MYB (gene)

Myb-like DNA-binding domain
Identifiers
Symbol	Myb_DNA-binding
Pfam	PF00249
InterPro	IPR001005
PROSITE	PDOC00037
CATH	1irz
SCOP2	1irz / SCOPe / SUPFAM
CDD	cd00167
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

MYB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GUU, 1GV2, 1GV5, 1GVD, 1H88, 1H89, 1IDY, 1IDZ, 1MBE, 1MBF, 1MBG, 1MBH, 1MBJ, 1MBK, 1MSE, 1MSF, 1SB0, 2AGH
Identifiers
Aliases	MYB , Cmyb, c-myb, c-myb_CDS, efg, MYB proto-oncogene, transcription factor
External IDs	OMIM: 189990; MGI: 97249; HomoloGene: 31311; GeneCards: MYB; OMA:MYB - orthologs
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6q23.3 Start 135,181,308 bp [1] End 135,219,173 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10 A3|10 9.75 cM Start 21,000,834 bp [2] End 21,036,883 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of sigmoid colon bronchial epithelial cell trabecular bone bone marrow thymus rectum buccal mucosa cell bone marrow cells mucosa of transverse colon right uterine tube Top expressed in thymus tibiofemoral joint left colon fetal liver hematopoietic progenitor cell crypt of lieberkuhn of small intestine Paneth cell hair follicle femur body of femur granulocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific protein binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nuclear matrix nucleus nucleoplasm Biological process positive regulation of transcription, DNA-templated chromatin remodeling negative regulation of transcription, DNA-templated regulation of transcription, DNA-templated negative regulation of transcription by RNA polymerase II positive regulation of histone H3-K4 methylation transcription, DNA-templated positive regulation of transcription by RNA polymerase II positive regulation of histone H3-K9 methylation positive regulation of T-helper cell differentiation transcription by RNA polymerase II mitotic cell cycle response to hypoxia positive regulation of collagen biosynthetic process positive regulation of neuron apoptotic process positive regulation of smooth muscle cell proliferation positive regulation of glial cell proliferation cellular response to hydrogen peroxide cellular response to retinoic acid positive regulation of transforming growth factor beta production positive regulation of neuron death positive regulation of hepatic stellate cell proliferation positive regulation of hepatic stellate cell activation positive regulation of testosterone secretion regulation of hematopoietic stem cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4602 17863 Ensembl ENSG00000118513 ENSMUSG00000019982 UniProt P10242 Q708E1 P06876 RefSeq (mRNA) NM_001130172 NM_001130173 NM_001161656 NM_001161657 NM_001161658 NM_001161659 NM_001161660 NM_005375 NM_001198914 NM_010848 NM_033597 RefSeq (protein) NP_001123644 NP_001123645 NP_001155128 NP_001155129 NP_001155130 NP_001155131 NP_001155132 NP_005366 NP_001185843 NP_034978 Location (UCSC) Chr 6: 135.18 – 135.22 Mb Chr 10: 21 – 21.04 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Myb genes are part of a large gene family of transcription factors found in animals and plants. In humans, it includes Myb proto-oncogene like 1 and Myb-related protein B in addition to MYB proper. ^{[5] [6]} Members of the extended SANT/Myb family also include the SANT domain and other similar all-helical homeobox-like domains.

Function

Viral

The Myb gene family is named after the eponymous gene in Avian myeloblastosis virus. The viral Myb (v-Myb, P01104 ) recognizes the sequence 5'-YAACKG-3'. It causes myeloblastosis (myeloid leukemia) in chickens. ^[7] Compared to the normal animal cellular Myb (c-myb), v-myb contains deletions in the C-terminal regulatory domain, leading to aberrant activation of other oncogenes. ^[8]

Animals

Myb proto-oncogene protein is a member of the MYB (myeloblastosis) family of transcription factors. The protein contains three domains, an N-terminal DNA-binding domain, a central transcriptional activation domain and a C-terminal domain involved in transcriptional repression. It may play a role in cell cycle regulation. Like the viral version, this gene is an oncogene, and rearrangements of the gene (often involving deletion in the C-terminal domain) causes cancer. ^[8]

Plants

MYB factors represent a family of proteins that include the conserved MYB DNA-binding domain. Plants contain a MYB-protein subfamily that is characterised by the R2R3-type MYB domain. ^[9]

In maize, phlobaphenes are synthesized in the flavonoids synthetic pathway ^[10] from polymerisation of flavan-4-ols ^{[11] [12]} which encodes an R2R3 myb-like transcriptional activator ^[13] of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols) ^[14] while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor. ^[15] The maize P gene encodes a Myb homolog that recognizes the sequence CCWACC, in sharp contrast with the YAACGG bound by vertebrate Myb proteins. ^[16]

In sorghum, the corresponding yellow seed 1 gene (y1) ^[17] also encodes a R2R3 type of Myb domain protein that regulates the expression of chalcone synthase, chalcone isomerase and dihydroflavonol reductase genes required for the biosynthesis of 3-deoxyflavonoids. ^[18]

Ruby is a MYB transcriptional activator of genes that produce anthocyanin in citrus fruits. In most citrus varieties Ruby is non-functional, but in blood oranges it upregulates anthocyanin production to produce the characteristic red color of the fruit. ^[19]

See also

• EZH1

References

1. GRCh38: Ensembl release 89: ENSG00000118513 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019982 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Chen Y, Xu H, Liu J, Zhang C, Leutz A, Mo X (Jul 2007). "The c-Myb functions as a downstream target of PDGF-mediated survival signal in vascular smooth muscle cells". Biochem Biophys Res Commun. 360 (2): 433–6. doi:10.1016/j.bbrc.2007.06.078. PMID   17599807.
6. "Entrez Gene: v-myb myeloblastosis viral oncogene homolog (avian)".
7. Klempnauer KH, Symonds G, Evan GI, Bishop JM (June 1984). "Subcellular localization of proteins encoded by oncogenes of avian myeloblastosis virus and avian leukemia virus E26 and by chicken c-myb gene". Cell. 37 (2): 537–47. doi:10.1016/0092-8674(84)90384-2. PMID   6327074. S2CID   46196167.
8. George OL, Ness SA (October 2014). "Situational awareness: regulation of the myb transcription factor in differentiation, the cell cycle and oncogenesis". Cancers. 6 (4): 2049–71. doi: 10.3390/cancers6042049 . PMC   4276956 . PMID   25279451.
9. Stracke R, Werber M, Weisshaar B (October 2001). "The R2R3-MYB gene family in Arabidopsis thaliana". Curr. Opin. Plant Biol. 4 (5): 447–56. Bibcode:2001COPB....4..447S. doi:10.1016/s1369-5266(00)00199-0. PMID   11597504.
10. Himi E, Mares DJ, Yanagisawa A, Noda K (July 2002). "Effect of grain colour gene (R) on grain dormancy and sensitivity of the embryo to abscisic acid (ABA) in wheat". J. Exp. Bot. 53 (374): 1569–74. doi: 10.1093/jxb/erf005 . PMID   12096095.
11. Winkel-Shirley B (June 2001). "Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology". Plant Physiol. 126 (2): 485–93. doi:10.1104/pp.126.2.485. PMC   1540115 . PMID   11402179.
12. Chopra S, Cocciolone SM, Bushman S, Sangar V, McMullen MD, Peterson T (March 2003). "The maize unstable factor for orange1 is a dominant epigenetic modifier of a tissue specifically silent allele of pericarp color1". Genetics. 163 (3): 1135–46. doi:10.1093/genetics/163.3.1135. PMC   1462483 . PMID   12663550.
13. Structural And Transcriptional Analysis Of The Complex P1-wr Cluster In Maize. Wolfgang Goettel, Joachim Messing. Plant & Animal Genomes XVI Conference Archived 2012-02-18 at the Wayback Machine
14. Dong X, Braun EL, Grotewold E (September 2001). "Functional conservation of plant secondary metabolic enzymes revealed by complementation of Arabidopsis flavonoid mutants with maize genes" (PDF). Plant Physiol. 127 (1): 46–57. doi:10.1104/pp.127.1.46. hdl:1811/48809. PMC   117961 . PMID   11553733.
15. Lee EA, Harper V (2002). "Suppressor of Pericarp Pigmentation 1 (SPP1), a novel gene involved in phlobaphene accumulation in maize (Zea mays L.) pericarps". Maydica. 47 (1): 51–58. INIST   13772300
16. Grotewold E, Drummond BJ, Bowen B, Peterson T (1994). "The myb-homologous P gene controls phlobaphene pigmentation in maize floral organs by directly activating a flavonoid biosynthetic gene subset". Cell. 76 (3): 543–554. doi:10.1016/0092-8674(94)90117-1. PMID   8313474. S2CID   42197232.
17. Boddu J, Svabek C, Ibraheem F, Jones AD, Chopra S (2005). "Characterization of a deletion allele of a sorghum Myb gene yellow seedl showing loss of 3-deoxyflavonoids". Plant Science. 169 (3): 542–552. Bibcode:2005PlnSc.169..542B. doi:10.1016/j.plantsci.2005.05.007. INIST   16983977
18. Boddu J, Jiang C, Sangar V, Olson T, Peterson T, Chopra S (January 2006). "Comparative structural and functional characterization of sorghum and maize duplications containing orthologous myb transcription regulators of 3-deoxyflavonoid biosynthesis". Plant Mol. Biol. 60 (2): 185–99. doi:10.1007/s11103-005-3568-1. PMID   16429259. S2CID   23841582.
19. Butelli E, Licciardello C, Zhang Y, Liu J, Mackay S, Bailey P, Reforgiato-Recupero G, Martin C (2012). "Retrotransposons control fruit-specific, cold-dependent accumulation of anthocyanins in blood oranges". Plant Cell. 24 (3): 1242–55. Bibcode:2012PlanC..24.1242B. doi:10.1105/tpc.111.095232. PMC   3336134 . PMID   22427337.

Further reading

• Oh IH, Reddy EP (1999). "The myb gene family in cell growth, differentiation and apoptosis". Oncogene. 18 (19): 3017–33. doi: 10.1038/sj.onc.1202839 . PMID   10378697.
• Nicolaides NC, Gualdi R, Casadevall C, Manzella L, Calabretta B (1991). "Positive autoregulation of c-myb expression via Myb binding sites in the 5' flanking region of the human c-myb gene". Mol. Cell. Biol. 11 (12): 6166–76. doi:10.1128/mcb.11.12.6166-6176.1991. PMC   361795 . PMID   1944282.
• Kalkbrenner F, Guehmann S, Moelling K (1990). "Transcriptional activation by human c-myb and v-myb genes". Oncogene. 5 (5): 657–61. PMID   2189102.
• Westin EH, Gorse KM, Clarke MF (1990). "Alternative splicing of the human c-myb gene". Oncogene. 5 (8): 1117–24. PMID   2202948.
• Dasgupta P, Reddy EP (1990). "Identification of alternatively spliced transcripts for human c-myb: molecular cloning and sequence analysis of human c-myb exon 9A sequences". Oncogene. 4 (12): 1419–23. PMID   2687764.
• Janssen JW, Vernole P, de Boer PA, Oosterhuis JW, Collard JG (1986). "Sublocalization of c-myb to 6q21----q23 by in situ hybridization and c-myb expression in a human teratocarcinoma with 6q rearrangements". Cytogenet. Cell Genet. 41 (3): 129–35. doi:10.1159/000132217. PMID   3007038.
• Slamon DJ, Boone TC, Murdock DC, Keith DE, Press MF, Larson RA, Souza LM (1986). "Studies of the human c-myb gene and its product in human acute leukemias". Science. 233 (4761): 347–51. Bibcode:1986Sci...233..347S. doi:10.1126/science.3014652. PMID   3014652.
• Majello B, Kenyon LC, Dalla-Favera R (1987). "Human c-myb protooncogene: nucleotide sequence of cDNA and organization of the genomic locus". Proc. Natl. Acad. Sci. U.S.A. 83 (24): 9636–40. doi: 10.1073/pnas.83.24.9636 . PMC   387195 . PMID   3540945.
• Szczylik C, Skorski T, Ku DH, Nicolaides NC, Wen SC, Rudnicka L, Bonati A, Malaguarnera L, Calabretta B (1993). "Regulation of proliferation and cytokine expression of bone marrow fibroblasts: role of c-myb". J. Exp. Med. 178 (3): 997–1005. doi:10.1084/jem.178.3.997. PMC   2191153 . PMID   7688794.
• Krieg J, Oelgeschläger M, Janknecht R, Lüscher B (1995). "High affinity DNA binding of native full length c-Myb and differential proteolytic sensitivity of its N- and C-terminal domains". Oncogene. 10 (11): 2221–8. PMID   7784067.
• Jacobs SM, Gorse KM, Westin EH (1994). "Identification of a second promoter in the human c-myb proto-oncogene". Oncogene. 9 (1): 227–35. PMID   8302584.
• Favier D, Gonda TJ (1994). "Detection of proteins that bind to the leucine zipper motif of c-Myb". Oncogene. 9 (1): 305–11. PMID   8302594.
• Glaser R, Lafuse WP, Bonneau RH, Atkinson C, Kiecolt-Glaser JK (1993). "Stress-associated modulation of proto-oncogene expression in human peripheral blood leukocytes". Behav. Neurosci. 107 (3): 525–9. doi:10.1037/0735-7044.107.3.525. PMID   8329139.
• Dash AB, Orrico FC, Ness SA (1996). "The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb". Genes Dev. 10 (15): 1858–69. doi: 10.1101/gad.10.15.1858 . PMID   8756344.
• Vorbrueggen G, Lovrić J, Moelling K (1997). "Functional analysis of phosphorylation at serine 532 of human c-Myb by MAP kinase". Biol. Chem. 377 (11): 721–30. doi:10.1515/bchm3.1996.377.11.721. PMID   8960373.
• Tavner FJ, Simpson R, Tashiro S, Favier D, Jenkins NA, Gilbert DJ, Copeland NG, Macmillan EM, Lutwyche J, Keough RA, Ishii S, Gonda TJ (1998). "Molecular cloning reveals that the p160 Myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb". Mol. Cell. Biol. 18 (2): 989–1002. doi:10.1128/MCB.18.2.989. PMC   108811 . PMID   9447996.
• Hedge SP, Kumar A, Kurschner C, Shapiro LH (1998). "c-Maf interacts with c-Myb to regulate transcription of an early myeloid gene during differentiation". Mol. Cell. Biol. 18 (5): 2729–37. doi:10.1128/mcb.18.5.2729. PMC   110652 . PMID   9566892.
• Leverson JD, Koskinen PJ, Orrico FC, Rainio EM, Jalkanen KJ, Dash AB, Eisenman RN, Ness SA (1998). "Pim-1 kinase and p100 cooperate to enhance c-Myb activity". Mol. Cell. 2 (4): 417–25. doi: 10.1016/S1097-2765(00)80141-0 . PMID   9809063.
• Thompson MA, Rosenthal MA, Ellis SL, Friend AJ, Zorbas MI, Whitehead RH, Ramsay RG (1998). "c-Myb down-regulation is associated with human colon cell differentiation, apoptosis, and decreased Bcl-2 expression". Cancer Res. 58 (22): 5168–75. PMID   9823328.
• Verbeek W, Gombart AF, Chumakov AM, Müller C, Friedman AD, Koeffler HP (1999). "C/EBPepsilon directly interacts with the DNA binding domain of c-myb and cooperatively activates transcription of myeloid promoters". Blood. 93 (10): 3327–37. doi: 10.1182/blood.V93.10.3327 . PMID   10233885.

External links

• MYB+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• DrosophilaMyb oncogene-like - The Interactive Fly
• Arabidospsis thaliana MYB family at Database of Arabidopsis Transcription Factors (DATF)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.