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Reviewed, UniProtKB/Swiss-Prot Q01844 (EWS_HUMAN)

Last modified November 25, 2008. Version 106. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    RNA-binding protein EWS
Alternative name(s):
    EWS oncogene
    Ewing sarcoma breakpoint region 1 protein
Gene names
Name: EWSR1
Synonyms: EWS
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length656 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Might normally function as a repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

Subunit structure

Binds POLR2C, SF1, calmodulin and RNA. Interacts with PTK2B/FAK2.

Subcellular location

Nucleus. Cytoplasm. Cell surface. Note= Relocates from cytoplasm to ribosomes upon PTK2B/FAK2 activation.

Tissue specificity

Ubiquitous.

Domain

EWS activation domain (EAD) functions as a potent activation domain in EFPS. EWSR1 binds POLR2C but not POLR2E or POLR2G, whereas the isolated EAD binds POLR2E and POLR2G but not POLR2C. Cis-linked RNA-binding domain (RBD) can strongly and specifically repress trans-activation by the EAD.

Post-translational modification

Phosphorylated; calmodulin-binding inhibits phosphorylation of Ser-266.

Involvement in disease

Chromosomal aberrations involving EWSR1 are a cause of Ewing sarcoma [MIM:133450]. Translocation t(11;22)(q24;q12) with FLI1; translocation t(7;22)(p22;q12) with ETV1; translocation t(21;22)(q22;q12) with ERG; translocation t(9;22)(q22-31;q11-12) with NR4A3. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with potential oncogenic activity.

A chromosomal aberration involving EWSR1 is associated with desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with WT1.

A chromosomal aberration involving EWSR1 is associated with malignant melanoma of soft parts (MMSP). Translocation t(12;22)(q13;q12) with ATF-1. Malignant melanoma of soft parts, also known as soft tissue clear cell sarcoma, is a rare tumor developing in tendons and aponeuroses.

A chromosomal aberration involving EWSR1 is associated with small round cell sarcoma. Translocation t(11;22)(p36.1;q12) with PATZ1.

Miscellaneous

EFPS arise due to chromosomal translocations in which EWSR1 is fused to a variety of cellular transcription factors. EFPS are very potent transcriptional activators dependent on the EAD and a C-terminal DNA-binding domain contributed by the fusion partner. The spectrum of malignancies associated with EFPS are thought to arise via EFP-induced transcriptional deregulation, with the tumor phenotype specified by the EWSR1 fusion partner and cell type. Transcriptional repression of the transforming growth factor beta type II receptor (TGF beta RII) is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 oncogene.

Binds calmodulin in the presence, but not in the absence, of calcium ion.

Sequence similarities

Belongs to the RRM TET family.

Contains 1 IQ domain.

Contains 1 RanBP2-type zinc finger.

Contains 1 RRM (RNA recognition motif) domain.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform EWS (identifier: Q01844-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform EWS-B (identifier: Q01844-2)

The sequence of this isoform differs from the canonical sequence as follows:
     266-338: Missing.
Notes: No experimental confirmation available.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 656656RNA-binding protein EWS
PRO_0000081586

Regions

Repeat8 – 1691
Repeat17 – 27112
Repeat28 – 3473
Repeat35 – 4284
Repeat43 – 5085
Repeat51 – 5996
Repeat60 – 6897
Repeat69 – 7578
Repeat76 – 8499
Repeat85 – 91710
Repeat92 – 1101911
Repeat111 – 116612
Repeat117 – 125913
Repeat126 – 1563114
Repeat157 – 163715
Repeat164 – 170716
Repeat171 – 177717
Repeat178 – 1881118
Repeat189 – 193519
Repeat194 – 201820
Repeat202 – 206521
Repeat207 – 212622
Repeat213 – 218623
Repeat219 – 224624
Repeat225 – 230625
Repeat231 – 238826
Repeat239 – 245727
Repeat246 – 252728
Repeat253 – 259729
Domain256 – 28530IQ
Repeat260 – 2761730
Repeat277 – 285931
Domain361 – 44787RRM
Zinc finger518 – 54932RanBP2-type
Region1 – 285285EAD (Gln/Pro/Thr-rich)
Region8 – 28527831 X approximate tandem repeats
Compositional bias300 – 34041Arg/Gly/Pro-rich
Compositional bias454 – 51360Arg/Gly/Pro-rich
Compositional bias559 – 64082Arg/Gly/Pro-rich

Sites

Site348 – 3492Breakpoint for insertion to form EWSR1-FEV fusion protein

Amino acid modifications

Modified residue2661Phosphoserine; by PKC By similarity
Modified residue3001Asymmetric dimethylarginine
Modified residue3021Asymmetric dimethylarginine
Modified residue3041Asymmetric dimethylarginine
Modified residue3091Asymmetric dimethylarginine
Modified residue3141Asymmetric dimethylarginine
Modified residue3171Asymmetric dimethylarginine
Modified residue3211Asymmetric dimethylarginine
Modified residue4551Asymmetric dimethylarginine
Modified residue4641Asymmetric dimethylarginine
Modified residue4711Asymmetric dimethylarginine; alternate
Modified residue4711Omega-N-methylarginine; alternate
Modified residue4901Asymmetric dimethylarginine
Modified residue4941Asymmetric dimethylarginine
Modified residue5001Asymmetric dimethylarginine
Modified residue5031Asymmetric dimethylarginine
Modified residue5061Asymmetric dimethylarginine
Modified residue5631Asymmetric dimethylarginine
Modified residue5651Asymmetric dimethylarginine
Modified residue5721Asymmetric dimethylarginine
Modified residue5751Asymmetric dimethylarginine
Modified residue5811Asymmetric dimethylarginine
Modified residue5891Asymmetric dimethylarginine
Modified residue5921Asymmetric dimethylarginine
Modified residue5961Asymmetric dimethylarginine
Modified residue6001Asymmetric dimethylarginine
Modified residue6031Asymmetric dimethylarginine
Modified residue6071Asymmetric dimethylarginine
Modified residue6151Asymmetric dimethylarginine
Modified residue6331Asymmetric dimethylarginine
Modified residue6361Asymmetric dimethylarginine

Natural variations

Alternative sequence266 – 33873Missing in isoform EWS-B.
VSP_005793

Secondary structure

1 ................. 656
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform EWS [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 0DA02CEE146720BB

FASTA65668,478
        10         20         30         40         50         60 
MASTDYSTYS QAAAQQGYSA YTAQPTQGYA QTTQAYGQQS YGTYGQPTDV SYTQAQTTAT 

        70         80         90        100        110        120 
YGQTAYATSY GQPPTGYTTP TAPQAYSQPV QGYGTGAYDT TTATVTTTQA SYAAQSAYGT 

       130        140        150        160        170        180 
QPAYPAYGQQ PAATAPTRPQ DGNKPTETSQ PQSSTGGYNQ PSLGYGQSNY SYPQVPGSYP 

       190        200        210        220        230        240 
MQPVTAPPSY PPTSYSSTQP TSYDQSSYSQ QNTYGQPSSY GQQSSYGQQS SYGQQPPTSY 

       250        260        270        280        290        300 
PPQTGSYSQA PSQYSQQSSS YGQQSSFRQD HPSSMGVYGQ ESGGFSGPGE NRSMSGPDNR 

       310        320        330        340        350        360 
GRGRGGFDRG GMSRGGRGGG RGGMGSAGER GGFNKPGGPM DEGPDLDLGP PVDPDEDSDN 

       370        380        390        400        410        420 
SAIYVQGLND SVTLDDLADF FKQCGVVKMN KRTGQPMIHI YLDKETGKPK GDATVSYEDP 

       430        440        450        460        470        480 
PTAKAAVEWF DGKDFQGSKL KVSLARKKPP MNSMRGGLPP REGRGMPPPL RGGPGGPGGP 

       490        500        510        520        530        540 
GGPMGRMGGR GGDRGGFPPR GPRGSRGNPS GGGNVQHRAG DWQCPNPGCG NQNFAWRTEC 

       550        560        570        580        590        600 
NQCKAPKPEG FLPPPFPPPG GDRGRGGPGG MRGGRGGLMD RGGPGGMFRG GRGGDRGGFR 

       610        620        630        640        650 
GGRGMDRGGF GGGRRGGPGG PPGPLMEQMG GRRGGRGGPG KMDKGEHRQE RRDRPY

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Isoform EWS-B [UniParc].

Checksum: 1B011799A0B290ED
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58361,217