Q01844 (EWS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RNA-binding protein EWS

Alternative name(s):
EWS oncogene
Ewing sarcoma breakpoint region 1 protein

Gene names

Name:	EWSR1
Synonyms:	EWS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	656 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Might normally function as a transcriptionnal 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 and TDRD3. Binds calmodulin in the presence, but not in the absence, of calcium ion. Ref.16 Ref.20
Subcellular location	Nucleus. Cytoplasm. Cell membrane. Note: Relocates from cytoplasm to ribosomes upon PTK2B/FAK2 activation. Ref.19
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. Ref.13 Highly methylated on arginine residues. Methylation is mediated by PRMT1 and, at lower level by PRMT8. Ref.10 Ref.12 Ref.21
Involvement in disease	Ewing sarcoma (ES) [MIM:612219]: A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note: The disease is caused by mutations affecting the gene represented in this entry. Chromosomal aberrations involving EWSR1 are found in patients with Ewing sarcoma. 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. Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note: The disease may be caused by mutations affecting the gene represented in this entry. Chromosomal aberrations involving EWSR1 are found in patients with angiomatoid fibrous histiocytoma. Translocation t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type. 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.
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.
Sequence caution	The sequence CAA70044.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Repeat Zinc-finger
Ligand	Calmodulin-binding Metal-binding RNA-binding Zinc
Molecular function	Repressor
PTM	Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Traceable author statement Ref.14. Source: ProtInc nucleotide binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RASSF1	Q9NS23-2	3	EBI-739737,EBI-438698
ZNF165	P49910	2	EBI-739737,EBI-741694

Alternative products

This entry describes 6 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.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q01844-3)

The sequence of this isoform differs from the canonical sequence as follows:
     326-326: Missing.

Isoform 4 (identifier: Q01844-4)

The sequence of this isoform differs from the canonical sequence as follows:
     326-354: SAGERGGFNKPGGPMDEGPDLDLGPPVDP → LQSESLVYTSILKKYPYSVLSRQHNEKWD
     355-656: Missing.

Note: No experimental confirmation available.

Isoform 5 (identifier: Q01844-5)

The sequence of this isoform differs from the canonical sequence as follows:
     74-74: P → PTVEGTS
     326-326: Missing.

Note: No experimental confirmation available.

Isoform 6 (identifier: Q01844-6)

The sequence of this isoform differs from the canonical sequence as follows:
     136-191: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 656

656

RNA-binding protein EWS

PRO_0000081586

Regions

Repeat

8 – 16

9

1

Repeat

17 – 27

11

2

Repeat

28 – 34

7

3

Repeat

35 – 42

8

4

Repeat

43 – 50

8

5

Repeat

51 – 59

9

6

Repeat

60 – 68

9

7

Repeat

69 – 75

7

8

Repeat

76 – 84

9

9

Repeat

85 – 91

7

10

Repeat

92 – 110

19

11

Repeat

111 – 116

6

12

Repeat

117 – 125

9

13

Repeat

126 – 156

31

14

Repeat

157 – 163

7

15

Repeat

164 – 170

7

16

Repeat

171 – 177

7

17

Repeat

178 – 188

11

18

Repeat

189 – 193

5

19

Repeat

194 – 201

8

20

Repeat

202 – 206

5

21

Repeat

207 – 212

6

22

Repeat

213 – 218

6

23

Repeat

219 – 224

6

24

Repeat

225 – 230

6

25

Repeat

231 – 238

8

26

Repeat

239 – 245

7

27

Repeat

246 – 252

7

28

Repeat

253 – 259

7

29

Domain

256 – 285

30

IQ

Repeat

260 – 276

17

30

Repeat

277 – 285

9

31

Domain

361 – 447

87

RRM

Zinc finger

518 – 549

32

RanBP2-type

Region

1 – 285

285

EAD (Gln/Pro/Thr-rich)

Region

8 – 285

278

31 X approximate tandem repeats

Motif

639 – 656

18

Nuclear localization signal Ref.19

Compositional bias

300 – 340

41

Arg/Gly/Pro-rich

Compositional bias

454 – 513

60

Arg/Gly/Pro-rich

Compositional bias

559 – 640

82

Arg/Gly/Pro-rich

Sites

Site

265

1

Breakpoint for translocation to form chimeric EWSR1/ATF1 protein

Site

348 – 349

2

Breakpoint for insertion to form EWSR1-FEV fusion protein

Amino acid modifications

Modified residue

266

1

Phosphoserine; by PKC By similarity

Modified residue

300

1

Asymmetric dimethylarginine Ref.10

Modified residue

302

1

Asymmetric dimethylarginine Ref.10

Modified residue

304

1

Asymmetric dimethylarginine Ref.10

Modified residue

309

1

Asymmetric dimethylarginine Ref.10

Modified residue

314

1

Asymmetric dimethylarginine Ref.10

Modified residue

317

1

Asymmetric dimethylarginine Ref.10

Modified residue

321

1

Asymmetric dimethylarginine Ref.10

Modified residue

455

1

Asymmetric dimethylarginine Ref.10

Modified residue

464

1

Asymmetric dimethylarginine Ref.10

Modified residue

471

1

Asymmetric dimethylarginine; alternate Ref.10

Modified residue

471

1

Omega-N-methylarginine; alternate Ref.10

Modified residue

490

1

Asymmetric dimethylarginine; by PRMT8 Ref.10 Ref.21

Modified residue

494

1

Asymmetric dimethylarginine Ref.10 Ref.12

Modified residue

500

1

Asymmetric dimethylarginine Ref.10

Modified residue

503

1

Asymmetric dimethylarginine Ref.10

Modified residue

506

1

Asymmetric dimethylarginine Ref.10

Modified residue

563

1

Asymmetric dimethylarginine Ref.10

Modified residue

565

1

Asymmetric dimethylarginine Ref.10

Modified residue

572

1

Asymmetric dimethylarginine; alternate; by PRMT8 Ref.10 Ref.21

Modified residue

572

1

Omega-N-methylarginine; alternate; by PRMT8 Ref.10 Ref.21

Modified residue

575

1

Asymmetric dimethylarginine Ref.10

Modified residue

581

1

Asymmetric dimethylarginine Ref.10

Modified residue

589

1

Asymmetric dimethylarginine Ref.10

Modified residue

592

1

Asymmetric dimethylarginine Ref.10

Modified residue

596

1

Asymmetric dimethylarginine; alternate; by PRMT8 Ref.10 Ref.21

Modified residue

596

1

Omega-N-methylarginine; alternate; by PRMT8 Ref.10 Ref.21

Modified residue

600

1

Asymmetric dimethylarginine Ref.10

Modified residue

603

1

Asymmetric dimethylarginine; by PRMT8 Ref.10 Ref.21

Modified residue

607

1

Asymmetric dimethylarginine; alternate; by PRMT8 Ref.10 Ref.21

Modified residue

607

1

Omega-N-methylarginine; alternate; by PRMT8 Ref.10 Ref.21

Modified residue

615

1

Asymmetric dimethylarginine Ref.10 Ref.12

Modified residue

633

1

Asymmetric dimethylarginine Ref.10

Modified residue

636

1

Asymmetric dimethylarginine Ref.10

Natural variations

Alternative sequence

74

1

P → PTVEGTS in isoform 5.

VSP_043451

Alternative sequence

136 – 191

56

Missing in isoform 6.

VSP_045412

Alternative sequence

266 – 338

73

Missing in isoform EWS-B.

VSP_005793

Alternative sequence

326 – 354

29

SAGER…PPVDP → LQSESLVYTSILKKYPYSVL SRQHNEKWD in isoform 4.

VSP_043452

Alternative sequence

326

1

Missing in isoform 3 and isoform 5.

VSP_043453

Alternative sequence

355 – 656

302

Missing in isoform 4.

VSP_043454

Experimental info

Mutagenesis

648

1

R → A: Cytoplasmic localization. Ref.19

Mutagenesis

648

1

R → K: No effect on nuclear targeting. Ref.19

Mutagenesis

651

1

R → A: No effect on nuclear targeting. Ref.19

Mutagenesis

652

1

R → A: Cytoplasmic localization. Ref.19

Mutagenesis

652

1

R → K: No effect on nuclear targeting. Ref.19

Mutagenesis

653

1

D → A: No effect on nuclear targeting. Ref.19

Mutagenesis

654

1

R → A: No effect on nuclear targeting. Ref.19

Mutagenesis

655

1

P → A: Cytoplasmic localization. Ref.19

Mutagenesis

656

1

Y → A: Cytoplasmic localization. Ref.19

Sequence conflict

224

1

S → G in BAB71252. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

656

Helix Strand Turn

Details...

Beta strand

362 – 366

5

Helix

374 – 381

8

Turn

382 – 384

3

Beta strand

391 – 393

3

Beta strand

396 – 399

4

Turn

404 – 406

3

Beta strand

411 – 419

9

Helix

420 – 430

11

Beta strand

441 – 443

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform EWS [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 0DA02CEE146720BB	FASTA	656	68,478
	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
	Isoform EWS-B [UniParc]. Checksum: 1B011799A0B290ED	FASTA	583	61,217
	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 YGQQSPMDEG PDLDLGPPVD PDEDSDNSAI YVQGLNDSVT 310 320 330 340 350 360 LDDLADFFKQ CGVVKMNKRT GQPMIHIYLD KETGKPKGDA TVSYEDPPTA KAAVEWFDGK 370 380 390 400 410 420 DFQGSKLKVS LARKKPPMNS MRGGLPPREG RGMPPPLRGG PGGPGGPGGP MGRMGGRGGD 430 440 450 460 470 480 RGGFPPRGPR GSRGNPSGGG NVQHRAGDWQ CPNPGCGNQN FAWRTECNQC KAPKPEGFLP 490 500 510 520 530 540 PPFPPPGGDR GRGGPGGMRG GRGGLMDRGG PGGMFRGGRG GDRGGFRGGR GMDRGGFGGG 550 560 570 580 RRGGPGGPPG PLMEQMGGRR GGRGGPGKMD KGEHRQERRD RPY
	Isoform 3 [UniParc]. Checksum: B539ED1E98C601ED	FASTA	655	68,391
	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 RGGMGAGERG GFNKPGGPMD EGPDLDLGPP VDPDEDSDNS 370 380 390 400 410 420 AIYVQGLNDS VTLDDLADFF KQCGVVKMNK RTGQPMIHIY LDKETGKPKG DATVSYEDPP 430 440 450 460 470 480 TAKAAVEWFD GKDFQGSKLK VSLARKKPPM NSMRGGLPPR EGRGMPPPLR GGPGGPGGPG 490 500 510 520 530 540 GPMGRMGGRG GDRGGFPPRG PRGSRGNPSG GGNVQHRAGD WQCPNPGCGN QNFAWRTECN 550 560 570 580 590 600 QCKAPKPEGF LPPPFPPPGG DRGRGGPGGM RGGRGGLMDR GGPGGMFRGG RGGDRGGFRG 610 620 630 640 650 GRGMDRGGFG GGRRGGPGGP PGPLMEQMGG RRGGRGGPGK MDKGEHRQER RDRPY
	Isoform 4 [UniParc]. Checksum: AE4B8FCDF458390B	FASTA	354	37,620
	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 GRGRGGFDRG GMSRGGRGGG RGGMGLQSES LVYTSILKKY PYSVLSRQHN EKWD
	Isoform 5 [UniParc]. Checksum: 5F84F52FDCD51269	FASTA	661	68,966
	10 20 30 40 50 60 MASTDYSTYS QAAAQQGYSA YTAQPTQGYA QTTQAYGQQS YGTYGQPTDV SYTQAQTTAT 70 80 90 100 110 120 YGQTAYATSY GQPPTVEGTS TGYTTPTAPQ AYSQPVQGYG TGAYDTTTAT VTTTQASYAA 130 140 150 160 170 180 QSAYGTQPAY PAYGQQPAAT APTRPQDGNK PTETSQPQSS TGGYNQPSLG YGQSNYSYPQ 190 200 210 220 230 240 VPGSYPMQPV TAPPSYPPTS YSSTQPTSYD QSSYSQQNTY GQPSSYGQQS SYGQQSSYGQ 250 260 270 280 290 300 QPPTSYPPQT GSYSQAPSQY SQQSSSYGQQ SSFRQDHPSS MGVYGQESGG FSGPGENRSM 310 320 330 340 350 360 SGPDNRGRGR GGFDRGGMSR GGRGGGRGGM GAGERGGFNK PGGPMDEGPD LDLGPPVDPD 370 380 390 400 410 420 EDSDNSAIYV QGLNDSVTLD DLADFFKQCG VVKMNKRTGQ PMIHIYLDKE TGKPKGDATV 430 440 450 460 470 480 SYEDPPTAKA AVEWFDGKDF QGSKLKVSLA RKKPPMNSMR GGLPPREGRG MPPPLRGGPG 490 500 510 520 530 540 GPGGPGGPMG RMGGRGGDRG GFPPRGPRGS RGNPSGGGNV QHRAGDWQCP NPGCGNQNFA 550 560 570 580 590 600 WRTECNQCKA PKPEGFLPPP FPPPGGDRGR GGPGGMRGGR GGLMDRGGPG GMFRGGRGGD 610 620 630 640 650 660 RGGFRGGRGM DRGGFGGGRR GGPGGPPGPL MEQMGGRRGG RGGPGKMDKG EHRQERRDRP Y
	Isoform 6 [UniParc]. Checksum: B3D01637474FFFB0	FASTA	600	62,508
	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 PAATAPTSYS STQPTSYDQS SYSQQNTYGQ PSSYGQQSSY GQQSSYGQQP 190 200 210 220 230 240 PTSYPPQTGS YSQAPSQYSQ QSSSYGQQSS FRQDHPSSMG VYGQESGGFS GPGENRSMSG 250 260 270 280 290 300 PDNRGRGRGG FDRGGMSRGG RGGGRGGMGS AGERGGFNKP GGPMDEGPDL DLGPPVDPDE 310 320 330 340 350 360 DSDNSAIYVQ GLNDSVTLDD LADFFKQCGV VKMNKRTGQP MIHIYLDKET GKPKGDATVS 370 380 390 400 410 420 YEDPPTAKAA VEWFDGKDFQ GSKLKVSLAR KKPPMNSMRG GLPPREGRGM PPPLRGGPGG 430 440 450 460 470 480 PGGPGGPMGR MGGRGGDRGG FPPRGPRGSR GNPSGGGNVQ HRAGDWQCPN PGCGNQNFAW 490 500 510 520 530 540 RTECNQCKAP KPEGFLPPPF PPPGGDRGRG GPGGMRGGRG GLMDRGGPGG MFRGGRGGDR 550 560 570 580 590 600 GGFRGGRGMD RGGFGGGRRG GPGGPPGPLM EQMGGRRGGR GGPGKMDKGE HRQERRDRPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours." Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., Kovar H., Joubert I., de Jong P., Rouleau G., Aurias A., Thomas G. Nature 359:162-165(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EWS). Tissue: Fetal brain.
[2]	"Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation." Plougastel B., Zucman J., Peter M., Thomas G., Delattre O. Genomics 18:609-615(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Genomic sequence of the human EWS gene with the 5' flanking region." Zucman-Rossi J., Legoix P., Thomas G. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6).
[6]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS EWS; 3 AND 4). Tissue: Lymph, Muscle, Placenta and Skin.
[9]	"Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region." Zucman-Rossi J., Legoix P., Thomas G. Genomics 38:247-254(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-345.
[10]	"Exposure on cell surface and extensive arginine methylation of Ewing sarcoma (EWS) protein." Belyanskaya L.L., Gehrig P.M., Gehring H. J. Biol. Chem. 276:18681-18687(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 128-158; 233-247; 268-324; 334-364; 393-439; 447-518 AND 551-641, METHYLATION AT ARG-300; ARG-302; ARG-304; ARG-309; ARG-314; ARG-317; ARG-321; ARG-455; ARG-464; ARG-471; ARG-490; ARG-494; ARG-500; ARG-503; ARG-506; ARG-563; ARG-565; ARG-572; ARG-575; ARG-581; ARG-589; ARG-592; ARG-596; ARG-600; ARG-603; ARG-607; ARG-615; ARG-633 AND ARG-636, MASS SPECTROMETRY.
[11]	"Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma." Bhagirath T., Abe S., Nojima T., Yoshida M.C. Genes Chromosomes Cancer 13:126-132(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 241-268. Tissue: Placenta.
[12]	Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Zebisch A., Kolch W. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 269-292; 393-404; 411-439; 491-500 AND 615-632, METHYLATION AT ARG-494 AND ARG-615, MASS SPECTROMETRY. Tissue: Colon carcinoma and Ovarian carcinoma.
[13]	"The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain." Deloulme J.C., Prichard L., Delattre O., Storm D.R. J. Biol. Chem. 272:27369-27377(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION AT SER-266.
[14]	"The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains." Ohno T., Ouchida M., Lee L., Gatalica Z., Rao V.N., Reddy E.S.P. Oncogene 9:3087-3097(1994) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, RNA-BINDING.
[15]	"A new member of the ETS family fused to EWS in Ewing tumors." Peter M., Couturier J., Pacquement H., Michon J., Thomas G., Magdelenat H., Delattre O. Oncogene 14:1159-1164(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH FEV.
[16]	"The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription." Zhang D., Paley A.J., Childs G. J. Biol. Chem. 273:18086-18091(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SF1.
[17]	"Transcriptional activation by the Ewing's sarcoma (EWS) oncogene can be cis-repressed by the EWS RNA-binding domain." Li K.K.C., Lee K.A.W. J. Biol. Chem. 275:23053-23058(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[18]	"Expression of EWS-ETS fusions in NIH3T3 cells reveals significant differences to Ewing's sarcoma." Braunreiter C.L., Hancock J.D., Coffin C.M., Boucher K.M., Lessnick S.L. Cell Cycle 5:2753-2759(2006) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE EWSR1-FEV FUSION PROTEIN.
[19]	"Identification and characterization of the nuclear localization/retention signal in the EWS proto-oncoprotein." Zakaryan R.P., Gehring H. J. Mol. Biol. 363:27-38(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, MUTAGENESIS OF ARG-648; ARG-651; ARG-652; ASP-653; ARG-654; PRO-655 AND TYR-656.
[20]	"TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic stress granules." Goulet I., Boisvenue S., Mokas S., Mazroui R., Cote J. Hum. Mol. Genet. 17:3055-3074(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TDRD3.
[21]	"Identification of proteins interacting with protein arginine methyltransferase 8: the Ewing sarcoma (EWS) protein binds independent of its methylation state." Pahlich S., Zakaryan R.P., Gehring H. Proteins 72:1125-1137(2008) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT ARG-490; ARG-572; ARG-596; ARG-603 AND ARG-607.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"Solution structure of the RNA recognition motif of Ewing sarcoma (EWS) protein." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 353-453.
[24]	"Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma." Hallor K.H., Mertens F., Jin Y., Meis-Kindblom J.M., Kindblom L.-G., Behrendtz M., Kalen A., Mandahl N., Panagopoulos I. Genes Chromosomes Cancer 44:97-102(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH ATF1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
[25]	"EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma." Antonescu C.R., Dal Cin P., Nafa K., Teot L.A., Surti U., Fletcher C.D., Ladanyi M. Genes Chromosomes Cancer 46:1051-1060(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH CREB1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X66899 mRNA. Translation: CAA47350.1.
X72990 , X72991, X72992, X72993, X72994, X72995, X72996, X72997, X72998, X72999, X73000, X73001, X73002, X73003, X73004 Genomic DNA. Translation: CAA51489.1.
Y07848 Genomic DNA. Translation: CAA69177.1.
CR456490 mRNA. Translation: CAG30376.1.
AK056309 mRNA. Translation: BAB71145.1.
AK056681 mRNA. Translation: BAB71252.1.
AL031186, AC000026, AC002059 Genomic DNA. Translation: CAI18001.1.
AL031186, AC000026, AC002059 Genomic DNA. Translation: CAQ10937.1.
AL031186, AC000026, AC002059 Genomic DNA. Translation: CAQ10938.1.
AL031186, AC000026, AC002059 Genomic DNA. Translation: CAQ10940.1.
CH471095 Genomic DNA. Translation: EAW59780.1.
CH471095 Genomic DNA. Translation: EAW59781.1.
CH471095 Genomic DNA. Translation: EAW59785.1.
CH471095 Genomic DNA. Translation: EAW59786.1.
CH471095 Genomic DNA. Translation: EAW59787.1.
BC000527 mRNA. Translation: AAH00527.1.
BC004817 mRNA. Translation: AAH04817.1.
BC011048 mRNA. Translation: AAH11048.1.
BC072442 mRNA. Translation: AAH72442.1.
Y08806 Genomic DNA. Translation: CAA70044.1. Different initiation.
AB016435 Genomic DNA. Translation: BAA31990.1.

IPI

IPI00065554.
IPI00293254.
IPI00335961.
IPI00872855.
IPI00879259.

PIR

A49358.

RefSeq

NP_001156757.1. NM_001163285.1.
NP_001156758.1. NM_001163286.1.
NP_001156759.1. NM_001163287.1.
NP_005234.1. NM_005243.3.
NP_053733.2. NM_013986.3.

UniGene

Hs.374477.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CPE	NMR	-	A	353-453	[»]

ProteinModelPortal

Q01844.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q01844. 127 interactions.

MINT

MINT-2858561.

STRING

9606.ENSP00000381031.

PTM databases

PhosphoSite

Q01844.

Polymorphism databases

DMDM

544261.

Proteomic databases

PaxDb

Q01844.

PRIDE

Q01844.

Protocols and materials databases

DNASU

2130.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000332035; ENSP00000331699; ENSG00000182944.
ENST00000333395; ENSP00000327456; ENSG00000182944.
ENST00000397938; ENSP00000381031; ENSG00000182944.
ENST00000406548; ENSP00000385726; ENSG00000182944.
ENST00000414183; ENSP00000400142; ENSG00000182944.

GeneID

2130.

KEGG

hsa:2130.

UCSC

uc003aet.3. human.

Organism-specific databases

CTD

2130.

GeneCards

GC22P029663.

HGNC

HGNC:3508. EWSR1.

HPA

CAB004230.

MIM

133450. gene.
612160. phenotype.
612219. phenotype.

neXtProt

NX_Q01844.

Orphanet

83469. Desmoplastic small round cell tumor.
319. Ewing sarcoma.
97338. Melanoma of soft part.

PharmGKB

PA27921.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG240581.

HOGENOM

HOG000038010.

HOVERGEN

HBG000970.

KO

K13209.

OMA

EGTSTGY.

OrthoDB

EOG42NJ15.

PhylomeDB

Q01844.

Enzyme and pathway databases

Pathway_Interaction_DB

bard1pathway. BARD1 signaling events.

Gene expression databases

ArrayExpress

Q01844.

Bgee

Q01844.

CleanEx

HS_EWSR1.

Genevestigator

Q01844.

GermOnline

ENSG00000182944. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
IPR001876. Znf_RanBP2.
[Graphical view]

Pfam

PF00641. zf-RanBP. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]

PROSITE

PS50096. IQ. False negative.
PS50102. RRM. 1 hit.
PS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

EWSR1. human.

EvolutionaryTrace

Q01844.

GenomeRNAi

2130.

NextBio

8605.

SOURCE

Search...

Entry information

Entry name

EWS_HUMAN

Accession

Primary (citable) accession number: Q01844
Secondary accession number(s): B0QYK1 , Q5THL0, Q92635, Q96FE8, Q96MN4, Q96MX4, Q9BWA2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	May 1, 2013
This is version 157 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.