| General information | | DisProt: | DP00632 | | Name: | RNA-binding protein EWS [Isoform EWS] | | Synonym(s): | EWS_HUMAN
EWS oncogene
Ewing sarcoma breakpoint region 1 protein
| | First appeared in release: | Release 5.2 (08/07/2010) | | UniProt: | Q01844 | | UniGene: | Hs.374477 | | SwissProt: | EWS_HUMAN | | TrEMBL: | | | NCBI (GI): | 544261 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 656 | | Percent disordered: | 40% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MASTDYSTYS QAAAQQGYSA YTAQPTQGYA QTTQAYGQQS YGTYGQPTDV SYTQAQTTAT - 60
YGQTAYATSY GQPPTGYTTP TAPQAYSQPV QGYGTGAYDT TTATVTTTQA SYAAQSAYGT - 120
QPAYPAYGQQ PAATAPTRPQ DGNKPTETSQ PQSSTGGYNQ PSLGYGQSNY SYPQVPGSYP - 180
MQPVTAPPSY PPTSYSSTQP TSYDQSSYSQ QNTYGQPSSY GQQSSYGQQS SYGQQPPTSY - 240
PPQTGSYSQA PSQYSQQSSS YGQQSSFRQD HPSSMGVYGQ ESGGFSGPGE NRSMSGPDNR - 300
GRGRGGFDRG GMSRGGRGGG RGGMGSAGER GGFNKPGGPM DEGPDLDLGP PVDPDEDSDN - 360
SAIYVQGLND SVTLDDLADF FKQCGVVKMN KRTGQPMIHI YLDKETGKPK GDATVSYEDP - 420
PTAKAAVEWF DGKDFQGSKL KVSLARKKPP MNSMRGGLPP REGRGMPPPL RGGPGGPGGP - 480
GGPMGRMGGR GGDRGGFPPR GPRGSRGNPS GGGNVQHRAG DWQCPNPGCG NQNFAWRTEC - 540
NQCKAPKPEG FLPPPFPPPG GDRGRGGPGG MRGGRGGLMD RGGPGGMFRG GRGGDRGGFR - 600
GGRGMDRGGF GGGRRGGPGG PPGPLMEQMG GRRGGRGGPG KMDKGEHRQE RRDRPY
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| Functional narrative |
Native EWS is a multifunctional single stranded nucleic acid binding protein.Much of the EWS nucleic acid binding domain is also highly disordered. Nuclear functions may include both transcription and splicing but EWS is also found in the cytoplasm and even on the cell surface. Versatility is also suggested by interaction of EWS with many protein partners as a network hub or as a scaffold protein. Naturally occuring EWS-fusion-proteins (EFPs) are associated with several human cancers and arise by chromosomal fusion of EWS region 1 (the EAD) to various transcription factors. In the context of EFPs EWS region 1 is a potent transcriptional activation domain and thus may contribute to tumorigenesis via aberrant activation of EFP target genes.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | EWS activation domain (EAD) | | Location: | 1 - 264 | | Length: | 264 | | Region sequence: |
MASTDYSTYSQAAAQQGYSAYTAQPTQGYAQTTQAYGQQSYGTYGQPTDVSYTQAQTTAT
YGQTAYATSYGQPPTGYTTPTAPQAYSQPVQGYGTGAYDTTTATVTTTQASYAAQSAYGT
QPAYPAYGQQPAATAPTRPQDGNKPTETSQPQSSTGGYNQPSLGYGQSNYSYPQVPGSYP
MQPVTAPPSYPPTSYSSTQPTSYDQSSYSQQNTYGQPSSYGQQSSYGQQSSYGQQPPTSY
PPQTGSYSQAPSQYSQQSSSYGQQ | | Modification type: | Complex
Native
| | PDB: | 2CPE:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular recognition effectors
| | Functional subclasses: | Transactivation (transcriptional activation)
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (EWS/fusion partner (varying concentrations); Various thermodynamical conditions)
- Circular dichroism (CD) spectroscopy, near-UV (EWS/fusion partner (varying concentrations); Various thermodynamical conditions)
- Fluorescence, intrinsic (Binding solvent; EWS/fusion partner (purified or refolded (8M urea)))
| References:
- Feng L, Lee KA. "A repetitive element containing a critical tyrosine residue is required for transcriptional activation by the EWS/ATF1 oncogene." Oncogene. 2001; 20(31): 4161-8. PubMed: 11464282
- Ng KP, Potikyan G, Savene RO, Denny CT, Uversky VN, Lee KA. "Multiple aromatic side chains within a disordered structure are critical for transcription and transforming activity of EWS family oncoproteins." Proc Natl Acad Sci U S A. 2007; 104(2): 479-84. PubMed: 17202261
- Tan AY, Manley JL. "The TET family of proteins: functions and roles in disease." J Mol Cell Biol. 2009; 1(2): 82-92. PubMed: 19783543
| Comments:Structure information also derived from Uren A, Tcherkasskaya O, Toretsky JA. "Recombinant EWS-FLI1 oncoprotein activates transcription." Biochemistry. 2004; 43(42): 13579-89. PubMed: 15491164
PDB structure 2CPE is from an unpublished document by authors: Nagata, T., Muto, Y., Inoue, M., Kigawa, T., Terada, T., Shirouzu, M., Yokoyama, S. of the RIKEN Structural Genomics/Proteomics Initiative (RSGI). PDB release date: Nov 19 2005.
Ng, et al. (2007), found that the side chain aromatic rings of multiple tyrosine residues are "critical for transactivation" of the oncogenic EWS/fusion partner combination.
Ng, et al., also found that, due to its aromaticity, phenylalanine could substitute for tyrosine in EWS Activation Domain (EAD) functioning.
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| References |
- Ng KP, Potikyan G, Savene RO, Denny CT, Uversky VN, Lee KA. "Multiple aromatic side chains within a disordered structure are critical for transcription and transforming activity of EWS family oncoproteins." Proc Natl Acad Sci U S A. 2007; 104(2): 479-84. PubMed: 17202261
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| Comments |
AV (7-28-2010) PubMed: 17202261
EWS has two very highly related siblings (TAF15 and TLS) and together, these proteins form the TET family.
Tan AY, Manley JL. "The TET family of proteins: functions and roles in disease." J Mol Cell Biol. 2009; 1(2): 82-92.
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