.. _BCL2A1: BCL2A1 ^^^^^^ .. contents:: :local: 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 | +------------+---------------+-----------+ .. _BCL2A1 Gene summary: 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 ID 601056 : http://omim.org/entry/601056 .. _BCL2A1 OMIM Text: OMIM **** :OMIM ID: `OMIM ID 601056 `_ .. _BCL2A1 Phenotype: NCBI Phenotypes *************** No phenotypes found linked to this gene. .. _BCL2A1 GO Term: Gene Ontology ************* * cytoplasm * protein binding * anti-apoptosis * apoptotic process .. _BCL2A1 Pathway: KEGG Pathways ************* * `Transcriptional misregulation in cancer `_ * `NF-kappa B signaling pathway `_ .. _BCL2A1 GeneRIF: 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`_] .. _PMID 22510878: http://www.ncbi.nlm.nih.gov/pubmed/22510878 .. _PMID 12771180: http://www.ncbi.nlm.nih.gov/pubmed/12771180 .. _PMID 16551634: http://www.ncbi.nlm.nih.gov/pubmed/16551634 .. _PMID 15499630: http://www.ncbi.nlm.nih.gov/pubmed/15499630 .. _PMID 10753914: http://www.ncbi.nlm.nih.gov/pubmed/10753914 .. _PMID 15501771: http://www.ncbi.nlm.nih.gov/pubmed/15501771 .. _PMID 18512730: http://www.ncbi.nlm.nih.gov/pubmed/18512730 .. _PMID 14747545: http://www.ncbi.nlm.nih.gov/pubmed/14747545 .. _PMID 12665576: http://www.ncbi.nlm.nih.gov/pubmed/12665576 .. _PMID 21491422: http://www.ncbi.nlm.nih.gov/pubmed/21491422 .. _PMID 15694340: http://www.ncbi.nlm.nih.gov/pubmed/15694340 .. _PMID 20855536: http://www.ncbi.nlm.nih.gov/pubmed/20855536 .. _PMID 16164629: http://www.ncbi.nlm.nih.gov/pubmed/16164629 .. _PMID 18206119: http://www.ncbi.nlm.nih.gov/pubmed/18206119 .. _PMID 22318606: http://www.ncbi.nlm.nih.gov/pubmed/22318606 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 22292048: http://www.ncbi.nlm.nih.gov/pubmed/22292048 .. _PMID 16572199: http://www.ncbi.nlm.nih.gov/pubmed/16572199 .. _PMID 20185581: http://www.ncbi.nlm.nih.gov/pubmed/20185581 .. _PMID 14966372: http://www.ncbi.nlm.nih.gov/pubmed/14966372 .. _PMID 17724464: http://www.ncbi.nlm.nih.gov/pubmed/17724464 .. _PMID 9731710: http://www.ncbi.nlm.nih.gov/pubmed/9731710 .. _PMID 12692420: http://www.ncbi.nlm.nih.gov/pubmed/12692420 .. _PMID 14981542: http://www.ncbi.nlm.nih.gov/pubmed/14981542 .. _PMID 17666431: http://www.ncbi.nlm.nih.gov/pubmed/17666431 .. _PMID 9356461: http://www.ncbi.nlm.nih.gov/pubmed/9356461 .. _PMID 17726463: http://www.ncbi.nlm.nih.gov/pubmed/17726463 .. _PMID 19759007: http://www.ncbi.nlm.nih.gov/pubmed/19759007 .. _PMID 17121585: http://www.ncbi.nlm.nih.gov/pubmed/17121585 .. _PMID 15696550: http://www.ncbi.nlm.nih.gov/pubmed/15696550 .. _PMID 15592513: http://www.ncbi.nlm.nih.gov/pubmed/15592513 .. _PMID 21843371: http://www.ncbi.nlm.nih.gov/pubmed/21843371 .. _PMID 16873269: http://www.ncbi.nlm.nih.gov/pubmed/16873269 .. _PMID 17942758: http://www.ncbi.nlm.nih.gov/pubmed/17942758 .. _PMID 11696595: http://www.ncbi.nlm.nih.gov/pubmed/11696595 .. _PMID 11929871: http://www.ncbi.nlm.nih.gov/pubmed/11929871 .. _PMID 22615379: http://www.ncbi.nlm.nih.gov/pubmed/22615379 .. _PMID 21167304: http://www.ncbi.nlm.nih.gov/pubmed/21167304 .. _PMID 18414982: http://www.ncbi.nlm.nih.gov/pubmed/18414982 .. _PMID 18812174: http://www.ncbi.nlm.nih.gov/pubmed/18812174 .. _PMID 15617521: http://www.ncbi.nlm.nih.gov/pubmed/15617521 .. _BCL2A1 Pubmed: 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`_ .. _PMID 21491422: http://www.ncbi.nlm.nih.gov/pubmed/21491422 .. _PMID 22510878: http://www.ncbi.nlm.nih.gov/pubmed/22510878 .. _PMID 20855536: http://www.ncbi.nlm.nih.gov/pubmed/20855536 .. _PMID 21843371: http://www.ncbi.nlm.nih.gov/pubmed/21843371 .. _PMID 20800603: http://www.ncbi.nlm.nih.gov/pubmed/20800603 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 22615379: http://www.ncbi.nlm.nih.gov/pubmed/22615379 .. _PMID 21167304: http://www.ncbi.nlm.nih.gov/pubmed/21167304 .. _PMID 22292048: http://www.ncbi.nlm.nih.gov/pubmed/22292048 .. _PMID 22318606: http://www.ncbi.nlm.nih.gov/pubmed/22318606 *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`_ .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 20800603: http://www.ncbi.nlm.nih.gov/pubmed/20800603 .. _PMID 19343319: http://www.ncbi.nlm.nih.gov/pubmed/19343319