BCL2L12 (BCL2-like 12 (proline-rich))

2008-08-01   Christos Kontos , Hellinida Thomadaki , Andreas Scorilas 

Department of Biochemistry, Molecular Biology, Faculty of Biology, University of Athens. 157 01, Panepistimiopolis, Athens, Greece

Identity

HGNC
LOCATION
19q13.33
LOCUSID
ALIAS
-
FUSION GENES

DNA/RNA

Description

Spanning 8.8 kb of genomic DNA, the BCL2L12 gene consists of 6 introns and 7 exons.

Transcription

The BCL2L12 gene has three splice variants with differences in exon 3. The predominant form is 1855 bp and encodes the full-length protein. The second splice variant lacks exon 3, which consists of 143 bp, thus resulting in no ORF. The third splice variant lacks 3 bp at the beginning of exon 3 and encodes a protein having one amino acid residue less than the full-lengh protein.

Pseudogene

Not identified so far.

Proteins

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.

Mutations

Note

No germinal or somatic mutations are identified to be associated with cancer so far.

Implicated in

Entity name
Human Leukemias, Solid Tumors.
Note
Significant alterations of BCL2L12 mRNA expression have been noticed in HL-60 leukemia cells as well as in MCF7 breast cancer cells, after treatment with various antineoplastic agents including cisplatin, carboplatin, doxorubicin, methotrexate, and etoposide. These important modulations of BCL2L12 mRNA levels seem to depend on both the apoptotic inducer and the specific apoptotic pathway, implying a strong relationship between alterations in BCL2L12 mRNA levels and apoptosis.
Expression analysis of the BCL2L12 gene has showed that BCL2L12 mRNA expression may be considered as a new prognostic marker for breast cancer, as breast tumours of lower stage or grade are more often BCL2L12-positive. Moreover, breast cancer patients with BCL2L12 mRNA expression are less likely to relapse or die, in comparison with BCL2L12-negative patients. Regarding BCL2L12 gene expression in colon cancer, the BCL2L12-A transcript is overexpressed in cancer tissues as compared to their normal mucosa counterparts. BCL2L12-A mRNA expression is also associated with colon cancer progression, since it is usually greater in patients being at the initial stages of the disease or having negative nodal status. BCL2L12 were found also to inhibits post-mitochondrial apoptosis signaling in glioblastoma.
Cytogenetics
No cytogenetic abnormalities are identified so far.
Hybrid gene
Not identified so far.

Bibliography

Pubmed IDLast YearTitleAuthors
173842502006Alterations 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 et al
154938712004Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer.Mathioudaki K et al
114014362001Molecular 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 et al
172107922007Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma.Stegh AH et al
127831222003Expression of BCL2L12, a new member of apoptosis-related genes, in breast tumors.Talieri M et al
166478102007Prognostic value of the apoptosis related genes BCL2 and BCL2L12 in breast cancer.Thomadaki H et al

Other Information

Locus ID:

NCBI: 83596
MIM: 610837
HGNC: 13787
Ensembl: ENSG00000126453

Variants:

dbSNP: 83596
ClinVar: 83596
TCGA: ENSG00000126453
COSMIC: BCL2L12

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000126453ENST00000246784A0A087WSV0
ENSG00000126453ENST00000246785Q9HB09
ENSG00000126453ENST00000441864Q9HB09
ENSG00000126453ENST00000594157M0R1K0
ENSG00000126453ENST00000598306M0R1Z8
ENSG00000126453ENST00000598979M0R1K0
ENSG00000126453ENST00000600947M0QZM6
ENSG00000126453ENST00000611631I6LK00
ENSG00000126453ENST00000614495I6LJZ9
ENSG00000126453ENST00000616144Q9HB09
ENSG00000126453ENST00000619007I6LJZ7

Expression (GTEx)

0
10
20
30
40
50
60
70

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
239011152013Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma.70
186696462008Bcl2L12-mediated inhibition of effector caspase-3 and caspase-7 via distinct mechanisms in glioblastoma.52
262975422015miR-125a-5p inhibits cell proliferation and induces apoptosis in colon cancer via targeting BCL2, BCL2L12 and MCL1.41
208555362010Germline variation in apoptosis pathway genes and risk of non-Hodgkin's lymphoma.18
222621802012GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl.14
255860562015Bcl2L12 with a BH3-like domain in regulating apoptosis and TMZ-induced autophagy: a prospective combination of ABT-737 and TMZ for treating glioma.13
189301352008Knockdown of BCL2L12 leads to cisplatin resistance in MDA-MB-231 breast cancer cells.12
211526972011BCL2L12 is a novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma.12
188444532008Quantitative expression analysis and prognostic significance of the novel apoptosis-related gene BCL2L12 in colon cancer.11

Citation

Christos Kontos ; Hellinida Thomadaki ; Andreas Scorilas

BCL2L12 (BCL2-like 12 (proline-rich))

Atlas Genet Cytogenet Oncol Haematol. 2008-08-01

Online version: http://atlasgeneticsoncology.org/gene/773/bcl2l12