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

2008-10-01   Olesya Chayka , Arturo Sala 

Institute of Child Health Molecular Haematology, Cancer Biology Unit 30 Guilford street London, WC1N 1EH UK

Identity

HGNC
LOCATION
20q13.12
LOCUSID
ALIAS
B-MYB,BMYB
FUSION GENES

DNA/RNA

Atlas Image
red boxes: untranslated regions; green boxes: coding regions.

Description

49,415 bases DNA with 14 exons.

Transcription

2,731 bases mRNA.

Proteins

Atlas Image
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 name
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 name
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 name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
186247222008Activation of B-Myb by E2F1 in hepatocellular carcinoma.Nakajima T et al
88125021996Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q 13.1.Noben-Trauth K et al
103786971999The myb gene family in cell growth, differentiation and apoptosis.Oh IH et al
77217531995Requirement of b-myb function for survival and differentiative potential of human neuroblastoma cells.Raschellà G et al
104165951999Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification.Raschellà G et al
102289421999B-Myb protein in cellular proliferation, transcription control, and cancer: latest developments.Sala A et al
180261322008Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk.Schwab R et al
175887872007B-MYB is hypophosphorylated and resistant to degradation in neuroblastoma: implications for cell survival.Schwab R et al
104971541999B-myb is required for inner cell mass formation at an early stage of development.Tanaka Y et al

Other Information

Locus ID:

NCBI: 4605
MIM: 601415
HGNC: 7548
Ensembl: ENSG00000101057

Variants:

dbSNP: 4605
ClinVar: 4605
TCGA: ENSG00000101057
COSMIC: MYBL2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000101057ENST00000217026P10244
ENSG00000101057ENST00000396863P10244

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G1-G1/S phasesREACTOMER-HSA-453279
G0 and Early G1REACTOMER-HSA-1538133
Mitotic G2-G2/M phasesREACTOMER-HSA-453274
G2/M TransitionREACTOMER-HSA-69275
Polo-like kinase mediated eventsREACTOMER-HSA-156711
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factorsREACTOMER-HSA-8864260
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiationREACTOMER-HSA-8869496

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
235552852013Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB.261
211874252011miR-29 and miR-30 regulate B-Myb expression during cellular senescence.82
208645102010ANCCA/ATAD2 overexpression identifies breast cancer patients with poor prognosis, acting to drive proliferation and survival of triple-negative cells through control of B-Myb and EZH2.61
171598992007The human synMuv-like protein LIN-9 is required for transcription of G2/M genes and for entry into mitosis.57
175637502007Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex.56
190434542009In vitro and in vivo analysis of B-Myb in basal-like breast cancer.41
193839082009B-MYB is required for recovery from the DNA damage-induced G2 checkpoint in p53 mutant cells.38
186766802008Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.32
196921682010Genetic susceptibility to distinct bladder cancer subphenotypes.25
213677502011miR-34a induces the downregulation of both E2F1 and B-Myb oncogenes in leukemic cells.25

Citation

Olesya Chayka ; Arturo Sala

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

Atlas Genet Cytogenet Oncol Haematol. 2008-10-01

Online version: http://atlasgeneticsoncology.org/gene/41469/mybl2