P14921 (ETS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein C-ets-1

Alternative name(s):
p54

Gene names

Name:	ETS1
Synonyms:	EWSR2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	441 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor. Ref.8
Subunit structure	Interacts with MAF and MAFB By similarity. Binds to DAXX. Interacts with UBE2I. Ref.7
Subcellular location	Nucleus.
Post-translational modification	Sumoylated on Lys-15 and Lys-227, preferentially by SUMO2; which inhibits transcriptional activity By similarity. Ubiquitinated; which induces proteasomal degradation By similarity.
Sequence similarities	Belongs to the ETS family. Contains 1 ETS DNA-binding domain. Contains 1 PNT (pointed) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Ligand	DNA-binding
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	PML body organization Inferred from direct assay. Source: BHF-UCL cell motility Inferred from mutant phenotype. Source: BHF-UCL immune response Traceable author statement. Source: ProtInc induction of apoptosis Inferred from direct assay. Source: UniProtKB negative regulation of cell cycle Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell proliferation Traceable author statement. Source: ProtInc positive regulation of cellular component movement Inferred from mutant phenotype. Source: BHF-UCL positive regulation of erythrocyte differentiation Inferred from direct assay. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.8. Source: UniProtKB response to antibiotic Inferred from direct assay. Source: UniProtKB transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay. Source: BHF-UCL
Molecular function	protein binding Inferred from physical interaction Ref.8. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from direct assay. Source: BHF-UCL transcription factor binding Non-traceable author statement Ref.8. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APLP2	Q06481	2	EBI-913209,EBI-79306
ARID4B	Q4LE39	2	EBI-913209,EBI-2680990
C17orf62	Q9BQA9	3	EBI-913209,EBI-2680384
DAXX	Q9UER7-1	3	EBI-913224,EBI-287635
EIF5B	O60841	2	EBI-913209,EBI-928530
JUN	P05412	3	EBI-913209,EBI-852823
MEIS1	O00470	2	EBI-913209,EBI-1210694
PRKDC	P78527	2	EBI-913209,EBI-352053
SRSF11	Q05519	2	EBI-913209,EBI-1051785

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform c-ETS-1A (identifier: P14921-1)

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 c-ETS-1B (identifier: P14921-2)

The sequence of this isoform differs from the canonical sequence as follows:
     244-330: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 441

441

Protein C-ets-1

PRO_0000204069

Regions

Domain

51 – 136

86

PNT

DNA binding

335 – 415

81

ETS

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.11

Modified residue

2

1

N6-acetyllysine Ref.11

Modified residue

8

1

N6-acetyllysine Ref.11

Modified residue

15

1

N6-acetyllysine; alternate Ref.11

Modified residue

38

1

Phosphothreonine; by MAPK By similarity

Modified residue

205

1

Phosphotyrosine Ref.9

Modified residue

223

1

Phosphotyrosine Ref.9

Modified residue

270

1

Phosphoserine Ref.10

Modified residue

285

1

Phosphoserine Ref.10

Modified residue

305

1

N6-acetyllysine Ref.11

Cross-link

15

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity

Cross-link

227

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence

244 – 330

87

Missing in isoform c-ETS-1B.

VSP_001464

Experimental info

Sequence conflict

162

1

Y → C in AAB28747. Ref.5

Sequence conflict

236 – 243

8

MCMGRTSR → FLPPPLPP in AAA52409. Ref.6

Sequence conflict

332 – 337

6

SGPIQL → RRPPAA in AAA52409. Ref.6

Secondary structure

1

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.

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441

Helix Strand Turn

Details...

Helix

304 – 313

10

Helix

323 – 330

8

Helix

337 – 345

9

Helix

348 – 350

3

Turn

351 – 353

3

Beta strand

354 – 356

3

Beta strand

362 – 364

3

Helix

368 – 379

12

Helix

386 – 395

10

Turn

396 – 400

5

Beta strand

401 – 404

4

Beta strand

408 – 414

7

Helix

418 – 422

5

Helix

426 – 432

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform c-ETS-1A [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 3B66BCC464B393FB	FASTA	441	50,408
	10 20 30 40 50 60 MKAAVDLKPT LTIIKTEKVD LELFPSPDME CADVPLLTPS SKEMMSQALK ATFSGFTKEQ 70 80 90 100 110 120 QRLGIPKDPR QWTETHVRDW VMWAVNEFSL KGVDFQKFCM NGAALCALGK DCFLELAPDF 130 140 150 160 170 180 VGDILWEHLE ILQKEDVKPY QVNGVNPAYP ESRYTSDYFI SYGIEHAQCV PPSEFSEPSF 190 200 210 220 230 240 ITESYQTLHP ISSEELLSLK YENDYPSVIL RDPLQTDTLQ NDYFAIKQEV VTPDNMCMGR 250 260 270 280 290 300 TSRGKLGGQD SFESIESYDS CDRLTQSWSS QSSFNSLQRV PSYDSFDSED YPAALPNHKP 310 320 330 340 350 360 KGTFKDYVRD RADLNKDKPV IPAAALAGYT GSGPIQLWQF LLELLTDKSC QSFISWTGDG 370 380 390 400 410 420 WEFKLSDPDE VARRWGKRKN KPKMNYEKLS RGLRYYYDKN IIHKTAGKRY VYRFVCDLQS 430 440 LLGYTPEELH AMLDVKPDAD E
	Isoform c-ETS-1B [UniParc]. Checksum: 6C3313F2DBE3CF88	FASTA	354	40,786
	10 20 30 40 50 60 MKAAVDLKPT LTIIKTEKVD LELFPSPDME CADVPLLTPS SKEMMSQALK ATFSGFTKEQ 70 80 90 100 110 120 QRLGIPKDPR QWTETHVRDW VMWAVNEFSL KGVDFQKFCM NGAALCALGK DCFLELAPDF 130 140 150 160 170 180 VGDILWEHLE ILQKEDVKPY QVNGVNPAYP ESRYTSDYFI SYGIEHAQCV PPSEFSEPSF 190 200 210 220 230 240 ITESYQTLHP ISSEELLSLK YENDYPSVIL RDPLQTDTLQ NDYFAIKQEV VTPDNMCMGR 250 260 270 280 290 300 TSRGSGPIQL WQFLLELLTD KSCQSFISWT GDGWEFKLSD PDEVARRWGK RKNKPKMNYE 310 320 330 340 350 KLSRGLRYYY DKNIIHKTAG KRYVYRFVCD LQSLLGYTPE ELHAMLDVKP DADE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure, expression and alternative splicing of the human c-ets-1 proto-oncogene." Reddy E.S.P., Rao V.N. Oncogene Res. 3:239-246(1988) [PubMed: 3060801] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mammalian ets-1 and ets-2 genes encode highly conserved proteins." Watson D.K., McWilliams M.J., Lapis P., Lautenberger J.A., Schweinfest C.W., Papas T.S. Proc. Natl. Acad. Sci. U.S.A. 85:7862-7866(1988) [PubMed: 2847145] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C-ETS-1A).
[4]	"Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter." Majerus M.-A., Bibollet-Ruche F., Telliez J.-B., Wasylyk B., Bailleul B. Nucleic Acids Res. 20:2699-2703(1992) [PubMed: 1614856] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
[5]	"Quantitative and qualitative variation of ETS-1 transcripts in hematologic malignancies." Collyn d'Hooghe M., Galiegue-Zouitina S., Szymiczek D., Lantoine D., Quief S., Loucheux-Lefebvre M.H., Kerckaert J.P. Leukemia 7:1777-1785(1993) [PubMed: 8231246] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 146-174.
[6]	"The ets sequence from the transforming gene of avian erythroblastosis virus, E26, has unique domains on human chromosomes 11 and 21: both loci are transcriptionally active." Watson D.K., McWilliams-Smith M.J., Nunn M.F., Duesberg P.H., O'Brien S.J., Papas T.S. Proc. Natl. Acad. Sci. U.S.A. 82:7294-7298(1985) [PubMed: 2997781] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 236-337.
[7]	"Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-conjugating enzyme." Hahn S.L., Criqui-Filipe P., Wasylyk B. Oncogene 15:1489-1495(1997) [PubMed: 9333025] [Abstract] Cited for: INTERACTION WITH UBE2I.
[8]	"EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes." Li R., Pei H., Watson D.K., Papas T.S. Oncogene 19:745-753(2000) [PubMed: 10698492] [Abstract] Cited for: FUNCTION.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-205 AND TYR-223, MASS SPECTROMETRY.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-270 AND SER-285, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-2; LYS-8; LYS-15 AND LYS-305, MASS SPECTROMETRY.
[12]	"The solution structure of the human ETS1-DNA complex reveals a novel mode of binding and true side chain intercalation." Werner M.H., Clore G.M., Fisher C.L., Fisher R.J., Trinh L., Shiloach J., Gronenborn A.M. Cell 83:761-771(1995) [PubMed: 8521493] [Abstract] Cited for: STRUCTURE BY NMR OF 320-415.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X14798 mRNA. Translation: CAA32904.1.
X14798 mRNA. Translation: CAA32903.1.
J04101 mRNA. Translation: AAA52410.1.
X65469 Genomic DNA. No translation available.
S67063 mRNA. Translation: AAB28747.1.
BT019452 mRNA. Translation: AAV38259.1.
M11921 Genomic DNA. Translation: AAA52409.1.

IPI

IPI00028127.
IPI00218351.

PIR

TVHUET. A32066.

RefSeq

NP_005229.1. NM_005238.3.

UniGene

Hs.369438.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GVJ	X-ray	1.53	A/B	297-441	[»]
2NNY	X-ray	2.58	A/B	280-441	[»]
2STT	NMR	-	A	320-415	[»]
2STW	NMR	-	A	320-415	[»]
3MFK	X-ray	3.00	A/B	280-441	[»]

ProteinModelPortal

P14921.

SMR

P14921. Positions 29-138, 297-441.

ModBase

Search...

Protein-protein interaction databases

IntAct

P14921. 57 interactions.

MINT

MINT-122911.

STRING

P14921.

PTM databases

PhosphoSite

P14921.

Polymorphism databases

DMDM

119641.

Proteomic databases

PRIDE

P14921.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000319397; ENSP00000324578; ENSG00000134954.

GeneID

2113.

KEGG

hsa:2113.

UCSC

uc001qei.1. human.

Organism-specific databases

CTD

2113.

GeneCards

GC11M128362.

H-InvDB

HIX0010260.

HGNC

HGNC:3488. ETS1.

HPA

CAB002575.

MIM

164720. gene.

neXtProt

NX_P14921.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05166.

HOVERGEN

HBG003088.

PhylomeDB

P14921.

Enzyme and pathway databases

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
bcr_5pathway. BCR signaling pathway.
hif1_tfpathway. HIF-1-alpha transcription factor network.
il4_2pathway. IL4-mediated signaling events.

Gene expression databases

ArrayExpress

P14921.

Bgee

P14921.

CleanEx

HS_ETS1.

Genevestigator

P14921.

GermOnline

ENSG00000134954. Homo sapiens.

Family and domain databases

InterPro

IPR000418. Ets.
IPR003118. Pointed_dom.
IPR013761. SAM/pointed.
IPR016311. Transforming_factor_C-ets.
IPR011991. WHTH_trsnscrt_rep_DNA-bd.
[Graphical view]

Gene3D

G3DSA:1.10.150.50. SAM_type. 1 hit.
G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.

KO

K02678.

Pfam

PF00178. Ets. 1 hit.
PF02198. SAM_PNT. 1 hit.
[Graphical view]

PIRSF

PIRSF001698. Transforming_factor_C-ets. 1 hit.

PRINTS

PR00454. ETSDOMAIN.

SMART

SM00413. ETS. 1 hit.
SM00251. SAM_PNT. 1 hit.
[Graphical view]

SUPFAM

SSF47769. SAM_homology. 1 hit.

PROSITE

PS00345. ETS_DOMAIN_1. 1 hit.
PS00346. ETS_DOMAIN_2. 1 hit.
PS50061. ETS_DOMAIN_3. 1 hit.
PS51433. PNT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

8539.

SOURCE

Search...

Entry information

Entry name

ETS1_HUMAN

Accession

Primary (citable) accession number: P14921
Secondary accession number(s): Q14278, Q16080

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	January 25, 2012
This is version 137 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.