PROSITE documentation PDOC00374

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) α 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.