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MYBL2 (v-myb myeloblastosis viral oncogene homolog (avian)-like 2)

Identity

Other namesB-MYB
B-Myb
BMYB
MGC15600
OTTHUMP00000031719
HGNC (Hugo) MYBL2
Location 20q13.1
Location_base_pair Starts at 42295709 and ends at 42345122 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  red boxes: untranslated regions; green boxes: coding regions.
Description 49,415 bases DNA with 14 exons.
Transcription 2,731 bases mRNA.

Protein

 
  R1, R2 and R3 form DNA-binding domain, TA - transactivation domain, CR - conserved region (the area of homology with c-Myb), RD - regulatory domain.
Description 704 amino acids, 93kDa protein.
R1, R2, R3 - three repeats 50 amino acids long, R2 and R3 contain HTH (helix-turn-helix) motives with unconventional turns required for DNA-binding activity, R1 serves as a DNA/protein complex stabilizer; TA contains acidic amino acids and is responsible for transcriptional activation; RD is responsible for repression of transactivation function of B-MYB.
Expression Widely expressed, expression is very high in proliferative cells, embryonic cells, haematopoietic progenitor cells.
Localisation Nucleus.
Function Transcription factor required for cell proliferation, cell cycle progression, chromosomal stability and differentiation. B-MYB knockout mice die at E4.5-E6.5 due to early developmental arrest.
Homology B-MYB is a member of MYB transcription factors family, which includes C-MYB and A-MYB, with high homology within TA and RD regions. DNA-binding domain is almost identical with that of A-MYB and C-MYB and conserved between mouse, human, chicken and drosophila.

Implicated in

Entity Neuroblastoma
Prognosis Overexpression is thought to be associated with a poor outcome of the disease.
Oncogenesis Was reported to be necessary for survival and differentiation of neuroblastoma cells.
  
Entity Hepatocellular carcinoma (HCC)
Oncogenesis B-MYB is reported to be a probable target of E2F1 transcription factor, which is dramatically overexpressed in HCC. There is a clear correlation between expression level of these two proteins. B-MYB overexpression in HCC causes the deregulation of apoptosis and cell cycle.
  
Entity Various cancer
Disease Amplification of B-MYB was described in breast carcinomas, liver carcinomas, ovarian carcinomas and in cutaneous T lymphoma. B-MYB expression was shown also to be increased in prostate and testicular malignancies. Moreover, B-MYB expression is notably increased in metastatic compared to localised prostate tumours.
The presence of B-MYB polymorphisms rs2070235 and rs11556379 is associated with a significant reduction of cancer risk.
Oncogenesis B-MYB overexpression may result in promotion of cancer cells survival and proliferation.
Polimorphisms can induce changes in protein conformation and therefore may in part deactivate B-MYB functions.
  

External links

Nomenclature
HGNC (Hugo)MYBL2   7548
Entrez_Gene (NCBI)MYBL2  4605  v-myb myeloblastosis viral oncogene homolog (avian)-like 2
Cards
AtlasMYBL2ID41469ch20q13
GeneCards (Weizmann)MYBL2
Ensembl (Hinxton)ENSG00000101057 [Gene_View]  MYBL2 [Vega]
AceView (NCBI)MYBL2
Genatlas (Paris)MYBL2
euGene (Indiana)4605
SOURCE (Stanford)NM_002466
Gene Expression (Array Express) ENSG00000101057
Genomic and cartography
GoldenPath (UCSC)MYBL2  -  20q13.1   chr20:42295709-42345122 +  20q13.1   [Description]    (hg19-Feb_2009)
EnsemblMYBL2 - 20q13.1 [CytoView]
Mapping of homologs : NCBIMYBL2 [Mapview]
OMIM601415   
Gene and transcription
Gene : Genbank (Entrez)AK223482 AK303249 AK314791 BC007585 BC053555
Reference sequence (RefSeq transcript) :SRSNM_002466
Reference transcript : EntrezNM_002466
RefSeq genomic : SRSAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
RefSeq genomic : EntrezAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
Consensus coding sequences : CCDS NCBIMYBL2
Cluster EST : UnigeneHs.179718 [ SRS ] Hs.179718 [ NCBI ]
Alternative Splicing : Fast-db (Paris)11694
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP10244 (SRS) P10244 (Expasy) P10244 (Uniprot)
With graphics : InterProP10244
Splice isoforms : VarSplice FASTAP10244(VarSplice FASTA)
Domaine pattern : Prosite (SRS)HTH_MYB (PS51294)   
Domain pattern : Prosite (Expaxy)HTH_MYB (PS51294)   
Domains : Interpro (SRS)C-myb_C    Homeodomain-like    Homeodomain-rel    HTH_Myb-type_DNA-bd    Myb_DNA-bd    Myb_trans_fac    SANT_DNA-bd   
Domains : Interpro (EBI)C-myb_C    Homeodomain-like    Homeodomain-rel    HTH_Myb-type_DNA-bd    Myb_DNA-bd    Myb_trans_fac    SANT_DNA-bd   
Related proteins : CluSTrP10244
Domain families : Pfam SRSCmyb_C (PF09316)    Myb_DNA-binding (PF00249)   
Domain families : Pfam SangerCmyb_C (PF09316)    Myb_DNA-binding (PF00249)   
Domain families : Pfam NCBIpfam09316    pfam00249   
Domain families : Smart EMBLSANT (SM00717)  
Blocks (Seattle)P10244
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
Human Protein AtlasENSG00000101057
HPRD03247
Protein Interaction databases
DIP (DOE-UCLA)P10244
IntAct (EBI)P10244
FunCoupENSG00000101057
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIMYBL2
SNP : GeneSNP UtahMYBL2
SNP : HGBaseMYBL2
Genetic variants : HAPMAPMYBL2
Somatic Mutations in Cancer : COSMICMYBL2 
Mutations and Diseases : HGMDMYBL2
Hereditary diseases : OMIM601415   
Hereditary diseases : GENETests601415   
Diseases : Genetic AssociationMYBL2
General knowledge
Homologs : HomoloGeneMYBL2
Homology/Alignments : Family Browser UCSCMYBL2
Phylogenetic Trees/Animal Genes : TreeFamMYBL2
Chemical/Protein Interactions : CTD4605
Keywords Ontology : AmiGOtranscription factor activity  nucleus  regulation of transcription  
Keywords Ontology : EGO-EBItranscription factor activity  nucleus  regulation of transcription  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesMYBL2 Related clones (RZPD - Berlin)
Literature
PubMed61 Pubmed reference(s) in Entrez
PubGeneMYBL2

Bibliography

Requirement of b-myb function for survival and differentiative potential of human neuroblastoma cells.
Raschell G, Negroni A, Sala A, Pucci S, Romeo A, Calabretta B.
J Biol Chem. 1995 Apr 14;270(15):8540-5.
PMID 7721753
 
Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q13.1.
Noben-Trauth K, Copeland NG, Gilbert DJ, Jenkins NA, Sonoda G, Testa JR, Klempnauer KH.
Genomics. 1996 Aug 1;35(3):610-2.
PMID 8812502
 
The myb gene family in cell growth, differentiation and apoptosis.
Oh IH, Reddy EP.
Oncogene. 1999 May 13;18(19):3017-33.(Review).
PMID 10378697
 
Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification.
Raschella G, Cesi V, Amendola R, Negroni A, Tanno B, Altavista P, Tonni GP, De Bernardi B, Calabretta B.
Cancer Res. 1999 Jul 15;59(14):3365-8.
PMID 10416595
 
B-Myb protein in cellular proliferation, transcription control, and cancer: latest developments.
Sala A, Watson R.
J Cell Physiol. 1999 Jun;179(3):245-50.(Review).
PMID 10228942
 
B-myb is required for inner cell mass formation at an early stage of development.
Tanaka Y, Patestos NP, Maekawa T, Ishii S.
J Biol Chem. 1999 Oct 1;274(40):28067-70.
PMID 10497154
 
B-MYB is hypophosphorylated and resistant to degradation in neuroblastoma: implications for cell survival.
Schwab R, Caccamo A, Bettuzzi S, Anderson J, Sala A.
Blood Cells Mol Dis 2007; 39(3):263-71. Epub 2007 Jun 27.
PMID 17588787
 
Activation of B-Myb by E2F1 in hepatocellular carcinoma.
Nakajima T, Yasui K, Zen K, Inagaki Y, Fujii H, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Inazawa J, Okanoue T.
Hepatol Res. 2008; 38(9): 886-95.
PMID 18624722
 
Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk.
Schwab R, Bussolari R, Corvetta D, Chayka O, Santilli G, Kwok JM-M, Amorotti GF, Tonini P, Iacoviello L, Bertorelle R, Menin C, Hubank M, Calabretta B, Sala A.
Oncogene 2008; 27(20): 2929-33.
PMID 18026132
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written10-2008Olesya Chayka, Arturo Sala
Institute of Child Health Molecular Haematology and Cancer Biology Unit 30 Guilford street London, WC1N 1EH UK

Citation

This paper should be referenced as such :
Chayka O, Sala A . MYBL2 (v-myb myeloblastosis viral oncogene homolog (avian)-like 2). Atlas Genet Cytogenet Oncol Haematol. October 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/MYBL2ID41469ch20q13.html

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indexed on : Thu Jul 15 14:48:09 CEST 2010

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