UniProtKB - P14921 (ETS1_HUMAN)
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Protein
Protein C-ets-1
Gene
ETS1
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| DNA bindingi | 335 – 415 | ETSPROSITE-ProRule annotationAdd BLAST | 81 |
GO - Molecular functioni
- DNA binding Source: UniProtKB
- histone acetyltransferase binding Source: Ensembl
- identical protein binding Source: IntAct
- RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
- transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
- transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
- transcription factor activity, sequence-specific DNA binding Source: BHF-UCL
- transcription factor binding Source: UniProtKB
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 function | DNA-binding |
| Biological process | Immunity, Transcription, Transcription regulation |
Enzyme and pathway databases
| Reactomei | R-HSA-2559585. Oncogene Induced Senescence. |
| SignaLinki | P14921. |
| SIGNORi | P14921. |
Names & Taxonomyi
| Protein namesi | Recommended name: Protein C-ets-1Alternative name(s): p54 |
| Gene namesi | Name:ETS1 Synonyms:EWSR2 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:3488. ETS1. |
Subcellular locationi
GO - Cellular componenti
- cytoplasm Source: UniProtKB-SubCell
- nucleoplasm Source: HPA
- nucleus Source: BHF-UCL
- transcription factor complex Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Keywords - Diseasei
Proto-oncogeneOrganism-specific databases
| DisGeNETi | 2113. |
| OpenTargetsi | ENSG00000134954. |
| Orphaneti | 536. Systemic lupus erythematosus. |
| PharmGKBi | PA27902. |
Polymorphism and mutation databases
| BioMutai | ETS1. |
| DMDMi | 119641. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000204069 | 1 – 441 | Protein C-ets-1Add BLAST | 441 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 8 | N6-acetyllysineCombined sources | 1 | |
| Modified residuei | 15 | N6-acetyllysine; alternateCombined sources | 1 | |
| Cross-linki | 15 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources | ||
| Modified residuei | 38 | Phosphothreonine; by MAPKBy similarity | 1 | |
| Modified residuei | 223 | PhosphotyrosineCombined sources | 1 | |
| Cross-linki | 227 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
| Modified residuei | 251 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 254 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 265 | PhosphothreonineCombined sources | 1 | |
| Modified residuei | 267 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 270 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 282 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 285 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 305 | N6-acetyllysineCombined sources | 1 |
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 conjugationProteomic databases
| EPDi | P14921. |
| MaxQBi | P14921. |
| PaxDbi | P14921. |
| PeptideAtlasi | P14921. |
| PRIDEi | P14921. |
PTM databases
| iPTMneti | P14921. |
| PhosphoSitePlusi | P14921. |
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
| Bgeei | ENSG00000134954. |
| CleanExi | HS_ETS1. |
| ExpressionAtlasi | P14921. baseline and differential. |
| Genevisiblei | P14921. HS. |
Organism-specific databases
| HPAi | CAB002575. 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
GO - Molecular functioni
- histone acetyltransferase binding Source: Ensembl
- identical protein binding Source: IntAct
- transcription factor binding Source: UniProtKB
Protein-protein interaction databases
| BioGridi | 108414. 52 interactors. |
| DIPi | DIP-35183N. |
| IntActi | P14921. 72 interactors. |
| MINTi | MINT-122911. |
| STRINGi | 9606.ENSP00000376436. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Helixi | 304 – 313 | Combined sources | 10 | |
| Helixi | 323 – 330 | Combined sources | 8 | |
| Beta strandi | 331 – 334 | Combined sources | 4 | |
| Helixi | 337 – 345 | Combined sources | 9 | |
| Helixi | 348 – 350 | Combined sources | 3 | |
| Turni | 351 – 353 | Combined sources | 3 | |
| Beta strandi | 354 – 356 | Combined sources | 3 | |
| Beta strandi | 358 – 361 | Combined sources | 4 | |
| Beta strandi | 362 – 364 | Combined sources | 3 | |
| Helixi | 368 – 379 | Combined sources | 12 | |
| Helixi | 386 – 395 | Combined sources | 10 | |
| Turni | 396 – 400 | Combined sources | 5 | |
| Beta strandi | 401 – 404 | Combined sources | 4 | |
| Beta strandi | 408 – 414 | Combined sources | 7 | |
| Helixi | 418 – 422 | Combined sources | 5 | |
| Helixi | 426 – 432 | Combined sources | 7 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
| 3RI4 | X-ray | 3.00 | A/D | 280-441 | [»] | |
| 3WTS | X-ray | 2.35 | C/H | 276-441 | [»] | |
| 3WTT | X-ray | 2.35 | C/H | 276-441 | [»] | |
| 3WTU | X-ray | 2.70 | C/H | 276-441 | [»] | |
| 3WTV | X-ray | 2.70 | C/H | 276-441 | [»] | |
| 3WTW | X-ray | 2.90 | C/H | 276-441 | [»] | |
| 3WTX | X-ray | 2.80 | C/H | 276-441 | [»] | |
| 3WTY | X-ray | 2.70 | C/H | 276-441 | [»] | |
| 3WTZ | X-ray | 2.61 | A/B | 276-441 | [»] | |
| 3WU0 | X-ray | 2.60 | A/B | 276-441 | [»] | |
| 3WU1 | X-ray | 2.40 | B | 333-441 | [»] | |
| 4L0Y | X-ray | 2.50 | B | 296-441 | [»] | |
| 4L0Z | X-ray | 2.70 | B | 296-441 | [»] | |
| 4L18 | X-ray | 2.30 | B/F | 296-441 | [»] | |
| 4LG0 | X-ray | 2.19 | B | 331-440 | [»] | |
| ProteinModelPortali | P14921. | |||||
| SMRi | P14921. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | P14921. |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 51 – 136 | PNTPROSITE-ProRule annotationAdd BLAST | 86 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 130 – 243 | Activation domain; required for transcription activationAdd BLAST | 114 |
Sequence similaritiesi
Belongs to the ETS family.Curated
Phylogenomic databases
| eggNOGi | KOG3806. Eukaryota. ENOG410Z0ZF. LUCA. |
| GeneTreei | ENSGT00760000118907. |
| HOGENOMi | HOG000285953. |
| HOVERGENi | HBG003088. |
| InParanoidi | P14921. |
| KOi | K02678. |
| OMAi | DEMATQE. |
| OrthoDBi | EOG091G0HJF. |
| PhylomeDBi | P14921. |
| TreeFami | TF316214. |
Family and domain databases
| Gene3Di | 1.10.10.10. 1 hit. |
| InterProi | View protein in InterPro IPR000418. Ets_dom. IPR003118. Pointed_dom. IPR013761. SAM/pointed. IPR016311. Transform_prot_C-ets. IPR011991. WHTH_DNA-bd_dom. |
| Pfami | View protein in Pfam PF00178. Ets. 1 hit. PF02198. SAM_PNT. 1 hit. |
| PIRSFi | PIRSF001698. Transforming_factor_C-ets. 1 hit. |
| PRINTSi | PR00454. ETSDOMAIN. |
| SMARTi | View protein in SMART SM00413. ETS. 1 hit. SM00251. SAM_PNT. 1 hit. |
| SUPFAMi | SSF46785. SSF46785. 1 hit. SSF47769. SSF47769. 1 hit. |
| PROSITEi | View 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.
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
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.
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 »Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 162 | Y → C in AAB28747 (PubMed:8231246).Curated | 1 | |
| Sequence conflicti | 236 – 243 | MCMGRTSR → FLPPPLPP in AAA52409 (PubMed:2997781).Curated | 8 | |
| Sequence conflicti | 255 | I → V in AAY19514 (PubMed:19377509).Curated | 1 | |
| Sequence conflicti | 332 – 337 | SGPIQL → RRPPAA in AAA52409 (PubMed:2997781).Curated | 6 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_043152 | 1 – 27 | MKAAV…LFPSP → MSYFVDSAGSSPVPYSAPRP AVVRQGPSNTYEDPRMNCGF QSNYHQQRPCYPFWDEMATQ EVPTGLEHCVS in isoform 3. 1 PublicationAdd BLAST | 27 | |
| Alternative sequenceiVSP_046056 | 28 – 243 | Missing in isoform Ets-1 p27. 1 PublicationAdd BLAST | 216 | |
| Alternative sequenceiVSP_001464 | 244 – 330 | Missing in isoform c-ETS-1B. CuratedAdd BLAST | 87 | |
| Alternative sequenceiVSP_055485 | 262 – 272 | DRLTQSWSSQS → GQEMGKEEKQT in isoform 5. 1 PublicationAdd BLAST | 11 | |
| Alternative sequenceiVSP_055486 | 273 – 441 | Missing in isoform 5. 1 PublicationAdd BLAST | 169 |
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. |
| CCDSi | CCDS44767.1. [P14921-3] CCDS53724.1. [P14921-4] CCDS81648.1. [P14921-2] CCDS8475.1. [P14921-1] |
| PIRi | A32066. TVHUET. |
| RefSeqi | NP_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] |
| UniGenei | Hs.369438. |
Genome annotation databases
| Ensembli | ENST00000319397; ENSP00000324578; ENSG00000134954. [P14921-1] ENST00000392668; ENSP00000376436; ENSG00000134954. [P14921-3] ENST00000526145; ENSP00000433500; ENSG00000134954. [P14921-2] ENST00000531611; ENSP00000435666; ENSG00000134954. [P14921-5] ENST00000535549; ENSP00000441430; ENSG00000134954. [P14921-4] |
| GeneIDi | 2113. |
| KEGGi | hsa:2113. |
| UCSCi | uc001qej.3. human. [P14921-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
Entry informationi
| Entry namei | ETS1_HUMAN | |
| Accessioni | P14921Primary (citable) accession number: P14921 Secondary accession number(s): A9UL17 Q96AC5 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1990 |
| Last sequence update: | April 1, 1990 | |
| Last modified: | May 10, 2017 | |
| This is version 193 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | 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. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
