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BCL2L14 (BCL2-like 14 (apoptosis facilitator))

Written2013-08Mark R Pickard, Gwyn T Williams
Institute of Science, Technology in Medicine, Keele University, Keele, United Kingdom

(Note : for Links provided by Atlas : click)

Identity

Alias_namesBCL2-like 14 (apoptosis facilitator)
Alias_symbol (synonym)BCLG
BCL-G
Other alias
HGNC (Hugo) BCL2L14
LocusID (NCBI) 79370
Atlas_Id 774
Location 12p13.2  [Link to chromosome band 12p13]
Location_base_pair Starts at 12071468 and ends at 12099693 bp from pter ( according to hg19-Feb_2009)  [Mapping BCL2L14.png]
Local_order Flanked by ETV6 and LOC100506248 (prothymosin alpha-like).
Fusion genes
(updated 2016)
BCL2L14 (12p13.2) / ETV6 (12p13.2)MSRB3 (12q14.3) / BCL2L14 (12p13.2)
Note BCL2L14 encodes members of the Bcl-2 family. Proteins in the family contain at least one Bcl-2 homology (BH) domain (of which there are four in total; termed BH1-4) and regulate cell life/death decisions at the level of the mitochondrion (intrinsic apoptotic pathway). Family members can be broadly divided into anti-apoptotic and pro-apoptotic regulators; the former class includes Bcl-2, Mcl-1 and Bcl-xL, which contain all four BH domains, whereas the latter class can be subdivided into: i. effector molecules, such as the multidomain (BH1-3) Bax and Bak molecules, and ii. upstream sentinel BH3-only proteins (e.g. Bim, Bid, Puma and Noxa). Bcl-2 family members undergo complex protein-protein interactions with each other. Crucially, it is the balance between pro- and anti-apoptotic Bcl-2 family members which determines if activation of the mitochondrial (intrinsic) apoptotic pathway occurs and, ultimately, whether the cell lives or dies.
Human BCL2L14 was first characterized in 2001 (Guo et al., 2001). Two full-length transcripts, encoding long and short protein isoforms (termed Bcl-GL and Bcl-GS), were isolated. Bcl-GS is a BH3-only protein, whereas Bcl-GL unusually contains only BH2 and BH3 domains (Guo et al., 2001); a similar Bcl-2 family member, termed Bfk, has subsequently been identified (Coultas et al., 2003). The two Bcl-G isoforms exhibit pro-apoptotic activity, but Bcl-GL is less potent than Bcl-GS, attributed to negative regulation by the BH2 domain (Guo et al., 2001). Differences are also apparent between Bcl-GS and Bcl-GL in their patterns of tissue expression (restricted to testes versus ubiquitous), subcellular distribution (cytosolic organelles versus diffuse) and interaction with other Bcl-2 family members (Bcl-GS only shows interaction) (Guo et al., 2001). Pig and mouse BCL2L14 encode only one BclG protein isoform (termed pBcl-G and mBcl-G, respectively), which contains BH2 and BH3 domains, similar to Bcl-GL (Giam et al., 2012a; Jiang et al., 2012). Phylogenetic analysis of Bcl-G protein sequences from 14 different species has revealed the presence of three different clades comprising human/apes, rodents and pigs/cattle, raising the possibility of species differences in Bcl-G action (Jiang et al., 2012).
The BCL2L14 promoter contains a cAMP responsive element, an interferon-γ-activated site (GAS) and an interferon regulatory factor element (IRF-E); interferon-α and γ co-operatively hyperactivate BCL2L14 expression in hepatoma cells (Zhang et al., 2006). A consensus site for certain proline- and acid rich basic region leucine zipper proteins is also present; binding of thyrotroph embryonic factor (TEF) or albumin D-site-binding protein (DBP) enhances promoter activity, whereas binding of nuclear factor, interleukin-3 regulated (NFIL3) is repressive (Benito et al., 2006). BCL2L14 has also been identified as a p53 target gene; the putative binding site is located within the first intron (Miled et al., 2005). BCL2L14 expression is regulated in a reciprocal manner by protein kinase C (PKC) isozyme signalling; its expression is repressed by PKCε but enhanced by PKCδ (Caino et al., 2011). Along with other apoptotic regulatory genes and the putative tumour suppressor gene, WISP3, BCL2L14 has been identified as a target for oncogenic miR-221 (Vandenboom et al., 2008).
Several different post-translational modifications, which impact upon protein function, have been reported for Bcl-G isoforms. Bcl-GL is a target for phosphorylation, catalysed by the candidate oncoprotein maternal embryonic leucine zipper kinase (MELK), which is overexpressed in breast cancer and a range of other solid tumors (Lin et al., 2007). The N-terminal region (amino acids 12 - 71) of Bcl-GL (conserved in Bcl-GS) is required for this interaction, and its phosphorylation inhibits apoptotic activity (Lin et al., 2007). Furthermore, in mouse cells, mBclG is a target for modification by a ubiquitin-like protein, termed FUBI, which in humans is encoded by the putative tumour suppressor gene FAU (Nakamura and Tanigawa, 2003; Nakamura and Yamaguchi, 2006). The N-terminal region of mBclG appears to be cleaved from the adduct. In mouse macrophages the FUBI/mBclG complex associates with ERKs and inhibits their activation by MEK1; recent work has further demonstrated that the adduct enhances lipopolysaccharide/interferon γ - induced apoptosis (Watanabe et al., 2013). Indeed, in human cells, ectopic expression of FAU promotes apoptosis, and both Fau and BclGL are thought to act in the same pathway, with the pro-apoptotic activity of Fau being mediated via BclGL (Pickard et al., 2009; Pickard et al., 2010; Pickard et al., 2011). Finally, interactions between Bcl-GS and JAB1 (c-Jun activation domain binding protein-1; aka the fifth subunit of the COP9 signalosome or CSN5) have also been reported (Liu et al., 2008). The N-terminal region (amino acids 1 - 67) of Bcl-GS is required for this interaction, and these two genes co-operatively induce apoptosis in HeLa cells; JAB1 inhibits Bcl-2/Bcl-XL binding by the BH3 domain of Bcl-GS and knock-down studies indicate that JAB1 is essential for Bcl-GS to induce apoptosis (Liu et al., 2008).
BCL2L14 lies within 12p12, which is frequently deleted in lymphoid/myeloid malignancies and solid tumours, suggestive of the presence of tumour suppressor gene(s) in this locus (Montpetit et al., 2002). In the case of pre-B acute lymphoblastic leukemia, ETV6 (rather than BCL2L14) is the target of deletions (Montpetit et al., 2004). In advanced prostate cancer however, the minimal deleted region is more distal to the telomere and extends into 12p13 (Kibel et al., 2004); expression mapping has demonstrated reduced BCL2L14 expression (Kibel et al., 2004). BCL2L14 expression is also dysregulated in breast cancer (Pickard et al., 2009), ovarian cancer (Heinzelmann-Schwarz et al., 2006) and in tongue squamous cell carcinoma (Zhang et al., 2013). Mutations in the BH3 domain are not however common occurences in cancer (Soung et al., 2006; Yoo et al., 2007).
BCL2L14 expression is markedly up-regulated in CD4+ T-cells from patients with the autoimmune disorder, systemic lupus erythematosus (SLE) and several lines of evidence implicate this dysregulation in pathogenesis (Luo et al., 2009). Dysregulated expression of BCL2L14 in mammalian cells has also been noted in response to infection with a variety of pathogens (Flori et al., 2008; Mehra et al., 2010; Balas et al., 2011; Singh et al., 2011; Taubert et al., 2010; Almeida et al., 2012; Wang et al., 2012), indicative of a role in innate immunity.

DNA/RNA

 
  Figure 1. Alternative splicing of BCL2L14 yields at least three transcript variants. Note that exons only are drawn to scale and that only those transcript variants for which reference sequences exist are shown. Transcript variants 1 and 4 differ only in their 5'-UTR sequence and produce an identical protein isoform (Bcl-GL), whereas the coding sequence of transcript variant 2 is shorter and gives rise to a protein isoform (Bcl-GS) with a distinct C-terminus.
Description The gene is located on chromosome 12 on the plus strand at 12202778 bp from pter to 12364018 from pter (size is 161241 bases). It was originally thought to comprise 6 exons (Guo et al., 2001) but 7 possible additional exons have subsequently been identified (Montpetit et al., 2002).
Transcription The gene encodes multiple transcripts; reference sequences exist for 3 transcript variants. These give rise to two different protein isoforms (Fig. 1). Transcript variants 1 and 4 differ only in their 5'-UTR and both encode the same protein, termed isoform 1 or Bcl-GL. Usage of a different splice acceptor site results in the production of transcript variant 2. This contains extra nucleotides within the coding sequence, resulting in a frameshift and consequently a truncated protein product with distinct C-terminal amino acids, termed isoform 2 or Bcl-GS. Transcript variant 2 may be a candidate for nonsense-mediated mRNA decay (NMD), but the RefSeq record (NM_030766.1) has been retained, since there is evidence for the expression of protein product. However, the RefSeq (NM_138724.1) for a further variant, originally termed variant 3, which encodes Bcl-G-Median (Bcl-GM) (Montpetit et al., 2002), has been permanently suppressed, as this transcript is also a candidate for NMD and evidence for protein expression is lacking.
Pseudogene There are no known pseudogenes.

Protein

 
  Figure 2. Protein isoforms encoded by BCL2L14. Homologous sequence between the two isoforms is depicted by the same colour pattern. Note that BclGL contains BH2 and BH3 domains whereas BclGS is a BH3-only protein. Potential sites of post-translational modification/interaction with non-Bcl-2 family members are also indicated.
Description The two protein isoforms are members of the Bcl-2 family. Bcl-GL comprises 327 amino acids and contains BH2 and BH3 domains, whereas Bcl-GS comprises 252 amino acids and contains the BH3 domain only (Fig. 2). The two proteins are identical in sequence for the first 226 amino acids.
Expression Highest levels of gene expression in the adult human are found in testis, hence the name Bcl-G, for Bcl-Gonad. Indeed Bcl-GS is uniquely expressed in this tissue (as also noted for Bcl-GM) (Guo et al., 2001; Montpetit et al., 2002). Bcl-GL is predominantly expressed in testis, with transcripts also present in lung, pancreas, prostate, bone marrow and colon (Guo et al., 2001; Montpetit et al., 2002). The expression of Bcl-GL has also been reported in freshly isolated human T-lymphocytes (CD4+ and CD8+ cells) and B-lymphocytes (Luo et al., 2009). Both Bcl-GL and Bcl-GS transcripts are expressed in a wide range of breast cancer cell lines and cultured mammary epithelial cells, but protein expression has been demonstrated for the former isoform only (Benito et al., 2006; Lin et al., 2007). Bcl-G transcript expression is more variable across prostate cell lines (Pickard et al., 2010). High levels of Bcl-GS transcripts are found in testicular embryonal cancer cell lines, with lower levels present in urinary bladder and mantle cell lymphoma cell lines, followed by myeloid and breast cancer cell lines, but protein was detected for the testicular embryonal cancer cell lines only (Benito et al., 2006).
Localisation Expression of GFP-tagged proteins in COS-7 cells has revealed a diffuse localization throughout the cell for Bcl-GL (similar to GFP alone), but a more punctate cytosolic localization, with partial co-localization to mitochondria, for Bcl-GS (Guo et al., 2001). The latter has been confirmed using Myc-tagged Bcl-GS (Liu et al., 2008). Deletion of the BH3 domain from Bcl-GS has no effect on its subcellular distribution, despite preventing interaction with Bcl-XL (Guo et al., 2001). However interaction with JAB1 results in a more diffuse cytoplasmic localisation for Bcl-GS (Liu et al., 2008).
Function The original paper on BCL2L14 reported that GFP- or FLAG-tagged Bcl-GL and Bcl-GS have pro-apoptotic activity in a range of cell lines (COS-7, HEK293T and PC3), and that the latter is the more potent isoform (Guo et al., 2001). Deletion of the BH2 domain from Bcl-GL allowed its interaction with Bcl-XL and enhanced apoptotic activity, whereas the BH3 domain of Bcl-GS was required for interaction with Bcl-XL and apoptotic activity (Guo et al., 2001).
The pro-apoptotic activity of Bcl-GL in COS-7 cells has been independently confirmed, and it has been further demonstrated that this activity is negatively regulated by phosphorylation, catalyzed by MELK (Lin et al., 2007). Similarly, Bcl-GS has been reported to induce basal apoptosis in HeLa cells; an effect that is potentiated by JAB1 (Liu et al., 2008). The latter is thought to out-compete Bcl-2/Bcl-XL for binding of Bcl-GS (Liu et al., 2008). On the other hand, transfection of Huh-7 cells with Bcl-GL has no effect on basal apoptosis (Zhang et al., 2006), while the survival of HCT116 and NTERA2 cells is unaffected by elevated levels of Bcl-GS consequent upon ectopic TEF expression (Benito et al., 2006), suggesting that cell context is important for the apoptotic activity of Bcl-G protein isoforms. Crucially lentiviral transfection of Bcl-GL results in enhanced apoptosis of CD4+ T-cells from healthy subjects, demonstrating that pro-apoptotic activity is not restricted to transformed cells (Luo et al., 2009).
Furthermore, siRNA-mediated silencing of BCL2L14 gene expression attenuates apoptosis induction in several cell lines in response to diverse stimuli, including: ultraviolet-C irradiation (22Rv1 and HEK293T cells) (Pickard et al., 2010; Pickard et al., 2011), etoposide (HCT116 cells) (Benito et al., 2006), neratinib (SKBR-3 cells) (Seyhan et al., 2012), p53-induction (Saos-2 cells) (Miled et al., 2005), and ectopic expression of the putative tumour suppressor gene FAU (HEK293T cells) (Pickard et al., 2011). BCL2L14 is itself a target gene for the apoptosis master regulator p53 (Miled et al., 2005), and it is one of a subset of pro-apoptotic genes whose expression is hyperactivated in response to interferon-α and -γ co-treatment of hepatoma cells (Zhang et al., 2006). Its expression is also increased in mammalian cells following exposure to a diverse range of apoptotic stimuli (including chemotherapeutic agents) such as: gamma- radiation therapy (Finnberg et al., 2008), UV-C irradiation (Pickard et al., 2011), arsenic trioxide (Galimberti et al., 2012), nanoparticulate tetraiodothyroacetic acid (Glinskii et al., 2009), etoposide and cisplatin (Benito et al., 2006).
Mutations in pancreatic/duodenum homeobox protein 1 (PDX1) can result in human type 2 diabetes. Haploinsufficiency of this gene in mice also causes diabetes and is associated with enhanced apoptosis/necrosis of β-cells. In this regard, BCL2L14 has been identified as one of several genes encoding pro-apoptotic Bcl-2 family members whose expression is markedly up-regulated following shRNA-mediated depletion of Pdx1 in mouse insulinoma MIN6 cells (Fujimoto et al., 2010). Additionally BCL2L14 is one of several pro-apoptotic genes that is up-regulated upon exposure of human fibroblasts to pressure-induced oxidative stress (Oh et al., 2008).
The recent production of a mouse in which BCL2L14 is inactivated has demonstrated no apparent deleterious effects on cell types that normally express this gene (Giam et al., 2012b), perhaps suggesting some degree of functional redundancy. These authors further demonstrated that mBclG had negligible pro-apoptotic activity in human 293T cells and that the BH3 domain was incapable of binding Bcl-2 family members. Rather mBclG was capable of binding several novel partners, including transport particle protein (TRAPP) complex proteins, suggesting a potential role for mBclG in vesicle trafficking (Giam et al., 2012b). As regards pig Bcl-G, its ectopic expression in a porcine kidney cell line stimulates apoptosis induced by polyinosinic: polycytidylic acid (synthetic analogue of dsRNA and mimic of viral infection) (Jiang et al., 2012).
Homology Homologues of BCL2L14 have been identified in a wide range of species (e.g. see Jiang et al., 2012). However, the Bcl-GS protein isoform is specific to humans (Giam et al., 2012a). Mouse and pig Bcl-G share 68% and 71% amino acid identity, respectively, with human Bcl-GL.

Implicated in

Note
  
Entity Prostate cancer
Note In advanced prostate cancer, deletion of 12p12 is frequently seen. Expression mapping of genes within/adjacent to the minimal deleted region in clinical tumours has demonstrated reduced expression of BCL2L14 and two other genes (DUSP16 and FLJ10298) (Kibel et al., 2004); reduced expression of BCL2L14 has been independently confirmed (Pickard et al., 2010). In the latter study, transcript levels were highly correlated with those of FAU, which also regulates apoptosis and which may act via the post-translational modification of Bcl-G (Pickard et al., 2010). Notably, down-regulation of BCL2L14 gene expression in the prostate cancer 22Rv1 cell line protects cells from apoptosis induction by ultraviolet-C irradiation (Pickard et al., 2010). BCL2L14 has been identified as a member of a four gene signature that accurately predicts prostate cancer recurrence, but high expression of BCL2L14 is associated with tumour recurrence (Latil et al., 2003).
  
  
Entity Breast cancer
Note Single nucleotide polymorphisms of high frequency loss of heterozygosity that affect BCL2L14 are found more commonly in infiltrating ductal carcinoma than in infiltrating lobular carcinoma of the breast (Loo et al., 2008). In breast ductal carcinoma, BCL2L14 expression is reduced, and silencing of BCL2L14 expression in the T-47D breast cancer cell line attenuates apoptosis induction by exogenous stimuli (Pickard et al., 2009). A genome-wide RNAi screen has recently shown that BCL2L14 silencing in SKBR-3 results in resistance to the novel pan-ErbB inhibitor, neratinib (Seyhan et al., 2012). BCL2L14 has also been implicated in the anti-survival effects of nanoparticulate tetraiodothyroacetic acid on MDA-MB-231 cells (Glinskii et al., 2009).
As regards genes involved in the post-translational modification of Bcl-G, FAU expression is down-regulated and MELK expression is up-regulated in breast tumour tissue (Pickard et al., 2009). These latter changes were associated with poor patient prognosis, but no relationship was apparent between BCL2L14 gene expression and patient survival (Pickard et al., 2009), suggesting that the regulation of Bcl-G activity by post-translational modification is more important than the level of BCL2L14 expression per se in determining patient survival.
  
  
Entity Ovarian cancer
Note Elevated levels of BCL2L14 gene expression have been reported for mucinous ovarian cancer relative to other histological subtypes of ovarian cancer (Heinzelmann-Schwarz et al., 2006). The functional significance of these changes are unknown. Subdivision of patients with high grade ovarian serous carcinoma into TP53 mutation-positive and p53 protein-null groups has revealed a number of differences in the genomic landscape, including gains of 12p13.2-12p13.1 (affecting DUSP16, BCL2L14 and ETV6) in the former group (Wojnarowicz et al., 2012). TP53 mutation-positive patients were also characterized by increased overall and disease-free survival (Wojnarowicz et al., 2012).
  
  
Entity Cervical cancer
Note An integration site for HPV16 in cervical carcinoma has been mapped to BCL2L14 (Xu et al., 2013).
  
  
Entity Lung cancer
Note Analysis of variants in inflammation pathway genes has identified single nucleotide polymorphisms of BCL2L14 in former smokers that are associated with increased risk of developing lung cancer (Spitz et al., 2012).
  
  
Entity Precursor B acute lymphoblastic leukemia (ALL)
Note A novel TEL-AML1 fusion transcript, comprising an in-frame insertion of 33 nucleotides derived from BCL2L14 between exon 5 of TEL and exon 2 of AML1 has been described in a case of pediatric precursor B ALL (Abdelhaleem et al., 2006). This fusion transcript appears to be rare, and its biological effects are unknown.
  
  
Entity Tongue squamous cell carcinoma
Note BCL2L14 expression has been reported to be markedly up-regulated in tongue squamous cell carcinoma tissue (Zhang et al., 2013).
  
  
Entity Systemic lupus erythematosus (SLE)
Note BCL2L14 expression is up-regulated (ca. 8-fold) in CD4+ T-cells (but not CD8+ or B-cells) from patients with systemic lupus erythematosus (SLE) (Luo et al., 2009). In SLE, apoptosis is increased in CD4+ T-cells, and the degree of apoptosis in freshly isolated cells from SLE patients was directly correlated with Bcl-GL levels, as were other measures of disease activity status (Luo et al., 2009). Healthy control CD4+ T-cells in vitro demonstrated enhanced apoptosis both after transfection with a lentiviral vector expressing BclGL and after treatment with serum from SLE patients; the latter effect was associated with increased BclGL cellular levels and could be partially inhibited by prior knockdown of BclGL (Luo et al., 2009). The serum factor(s) that mediate this response remain unknown; whilst interferon-α was increased in SLE sera it alone could not account for enhanced Bcl-GL cellular levels (Luo et al., 2009).
  
  
Entity Innate immune response
Note There are several reports of dysregulated expression of BCL2L14 in response to infection with a wide range of pathogens/parasites. For example, in Rhesus Macaque monkeys infected with Mycobacterium tuberculosis, BCL2L14 expression is initially enhanced in granulomas relative to normal lung tissue during the acute phase of disease but silenced several weeks post-infection (Mehra et al., 2010). While multiple markers of the pro-inflammatory response show a similar pattern, the silencing of BCL2L14 in chronic disease may contribute to pathogen survival. Studies with murine cells have further shown that exosomes derived from macrophages infected with Mycobacterium tuberculosis can block the activation of a subset of interferon-γ inducible genes, including BCL2L14, which may serve to suppress the host innate immune response beyond the site of infection (Singh et al., 2011). BCL2L14 is one of several Bcl-2 family members that is dysregulated in bovine endothelial cells following infection with the parasite Eimeria bovis (Taubert et al., 2010). It is markedly upregulated in human alveolar macrophages within a few hours of infection with H1N1 influenza A virus PR/8 (Wang et al., 2012) and it is also induced following the infection of human monocyte-derived dendritic cells with wild type Dengue 3 virus (a Flavivirus) or the chimeric CYD3 vaccine virus (Balas et al., 2011). On the other hand, BCL2L14 expression is down-regulated in porcine epithelial cells following infection with Pseudorabies virus (a herpes virus) (Flori et al., 2008).
BCL2L14 may also be implicated in the host response to viral evasion mechanisms per se. For example, selective expression of the African Swine Fever Virus evasion gene, A238L, in mouse T-lymphocytes results in the production of an aggressive lymphoma (Almeida et al., 2012). Transgenic animals exhibit massively enlarged thymuses characterized, inter alia, by enhanced BCL2L14 expression and apoptosis (Almeida et al., 2012).
While attendant changes in host cell interferon signalling may account for many of the above changes in BCL2L14 expression, it should be noted that Bcl-G can directly interact with a component of the Flavivirus replication complex (Le Breton et al., 2011). However, the biological significance of this interaction for both host and virus remains to be determined. The 3'-UTR of BCL2L14 transcripts also contains potential binding sites for Epstein-Barr virus-derived miRNAs (Marquitz et al., 2011).
  

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PLoS One. 2010 Aug 31;5(8):e12266. doi: 10.1371/journal.pone.0012266.
PMID 20824205
 
A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network.
Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB.
Cancer Res. 2005 Jun 15;65(12):5096-104.
PMID 15958553
 
Mutational and expression analysis of the chromosome 12p candidate tumor suppressor genes in pre-B acute lymphoblastic leukemia.
Montpetit A, Larose J, Boily G, Langlois S, Trudel N, Sinnett D.
Leukemia. 2004 Sep;18(9):1499-504.
PMID 15284860
 
The ubiquitin-like protein MNSFbeta regulates ERK-MAPK cascade.
Nakamura M, Yamaguchi S.
J Biol Chem. 2006 Jun 23;281(25):16861-9. Epub 2006 Apr 18.
PMID 16621790
 
Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts.
Oh S, Lee E, Lee J, Lim Y, Kim J, Woo S.
Cell Stress Chaperones. 2008 Dec;13(4):447-58. doi: 10.1007/s12192-008-0041-5. Epub 2008 May 9.
PMID 18465208
 
Candidate tumour suppressor Fau regulates apoptosis in human cells: an essential role for Bcl-G.
Pickard MR, Mourtada-Maarabouni M, Williams GT.
Biochim Biophys Acta. 2011 Sep;1812(9):1146-53. doi: 10.1016/j.bbadis.2011.04.009. Epub 2011 Apr 29.
PMID 21550398
 
A genome-wide RNAi screen identifies novel targets of neratinib resistance leading to identification of potential drug resistant genetic markers.
Seyhan AA, Varadarajan U, Choe S, Liu W, Ryan TE.
Mol Biosyst. 2012 Apr;8(5):1553-70. doi: 10.1039/c2mb05512k. Epub 2012 Mar 23.
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Exosomes released from M. tuberculosis infected cells can suppress IFN-γ mediated activation of naive macrophages.
Singh PP, LeMaire C, Tan JC, Zeng E, Schorey JS.
PLoS One. 2011 Apr 14;6(4):e18564. doi: 10.1371/journal.pone.0018564.
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BH3 domain mutation of proapoptotic genes Bad, Bmf and Bcl-G is rare in transitional cell carcinomas of the urinary bladder.
Soung YH, Lee JW, Park WS, Nam SW, Lee JY, Yoo NJ, Lee SH.
Pathology. 2006 Feb;38(1):33-4.
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Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1213-21. doi: 10.1158/1055-9965.EPI-12-0352-T. Epub 2012 May 9.
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Vet Res. 2010 Sep-Oct;41(5):70. doi: 10.1051/vetres/2010041. Epub 2010 Jul 12.
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Curr Genomics. 2008 Apr;9(2):97-109. doi: 10.2174/138920208784139555.
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FEBS J. 2013 Mar;280(5):1281-93. doi: 10.1111/febs.12120. Epub 2013 Feb 11.
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Citation

This paper should be referenced as such :
Pickard, MR ; Williams, GT
BCL2L14 (BCL2-like 14 (apoptosis facilitator))
Atlas Genet Cytogenet Oncol Haematol. 2014;18(3):152-159.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BCL2L14ID774ch12p13.html


External links

Nomenclature
HGNC (Hugo)BCL2L14   16657
Cards
AtlasBCL2L14ID774ch12p13
Entrez_Gene (NCBI)BCL2L14  79370  BCL2 like 14
AliasesBCLG
GeneCards (Weizmann)BCL2L14
Ensembl hg19 (Hinxton)ENSG00000121380 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000121380 [Gene_View]  chr12:12071468-12099693 [Contig_View]  BCL2L14 [Vega]
ICGC DataPortalENSG00000121380
TCGA cBioPortalBCL2L14
AceView (NCBI)BCL2L14
Genatlas (Paris)BCL2L14
WikiGenes79370
SOURCE (Princeton)BCL2L14
Genetics Home Reference (NIH)BCL2L14
Genomic and cartography
GoldenPath hg38 (UCSC)BCL2L14  -     chr12:12071468-12099693 +  12p13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)BCL2L14  -     12p13.2   [Description]    (hg19-Feb_2009)
EnsemblBCL2L14 - 12p13.2 [CytoView hg19]  BCL2L14 - 12p13.2 [CytoView hg38]
Mapping of homologs : NCBIBCL2L14 [Mapview hg19]  BCL2L14 [Mapview hg38]
OMIM606126   
Gene and transcription
Genbank (Entrez)AF281254 AF281255 AK000127 AK026440 AK223415
RefSeq transcript (Entrez)NM_030766 NM_138722 NM_138723 NM_138724
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)BCL2L14
Cluster EST : UnigeneHs.734567 [ NCBI ]
CGAP (NCI)Hs.734567
Alternative Splicing GalleryENSG00000121380
Gene ExpressionBCL2L14 [ NCBI-GEO ]   BCL2L14 [ EBI - ARRAY_EXPRESS ]   BCL2L14 [ SEEK ]   BCL2L14 [ MEM ]
Gene Expression Viewer (FireBrowse)BCL2L14 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)79370
GTEX Portal (Tissue expression)BCL2L14
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BZR8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9BZR8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BZR8
Splice isoforms : SwissVarQ9BZR8
PhosPhoSitePlusQ9BZR8
Domaine pattern : Prosite (Expaxy)BCL2_FAMILY (PS50062)   
Domains : Interpro (EBI)Bcl2-like    BCL2L14   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)BCL2L14
DMDM Disease mutations79370
Blocks (Seattle)BCL2L14
SuperfamilyQ9BZR8
Human Protein AtlasENSG00000121380
Peptide AtlasQ9BZR8
HPRD05841
IPIIPI00032174   IPI00006162   IPI00045049   IPI00945022   IPI00789122   
Protein Interaction databases
DIP (DOE-UCLA)Q9BZR8
IntAct (EBI)Q9BZR8
FunCoupENSG00000121380
BioGRIDBCL2L14
STRING (EMBL)BCL2L14
ZODIACBCL2L14
Ontologies - Pathways
QuickGOQ9BZR8
Ontology : AmiGOprotein binding  cytosol  cytosol  apoptotic process  endomembrane system  membrane  protein kinase binding  regulation of apoptotic process  intracellular organelle  
Ontology : EGO-EBIprotein binding  cytosol  cytosol  apoptotic process  endomembrane system  membrane  protein kinase binding  regulation of apoptotic process  intracellular organelle  
REACTOMEQ9BZR8 [protein]
REACTOME PathwaysR-HSA-6803205 [pathway]   
NDEx NetworkBCL2L14
Atlas of Cancer Signalling NetworkBCL2L14
Wikipedia pathwaysBCL2L14
Orthology - Evolution
OrthoDB79370
GeneTree (enSembl)ENSG00000121380
Phylogenetic Trees/Animal Genes : TreeFamBCL2L14
HOVERGENQ9BZR8
HOGENOMQ9BZR8
Homologs : HomoloGeneBCL2L14
Homology/Alignments : Family Browser (UCSC)BCL2L14
Gene fusions - Rearrangements
Fusion : MitelmanBCL2L14/ETV6 [12p13.2/12p13.2]  
Fusion : MitelmanMSRB3/BCL2L14 [12q14.3/12p13.2]  [t(12;12)(p13;q14)]  
Fusion: TCGABCL2L14 12p13.2 ETV6 12p13.2 BRCA
Fusion: TCGAMSRB3 12q14.3 BCL2L14 12p13.2 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBCL2L14 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BCL2L14
dbVarBCL2L14
ClinVarBCL2L14
1000_GenomesBCL2L14 
Exome Variant ServerBCL2L14
ExAC (Exome Aggregation Consortium)BCL2L14 (select the gene name)
Genetic variants : HAPMAP79370
Genomic Variants (DGV)BCL2L14 [DGVbeta]
DECIPHERBCL2L14 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisBCL2L14 
Mutations
ICGC Data PortalBCL2L14 
TCGA Data PortalBCL2L14 
Broad Tumor PortalBCL2L14
OASIS PortalBCL2L14 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBCL2L14  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDBCL2L14
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch BCL2L14
DgiDB (Drug Gene Interaction Database)BCL2L14
DoCM (Curated mutations)BCL2L14 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BCL2L14 (select a term)
intoGenBCL2L14
NCG5 (London)BCL2L14
Cancer3DBCL2L14(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606126   
Orphanet
MedgenBCL2L14
Genetic Testing Registry BCL2L14
NextProtQ9BZR8 [Medical]
TSGene79370
GENETestsBCL2L14
Target ValidationBCL2L14
Huge Navigator BCL2L14 [HugePedia]
snp3D : Map Gene to Disease79370
BioCentury BCIQBCL2L14
ClinGenBCL2L14
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD79370
Chemical/Pharm GKB GenePA134870762
Clinical trialBCL2L14
Miscellaneous
canSAR (ICR)BCL2L14 (select the gene name)
Probes
Litterature
PubMed24 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBCL2L14
EVEXBCL2L14
GoPubMedBCL2L14
iHOPBCL2L14
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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