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FLASH GENE

Symbol

MYB

contributors: mct - updated : 14-12-2018

HGNC name	v-myb myeloblastosis viral oncogene homolog (avian)
HGNC id	7545

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	arranged in tandem
text	HBS1L-MYB intergenic region (chr6q23) regulates erythroid cell proliferation, maturation, and fetal hemoglobin (HbF) expression
STRUCTURE	37.86 kb     15 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001161656 16 - 3369 NP_001155128 - 758 - 1990 2202948 isoform 4 NM_001130173 16 - 3681 NP_001123645 - 761 - 1990 2202948 isoform 1 NM_001130172 15 - 3309 NP_001123644 - 637 - 1990 2202948 isoform 3 NM_005375 15 - 3342 NP_005366 - 640 - 1990 2202948 isoform 2 NM_001161657 14 - 3060 NP_001155129 - 555 - 1990 2202948 isoform 5 NM_001161658 16 - 3630 NP_001155130 - 745 - 1990 2202948 isoform 6 NM_001161659 14 - 3204 NP_001155131 - 603 - 1990 2202948 isoform 7 NM_001161660 14 - 3210 NP_001155132 - 605 - 1990 2202948 isoform 8

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly   salivary gland       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythroid Blood/Hematopoietic progenitor cell Digestive ameloblast Homo sapiens Digestive odontoblast Homo sapiens not specific fibroblast Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

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 51–52 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
	RUVBL2 is essential for the oncogenic function of MYB in AML (acute myeloid leukemia) by governing inhibition of myeloid differentiation
	ATF4 binds within the HBS1L-MYB intergenic enhancer and regulates expression of MYB, a known gamma-globin regulator

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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