BCL BCL (B-Cell lymphoma); contains BH1, BH2 regions
SMART ACC:	SM000337
Description:	(BH1, BH2, (BH3 (one helix only)) and not BH4(one helix only)). Involved in apoptosis regulation
InterPro ACC:	IPR046371
InterPro abstract:	B cell CLL/lymphoma-2 (Bcl-2) and related proteins comprise the Bcl-2 family. 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 ]. Though originally characterised with … expand B cell CLL/lymphoma-2 (Bcl-2) and related proteins comprise the Bcl-2 family. 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 ]. Though originally characterised with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis, the members of the Bcl-2 family are involved in numerous cellular pathways [ PUBMED:20159550 ]. Bcl-2 and its relatives are functionally classified as either antiapoptotic or proapoptotic. All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Antiapoptotic BCL-2 proteins contain four Bcl-2 homology domains (BH1-4). The major antiapoptotic proteins are Bcl-2-related gene A1 (A1), Bcl-2, Bcl-2-related gene, long isoform (Bcl-xL), Bcl-w, and myeloid cell leukemia 1 (MCL-1). They preserve outer mitochondrial membrane (OMM) integrity by directly inhibiting the proapoptotic Bcl-2 proteins [ PUBMED:20159550 ]. The proapoptotic Bcl-2 members are divided into the effector proteins and the BH3-only proteins. The effector proteins Bcl-2 antagonist killer 1 (BAK) and Bcl-2-associated x protein (BAX) were originally described to contain only BH1-3; however, structure-based alignments revealed a conserved BH4 motif [ PUBMED:18551131 ]. Upon activation BAK and BAX homo-oligomerise into proteolipid pores within the OMM to promote MOMP (mitochondrial outer membrane permeabilisation). The BH3-only proteins function in distinct cellular stress scenarios and are subdivided based on their ability to interact with the antiapoptotic or both the antiapoptotic and the effector proteins [ PUBMED:20159550 ]. This entry covers the Bcl-2 homology regions 1, 2 and 3 (BH1-3). collapse
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 4 976 BCL domains in 4 959 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing BCL domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing BCL domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the BCL domain is listed below. Automatically-derived, secondary literature is also available.

Disease genes where sequence variants are found in this domain

UniRef sequences and OMIM curated human diseases associated with missense mutations within the BCL domain.

Protein	Description	Disease / phenotype
BAX_HUMAN		OMIM:600040 : Colorectal cancer ; T-cell acute lymphoblastic leukemia

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a BCL domain which could be assigned to a KEGG orthologous group, and not all proteins containing BCL domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

PROSITE	BCL2_FAMILY
InterPro	IPR046371
Pfam	Bcl-2