BCL2 (Bcl-2)

BCL2 (B-cell leukemia/lymphoma 2, N-Histidine-tagged), also known as Bcl-2, belongs to the Bcl-2 family. Bcl-2 family proteins regulate and contribute to programmed cell death or apoptosis. It is a large protein family and all members contain at least one of four BH (bcl-2 homology) domains. Certain members such as Bcl-2, Bcl-xl and Mcl1 are anti-apoptotic, whilst others are pro-apoptotic. Most Bcl-2 family members contain a C-terminal transmembrane domain that functions to target these proteins to the outer mitochondrial and other intracellular membranes. It is expressed in a variety of tissues. BCL2 blocks the apoptotic death of some cells such as lymphocytes. It also regulates cell death by controlling the mitochondrial membrane permeability and inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends.

BCL2 (Bcl-2) Related Areas

Cancer>>Apoptosis>>Bcl-2 Family>> BCL2 / Bcl-2

BCL2 (Bcl-2) Alternative Names

Bcl-2, PPP1R50, apoptosis regulator Bcl-2, protein phosphatase 1, regulatory subunit 50 [Homo sapiens]

AW986256, Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik, B-cell leukemia/lymphoma 2, apoptosis regulator Bcl-2 [Mus musculus]

Summaries for BCL2 (Bcl-2)

Entrez Gene summary for BCL2:

This BCL2 gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends. [provided by RefSeq, Jul 2008]

Wikipedia summary for BCL2:

BCL2 (B-cell lymphoma 2) is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. BCL2derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. BCL2 orthologs have been identified in numerous mammals for which complete genome data are available. The two isoforms of BCL2, Isoform 1, also known as 1G5M, and Isoform 2, also known as 1G5O/1GJH, exhibit similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, suggest differences in antiapoptotic activity for the two isoforms

Human BCL2 (Bcl-2) Protein General Information

 

• Protein names: Apoptosis regulator Bcl-2
• Sequence length: 239 AA.
• Domain: The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
• Sequence similarities: BCL2 belongs to the Bcl-2 family.
• Post-translational modification: Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy. Dephosphorylated by protein phosphatase 2A (PP2A)
• Subunit structure: BCL2 forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity. BCL2 interacts with EI24. BCL2 also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. BCL2 interacts with BAG1 in an ATP-dependent manner. BCL2 interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2. BCL2 interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex.
• Subcellular location: Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein
• Tissue specificity: BCL2 is expressed in a variety of tissues.
• Involvement in disease: Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.

General information above from UniProt

Function for BCL2 (Bcl-2) Protein

UniProtKB:

BCL2 suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. BCL2 regulates cell death by controlling the mitochondrial membrane permeability. BCL2 appears to function in a feedback loop system with caspases. BCL2 inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).

Genatlas:

• BCL2 blocks the apoptotic death of cells such as lymphocytes
• BCL2 can target RAF1 to the mitochondria
• BCL2 inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to APAF1
• BCL2 is prediction of prognosis in diffuse large B-cell lymphoma
• BCL2 has antiautophagy function (inhibiting the formation of BECN1/PI3K complex) that may help to maintain autophagy at levels compatible with cell survival
• BCL2 is prototypic anti-apoptotic protein involved in the regulation of apoptosis
• BCL2 functions as an activator of the AKT1 signaling pathway in pancreatic cancer
• BCL2 plays critical roles in the control of apoptosis
• BCL2 is essential mediator for the cancer-specific cell survival function of ATF5 in glioblastoma and breast cancer cells
• BCL2 plays an essential role in mediating the cell type-dependent prosurvival function of ATF5
• in addition to BCL2's canonical anti-apoptotic role, negatively impacts genome stability

Homology for human BCL2 (Bcl-2)

• ortholog to Bcl2, Mus musculus
• ortholog to Bcl2, Rattus norvegicus
• ortholog to BCL2, Pan troglodytes

Phenotype Information for BCL2 (Bcl-2)

• Gene/Locus: BCL2
• Phenotype: Leukemia/lymphoma, B-cell, 2

Phenotype Information for BCL2 from OMIM (Online Mendelian Inheritance in Man)

Drugs for BCL2 (Bcl-2)

Drugs for BCL2 from TTD (Therapeutic Targets Database)