| SMART accession number: | SM00413
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| Description: |
variation of the helix-turn-helix motif |
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| Interpro abstract (IPR000418): |
Transcription factors are protein molecules that bind to specific DNA sequences in the genome, resulting in the induction or inhibition of gene transcription [(PUBMED:2163347)]. The ets oncogene is such a factor, possessing a region of 85-90 amino acids known as the ETS (erythroblast transformation specific) domain [(PUBMED:2163347), (PUBMED:2253872), (PUBMED:14693367)]. This domain is rich in positively-charged and aromatic residues, and binds to purine-rich segments of DNA. The ETS domain has been identified in other transcription factors such as PU.1, human erg, human elf-1, human elk-1, GA binding protein, and a number of others [(PUBMED:2163347), (PUBMED:2253872), (PUBMED:8425553)]. 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. NMR-analysis of the structure of the Ets domains revealed that it contains three alpha-helixes (1-3) and four-stranded beta-sheets (1-4) arranged in the order alpha1-beta1-beta2-alpha2-alpha3-beta3-beta4 forming a winged helix-turn-helix (wHTH) topology [(PUBMED:12559563)]. The third alpha-helix is responsive to contact to the major groove of the DNA. Different members of the Ets family proteins display distinct DNA binding specificities. The Ets domains and the flanking amino acid sequences of the proteins influence the binding affinity, and the alteration of a single amino acid in the Ets domain can change its DNA binding specificities. Avian leukemia virus E26 is a replication defective retrovirus that induces a mixed erythroid/myeloid leukemia in chickens.This 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 [(PUBMED:2165853)] 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.
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| GO process: | regulation of transcription, DNA-dependent (GO:0006355) |
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| GO function: | sequence-specific DNA binding (GO:0043565), sequence-specific DNA binding transcription factor activity (GO:0003700) |
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| Family alignment: |
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Click on the following links for more information.
- Evolution (species in which this domain is found)
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- Cellular role (predicted cellular role)
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Binding / catalysis: DNA-binding
- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Wasylyk B, Hagman J, Gutierrez-Hartmann A
- Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway.
- Trends Biochem Sci. 1998; 23: 213-6
- Display abstract
The Ets family of transcription factors includes nuclear phosphoproteins that are involved in cell proliferation, differentiation and oncogenic transformation. The family is defined by a conserved DNA-binding domain (the ETS-DBD), which forms a highly conserved, winged, helix-turn-helix structural motif. As targets of the Ras-MAPK signaling pathway, Ets proteins function as critical nuclear integrators of ubiquitous signaling cascades. To direct signals to specific target genes, Ets proteins interact with (other) transcription factors that promote the binding of Ets proteins to composite Ras-responsive elements.
- Liang H et al.
- Solution structure of the ets domain of Fli-1 when bound to DNA.
- Nat Struct Biol. 1994; 1: 871-5
- Display abstract
Members of the ets family of transcription factors share a conserved DNA-binding domain, the ets domain. By using multidimensional NMR, we have determined the structure of the ets domain of human Fli-1 in the DNA-bound form. It consists of three alpha-helices and a four-stranded beta-sheet, similar to structures of the class of helix-turn-helix DNA binding proteins first found in the catabolite activator protein of Escherichia coli. NMR and mutagenesis experiments suggest that in comparison to structurally related proteins, the ets domain uses a new variation of the helix-turn-helix motif for binding to DNA.
- Wasylyk B, Hahn SL, Giovane A
- The Ets family of transcription factors.
- Eur J Biochem. 1993; 211: 7-18
- Display abstract
Interest in the Ets proteins has grown enormously over the last decade. The v-ets oncogene was originally discovered as part of a fusion protein expressed by a transforming retrovirus (avian E26), and later shown to be transduced from a cellular gene. About 30 related proteins have now been found in species ranging from flies to humans, that resemble the vEts protein in the so-called 'ets domain'. The ets domain has been shown to be a DNA-binding domain, that specifically interacts with sequences containing the common core trinucleotide GGA. Furthermore, it is involved in protein-protein interactions with co-factors that help determine its biological activity. Many of the Ets-related proteins have been shown to be transcription activators, like other nuclear oncoproteins and anti-oncoproteins (Jun, Fos, Myb, Myc, Rel, p53, etc.). However, Ets-like proteins may have other functions, such as in DNA replication and a general role in transcription activation. Ets proteins have been implicated in regulation of gene expression during a variety of biological processes, including growth control, transformation, T-cell activation, and developmental programs in many organisms. Signals regulating cell growth are transmitted from outside the cell to the nucleus by growth factors and their receptors. G-proteins, kinases and transcription factors. We will discuss how several Ets-related proteins fit into this scheme, and how their activity is regulated both post- and pre-translationally. Loss of normal control is often associated with conversion to an oncoprotein. vEts has been shown to have different properties from its progenitor, which might explain how it has become oncogenic. Oncogene-related products have been implicated in the control of various developmental processes. Evidence is accumulating for a role for Ets family members in Drosophila development, Xenopus oocyte maturation, lymphocyte differentiation, and viral infectious cycles. An ultimate hope in studying transformation by oncoproteins is to understand how cells become cancerous in humans, which would lead to more effective treatments. vEts induces erythroblastosis in chicken. Cellular Ets-family proteins can be activated by proviral insertion in mice and, most interestingly, by chromosome translocation in humans. We are at the beginning of understanding the multiple facets of regulation of Ets activity. Future work on the Ets family promises to provide important insights into both normal control of growth and differentiation, and deregulation in illness.
- Karim FD et al.
- The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence.
- Genes Dev. 1990; 4: 1451-3
- Metabolism (metabolic pathways involving proteins which contain this domain)
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| % proteins involved | KEGG pathway ID | Description |
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| 34.15 | map04320 | Dorso-ventral axis formation | | 18.29 | map04010 | MAPK signaling pathway | | 8.54 | map05221 | Acute myeloid leukemia | | 8.54 | map04510 | Focal adhesion | | 7.32 | map04012 | ErbB signaling pathway | | 7.32 | map05213 | Endometrial cancer | | 7.32 | map04912 | GnRH signaling pathway | | 7.32 | map04910 | Insulin signaling pathway | | 1.22 | map02010 | ABC transporters - General |
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with ETS domain which could be assigned to a KEGG orthologous group, and not all proteins containing ETS domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%. |
- Structure (3D structures containing this domain)
3D Structures of ETS domains in PDB
| PDB code | Main view | Title | | 1awc |  | Mouse gabp alpha/beta domain bound to dna |
| 1bc7 |  | Serum response factor accessory protein 1a (sap-1)/dna complex |
| 1bc8 |  | Structures of sap-1 bound to dna sequences from the e74 and c-fos promoters provide insights into how ets proteins discriminate between related dna targets |
| 1dux |  | Elk-1/dna structure reveals how residues distal from dna- binding surface affect dna-recognition |
| 1fli |  | Dna-binding domain of fli-1 |
| 1gvj |  | Ets-1 dna binding and autoinhibitory domains |
| 1hbx |  | Ternary complex of sap-1 and srf with specific sre dna |
| 1k6o |  | Crystal structure of a ternary sap-1/srf/c-fos sre dna complex |
| 1k78 |  | Pax5(1-149)+ets-1(331-440)+dna |
| 1k79 |  | Ets-1(331-440)+ggaa duplex |
| 1k7a |  | Ets-1(331-440)+ggag duplex |
| 1md0 |  | Crystal structure of an inhibited fragment of ets-1 |
| 1mdm |  | Inhibited fragment of ets-1 and paired domain of pax5 bound to dna |
| 1pue |  | Pu.1 ets domain-dna complex |
| 1r36 |  | Nmr-based structure of autoinhibited murine ets-1 deltan301 |
| 1wwx |  | Solution structure of the ets-domain of the ets domain transcription factor |
| 1yo5 |  | Analysis of the 2.0a crystal structure of the protein-dna complex of human pdef ets domain bound to the prostate specific antigen regulatory site |
| 2dao |  | Solution structure of ets domain transcriptional factor etv6 protein |
| 2nny |  | Crystal structure of the ets1 dimer dna complex. |
| 2stt |  | Solution nmr structure of the human ets1/dna complex, 25 structures |
| 2stw |  | Solution nmr structure of the human ets1/dna complex, restrained regularized mean structure |
| 3g9w |  | Crystal structure of talin2 f2-f3 in complex with the integrin beta1d cytoplasmic tail |
- Links (links to other resources describing this domain)
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to expand nodes. To display all proteins with a ETS domain in a specific node, click on it.