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41  structures 255  species 2  interactions 2375  sequences 22  architectures

Family: Ets (PF00178)

Summary: Ets-domain

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This is the Wikipedia entry entitled "ETS transcription factor family". More...

ETS transcription factor family Edit Wikipedia article

Ets-domain
PDB 1r36 EBI.jpg
Structure of Ets-1 DNA binding autoinhibition.[1]
Identifiers
Symbol Ets
Pfam PF00178
Pfam clan CL0123
InterPro IPR000418
SMART SM00413
PROSITE PDOC00374
SCOP 1r36
SUPERFAMILY 1r36

In the field of molecular biology, the ETS (E26 transformation-specific[2] or E-twenty-six[3]) family is one of the largest families of transcription factors and is unique to metazoans. There are 29 genes in humans, 28 in the mouse, 10 in Caenorhabditis elegans and 9 in Drosophila. The founding member of this family was identified as a gene transduced by the leukemia virus, E26. The members of the family have been implicated in the development of different tissues as well as cancer progression.

Subfamilies

The ETS family is divided into 12 subfamilies, which are listed below:[4]

Subfamily Mammalian family members Invertebrate orthologs
ELF ELF1, ELF2 (NERF), ELF4 (MEF)
ELG GABPα ELG
ERG ERG, FLI1, FEV
ERF ERF (PE2), ETV3 (PE1)
ESE ELF3 (ESE1/ESX), ELF5 (ESE2), ESE3 (EHF)
ETS ETS1, ETS2 POINTED
PDEF SPDEF (PDEF/PSE)
PEA3 ETV4 (PEA3/E1AF), ETV5 (ERM), ETV1 (ER81)
ER71 ETV2 (ER71)
SPI SPI1 (PU.1), SPIB, SPIC
TCF ELK1, ELK4 (SAP1), ELK3 (NET/SAP2) LIN
TEL ETV6 (TEL), ETV7 (TEL2) YAN

Structure

All ETS family members are identified through a highly conserved DNA binding domain, the ETS domain, which is a winged helix-turn-helix structure that binds to DNA sites with a central GGA(A/T) DNA sequence. As well as DNA-binding functions, evidence suggests that the ETS domain is also involved in protein-protein interactions. There is limited similarity outside the ETS DNA binding domain.

Other domains are also present and vary from ETS member to ETS member, including the Pointed domain, a subclass of the SAM domain family.

Function

The ETS family is present throughout the body and is involved in a wide variety of functions including the regulation of cellular differentiation, cell cycle control, cell migration, cell proliferation, apoptosis (programmed cell death) and angiogenesis.

Multiple Ets factors have been found to be associated with cancer, such as through gene fusion. For example, the ERG ETS transcription factor is fused to the EWS gene, resulting in a condition called Ewing's sarcoma.[5] The fusion of TEL to the JAK2 protein results in early pre-B acute lymphoid leukaemia.[6] ERG and ETV1 are known gene fusions found in prostate cancer. [7]

In addition, Ets factors, e.g. the vertebrate Etv1 and the invertebrate Ast-1, have been shown to be important players in the specification and differentiation of dopaminergic neurons in both C. elegans and olfactory bulbs of mice.[8]

Mode of action

Amongst members of the ETS family, there is extensive conservation in the DNA-binding ETS domain and, therefore, a lot of redundancy in DNA binding. It is thought that interactions with other proteins is one way in which specific binding to DNA is achieved.[9] ETS factors act as transcriptional repressors, transcriptional activators, or both.[10]

References

  1. ^ Lee GM, Donaldson LW, Pufall MA et al. (February 2005). "The structural and dynamic basis of Ets-1 DNA binding autoinhibition". J. Biol. Chem. 280 (8): 7088–99. doi:10.1074/jbc.M410722200. PMID 15591056. 
  2. ^ Nunn, M. F.; Seeburg, P. H.; Moscovici, C.; Duesberg, P. H. (1983). "Tripartite structure of the avian erythroblastosis virus E26 transforming gene". Nature 306 (5941): 391–395. doi:10.1038/306391a0. PMID 6316155.  edit
  3. ^ Leprince, D.; Gegonne, A.; Coll, J.; De Taisne, C.; Schneeberger, A.; Lagrou, C.; Stehelin, D. (1983). "A putative second cell-derived oncogene of the avian leukaemia retrovirus E26". Nature 306 (5941): 395–397. doi:10.1038/306395a0. PMID 6316156.  edit
  4. ^ Gutierrez-Hartman A, Duval DL, Bradford AP (2007). "ETS transcription factors in endocrine systems". Trends Endocrinol Metab 18 (4): 150–8. doi:10.1016/j.tem.2007.03.002. PMID 17387021. 
  5. ^ Ida K, Kobayashi S, Taki T, Hanada R, Bessho F, Yamamori S, Sugimoto T, Ohki M, Hayashi Y (1995). "EWS-FLI-1 and EWS-ERG chimeric mRNAs in Ewing's sarcoma and primitive neuroectodermal tumor". Int J Cancer 63 (4): 500–4. doi:10.1002/ijc.2910630407. PMID 7591257. 
  6. ^ Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P (1997). "Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia". Blood 90 (7): 2535–40. PMID 9326218. 
  7. ^ Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM (October 2005). "Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer". Science 310 (5748): 644–8. doi:10.1126/science.1117679. PMID 16254181. 
  8. ^ Flames N and Hobert O (2009). "Gene regulatory logic of dopaminergic neuron differentiation". Nature 458 (7240): 885–890. doi:10.1038/nature07929. PMC 2671564. PMID 19287374. 
  9. ^ Verger A, Duterque-Coquillaud M (2002). "When Ets transcription factors meet their partners". BioEssays 24 (4): 362–70. doi:10.1002/bies.10068. PMID 11948622. 
  10. ^ Sharrocks AD (2001). "The ETS-domain transcription factor family". Nat Rev Mol Cell Biol 2 (11): 827–37. doi:10.1038/35099076. PMID 11715049. 

Further reading

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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Literature references

  1. Wasylyk B, Hagman J, Gutierrez-Hartmann A; , Trends Biochem Sci 1998;23:213-216.: Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway. PUBMED:9644975 EPMC:9644975


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry 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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 202 members:

AphA_like Arg_repressor B-block_TFIIIC Bac_DnaA_C BetR Bot1p BrkDBD CENP-B_N Cro Crp DDRGK Dimerisation DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF3116 DUF3853 DUF387 DUF3908 DUF4095 DUF4364 DUF739 DUF742 DUF977 E2F_TDP ELK Ets Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC Ftsk_gamma FUR GcrA GerE GntR HARE-HTH HemN_C Homeobox Homeobox_KN Homez HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_5 HTH_6 HTH_7 HTH_8 HTH_9 HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_OrfB_IS605 HTH_psq HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IF2_N KorB LacI LexA_DNA_bind LZ_Tnp_IS481 MADF_DNA_bdg MarR MarR_2 Med9 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 Mor MotA_activ MRP-L20 Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-binding Neugrin NUMOD1 OST-HTH P22_Cro PaaX PadR PAX PCI PCI_Csn8 Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_rep_org_N Phage_terminase Pou Pox_D5 PuR_N Put_DNA-bind_N Rap1-DNA-bind Rep_3 RepA_C RepA_N RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RP-C RPA RPA_C RQC Rrf2 RTP SAC3_GANP SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SpoIIID Sulfolobus_pRN TBPIP Terminase_5 TetR_N TFIIE_alpha Tn916-Xis Trans_reg_C TrfA TrmB Trp_repressor UPF0122 z-alpha

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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(15)
Full
(2375)
Representative proteomes NCBI
(2070)
Meta
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RP15
(249)
RP35
(337)
RP55
(689)
RP75
(1162)
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  Seed
(15)
Full
(2375)
Representative proteomes NCBI
(2070)
Meta
(0)
RP15
(249)
RP35
(337)
RP55
(689)
RP75
(1162)
Alignment:
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  Seed
(15)
Full
(2375)
Representative proteomes NCBI
(2070)
Meta
(0)
RP15
(249)
RP35
(337)
RP55
(689)
RP75
(1162)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Finn RD
Number in seed: 15
Number in full: 2375
Average length of the domain: 80.40 aa
Average identity of full alignment: 50 %
Average coverage of the sequence by the domain: 21.09 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 21.5 21.5
Noise cut-off 20.9 20.7
Model length: 85
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Ets SRF-TF

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Ets domain has been found. There are 41 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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