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TAL2 (T-cell acute lymphoblastic leukemia 2)

Written2005-08Katrina Vanura
Medical University of Vienna, Dept. of Medicine I, Div. of Hematology, Waehringer Guertel 18-20, A - 1090 Vienna, Austria

(Note : for Links provided by Atlas : click)

Identity

Alias_namesT-cell acute lymphocytic leukemia 2
Alias_symbol (synonym)bHLHa19
Other alias
HGNC (Hugo) TAL2
LocusID (NCBI) 6887
Atlas_Id 28
Location 9q31.2  [Link to chromosome band 9q31]
Location_base_pair Starts at 108424738 and ends at 108425385 bp from pter ( according to hg19-Feb_2009)  [Mapping TAL2.png]
Local_order from centromere to telomere: CSDUFD1, MGC45564, FCMD, TAL2, C9ort87, ZNF462
Fusion genes
(updated 2016)
TAL2 (9q31.2) / TRB ()TRB () / TAL2 (9q31.2)

DNA/RNA

Description exons 1a, 2, 3, and 1b located 5-8 kb upstream of exon 4; coding region in exon 4 (326 bp)
Transcription various mRNA isoforms were found in SUP-T3 and in the mouse, which also encompass upstream exons; gene products, however, always corresponded to the TAL2 protein encoded by exon 4

Protein

Description 108 amino acids; basic Helix Loop Helix motif for protein dimerization and DNA-binding
Expression in adult testes; in developing midbrain, dorsal diencephalon, rostroventral diencaphalic/telencephalic boundary, and anterior pons; pivotal role in the development of the mature central nervous system; not expressed during normal hematopoietic development
Function transcription factor; TAL2 dimerizes with members of the class A subgroup of bHLH proteins (ie E47, E12, E2-2, HEB), as well as LIM-only proteins LMO1 and LMO2; heterodimers are formed intracellularly through stable interaction between bHLH domains of TAL2 and E47; TAL2/E47 heterodimers bind DNA in a sequence-specific manner that is dependent on the E-box element; TAL2/E12 heterodimers also have DNA-binding activity; TAL2 does not bind DNA in absence of E2A proteins; a significant fraction (60%) of TAL2 polypeptides from SUP-T3 exist in phosphorylated form, the rest is unphosphorylated; serine residue 100 of TAL2 is the potential site of phosphorylation by MAP kinases.
Homology TAL1 at 1p31, LYL1 at 19p13; TAL2, TAL1, and LYL1 share more than 85% amino acid identity in the bHLH domain and are thus more related to one other than to other bHLH proteins, for instance c-myc

Implicated in

Note
  
Entity t(7;9)(q34;q32) -->TAL2-TCRB
Disease T cell acute lymphoblastic leukemia found in < 1% of ALL, in 1-2% of T-ALL, rare but recurrent
Hybrid/Mutated Gene Translocation of part of TCRB locus to a breakpoint 33 kb downstream of TAL2 mediated by the V(D)J recombinase via a fortuitous recombination signal sequence (YRSS) on chromosome 9; the translocation results in a signal joint fusion of TAL2 YRSS with the Db1 23-RSS; this gene product was detected in 6 of 10 thymus samples of healthy children with an estimated frequency of 1 in 10 million thymic cells; only upon secondary rearrangement of the TAL2/Db signal joint to the Jb2.6 segment, and deletion of the intervening sequence, the typical TAL2/Jb2.6 T-ALL junctions could be observed which presumably lead to overexpression of TAL2 and development of leukemia.
Abnormal Protein TAL2 placed under control of TCRB enhancer leading to overexpression of TAL2 in T-cells and development of leukemia
  

Bibliography

TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia.
Baer R
Seminars in cancer biology. 1993 ; 4 (6) : 341-347.
PMID 8142619
 
The T cell oncogene Tal2 is necessary for normal development of the mouse brain.
Bucher K, Sofroniew MV, Pannell R, Impey H, Smith AJ, Torres EM, Dunnett SB, Jin Y, Baer R, Rabbitts TH
Developmental biology. 2000 ; 227 (2) : 533-544.
PMID 11071772
 
Distinct t(7;9)(q34;q32) breakpoints in healthy individuals and individuals with T-ALL.
Marculescu R, Vanura K, Le T, Simon P, Jäger U, Nadel B
Nature genetics. 2003 ; 33 (3) : 342-344.
PMID 12567187
 
The leukemic oncogene tal-2 is expressed in the developing mouse brain.
Mori S, Sugawara S, Kikuchi T, Tanji M, Narumi O, Stoykova A, Nishikawa SI, Yokota Y
Brain research. Molecular brain research. 1999 ; 64 (2) : 199-210.
PMID 9931488
 
Consistent breakage between consensus recombinase heptamers of chromosome 9 DNA in a recurrent chromosomal translocation of human T cell leukemia.
Tycko B, Reynolds TC, Smith SD, Sklar J
The Journal of experimental medicine. 1989 ; 169 (2) : 369-377.
PMID 2536065
 
TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia.
Xia Y, Brown L, Yang CY, Tsan JT, Siciliano MJ, Espinosa R III, Le Beau MM, Baer RJ
Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (24) : 11416-11420.
PMID 1763056
 
Products of the TAL2 oncogene in leukemic T cells: bHLH phosphoproteins with DNA-binding activity.
Xia Y, Hwang LY, Cobb MH, Baer R
Oncogene. 1994 ; 9 (5) : 1437-1446.
PMID 8152805
 

Citation

This paper should be referenced as such :
Vanura, K
TAL2 (T-cell acute lymphoblastic leukemia 2)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):319-320.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TAL2ID28ch9q31.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(7;9)(q34;q32) TRB/TAL2
T-lineage acute lymphoblastic leukemia (T-ALL)


External links

Nomenclature
HGNC (Hugo)TAL2   11557
Cards
AtlasTAL2ID28ch9q31
Entrez_Gene (NCBI)TAL2  6887  T-cell acute lymphocytic leukemia 2
Aliases
GeneCards (Weizmann)TAL2
Ensembl hg19 (Hinxton)ENSG00000186051 [Gene_View]  chr9:108424738-108425385 [Contig_View]  TAL2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000186051 [Gene_View]  chr9:108424738-108425385 [Contig_View]  TAL2 [Vega]
ICGC DataPortalENSG00000186051
TCGA cBioPortalTAL2
AceView (NCBI)TAL2
Genatlas (Paris)TAL2
WikiGenes6887
SOURCE (Princeton)TAL2
Genetics Home Reference (NIH)TAL2
Genomic and cartography
GoldenPath hg19 (UCSC)TAL2  -     chr9:108424738-108425385 +  9q32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TAL2  -     9q32   [Description]    (hg38-Dec_2013)
EnsemblTAL2 - 9q32 [CytoView hg19]  TAL2 - 9q32 [CytoView hg38]
Mapping of homologs : NCBITAL2 [Mapview hg19]  TAL2 [Mapview hg38]
OMIM186855   613065   
Gene and transcription
Genbank (Entrez)AA767775 BC069422 BC126373 BC126375 HQ258056
RefSeq transcript (Entrez)NM_005421
RefSeq genomic (Entrez)NC_000009 NC_018920 NT_008470 NW_004929366
Consensus coding sequences : CCDS (NCBI)TAL2
Cluster EST : UnigeneHs.247978 [ NCBI ]
CGAP (NCI)Hs.247978
Alternative Splicing GalleryENSG00000186051
Gene ExpressionTAL2 [ NCBI-GEO ]   TAL2 [ EBI - ARRAY_EXPRESS ]   TAL2 [ SEEK ]   TAL2 [ MEM ]
Gene Expression Viewer (FireBrowse)TAL2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6887
GTEX Portal (Tissue expression)TAL2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ16559   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ16559  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ16559
Splice isoforms : SwissVarQ16559
PhosPhoSitePlusQ16559
Domaine pattern : Prosite (Expaxy)BHLH (PS50888)   
Domains : Interpro (EBI)bHLH_dom   
Domain families : Pfam (Sanger)HLH (PF00010)   
Domain families : Pfam (NCBI)pfam00010   
Domain families : Smart (EMBL)HLH (SM00353)  
Conserved Domain (NCBI)TAL2
DMDM Disease mutations6887
Blocks (Seattle)TAL2
SuperfamilyQ16559
Human Protein AtlasENSG00000186051
Peptide AtlasQ16559
HPRD01735
IPIIPI00002906   
Protein Interaction databases
DIP (DOE-UCLA)Q16559
IntAct (EBI)Q16559
FunCoupENSG00000186051
BioGRIDTAL2
STRING (EMBL)TAL2
ZODIACTAL2
Ontologies - Pathways
QuickGOQ16559
Ontology : AmiGORNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  DNA binding  protein binding  nucleus  transcription, DNA-templated  regulation of transcription from RNA polymerase II promoter  post-embryonic development  thalamus development  midbrain development  multicellular organism growth  protein dimerization activity  
Ontology : EGO-EBIRNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  DNA binding  protein binding  nucleus  transcription, DNA-templated  regulation of transcription from RNA polymerase II promoter  post-embryonic development  thalamus development  midbrain development  multicellular organism growth  protein dimerization activity  
NDEx NetworkTAL2
Atlas of Cancer Signalling NetworkTAL2
Wikipedia pathwaysTAL2
Orthology - Evolution
OrthoDB6887
GeneTree (enSembl)ENSG00000186051
Phylogenetic Trees/Animal Genes : TreeFamTAL2
HOVERGENQ16559
HOGENOMQ16559
Homologs : HomoloGeneTAL2
Homology/Alignments : Family Browser (UCSC)TAL2
Gene fusions - Rearrangements
Fusion : MitelmanTRB/TAL2 [-/9q31.2]  [t(7;9)(q34;q31)]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTAL2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TAL2
dbVarTAL2
ClinVarTAL2
1000_GenomesTAL2 
Exome Variant ServerTAL2
ExAC (Exome Aggregation Consortium)TAL2 (select the gene name)
Genetic variants : HAPMAP6887
Genomic Variants (DGV)TAL2 [DGVbeta]
DECIPHER (Syndromes)9:108424738-108425385  ENSG00000186051
CONAN: Copy Number AnalysisTAL2 
Mutations
ICGC Data PortalTAL2 
TCGA Data PortalTAL2 
Broad Tumor PortalTAL2
OASIS PortalTAL2 [ Somatic mutations - Copy number]
Cancer Gene: CensusTAL2 
Mutations and Diseases : HGMDTAL2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TAL2
DgiDB (Drug Gene Interaction Database)TAL2
DoCM (Curated mutations)TAL2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TAL2 (select a term)
intoGenTAL2
NCG5 (London)TAL2
Cancer3DTAL2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM186855    613065   
Orphanet
MedgenTAL2
Genetic Testing Registry TAL2
NextProtQ16559 [Medical]
TSGene6887
GENETestsTAL2
Huge Navigator TAL2 [HugePedia]
snp3D : Map Gene to Disease6887
BioCentury BCIQTAL2
ClinGenTAL2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6887
Chemical/Pharm GKB GenePA36327
Clinical trialTAL2
Miscellaneous
canSAR (ICR)TAL2 (select the gene name)
Probes
Litterature
PubMed15 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTAL2
EVEXTAL2
GoPubMedTAL2
iHOPTAL2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Mar 14 13:50:25 CET 2017

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