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

Written2008-08Christos Kontos, Hellinida Thomadaki, Andreas Scorilas
Department of Biochemistry, Molecular Biology, Faculty of Biology, University of Athens. 157 01, Panepistimiopolis, Athens, Greece

(Note : for Links provided by Atlas : click)

Identity

Other namesBPR
MGC120313
MGC120314
MGC120315
HGNC (Hugo) BCL2L12
LocusID (NCBI) 83596
Atlas_Id 773
Location 19q13.33  [Link to chromosome band 19q13]
Location_base_pair Starts at 50168399 and ends at 50177173 bp from pter ( according to hg19-Feb_2009)  [Mapping BCL2L12.png]
Local_order Telomere to centromere.
Fusion genes
(updated 2016)
BCL2L12 (19q13.33) / LENG8 (19q13.42)BCL2L12 (19q13.33) / LOC100507412 (-)BCL2L12 (19q13.33) / PRMT1 (19q13.33)
PRMT1 (19q13.33) / BCL2L12 (19q13.33)TBC1D17 (19q13.33) / BCL2L12 (19q13.33)

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.

Protein

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

Note
Entity 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/Mutated Gene Not identified so far.
  

Bibliography

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
 

Citation

This paper should be referenced as such :
Kontos, C ; Thomadaki, H ; Scorilas, A
BCL2L12 (BCL2-like 12 (proline-rich))
Atlas Genet Cytogenet Oncol Haematol. 2009;13(7):467-468.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BCL2L12ID773ch19q13.html


External links

Nomenclature
HGNC (Hugo)BCL2L12   13787
Cards
AtlasBCL2L12ID773ch19q13
Entrez_Gene (NCBI)BCL2L12  83596  BCL2 like 12
Aliases
GeneCards (Weizmann)BCL2L12
Ensembl hg19 (Hinxton)ENSG00000126453 [Gene_View]  chr19:50168399-50177173 [Contig_View]  BCL2L12 [Vega]
Ensembl hg38 (Hinxton)ENSG00000126453 [Gene_View]  chr19:50168399-50177173 [Contig_View]  BCL2L12 [Vega]
ICGC DataPortalENSG00000126453
TCGA cBioPortalBCL2L12
AceView (NCBI)BCL2L12
Genatlas (Paris)BCL2L12
WikiGenes83596
SOURCE (Princeton)BCL2L12
Genomic and cartography
GoldenPath hg19 (UCSC)BCL2L12  -     chr19:50168399-50177173 +  19q13.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)BCL2L12  -     19q13.3   [Description]    (hg38-Dec_2013)
EnsemblBCL2L12 - 19q13.3 [CytoView hg19]  BCL2L12 - 19q13.3 [CytoView hg38]
Mapping of homologs : NCBIBCL2L12 [Mapview hg19]  BCL2L12 [Mapview hg38]
OMIM610837   
Gene and transcription
Genbank (Entrez)BC007724 BC104004 BC104005 BC104006 BI159786
RefSeq transcript (Entrez)NM_001040668 NM_001282516 NM_001282517 NM_001282519 NM_001282520 NM_001282521 NM_138639
RefSeq genomic (Entrez)NC_000019 NC_018930 NT_011109 NW_004929415
Consensus coding sequences : CCDS (NCBI)BCL2L12
Cluster EST : UnigeneHs.289052 [ NCBI ]
CGAP (NCI)Hs.289052
Alternative Splicing GalleryENSG00000126453
Gene ExpressionBCL2L12 [ NCBI-GEO ]   BCL2L12 [ EBI - ARRAY_EXPRESS ]   BCL2L12 [ SEEK ]   BCL2L12 [ MEM ]
Gene Expression Viewer (FireBrowse)BCL2L12 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)83596
GTEX Portal (Tissue expression)BCL2L12
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9HB09 (Uniprot)
NextProtQ9HB09  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9HB09
Splice isoforms : SwissVarQ9HB09 (Swissvar)
PhosPhoSitePlusQ9HB09
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
DMDM Disease mutations83596
Blocks (Seattle)BCL2L12
SuperfamilyQ9HB09
Human Protein AtlasENSG00000126453
Peptide AtlasQ9HB09
HPRD16543
IPIIPI00019835   IPI00216001   IPI00759647   
Protein Interaction databases
DIP (DOE-UCLA)Q9HB09
IntAct (EBI)Q9HB09
FunCoupENSG00000126453
BioGRIDBCL2L12
STRING (EMBL)BCL2L12
ZODIACBCL2L12
Ontologies - Pathways
QuickGOQ9HB09
Ontology : AmiGOp53 binding  protein binding  nucleus  membrane  positive regulation of transcription from RNA polymerase II promoter  negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  inhibition of cysteine-type endopeptidase activity involved in apoptotic process  negative regulation of cellular senescence  
Ontology : EGO-EBIp53 binding  protein binding  nucleus  membrane  positive regulation of transcription from RNA polymerase II promoter  negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  inhibition of cysteine-type endopeptidase activity involved in apoptotic process  negative regulation of cellular senescence  
NDEx Network
Atlas of Cancer Signalling NetworkBCL2L12
Wikipedia pathwaysBCL2L12
Orthology - Evolution
OrthoDB83596
GeneTree (enSembl)ENSG00000126453
Phylogenetic Trees/Animal Genes : TreeFamBCL2L12
Homologs : HomoloGeneBCL2L12
Homology/Alignments : Family Browser (UCSC)BCL2L12
Gene fusions - Rearrangements
Fusion : MitelmanBCL2L12/PRMT1 [19q13.33/19q13.33]  
Polymorphisms : SNP, variants
NCBI Variation ViewerBCL2L12 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BCL2L12
dbVarBCL2L12
ClinVarBCL2L12
1000_GenomesBCL2L12 
Exome Variant ServerBCL2L12
ExAC (Exome Aggregation Consortium)BCL2L12 (select the gene name)
Genetic variants : HAPMAP83596
Genomic Variants (DGV)BCL2L12 [DGVbeta]
Mutations
ICGC Data PortalBCL2L12 
TCGA Data PortalBCL2L12 
Broad Tumor PortalBCL2L12
OASIS PortalBCL2L12 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBCL2L12 
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 BCL2L12
DgiDB (Drug Gene Interaction Database)BCL2L12
DoCM (Curated mutations)BCL2L12 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BCL2L12 (select a term)
intoGenBCL2L12
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)19:50168399-50177173  ENSG00000126453
CONAN: Copy Number AnalysisBCL2L12 
Mutations and Diseases : HGMDBCL2L12
OMIM610837   
MedgenBCL2L12
Genetic Testing Registry BCL2L12
NextProtQ9HB09 [Medical]
TSGene83596
GENETestsBCL2L12
Huge Navigator BCL2L12 [HugePedia]
snp3D : Map Gene to Disease83596
BioCentury BCIQBCL2L12
ClinGenBCL2L12
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD83596
Chemical/Pharm GKB GenePA25306
Clinical trialBCL2L12
Miscellaneous
canSAR (ICR)BCL2L12 (select the gene name)
Probes
Litterature
PubMed55 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBCL2L12
EVEXBCL2L12
GoPubMedBCL2L12
iHOPBCL2L12
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue May 31 15:49:35 CEST 2016

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