ETV6 is an oncogene. This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in the protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia, congenital fibrosarcoma and more recently an unusual salivary tumor that has been termed "mammary analogue secretory carcinoma of salivary glands."[1]
Example structure of targeted conditional mutant allele for this gene
These Mutant ES Cells can be studied directly or used to generate mice with this gene knocked out. Study of these mice can shed light on the function of Etv6:
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Andreasson P, Johansson B, Arheden K et al. (1997). "Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities.". Genes Chromosomes Cancer19 (2): 77–83. doi:10.1002/(SICI)1098-2264(199706)19:2<77::AID-GCC2>3.0.CO;2-X. PMID9171997.
Lacronique V, Boureux A, Valle VD et al. (1997). "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.". Science278 (5341): 1309–12. doi:10.1126/science.278.5341.1309. PMID9360930.
Knezevich SR, McFadden DE, Tao W et al. (1998). "A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma.". Nat. Genet.18 (2): 184–7. doi:10.1038/ng0298-184. PMID9462753.
Kwiatkowski BA, Bastian LS, Bauer TR et al. (1998). "The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity.". J. Biol. Chem.273 (28): 17525–30. doi:10.1074/jbc.273.28.17525. PMID9651344.
Hannemann JR, McManus DM, Kabarowski JH, Wiedemann LM (1998). "Haemopoietic transformation by the TEL/ABL oncogene.". Br. J. Haematol.102 (2): 475–85. doi:10.1046/j.1365-2141.1998.00803.x. PMID9695962.
Cools J, Bilhou-Nabera C, Wlodarska I et al. (1999). "Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).". Blood94 (5): 1820–4. PMID10477709.
Wai DH, Knezevich SR, Lucas T et al. (2000). "The ETV6-NTRK3 gene fusion encodes a chimeric protein tyrosine kinase that transforms NIH3T3 cells.". Oncogene19 (7): 906–15. doi:10.1038/sj.onc.1203396. PMID10702799.
PDB gallery
1ji7: Crystal Structure of TEL SAM Polymer
1lky: Structure of the wild-type TEL-SAM polymer
2dao: Solution structure of ETS domain Transcriptional factor ETV6 protein