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Protein

Transcription factor ETV6

Gene

ETV6

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

Functioni

Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi339 – 420ETSPROSITE-ProRule annotationAdd BLAST82

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: GO_Central
  • hematopoietic stem cell proliferation Source: UniProtKB
  • mesenchymal cell apoptotic process Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • neurogenesis Source: Ensembl
  • vitellogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139083-MONOMER.
SIGNORiP41212.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor ETV6
Alternative name(s):
ETS translocation variant 6
ETS-related protein Tel1
Short name:
Tel
Gene namesi
Name:ETV6
Synonyms:TEL, TEL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3495. ETV6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML).

Chromosomal aberrations involving ETV6 are found in acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1 (PubMed:7731705). Translocation t(4;12)(q12;p13) with CHIC2 (PubMed:10477709).

Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1.

A chromosomal aberration involving ETV6 is found in a form of pre-B acute lymphoid leukemia. Translocation t(9;12)(p24;p13) with JAK2.

A chromosomal aberration involving ETV6 and JAK2 is found in an atypical chronic myelogenous leukemia. Translocation t(9;15;12)(p24;q15;p13).

A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6.

A chromosomal aberration involving ETV6 is found in acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6.

A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2.

A chromosomal aberration involving ETV6 is found in acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5.

Myeloproliferative disorder chronic with eosinophilia (MPE)1 Publication
The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ETV6 is found in many instances of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein.1 Publication
Disease descriptionA hematologic disorder characterized by malignant eosinophils proliferation.
See also OMIM:131440
Leukemia, acute myelogenous (AML)1 Publication
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionA subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
See also OMIM:601626
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034600344Y → YG in one individual with AML; somatic mutation; unable to repress transcription. 1 Publication1
Thrombocytopenia 5 (THC5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC5 is an autosomal dominant disorder, associated with an increased susceptibility to the development of hematologic and solid malignancies.
See also OMIM:616216
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073322214P → L in THC5; abrogates DNA binding; alters subcellular location; decreases transcriptional repression in a dominant-negative fashion. 1 PublicationCorresponds to variant rs724159947dbSNPEnsembl.1
Natural variantiVAR_073323369R → Q in THC5; abrogates DNA binding; alters subcellular location; decreases transcriptional repression in a dominant-negative fashion. 1 PublicationCorresponds to variant rs724159946dbSNPEnsembl.1
Natural variantiVAR_073324399R → C in THC5; abrogates DNA binding; alters subcellular location; decreases transcriptional repression in a dominant-negative fashion. 1 PublicationCorresponds to variant rs724159945dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22S → A: No effect. 1
Mutagenesisi213S → A: No effect. 1 Publication1
Mutagenesisi238S → A: No effect. 1 Publication1
Mutagenesisi257S → A: No phosphorylation by MAPK14. 1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei11 – 12Breakpoint for translocation to form CHIC2-ETV6 in AML2
Sitei54 – 55Breakpoint for translocation to form ETV6-MDS2 in MDS2
Sitei55 – 56Breakpoint for translocation to form PAX5-ETV62
Sitei336 – 337Breakpoint for translocation to form ETV6-AML1 in ALL2

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi2120.
MalaCardsiETV6.
MIMi131440. phenotype.
601626. phenotype.
616216. phenotype.
OpenTargetsiENSG00000139083.
Orphaneti98823. Chronic myelomonocytic leukemia.
2665. Congenital mesoblastic nephroma.
2030. Fibrosarcoma.
99860. Precursor B-cell acute lymphoblastic leukemia.
314950. Primary hypereosinophilic syndrome.
PharmGKBiPA27909.

Chemistry databases

ChEMBLiCHEMBL2401606.

Polymorphism and mutation databases

BioMutaiETV6.
DMDMi730927.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002041211 – 452Transcription factor ETV6Add BLAST452

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei11N6-acetyllysine; alternateCombined sources1
Cross-linki11Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei18PhosphothreonineCombined sources1
Modified residuei22PhosphoserineCombined sources1 Publication1
Modified residuei213PhosphoserineCombined sources1
Modified residuei238PhosphoserineBy similarity1
Modified residuei257Phosphoserine; by MAPK141 Publication1
Cross-linki288Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei302N6-acetyllysineCombined sources1
Modified residuei323PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation of Ser-257 by MAPK14 (p38) inhibits ETV6 transcriptional repression.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP41212.
MaxQBiP41212.
PaxDbiP41212.
PeptideAtlasiP41212.
PRIDEiP41212.

PTM databases

iPTMnetiP41212.
PhosphoSitePlusiP41212.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000139083.
CleanExiHS_ETV6.
ExpressionAtlasiP41212. baseline and differential.
GenevisibleiP41212. HS.

Organism-specific databases

HPAiHPA000264.

Interactioni

Subunit structurei

Can form homodimers or heterodimers with TEL2 or FLI1. Interacts with L3MBTL1 and HDAC9.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AP1M1Q9BXS53EBI-1372759,EBI-541426
HDAC9Q9UKV0-33EBI-1372759,EBI-765476
WDYHV1Q96HA83EBI-1372759,EBI-741158

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108421. 33 interactors.
DIPiDIP-17028N.
IntActiP41212. 14 interactors.
MINTiMINT-7944472.
STRINGi9606.ENSP00000379658.

Chemistry databases

BindingDBiP41212.

Structurei

Secondary structure

1452
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi52 – 54Combined sources3
Helixi58 – 60Combined sources3
Helixi63 – 76Combined sources14
Turni84 – 87Combined sources4
Helixi91 – 94Combined sources4
Helixi99 – 105Combined sources7
Turni107 – 109Combined sources3
Helixi110 – 122Combined sources13
Helixi341 – 350Combined sources10
Helixi352 – 354Combined sources3
Turni355 – 357Combined sources3
Beta strandi358 – 362Combined sources5
Helixi363 – 365Combined sources3
Beta strandi367 – 371Combined sources5
Helixi373 – 383Combined sources11
Helixi391 – 403Combined sources13
Beta strandi406 – 408Combined sources3
Beta strandi411 – 419Combined sources9
Helixi424 – 426Combined sources3
Beta strandi430 – 432Combined sources3
Helixi434 – 438Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JI7X-ray1.45A/B/C47-123[»]
1LKYX-ray2.30A/B/C/D/E/F47-123[»]
2DAONMR-A338-442[»]
2QARX-ray2.40A/D47-142[»]
B/E47-148[»]
2QB0X-ray2.56A/C47-123[»]
2QB1X-ray2.61A/B47-121[»]
ProteinModelPortaliP41212.
SMRiP41212.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP41212.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 124PNTPROSITE-ProRule annotationAdd BLAST85

Sequence similaritiesi

Belongs to the ETS family.Curated
Contains 1 ETS DNA-binding domain.PROSITE-ProRule annotation
Contains 1 PNT (pointed) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3804. Eukaryota.
ENOG4111K4J. LUCA.
GeneTreeiENSGT00760000118996.
HOGENOMiHOG000012982.
HOVERGENiHBG005617.
InParanoidiP41212.
KOiK03211.
OMAiHQEPYPL.
OrthoDBiEOG091G05Q3.
PhylomeDBiP41212.
TreeFamiTF318679.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
1.10.150.50. 1 hit.
InterProiIPR000418. Ets_dom.
IPR003118. Pointed_dom.
IPR013761. SAM/pointed.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00178. Ets. 1 hit.
PF02198. SAM_PNT. 1 hit.
[Graphical view]
PRINTSiPR00454. ETSDOMAIN.
SMARTiSM00413. ETS. 1 hit.
SM00251. SAM_PNT. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF47769. SSF47769. 1 hit.
PROSITEiPS00346. ETS_DOMAIN_2. 1 hit.
PS50061. ETS_DOMAIN_3. 1 hit.
PS51433. PNT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P41212-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSETPAQCSI KQERISYTPP ESPVPSYASS TPLHVPVPRA LRMEEDSIRL
60 70 80 90 100
PAHLRLQPIY WSRDDVAQWL KWAENEFSLR PIDSNTFEMN GKALLLLTKE
110 120 130 140 150
DFRYRSPHSG DVLYELLQHI LKQRKPRILF SPFFHPGNSI HTQPEVILHQ
160 170 180 190 200
NHEEDNCVQR TPRPSVDNVH HNPPTIELLH RSRSPITTNH RPSPDPEQRP
210 220 230 240 250
LRSPLDNMIR RLSPAERAQG PRPHQENNHQ ESYPLSVSPM ENNHCPASSE
260 270 280 290 300
SHPKPSSPRQ ESTRVIQLMP SPIMHPLILN PRHSVDFKQS RLSEDGLHRE
310 320 330 340 350
GKPINLSHRE DLAYMNHIMV SVSPPEEHAM PIGRIADCRL LWDYVYQLLS
360 370 380 390 400
DSRYENFIRW EDKESKIFRI VDPNGLARLW GNHKNRTNMT YEKMSRALRH
410 420 430 440 450
YYKLNIIRKE PGQRLLFRFM KTPDEIMSGR TDRLEHLESQ ELDEQIYQED

EC
Length:452
Mass (Da):53,000
Last modified:February 1, 1995 - v1
Checksum:iDEC45682ECADECBB
GO

Sequence cautioni

The sequence ABI30005 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073322214P → L in THC5; abrogates DNA binding; alters subcellular location; decreases transcriptional repression in a dominant-negative fashion. 1 PublicationCorresponds to variant rs724159947dbSNPEnsembl.1
Natural variantiVAR_034600344Y → YG in one individual with AML; somatic mutation; unable to repress transcription. 1 Publication1
Natural variantiVAR_073323369R → Q in THC5; abrogates DNA binding; alters subcellular location; decreases transcriptional repression in a dominant-negative fashion. 1 PublicationCorresponds to variant rs724159946dbSNPEnsembl.1
Natural variantiVAR_073324399R → C in THC5; abrogates DNA binding; alters subcellular location; decreases transcriptional repression in a dominant-negative fashion. 1 PublicationCorresponds to variant rs724159945dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11732 mRNA. Translation: AAA19786.1.
AK289441 mRNA. Translation: BAF82130.1.
CH471094 Genomic DNA. Translation: EAW96240.1.
BC043399 mRNA. Translation: AAH43399.1.
U61375 Genomic DNA. Translation: AAC50690.1.
U63312 Genomic DNA. Translation: AAB17134.1.
U63313 Genomic DNA. Translation: AAB17135.1.
DQ841178 mRNA. Translation: ABI30005.1. Different initiation.
CCDSiCCDS8643.1.
RefSeqiNP_001978.1. NM_001987.4.
UniGeneiHs.504765.

Genome annotation databases

EnsembliENST00000396373; ENSP00000379658; ENSG00000139083.
GeneIDi2120.
KEGGihsa:2120.
UCSCiuc001qzz.4. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11732 mRNA. Translation: AAA19786.1.
AK289441 mRNA. Translation: BAF82130.1.
CH471094 Genomic DNA. Translation: EAW96240.1.
BC043399 mRNA. Translation: AAH43399.1.
U61375 Genomic DNA. Translation: AAC50690.1.
U63312 Genomic DNA. Translation: AAB17134.1.
U63313 Genomic DNA. Translation: AAB17135.1.
DQ841178 mRNA. Translation: ABI30005.1. Different initiation.
CCDSiCCDS8643.1.
RefSeqiNP_001978.1. NM_001987.4.
UniGeneiHs.504765.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JI7X-ray1.45A/B/C47-123[»]
1LKYX-ray2.30A/B/C/D/E/F47-123[»]
2DAONMR-A338-442[»]
2QARX-ray2.40A/D47-142[»]
B/E47-148[»]
2QB0X-ray2.56A/C47-123[»]
2QB1X-ray2.61A/B47-121[»]
ProteinModelPortaliP41212.
SMRiP41212.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108421. 33 interactors.
DIPiDIP-17028N.
IntActiP41212. 14 interactors.
MINTiMINT-7944472.
STRINGi9606.ENSP00000379658.

Chemistry databases

BindingDBiP41212.
ChEMBLiCHEMBL2401606.

PTM databases

iPTMnetiP41212.
PhosphoSitePlusiP41212.

Polymorphism and mutation databases

BioMutaiETV6.
DMDMi730927.

Proteomic databases

EPDiP41212.
MaxQBiP41212.
PaxDbiP41212.
PeptideAtlasiP41212.
PRIDEiP41212.

Protocols and materials databases

DNASUi2120.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000396373; ENSP00000379658; ENSG00000139083.
GeneIDi2120.
KEGGihsa:2120.
UCSCiuc001qzz.4. human.

Organism-specific databases

CTDi2120.
DisGeNETi2120.
GeneCardsiETV6.
HGNCiHGNC:3495. ETV6.
HPAiHPA000264.
MalaCardsiETV6.
MIMi131440. phenotype.
600618. gene.
601626. phenotype.
616216. phenotype.
neXtProtiNX_P41212.
OpenTargetsiENSG00000139083.
Orphaneti98823. Chronic myelomonocytic leukemia.
2665. Congenital mesoblastic nephroma.
2030. Fibrosarcoma.
99860. Precursor B-cell acute lymphoblastic leukemia.
314950. Primary hypereosinophilic syndrome.
PharmGKBiPA27909.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3804. Eukaryota.
ENOG4111K4J. LUCA.
GeneTreeiENSGT00760000118996.
HOGENOMiHOG000012982.
HOVERGENiHBG005617.
InParanoidiP41212.
KOiK03211.
OMAiHQEPYPL.
OrthoDBiEOG091G05Q3.
PhylomeDBiP41212.
TreeFamiTF318679.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139083-MONOMER.
SIGNORiP41212.

Miscellaneous databases

ChiTaRSiETV6. human.
EvolutionaryTraceiP41212.
GeneWikiiETV6.
GenomeRNAii2120.
PROiP41212.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139083.
CleanExiHS_ETV6.
ExpressionAtlasiP41212. baseline and differential.
GenevisibleiP41212. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
1.10.150.50. 1 hit.
InterProiIPR000418. Ets_dom.
IPR003118. Pointed_dom.
IPR013761. SAM/pointed.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00178. Ets. 1 hit.
PF02198. SAM_PNT. 1 hit.
[Graphical view]
PRINTSiPR00454. ETSDOMAIN.
SMARTiSM00413. ETS. 1 hit.
SM00251. SAM_PNT. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF47769. SSF47769. 1 hit.
PROSITEiPS00346. ETS_DOMAIN_2. 1 hit.
PS50061. ETS_DOMAIN_3. 1 hit.
PS51433. PNT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiETV6_HUMAN
AccessioniPrimary (citable) accession number: P41212
Secondary accession number(s): A3QVP6
, A8K076, Q9UMF6, Q9UMF7, Q9UMG0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 30, 2016
This is version 180 of the entry and version 1 of the sequence. [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 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar 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.