{PDOC00374} {PS00345; ETS_DOMAIN_1} {PS00346; ETS_DOMAIN_2} {PS50061; ETS_DOMAIN_3} {BEGIN} ************************************* * Ets-domain signatures and profile * ************************************* Avian leukemia virus E26 is a replication defective retrovirus that induces a mixed erythroid/myeloid leukemia in chickens. E26 virus carries two distinct oncogenes, v-myb and v-ets. The ets portion of this oncogene is required for the induction of erythroblastosis. V-ets and c-ets-1, its cellular progenitor, have been shown [1] to be nuclear DNA-binding proteins. Ets-1 differs slightly from v-ets at its carboxy-terminal region. In most species where it has been sequenced, c-ets-1 exists in various isoforms generated by alternative splicing and differential phosphorylation. A number of proteins, that share regions of similarity with v-ets/c-ets-1, have been found and are listed below: - Ets-2, which has been sequenced in mammals, chicken, Xenopus and Drosophila. - Human ELF-1, a transcription factor that appears to be required for the T- cell-receptor-mediated trans activation of HIV-2 genes. - Mammalian ELK-1, ELK-3 (also known as Net or SAP-2) and ELK-4 (also known as SRF accessory protein 1 (SAP-1)), which all form a ternary complex with the serum response factor (SRF). - Human ERF, a potent transcriptional repressor that binds to the HI element of the Ets-2 promoter. - Human ERG. - Human ERM. - Mammalian ETV1, a transcriptional activator. - FLI-1, a sequence specific transcriptional activator. - Adenovirus E1A enhancer-binding protein (E1A-F) (ETV4) (PEA3). - PU.1 (also known as Spi-1), a protein that binds to a purine-rich sequence, the PU-box, that can act as a lymphoid-specific enhancer. PU.1 is probably a transcriptional activator that may be specifically involved in the differentiation or activation of macrophages or B cells. In mouse, Spi-1 is an oncogene involved in murine acute friend erythroleukemia. - Spi-B, a transcription factor that binds the PU-box. - GA binding protein (GAPB) alpha subunit. GAPB is a transcription factor capable of interacting with purine-rich repeats (GA repeats). - Drosophila protein elg-1. - Drosophila protein pokkuri (pok) (also known as yan), which is a negative regulator of photoreceptor development. - Drosophila protein pointed (pnt) which is required for glial-neuronal cell interactions. - Drosophila ecdysone induced protein 74E. All these proteins contain a conserved domain, the 'ETS-domain', [2,3,4,5] involved in DNA-binding. It seems to recognize purine-rich sequences [5]. This domain, of about 85 to 90 amino acids, is rich in aromatic and positively charged residues. It is generally localized at the C-terminus of the protein, with the exception of ELF-1, ELK-1, ELK-3, ELK-4 and ERF where it is found at the N-terminus. We have derived two signature patterns for the ETS-domain. The first one is based on a highly conserved region in the N-terminal part of the domain, while the second is based on a region in the second third of the domain. The profile spans the complete domain. -Consensus pattern: L-[FYW]-[QEDH]-F-[LI]-[LVQK]-{N}-[LI]-L -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: 1. -Consensus pattern: [RKHN]-x(2)-M-x-Y-[DENQ]-x-[LIVM]-[STAG]-R-[STAG]-[LI]-R- x-Y -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: April 2006 / Pattern revised. [ 1] Reddy E.S.P., Rao V.N. "Localization and modulation of the DNA-binding activity of the human c-ets-1 protooncogene." Cancer Res. 50:5013-5016(1990). PubMed=2165853 [ 2] Karim F.D., Urness L.D., Thummel C.S., Klemsz M.J., McKercher S.R., Celada A., Van Beveren C., Maki R.A., Gunther C.V., Nye J.A. "The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence." Genes Dev. 4:1451-1453(1990). PubMed=2253872 [ 3] McLeod K., Leprince D., Stehelin D. Trends Biochem. Sci. 17:251-256(1992). [ 4] Laudet V., Niel C., Duterque-Coquillaud M., Leprince D., Stehelin D. "Evolution of the ets gene family." Biochem. Biophys. Res. Commun. 190:8-14(1993). PubMed=8422262 [ 5] Wasylyk B., Hahn S.L., Giovane A. "The Ets family of transcription factors." Eur. J. Biochem. 211:7-18(1993). PubMed=8425553 [ 6] Wang C.-Y., Petryniak B., Ho I.-C., Thompson C.B., Leiden J.M. "Evolutionarily conserved Ets family members display distinct DNA binding specificities." J. Exp. Med. 175:1391-1399(1992). 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