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Protein

Protein C-ets-1

Gene

ETS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor. Directly controls the expression of cytokine and chemokine genes in a wide variety of different cellular contexts. May control the differentiation, survival and proliferation of lymphoid cells. May also regulate angiogenesis through regulation of expression of genes controlling endothelial cell migration and invasion.4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi335 – 415ETSPROSITE-ProRule annotationAdd BLAST81

GO - Molecular functioni

GO - Biological processi

  • angiogenesis involved in wound healing Source: Ensembl
  • cell motility Source: BHF-UCL
  • cellular response to hydrogen peroxide Source: Ensembl
  • estrous cycle Source: Ensembl
  • female pregnancy Source: Ensembl
  • hypothalamus development Source: Ensembl
  • immune response Source: ProtInc
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of cell proliferation Source: ProtInc
  • negative regulation of inflammatory response Source: Ensembl
  • pituitary gland development Source: Ensembl
  • PML body organization Source: BHF-UCL
  • positive regulation of angiogenesis Source: Ensembl
  • positive regulation of cell proliferation Source: Ensembl
  • positive regulation of cellular component movement Source: BHF-UCL
  • positive regulation of endothelial cell migration Source: UniProtKB
  • positive regulation of erythrocyte differentiation Source: UniProtKB
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of leukocyte adhesion to vascular endothelial cell Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • pri-miRNA transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of angiogenesis Source: UniProtKB
  • regulation of apoptotic process Source: UniProtKB
  • regulation of extracellular matrix disassembly Source: Ensembl
  • response to antibiotic Source: UniProtKB
  • response to estradiol Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to interleukin-1 Source: Ensembl
  • response to laminar fluid shear stress Source: Ensembl
  • response to mechanical stimulus Source: Ensembl
  • transcription from RNA polymerase II promoter Source: UniProtKB

Keywordsi

Molecular functionDNA-binding
Biological processImmunity, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2559585. Oncogene Induced Senescence.
SignaLinkiP14921.
SIGNORiP14921.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein C-ets-1
Alternative name(s):
p54
Gene namesi
Name:ETS1
Synonyms:EWSR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000134954.14.
HGNCiHGNC:3488. ETS1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi2113.
OpenTargetsiENSG00000134954.
Orphaneti536. Systemic lupus erythematosus.
PharmGKBiPA27902.

Polymorphism and mutation databases

BioMutaiETS1.
DMDMi119641.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002040691 – 441Protein C-ets-1Add BLAST441

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8N6-acetyllysine; alternateCombined sources1
Cross-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei15N6-acetyllysine; alternateCombined sources1
Cross-linki15Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei38Phosphothreonine; by MAPKBy similarity1
Cross-linki138Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei223PhosphotyrosineCombined sources1
Cross-linki227Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei251PhosphoserineCombined sources1
Modified residuei254PhosphoserineBy similarity1
Modified residuei265PhosphothreonineCombined sources1
Modified residuei267PhosphoserineCombined sources1
Modified residuei270PhosphoserineCombined sources1
Modified residuei282PhosphoserineBy similarity1
Modified residuei285PhosphoserineCombined sources1
Modified residuei305N6-acetyllysineCombined sources1

Post-translational modificationi

Sumoylated on Lys-15 and Lys-227, preferentially with SUMO2; which inhibits transcriptional activity.By similarity
Ubiquitinated; which induces proteasomal degradation.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP14921.
MaxQBiP14921.
PaxDbiP14921.
PeptideAtlasiP14921.
PRIDEiP14921.

PTM databases

iPTMnetiP14921.
PhosphoSitePlusiP14921.

Expressioni

Tissue specificityi

Highly expressed within lymphoid cells. Isoforms c-ETS-1A and Ets-1 p27 are both detected in all fetal tissues tested, but vary with tissue type in adult tissues. None is detected in brain or kidney.2 Publications

Inductioni

Up-regulated by retinoic acid, VEGF, TNF-alpha/TNFA, lipopolysaccharide and in response to hypoxia (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000134954.
CleanExiHS_ETS1.
ExpressionAtlasiP14921. baseline and differential.
GenevisibleiP14921. HS.

Organism-specific databases

HPAiCAB002575.
HPA063230.

Interactioni

Subunit structurei

Binds DNA as a homodimer; homodimerization is required for transcription activation. Interacts with MAF and MAFB. Interacts with PAX5; the interaction alters DNA-binding properties (By similarity). Interacts with DAXX. Interacts with UBE2I. Interacts with SP100; the interaction is direct and modulates ETS1 transcriptional activity.By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • histone acetyltransferase binding Source: Ensembl
  • identical protein binding Source: IntAct
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108414. 53 interactors.
CORUMiP14921.
DIPiDIP-35183N.
IntActiP14921. 73 interactors.
MINTiMINT-122911.
STRINGi9606.ENSP00000376436.

Structurei

Secondary structure

1441
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi304 – 313Combined sources10
Helixi323 – 330Combined sources8
Beta strandi331 – 334Combined sources4
Helixi337 – 345Combined sources9
Helixi348 – 350Combined sources3
Turni351 – 353Combined sources3
Beta strandi354 – 356Combined sources3
Beta strandi358 – 361Combined sources4
Beta strandi362 – 364Combined sources3
Helixi368 – 379Combined sources12
Helixi386 – 395Combined sources10
Turni396 – 400Combined sources5
Beta strandi401 – 404Combined sources4
Beta strandi408 – 414Combined sources7
Helixi418 – 422Combined sources5
Helixi426 – 432Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GVJX-ray1.53A/B297-441[»]
2NNYX-ray2.58A/B280-441[»]
2STTNMR-A320-415[»]
2STWNMR-A320-415[»]
3MFKX-ray3.00A/B280-441[»]
3RI4X-ray3.00A/D280-441[»]
3WTSX-ray2.35C/H276-441[»]
3WTTX-ray2.35C/H276-441[»]
3WTUX-ray2.70C/H276-441[»]
3WTVX-ray2.70C/H276-441[»]
3WTWX-ray2.90C/H276-441[»]
3WTXX-ray2.80C/H276-441[»]
3WTYX-ray2.70C/H276-441[»]
3WTZX-ray2.61A/B276-441[»]
3WU0X-ray2.60A/B276-441[»]
3WU1X-ray2.40B333-441[»]
4L0YX-ray2.50B296-441[»]
4L0ZX-ray2.70B296-441[»]
4L18X-ray2.30B/F296-441[»]
4LG0X-ray2.19B331-440[»]
ProteinModelPortaliP14921.
SMRiP14921.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14921.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini51 – 136PNTPROSITE-ProRule annotationAdd BLAST86

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni130 – 243Activation domain; required for transcription activationAdd BLAST114

Sequence similaritiesi

Belongs to the ETS family.Curated

Phylogenomic databases

eggNOGiKOG3806. Eukaryota.
ENOG410Z0ZF. LUCA.
GeneTreeiENSGT00760000118907.
HOGENOMiHOG000285953.
HOVERGENiHBG003088.
InParanoidiP14921.
KOiK02678.
OMAiDEMATQE.
OrthoDBiEOG091G0HJF.
PhylomeDBiP14921.
TreeFamiTF316214.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiView protein in InterPro
IPR000418. Ets_dom.
IPR003118. Pointed_dom.
IPR013761. SAM/pointed_sf.
IPR016311. Transform_prot_C-ets.
IPR036388. WH-like_DNA-bd_sf.
IPR036390. WH_DNA-bd_sf.
PfamiView protein in Pfam
PF00178. Ets. 1 hit.
PF02198. SAM_PNT. 1 hit.
PIRSFiPIRSF001698. Transforming_factor_C-ets. 1 hit.
PRINTSiPR00454. ETSDOMAIN.
SMARTiView protein in SMART
SM00413. ETS. 1 hit.
SM00251. SAM_PNT. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF47769. SSF47769. 1 hit.
PROSITEiView protein in PROSITE
PS00345. ETS_DOMAIN_1. 1 hit.
PS00346. ETS_DOMAIN_2. 1 hit.
PS50061. ETS_DOMAIN_3. 1 hit.
PS51433. PNT. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform c-ETS-1A (identifier: P14921-1) [UniParc]FASTAAdd to basket
Also known as: Ets-1 p51

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.

« Hide

        10         20         30         40         50
MKAAVDLKPT LTIIKTEKVD LELFPSPDME CADVPLLTPS SKEMMSQALK
60 70 80 90 100
ATFSGFTKEQ QRLGIPKDPR QWTETHVRDW VMWAVNEFSL KGVDFQKFCM
110 120 130 140 150
NGAALCALGK DCFLELAPDF VGDILWEHLE ILQKEDVKPY QVNGVNPAYP
160 170 180 190 200
ESRYTSDYFI SYGIEHAQCV PPSEFSEPSF ITESYQTLHP ISSEELLSLK
210 220 230 240 250
YENDYPSVIL RDPLQTDTLQ NDYFAIKQEV VTPDNMCMGR TSRGKLGGQD
260 270 280 290 300
SFESIESYDS CDRLTQSWSS QSSFNSLQRV PSYDSFDSED YPAALPNHKP
310 320 330 340 350
KGTFKDYVRD RADLNKDKPV IPAAALAGYT GSGPIQLWQF LLELLTDKSC
360 370 380 390 400
QSFISWTGDG WEFKLSDPDE VARRWGKRKN KPKMNYEKLS RGLRYYYDKN
410 420 430 440
IIHKTAGKRY VYRFVCDLQS LLGYTPEELH AMLDVKPDAD E
Length:441
Mass (Da):50,408
Last modified:April 1, 1990 - v1
Checksum:i3B66BCC464B393FB
GO
Isoform c-ETS-1B (identifier: P14921-2) [UniParc]FASTAAdd to basket
Also known as: Ets-1 p42

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

Show »
Length:354
Mass (Da):40,786
Checksum:i6C3313F2DBE3CF88
GO
Isoform 3 (identifier: P14921-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MKAAVDLKPTLTIIKTEKVDLELFPSP → MSYFVDSAGS...VPTGLEHCVS

Note: No experimental confirmation available.
Show »
Length:485
Mass (Da):55,412
Checksum:i8A6B816BAEB91149
GO
Isoform Ets-1 p27 (identifier: P14921-4) [UniParc]FASTAAdd to basket
Also known as: Ets-1Delta(III-VI)

The sequence of this isoform differs from the canonical sequence as follows:
     28-243: Missing.

Note: Acts as a dominant-negative for isoform c-ETS-1A.
Show »
Length:225
Mass (Da):25,697
Checksum:i5A01096FCEDE9FEA
GO
Isoform 5 (identifier: P14921-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     262-272: DRLTQSWSSQS → GQEMGKEEKQT
     273-441: Missing.

Note: No experimental confirmation available.
Show »
Length:272
Mass (Da):30,860
Checksum:i20D7FF9557D80D46
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162Y → C in AAB28747 (PubMed:8231246).Curated1
Sequence conflicti236 – 243MCMGRTSR → FLPPPLPP in AAA52409 (PubMed:2997781).Curated8
Sequence conflicti255I → V in AAY19514 (PubMed:19377509).Curated1
Sequence conflicti332 – 337SGPIQL → RRPPAA in AAA52409 (PubMed:2997781).Curated6

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0431521 – 27MKAAV…LFPSP → MSYFVDSAGSSPVPYSAPRP AVVRQGPSNTYEDPRMNCGF QSNYHQQRPCYPFWDEMATQ EVPTGLEHCVS in isoform 3. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_04605628 – 243Missing in isoform Ets-1 p27. 1 PublicationAdd BLAST216
Alternative sequenceiVSP_001464244 – 330Missing in isoform c-ETS-1B. CuratedAdd BLAST87
Alternative sequenceiVSP_055485262 – 272DRLTQSWSSQS → GQEMGKEEKQT in isoform 5. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_055486273 – 441Missing in isoform 5. 1 PublicationAdd BLAST169

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AY943926 mRNA. Translation: AAY19514.1.
BT019452 mRNA. Translation: AAV38259.1.
BX640634 mRNA. Translation: CAE45783.1.
AP001995 Genomic DNA. No translation available.
AP003397 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67709.1.
BC017314 mRNA. Translation: AAH17314.1.
M11921 Genomic DNA. Translation: AAA52409.1.
CCDSiCCDS44767.1. [P14921-3]
CCDS53724.1. [P14921-4]
CCDS81648.1. [P14921-2]
CCDS8475.1. [P14921-1]
PIRiA32066. TVHUET.
RefSeqiNP_001137292.1. NM_001143820.1. [P14921-3]
NP_001155894.1. NM_001162422.1. [P14921-4]
NP_001317380.1. NM_001330451.1. [P14921-2]
NP_005229.1. NM_005238.3. [P14921-1]
XP_016872803.1. XM_017017314.1. [P14921-3]
UniGeneiHs.369438.

Genome annotation databases

EnsembliENST00000319397; ENSP00000324578; ENSG00000134954. [P14921-1]
ENST00000392668; ENSP00000376436; ENSG00000134954. [P14921-3]
ENST00000526145; ENSP00000433500; ENSG00000134954. [P14921-2]
ENST00000531611; ENSP00000435666; ENSG00000134954. [P14921-5]
ENST00000535549; ENSP00000441430; ENSG00000134954. [P14921-4]
GeneIDi2113.
KEGGihsa:2113.
UCSCiuc001qej.3. human. [P14921-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiETS1_HUMAN
AccessioniPrimary (citable) accession number: P14921
Secondary accession number(s): A9UL17
, F5GYX9, Q14278, Q16080, Q6N087, Q96AC5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 22, 2017
This is version 197 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families