| Description | The BCL2L12 protein is composed of 334 amino acids, with a calculated molecular mass of 36.8 kDa and an isoelectric point of 9.45. The BCL2L12 protein contains one BH2 and one putative BH3 domain, one proline-rich region similar to the TC21 protein, and five consensus PXXP tetrapeptide sequences.
BCL2L12 protein also includes various putative posttranslational modification sites. There are numerous potential sites for O-glycosylation. Furthermore, several possible sites of phosphorylation have been identified for cAMP-dependent protein kinase, protein kinase C, and casein kinase 2. In addition, several N-myristoylation sites have been predicted. The BCL2L12 protein was found to have proline-rich sites. One PPPP site as well as five PP amino acid sites are present in this protein. Eight putative PXXP motifs were also identified. Proline-rich motifs are characterized by the presence of the consensus PXXP tetrapeptide, found in all proline-rich proteins identified to date. It is known that SH3 domains recognize proline-rich sequences and that all known SH3-binding proteins contain proline-rich regions with at least one PXXP motif. Proline-rich domains have been identified in a number of diverse proteins such as epidermal growth factors, phosphatidylinositol 3-kinase, and, more recently, the small GTPase RRAS protein and members of the RRAS superfamily such as the TC21 protein. Moreover, the amino acid loop (PPSPEP) at positions 271-276 of the BCL2L12 protein is identical with the PXXP motif present in the RRAS and TC21 oncogenes. This motif is required for integrin activation.
The splice variant BCL2L12-A is expected to encode a truncated protein of 176 amino acids with five PP proline sites, two putative PXXP motifs, and no BH2 homology domain. |
| Expression | High levels of BCL2L12 expression are typically found in glandular epithelia in various organs, such as gastrointestinal tract and/or breast. Lower BCL2L12 protein expression has been found in prostate tissue. |
| Function | BCL2L12 is involved in apoptosis. However, its proapoptotic or antiapoptotic role in different types of cells and conditions remains unclear. |
| Homology | Human BCL2L12 shares 98% and 96% identity with chimpanzee and Rhesus monkey Bcl2l12, respectively, and 83% identity with rat/mouse Bc2l12 as well. |
| Molecular cloning, physical mapping, and expression analysis of a novel gene, BCL2L12, encoding a proline-rich protein with a highly conserved BH2 domain of the Bcl-2 family. |
| Scorilas A, Kyriakopoulou L, Yousef GM, Ashworth LK, Kwamie A, Diamandis EP. |
| Genomics 2001; 72: 217-221. |
| PMID 11401436 |
| |
| Cisplatin-induced apoptosis in HL-60 human promyelocytic leukemia cells: differential expression of BCL2 and novel apoptosis-related gene BCL2L12. |
| Floros KV, Thomadaki H, Lallas G, Katsaros N, Talieri M, Scorilas A. |
| Ann N Y Acad Sci 2003; 1010: 153-158. |
| PMID 15033711 |
| |
| Expression of BCL2L12, a new member of apoptosis-related genes, in breast tumors. |
| Talieri M, Diamandis EP, Katsaros N, Gourgiotis D, Scorilas A. |
| Thromb Haemost 2003; 89: 1081-1088. |
| PMID 12783122 |
| |
| mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment with carboplatin and doxorubicin. |
| Floros KV, Thomadaki H, Katsaros N, Talieri M, Scorilas A. |
| Biol Chem 2004; 385: 1099-1103. |
| PMID 15576332 |
| |
| Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer. |
| Mathioudaki K, Scorilas A, Papadokostopoulou A, Xynopoulos D, Arnogianaki N, Agnanti N, Talieri M. |
| Biol Chem 2004; 385: 779-783. |
| PMID 15493871 |
| |
| Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells. |
| Floros KV, Talieri M, Scorilas A. |
| Biol Chem 2006; 387: 1629-1633. |
| PMID 17132110 |
| |
| Alterations in mRNA expression of apoptosis-related genes BCL2, BAX, FAS, caspase-3, and the novel member BCL2L12 after treatment of human leukemic cell line HL60 with the antineoplastic agent etoposide. |
| Floros KV, Thomadaki H, Florou D, Talieri M, Scorilas A. |
| Ann N Y Acad Sci 2006; 1090: 89-97. |
| PMID 17384250 |
| |
| BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. |
| Thomadaki H, Scorilas A. |
| Crit Rev Clin Lab Sci 2006; 43: 1-67. (REVIEW) |
| PMID 16531274 |
| |
| Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS. |
| Thomadaki H, Talieri M, Scorilas A. |
| Biol Chem 2006; 387: 1081-1086. |
| PMID 16895478 |
| |
| BCL2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. |
| Stegh AH, Kim H, Bachoo RM, Forloney KL, Zhang J, Schulze H, Park K, Hannon GJ, Yuan J, Louis DN, DePinho RA, Chin L. |
| Genes Dev. 2007 Jan 1;21(1):98-111. |
| PMID 17210792 |
| |
| Breast cancer cells response to the antineoplastic agent's cisplatin, carboplatin, and doxorubicin at the mRNA expression levels of distinct apoptosis-related genes, including the new member, BCL2L12. |
| Thomadaki H, Scorilas A. |
| Ann N Y Acad Sci 2007; 1095: 35-44. |
| PMID 17404015 |
| |
| Prognostic value of the apoptosis related genes BCL2 and BCL2L12 in breast cancer. |
| Thomadaki H, Talieri M, Scorilas A. |
| Cancer Lett 2007; 247: 48-55. |
| PMID 16647810 |
| |