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PROSITE documentation PDOC00374 [for PROSITE entry PS00346]

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.

Last update:

April 2006 / Pattern revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

ETS_DOMAIN_2, PS00346; Ets-domain signature 2  (PATTERN)

ETS_DOMAIN_3, PS50061; Ets-domain profile  (MATRIX)

ETS_DOMAIN_1, PS00345; Ets-domain signature 1  (PATTERN)


1AuthorsReddy E.S.P., Rao V.N.
TitleLocalization and modulation of the DNA-binding activity of the human c-ets-1 protooncogene.
SourceCancer Res. 50:5013-5016(1990).
PubMed ID2165853

2AuthorsKarim 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.
TitleThe ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence.
SourceGenes Dev. 4:1451-1453(1990).
PubMed ID2253872

3AuthorsMcLeod K., Leprince D., Stehelin D.
SourceTrends Biochem. Sci. 17:251-256(1992).

4AuthorsLaudet V., Niel C., Duterque-Coquillaud M., Leprince D., Stehelin D.
TitleEvolution of the ets gene family.
SourceBiochem. Biophys. Res. Commun. 190:8-14(1993).
PubMed ID8422262

5AuthorsWasylyk B., Hahn S.L., Giovane A.
TitleThe Ets family of transcription factors.
SourceEur. J. Biochem. 211:7-18(1993).
PubMed ID8425553

6AuthorsWang C.-Y., Petryniak B., Ho I.-C., Thompson C.B., Leiden J.M.
TitleEvolutionarily conserved Ets family members display distinct DNA binding specificities.
SourceJ. Exp. Med. 175:1391-1399(1992).
PubMed ID1569404

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