BCL2A1

General Information

Full gene name:BCL2-related protein A1 Entrez Gene ID:597 Location:15q24.3 Synonyms:BCL2L5, GRS, BFL1, ACC-1, ACC-2, HBPA1 Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP	Distance (bp)	Direction
rs11634397	168579	upstream

NCBI Summary

This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators that are involved in a wide variety of cellular activities such as embryonic development, homeostasis and tumorigenesis. The protein encoded by this gene is able to reduce the release of pro-apoptotic cytochrome c from mitochondria and block caspase activation. This gene is a direct transcription target of NF-kappa B in response to inflammatory mediators, and is up-regulated by different extracellular signals, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), CD40, phorbol ester and inflammatory cytokine TNF and IL-1, which suggests a cytoprotective function that is essential for lymphocyte activation as well as cell survival. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM

OMIM ID:`OMIM ID 601056 `_

NCBI Phenotypes

No phenotypes found linked to this gene.

Gene Ontology

• cytoplasm
• protein binding
• anti-apoptosis
• apoptotic process

KEGG Pathways

• Transcriptional misregulation in cancer
• NF-kappa B signaling pathway

GeneRIFs

• The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1. [PMID 22510878]
• identification of two novel minor histocompatibility antigens, encoded by two separate single nucleotide polymorphisms on a single gene, BCL2A1, and restricted by HLA-A*2402 and B*4403 [PMID 12771180]
• The C terminus of A1 did not function as a membrane anchor; it serves a dual function by controlling the stability of A1 and by amplifying the capacity of the protein to protect cells against apoptosis. [PMID 16551634]
• High expression of bfl-1 contributes to the apoptosis resistant phenotype in B-cell chronic lymphocytic leukemia [PMID 15499630]
• Reconstituted Complex; Two-hybrid [PMID 10753914]
• expression in urethral epithelium upregulated by Neisseria gonorrhoeae PorB IB and upregulation dependent on NF-kappaB activation [PMID 15501771]
• C/EBP beta overexpression significantly upregulated promoter activities of IL-8, COX-2, and anti-apoptotic Bfl-1 genes in prostate cancer cells. [PMID 18512730]
• Epstein Barr virus LMP1 drives bfl-1 promoter activity through interactions with components of the tumor necrosis factor receptor (TNFR)/CD40 signaling pathway; evidence presented that this process is NF-kappa B dependent [PMID 14747545]
• role for NF-kappa B in bfl-1 transcription [PMID 12665576]
• These findings are the first indication that Bfl-1 plays a crucial role in setting the elevated threshold of resistance of this malignant cell type to apoptosis [PMID 21491422]
• Protein-peptide; Two-hybrid [PMID 15694340]
• Protein-peptide [PMID 15694340]
• Protein-peptide; Reconstituted Complex; Two-hybrid [PMID 15694340]
• Protein-peptide [PMID 15694340]
• Protein-peptide [PMID 15694340]
• Protein-peptide [PMID 15694340]
• Noxa interacts with A1. This interaction was modelled on a demonstrated interaction between human Noxa and mouse A1. [PMID 15694340]
• Bid interacts with A1. This interaction was modelled on a demonstrated interaction between human Bid and mouse A1. [PMID 15694340]
• Hrk interacts with A1. This interaction was modelled on a demonstrated interaction between human Hrk and mouse A1. [PMID 15694340]
• Puma interacts with A1. This interaction was modelled on a demonstrated interaction between human Puma and mouse A1. [PMID 15694340]
• Bad interacts with A1. This interaction was modelled on a demonstrated interaction between human Bad and mouse A1. [PMID 15694340]
• Bik interacts with A1. This interaction was modelled on a demonstrated interaction between human Bik and mouse A1. [PMID 15694340]
• Observational study of gene-disease association. (HuGE Navigator) [PMID 20855536]
• A1 and A20 are both required for optimal protection from apoptosis (A1) and inflammation (A20) in conditions leading to renal damage [PMID 16164629]
• Results clearly indicated that differential expression of bfl-1/A1 in M. tuberculosis H37Rv and M. tuberculosis H37Ra infected THP-1 cells probably account for the difference in infection outcome. [PMID 18206119]
• Negative Genetic [PMID 22318606]
• Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [PMID 20628086]
• Inhibition of Mcl-1 and A1 strongly induced cell death in some melanoma cell lines. [PMID 22292048]
• Bfl-1/A1 mRNA is not expressed in these cell lines, however, its expression is markedly induced by ATRA treatment in NB4 and HL-60 cells, but not in R4 or HL-60/Res cells, which correlates with inhibition of apoptosis. [PMID 16572199]
• Defective ubiquitin-mediated degradation of antiapoptotic Bfl-1 predisposes to lymphoma. [PMID 20185581]
• confers protection from hydrogen peroxide- and peroxynitrite- induced apoptosis in neutrophils and HL-60 cells [PMID 14966372]
• Bfl-1 associates with tBid to prevent activation of proapoptotic Bax and Bak, and it also interacts directly with Bak to antagonize Bak-mediated cell death, similar to myeloid cell factor (Mcl)-1. [PMID 17724464]
• Two-hybrid [PMID 9731710]
• the level of Bfl-1 gene expression was higher in more advanced breast cancers than in early cancers; it seems that the increased expression of the Bfl-1 gene serves as a contributory factor in breast cancer in the same way that another group of genes [PMID 12692420]
• The expression of BCL2A1 was compared in two inbred strains of mice. [PMID 14981542]
• Amphipathic tail-anchoring peptide (ATAP) targets specifically to mitochondria, and induces caspase-dependent apoptosis that does not require Bax or Bak. [PMID 17666431]
• Two-hybrid [PMID 9356461]
• Specific downregulation of bfl-1 using siRNA induced apoptosis in resistant cells. Our data suggest that bfl-1 contributes to chemoresistance and might be a therapeutic target in B-CLL. [PMID 17726463]
• the amphipathic character of Bfl-1 C-terminal helix alpha9 is required for the anchorage of Bfl-1 to the mitochondria and regulation the antiapoptotic function Bfl-1 [PMID 19759007]
• the known polymorphisms of exon 1 and a novel polymorphism in the promoter region provide evidence for an association between bfl-1 polymorphisms and genetic predisposition to atopic dermatitis [PMID 17121585]
• performed a Bfl-1 deletion study in order to elucidate the underlying mechanism of GFP-Bfl-1-induced cell death [PMID 15696550]
• Oxidative stress induces the expression of Bfl-1 via NF-kappaB activation, and this early-response gene protects cells from Fas-mediated apoptosis. [PMID 15592513]
• Bfl-1 importantly regulates lung cancer cell sensitivity to gemcitabine. [PMID 21843371]
• EBNA2 trans-activates bfl-1, which requires CBF1 (or RBP-J kappa). [PMID 16873269]
• While TNFalpha had no effect on MCL-1 transcription, it induced expression of another antiapoptotic molecule, BFL-1. [PMID 17942758]
• Levels of A1/Bfl-1 are reduced in T cells as a result of HIV-1 Vpu-mediated inhibition of NF-kappa B activation [PMID 11696595]
• Bcl-2 family member Bfl-1/A1 sequesters truncated bid to inhibit is collaboration with pro-apoptotic Bak or Bax. [PMID 11929871]
• Affinity Capture-Western [PMID 11929871]
• Co-crystal Structure [PMID 22615379]
• Bfl-1/A1 negatively regulates autophagy and expression of Bfl-1/A1 in H37Rv infected macrophages [PMID 21167304]
• targeting mHags encoded not only by HMHA1, whose aberrant expression in solid tumors has been reported, but also BCL2A1 may bring about beneficial selective graft-versus-tumor effects [PMID 18414982]
• The crystal structure of Bfl-1, the last anti-apoptotic Bcl-2 family member to be structurally characterized, in complex with a peptide corresponding to the BH3 region of the pro-apoptotic protein Bim is presented. [PMID 18812174]
• results suggest that Anaplasma phagocytophilum inhibits human neutrophil apoptosis via transcriptional upregulation of bfl-1 and inhibition of mitochondria-mediated activation of caspase 3 [PMID 15617521]

PubMed Articles

Recent articles:

• Wu H et al. “Structural basis for substrate specificity and catalysis of human histone acetyltransferase 1.” Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):8925-30. PMID 22615379
• Karrich JJ et al. “The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1.” Blood. 2012 May 31;119(22):5191-200. PMID 22510878
• Lin YY et al. “Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK.” Nature. 2012 Feb 8;482(7384):251-5. PMID 22318606
• Senft D et al. “Selective induction of cell death in melanoma cell lines through targeting of Mcl-1 and A1.” PLoS One. 2012;7(1):e30821. PMID 22292048
• Loughran ST et al. “Bfl-1 is a crucial pro-survival nuclear factor-κB target gene in Hodgkin/Reed-Sternberg cells.” Int J Cancer. 2011 Dec 15;129(12):2787-96. PMID 21491422
• Kim MK et al. “The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-κB activity and down-regulating Bfl-1.” Mol Cancer. 2011 Aug 16;10:98. PMID 21843371
• Kathania M et al. “Bfl-1/A1 acts as a negative regulator of autophagy in mycobacteria infected macrophages.” Int J Biochem Cell Biol. 2011 Apr;43(4):573-85. PMID 21167304
• Flachsbart F et al. “Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.” Mutat Res. 2010 Dec 10;694(1-2):13-9. PMID 20800603
• Kelly JL et al. “Germline variation in apoptosis pathway genes and risk of non-Hodgkin’s lymphoma.” Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2847-58. PMID 20855536
• Bailey SD et al. “Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.” Diabetes Care. 2010 Oct;33(10):2250-3. PMID 20628086

Top Pubmed articles linked to gene BCL2A1 matching any search term:

• Flachsbart F et al. “Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.” Mutat Res. 2010 Dec 10;694(1-2):13-9. PMID 20800603
• Bailey SD et al. “Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.” Diabetes Care. 2010 Oct;33(10):2250-3. PMID 20628086
• Sarkar SA et al. “Cytokine-mediated induction of anti-apoptotic genes that are linked to nuclear factor kappa-B (NF-kappaB) signalling in human islets and in a mouse beta cell line.” Diabetologia. 2009 Jun;52(6):1092-101. PMID 19343319