Summary: Bcl-2 homology region 4
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This is the Wikipedia entry entitled "Bcl-2 family". More...
Bcl-2 family Edit Wikipedia article
Apoptosis regulator proteins, Bcl-2 family | |||||||||||
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Identifiers | |||||||||||
Symbol | Bcl-2 | ||||||||||
Pfam | PF00452 | ||||||||||
InterPro | IPR000712 | ||||||||||
PROSITE | PDOC00829 | ||||||||||
SCOP2 | 1maz / SCOPe / SUPFAM | ||||||||||
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Apoptosis regulator Bcl-2, BH is a family of evolutionarily related proteins.
Function
Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins. It is controlled by regulators, which have either an inhibitory effect on programmed cell death (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic)[1][2]. Many viruses have found a way of countering defensive apoptosis by encoding their own anti-apoptosis genes preventing their target-cells from dying too soon.
Structure
All proteins belonging to the Bcl-2 family[3] contain either a BH1, BH2, BH3, or BH4 domain. All anti-apoptotic proteins contain BH1 and BH2 domains, some of them contain an additional N-terminal BH4 domain (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the other hand, all pro-apoptotic proteins contain a BH3 domain (except for Bad) necessary for dimerization with other proteins of Bcl-2 family and crucial for their killing activity, some of them also contain BH1 and BH2 domains (Bax, Bak). The BH3 domain is also present in some anti-apoptotic protein, such as Bcl-2 or Bcl-x(L).
Examples
Proteins that are known to contain these domains include vertebrate Bcl-2 (alpha and beta isoforms) and Bcl-x (isoforms (Bcl-x(L) and Bcl-x(S)); mammalian proteins Bax and Bak; mouse protein Bid; Xenopus laevis proteins Xr1 and Xr11; human induced myeloid leukemia cell differentiation protein MCL1 and Caenorhabditis elegans protein ced-9.
Human genes encoding proteins that belong to this family include:
References
- ^ Vaux DL (1993). "A boom time for necrobiology". Curr. Biol. 3 (12): 877–878. PMID 15335822.
- ^ Milliman CL, Korsmeyer SJ, Wang K, Yin XM, Chao DT (1996). "BID: a novel BH3 domain-only death agonist". Genes Dev. 10 (22): 2859–2869. PMID 8918887.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Reed JC, Zha H, Aime-Sempe C, Takayama S, Wang HG (1996). "Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death". Adv. Exp. Med. Biol. 406: 99–112. PMID 8910675.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)
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Bcl-2 homology region 4 Provide feedback
No Pfam abstract.
External database links
SCOP: | 1af3 |
SMART: | BH4 |
Transporter classification: | 1.A.21 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR003093
Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans [ PUBMED:11341280 ]. In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.
Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes [ PUBMED:12631689 ]. At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.
Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 [ PUBMED:9735050 ]. Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily [ PUBMED:9735050 ]. Full-length Bcl-2 proteins feature all four BH domains, seven alpha-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope.
Active cell suicide (apoptosis) is induced by events such as growth factor withdrawal and toxins. It is controlled by regulators, which have either an inhibitory effect on programmed cell death (anti-apoptotic) or block the protective effect of inhibitors (pro-apoptotic) [ PUBMED:15335822 , PUBMED:8918887 ]. Many viruses have found a way of countering defensive apoptosis by encoding their own anti-apoptosis genes preventing their target-cells from dying too soon.
All proteins belonging to the Bcl-2 family [ PUBMED:8910675 ] contain either a BH1, BH2, BH3, or BH4 domain. All anti-apoptotic proteins contain BH1 and BH2 domains, some of them contain an additional N-terminal BH4 domain (Bcl-2, Bcl-x(L), Bcl-w), which is never seen in pro-apoptotic proteins, except for Bcl-x(S). On the other hand, all pro-apoptotic proteins contain a BH3 domain (except for Bad) necessary for dimerisation with other proteins of Bcl-2 family and crucial for their killing activity, some of them also contain BH1 and BH2 domains (Bax, Bak). The BH3 domain is also present in some anti-apoptotic protein, such as Bcl-2 or Bcl-x(L). Proteins that are known to contain these domains include vertebrate Bcl-2 (alpha and beta isoforms) and Bcl-x (isoforms (Bcl-x(L) and Bcl-x(S)); mammalian proteins Bax and Bak; mouse protein Bid; Xenopus laevis proteins Xr1 and Xr11; human induced myeloid leukemia cell differentiation protein MCL1 and Caenorhabditis elegans protein ced-9.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Biological process | regulation of apoptotic process (GO:0042981) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
View options
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (11) |
Full (824) |
Representative proteomes | UniProt (1534) |
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RP15 (60) |
RP35 (214) |
RP55 (554) |
RP75 (814) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Seed (11) |
Full (824) |
Representative proteomes | UniProt (1534) |
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RP15 (60) |
RP35 (214) |
RP55 (554) |
RP75 (814) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Alignment kindly provided by SMART |
Previous IDs: | none |
Type: | Family |
Sequence Ontology: | SO:0100021 |
Author: | SMART |
Number in seed: | 11 |
Number in full: | 824 |
Average length of the domain: | 24.9 aa |
Average identity of full alignment: | 51 % |
Average coverage of the sequence by the domain: | 11.04 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 26 | ||||||||||||
Family (HMM) version: | 20 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the BH4 domain has been found. There are 269 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.