:pfam00452  81 EWLVDYLEERLADWIIQQGGW 101
bcl-2 TIGR00865
apoptosis regulator; The Bcl-2 (Bcl-2) Family (TC 1.A.21) The Bcl-2 family consists of the ...
 71-182 6.42e-18

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: 77.94  E-value: 6.42e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623   71 KALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVtNWGRIVTLISFGAFVAkhLKTINQEscI 150
Cdd:TIGR00865  66 AVHQALRRAGDEFERRYRRAFSDMTSQLHITPFTARQSFFQVAAELFRDGV-NWGRIVAFFSFGGALC--VESVNKE--M 140

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 315583623  151 EPLAESI----TDVLVRTKRDWLVKQRGWDGFVEFF 182
Cdd:TIGR00865 141 SELVSRIagwmTEYLNEHLHPWIQENGGWDGFVELY 176
RNAse_Pc smart00092
Pancreatic ribonuclease;
5-26 1.57e-04

Pancreatic ribonuclease;


Pssm-ID: 128403  Cd Length: 123  Bit Score: 39.58  E-value: 1.57e-04
                           10        20
                   ....*....|....*....|..
gi 315583623     5 KETAAAKFERQHMDSPDLGTDD 26
Cdd:smart00092   1 KETRAQKFLRQHIDSTPSSSSS 22
PHA03159 PHA03159
hypothetical protein; Provisional
 91-181 7.19e-03

hypothetical protein; Provisional


Pssm-ID: 165430  Cd Length: 160  Bit Score: 35.75  E-value: 7.19e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315583623  91 FQGMLRKLDIKNEDDVKSLSRVmIHVFSDGVTNWGRIVTLISFGAFVakhLKTINQE-SCIEplAESITDVLVRT-KRDW 168
Cdd:PHA03159  41 FEALMPDFSICAHDRIKFTGEA-ILLTTEHNTNWGKVVAMISFSAAA---LQTIDEDyKCVA--TSMLSSYIAKSvGANW 114

                         90
                 ....*....|...
gi 315583623 169 LVKQRGWDGFVEF 181
Cdd:PHA03159 115 FIDHGGEKGLVEF 127
 
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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