Alternative titles; symbolsAPOPTOSIS REGULATOR BCLG; BCLGHGNC Approved Gene Symbol: BCL2L14Cytogenetic location: 12p13.2 Genomic coordinates (GRCh38): 12:12,...
Alternative titles; symbols
HGNC Approved Gene Symbol: BCL2L14
Cytogenetic location: 12p13.2 Genomic coordinates (GRCh38): 12:12,049,848-12,099,694 (from NCBI)
The BCL2 (151430) family of proteins comprises both pro- and antiapoptotic regulators of programmed cell death (e.g., BAX (600040) and BCLXL (600039), respectively). These proteins control cell life/death decisions through their effects on such events as mitochondrial release of proteins involved in activation of caspase family cell death proteases or by binding sequestering caspase-activating proteins. BCL2 proteins contain up to 4 conserved BCL2 homology (BH) domains.
▼ Cloning and Expression
By EST database searching using BCL2 as the probe, followed by 5-prime RACE, Guo et al. (2001) obtained cDNAs encoding short and long variants of BCLG (BCL-gonad), which they termed BCLGS and BCLGL, respectively. The deduced 327-amino acid BCLGL and 252-amino acid BCLGS proteins both contain a candidate BH3 domain, but only BCLGL possesses a BH2 domain. Northern blot analysis revealed wide expression of 1.5- to 2.5-kb BCLG transcripts, with highest levels in testis. RT-PCR analysis detected strong expression of BCLGL in lung, pancreas, prostate, and testis, whereas BCLGS was expressed only in testis.
▼ Gene Structure
By genomic sequence analysis, Guo et al. (2001) determined that the BCLG gene contains 6 exons and uses different splice acceptor sites in exon 5 to generate variant cDNAs.
Montpetit et al. (2002) constructed a detailed transcription map of the 750-kb interval spanning the putative chromosome 12p12 tumor suppressor locus, frequently rearranged in a wide variety of hematologic malignancies as well as in certain solid tumors. Within this region, they identified 7 putative transcription units, including the BCLG gene. BLAST analyses and RACE experiments suggested the presence of 7 additional exons compared to the findings of Guo et al. (2001). The first 3 5-prime upstream exons (exons 1A to 1C) are noncoding. Alternative splicing involving the 4 additional 3-prime exons (exons 7 to 10) could generate a new isoform, BCLGM (for median), whose 276-amino acid product would also lack box BH2, thus predicting a function similar to the BCLGS transcript. BCLGM, like BCLGS, was shown to be expressed only in the testis, while BCLGL was expressed in many tissues including bone marrow, prostate, pancreas, and colon, but predominantly in testis, which was in agreement with Guo et al. (2001).
Guo et al. (2001) identified a BAC clone from 12p12 that contains the BCLG gene.
Stumpf (2021) mapped the BCL2L14 gene to chromosome 12p13.2 based on an alignment of the BCL2L14 sequence (GenBank AF281254) with the genomic sequence (GRCh38).
▼ Gene Function
Guo et al. (2001) showed that overexpression of both BCLG variants in cell lines induced apoptosis. BCLGS had a more potent activity that was dependent on its BH3 domain. BCLGL with a deleted BH2 domain was as potent as BCLGS, suggesting that the BH2 domain negatively regulates BCLGL proapoptotic activity. Coimmunoprecipitation and yeast 2-hybrid analysis showed that BCLGS interacts with antiapoptotic BCL2 family members, such as BCLXL, through its BH3 domain. Confocal microscopy and cellular fractionation analysis demonstrated that BCLGS colocalizes with mitochondria independently of the BH3 domain.