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FLASH GENE
Symbol MYB contributors: mct - updated : 14-12-2016
HGNC name v-myb myeloblastosis viral oncogene homolog (avian)
HGNC id 7545
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three functional domains responsible for DNA binding, transcriptional activation, and negative regulation
  • DNA-binding domain in the N terminus consists of three imperfect tandem repeats of 5152 amino acids and binds to the DNA sequence 5'-AACNG-3'
  • centrally located transcriptional activation domain binds to the transcriptional coactivator CBP
  • a WD40 domain, negative regulator in the C-terminal portion of MYB interacts with the corepressors TRIM28 and ZMYND11
  • HOMOLOGY
    interspecies homolog to avian myeloblastosis viral (v-myb) oncogene
    homolog to murine Myb (91.0pc)
    Homologene
    FAMILY
    CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • involved in the proliferation of immature hematopoietic cells, as well as hematopoietic cell differentiation
  • inducing DNA binding
  • effector of estrogen/ER signaling and have a functional role in breast cancer
  • controls SNAI2 transcription in tumor cells of different origin
  • functional relationship between MYB and metastasis-associated SNAI2 in hematopoietic and non-hematopoietic cancer cells
  • role for MYB at the hub of ER- and HER2-dependent pathways in mammary carcinogenesis
  • critical role of MYB in promoting ERBIN transcription in G2/M phase
  • MYB- activity is regulated by various post-translational modifications
  • potential integration of MYB into regulatory networks during hard-tissue differentiation and mineralization
  • role for MYB in the regulation of stem cells
  • is identified as a novel regulator of PAX7 in early neural crest development
  • has an early, crucial and conserved role in multiciliogenesis, and it promotes likely a novel S-like phase in which centriole amplification occurs uncoupled from DNA synthesis
  • acts in a conserved pathway downstream of Notch signaling and multicilin, a protein related to the S-phase regulator geminin, and upstream of FOXJ1
  • is involved in regulating the differentiation program of myogenic progenitor cells as its expression blocks myoblast fusion
  • MYB and BCL11A cooperate with DNMT1 to achieve developmental repression of embryonic and fetal beta-like globin genes in the adult erythroid environment
  • transcription factor MYB is a key regulator that permits early multilineage differentiation of airway epithelial cells
  • key regulator of hematopoiesis, including having critical roles in hematopoietic stem cells (HSCs)
  • specific role for MYB in KRT14+ epithelial cells in the preservation of adult skin integrity and function
  • may play a specific role in hard tissue formation
  • transcription factor involved in the regulation and promotion of endochondral bone formation
  • is a transcription factor with multifaceted target regulation depending on cell type
  • transcription factor regulating the expression of a wide array of genes involved in cellular functions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    unique MYB-DHRS2-MDM2-TP53 mitochondria-to-nucleus signaling pathway that may have functional significance for ER-positive breast cancers
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • target of estrogen/ER signaling
  • interacting with MAF (modulation of MYB activity may be an important mechanism for the control of gene transcription during hematopoietic cell development)
  • cooperates with CASP8AP2 in foci associated with active POLR2A, leading to enhancement of MYB-dependent gene activation
  • target genes including MYC, BCL2 and GBX2 which are involved in cell cycle control, blockage of apoptosis, and growth and differentiation control, respectively
  • interacting with HIPK1
  • HBS1L-MYB intergenic interval associated with elevated HbF levels
  • activates SNAI2 expression through a transcriptional mechanism in embryonic kidney, colon carcinoma, chronic myeloid leukemia and neuroblastoma cells
  • PIAS1 is a common partner for two cancer-related nuclear factors, MYB and CASP8AP2 (functional cooperation between CASP8AP2 and PIAS1 in the enhancement of MYB activity in active nuclear foci)
  • interaction of MYB with MYB site in the ERBIN promoter was significantly enhanced in G2/M phase
  • FBXW5 enhanced sumoylation of nuclear MYB and induced the localization of MYB to nuclear dot-like domains
  • FBXW5 enhances sumoylation of MYB in the nucleus, which suppresses MYB activity
  • FBXW5-mediated sumoylation of MYB may enhance the repression of some MYB target gene
  • MYB is identified as a novel regulator of PAX7 in early neural crest development
  • KIX domains of CREBBP, and especially EP300, are principal mediators of MYB-dependent gene activation and repression that is required for definitive hematopoiesis
  • PIAS1 causes activation or repression of MYB dependent target genes
  • PIAS1 acts as a "protein inhibitor of activated MYB" in the absence of SUMOylation while, in its presence, PIAS1 behaves as a "protein activator of repressed MYB"
  • MYB expression is critical for myeloid leukemia development induced by SETBP1 activation
  • TGFB1I1 is a novel interaction partner of the nuclear kinase HIPK1 and TGFB1I1, like HIPK1, also interacts with the transcription factor MYB
  • TGFB1I1 and HIPK1 assist MYB in recruiting the coactivator and acetyltransferase EP300 to chromatin
  • MAZ is essential to bypass MYB promoter repression by RB1 family members and to induce MYB expression
  • cell & other
    REGULATION
    Other phosphorylated and degraded in response to Wnt1 signaling
    phosphorylated by HIPK1, repressing the ability to activate MIM1 in haematopoietic cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    contribute to leukemogenesis
    tumoral     --over  
    at relatively high levels in at least two epithelial tumors: colon and breast cancer
    tumoral     --over  
    in T cell acute lymphoblastic leukemia
    constitutional     --over  
    promotes nuclear accumulation of DHRS2, which is able to support P53 stabilization and activation
    tumoral fusion translocation    
    t(6;9)(q23.3;p22.3) translocation in adenoid cystic carcinomas (ACC) of the breast and head and neck results in fusions encoding chimeric transcripts predominantly consisting of MYB exon 14 linked to the last coding exon(s) of NFIB
    constitutional   deletion    
    in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression
    tumoral fusion      
    MYB-GATA1 fusion gene in acute basophilic leukemia
    tumoral     --over  
    aberrantly overexpressed in pancreatic cancer cells and acts as a key determinant of pancreatic tumour growth and metastasis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target could be a therapeutic target in human T-ALL
    ANIMAL & CELL MODELS