ETS2 ETS proto-oncogene 2, transcription factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: ETS2provided by HGNC
Official Full Name: ETS proto-oncogene 2, transcription factorprovided by HGNC
Primary source: HGNC:HGNC:3489
See related: Ensembl:ENSG00000157557 MIM:164740
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ETS2IT1
Summary: This gene encodes a transcription factor which regulates genes involved in development and apoptosis. The encoded protein is also a protooncogene and shown to be involved in regulation of telomerase. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
Expression: Ubiquitous expression in spleen (RPKM 50.4), small intestine (RPKM 39.5) and 22 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 21q22.2

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	21	NC_000021.9 (38805307..38824955)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	21	NC_000021.8 (40177231..40196879)

Chromosome 21 - NC_000021.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

ETS2 is of potential value as a molecular target for RCC treatment.
Title: Down-regulation of ETS2 inhibits the invasion and metastasis of renal cell carcinoma cells by inducing EMT via the PI3K/Akt signaling pathway.
ETS2 functions as an oncogene and plays a key role in the progression of hypopharyngeal cancer.
Title: E26 Transformation-Specific Transcription Factor ETS2 as an Oncogene Promotes the Progression of Hypopharyngeal Cancer.
ETS2 (high) is a poor prognostic factor in acute myeloid leukemia and may guide treatment decisions towards allogeneic hematopoietic stem cell transplantation.
Title: High expression of ETS2 predicts poor prognosis in acute myeloid leukemia and may guide treatment decisions.
Findings strongly suggest a critical role of Ets2 in human esophageal squamous cell carcinoma pathogenesis via the inactivation of the mTOR/p70S6K signaling pathway.
Title: Ets2 knockdown inhibits tumorigenesis in esophageal squamous cell carcinoma in vivo and in vitro.
Authors demonstrate that mtp53 prevents the COP1/DET1 complex from ubiquitinating ETS2 and thereby marking it for destruction. Authors show that mtp53 destabilizes DET1 and also disrupts the DET1/ETS2 complex thereby preventing ETS2 degradation.
Title: Mutant p53 protects ETS2 from non-canonical COP1/DET1 dependent degradation.
These findings suggest that ETS2 rs461155A>G, could be used as a biomarker predicting the clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy.
Title: A genetic variation in microRNA target site of ETS2 is associated with clinical outcomes of paclitaxel-cisplatin chemotherapy in non-small cell lung cancer.
Interaction with ZMYND11 mediates opposing roles of Ras-responsive ETS1 and ETS2.
Title: Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2.
These results suggest an unappreciated role for ETS2 in fibroblasts in establishing an immune-suppressive microenvironment in response to oncogenic Kras(G12D) signaling during the initial stages of tumor development.
Title: Stromal ETS2 Regulates Chemokine Production and Immune Cell Recruitment during Acinar-to-Ductal Metaplasia.
Data suggest marked changes in DNA methylation occur at a single CpG site (CpG4) in promoter region of ESR1 as breast cancer cells become resistant to hormonal/aromatase inhibitor antineoplastic agents; this CpG region is completely conserved among species, suggesting that it acts as a methylation-sensitive ETS2 transcription factor binding site/response element. (ESR1 = estrogen receptor 1; ETS2 = ETS proto-oncogene 2)
Title: Single CpG site methylation controls estrogen receptor gene transcription and correlates with hormone therapy resistance.
ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2
Title: ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.

Submit: New GeneRIF Correction See all GeneRIFs (71)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Genome-wide association study of chronic periodontitis in a general German population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study on overall survival of advanced non-small cell lung cancer patients treated with carboplatin and paclitaxel. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of v-ets erythroblastosis virus E26 oncogene homolog 2 (avian, ETS2) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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C-MYB transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
C-MYB transcription factor network, organism-specific biosystem
C-MYB transcription factor network
Cellular Senescence, organism-specific biosystem (from REACTOME)
Cellular Senescence, organism-specific biosystemCellular senescence involves irreversible growth arrest accompanied by phenotypic changes such as enlarged morphology, reorganization of chromatin through formation of senescence-associated heterochr...
Cellular responses to stress, organism-specific biosystem (from REACTOME)
Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
Dorso-ventral axis formation, organism-specific biosystem (from KEGG)
Dorso-ventral axis formation, organism-specific biosystem
Dorso-ventral axis formation
Dorso-ventral axis formation, conserved biosystem (from KEGG)
Dorso-ventral axis formation, conserved biosystem
Dorso-ventral axis formation
HTLV-I infection, organism-specific biosystem (from KEGG)
HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
HTLV-I infection, conserved biosystem (from KEGG)
HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
Oncogene Induced Senescence, organism-specific biosystem (from REACTOME)
Oncogene Induced Senescence, organism-specific biosystemOncogene-induced senescence is triggered by high level of RAS/RAF/MAPK signaling that can be caused, for example, by oncogenic mutations in RAS or RAF proteins, or by oncogenic mutations in growth fa...
Ras signaling pathway, organism-specific biosystem (from KEGG)
Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

ETV2 (e-PCR)
- UniSTS:266755

GDB:185172 (e-PCR)
- UniSTS:155427

SHGC-83279 (e-PCR)
- UniSTS:101157

GDB:192320 (e-PCR)
- UniSTS:155711

D21S1959 (e-PCR)
- UniSTS:61534

D21S1843 (e-PCR)
- UniSTS:68966

SHGC-51836 (e-PCR)
- UniSTS:70565

D21S1956 (e-PCR)
- UniSTS:428

SHGC-6939 (e-PCR)
- UniSTS:67504

WI-9128 (e-PCR)
- UniSTS:69308

Homology

Homologs of the ETS2 gene: The ETS2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 223 organisms have orthologs with human gene ETS2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	TAS Traceable Author Statement more info	PubMed
DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
glucocorticoid receptor binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ectodermal cell fate commitment	IEA Inferred from Electronic Annotation more info
mesoderm development	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
primitive streak formation	IEA Inferred from Electronic Annotation more info
regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
skeletal system development	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytosol	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	HDA more info	PubMed
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: protein C-ets-2

Names: oncogene ETS-2; v-ets avian erythroblastosis virus E2 oncogene homolog 2; v-ets avian erythroblastosis virus E26 oncogene homolog 2; v-ets erythroblastosis virus E26 oncogene homolog 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001256295.1 → NP_001243224.1 protein C-ets-2 isoform 2

See identical proteins and their annotated locations for NP_001243224.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding region, and initiates translation at an alternate start codon, compared to variant 1. The resulting protein (isoform 2) has a longer N-terminus compared to isoform 1.

Source sequence(s)

AK000535, AK096841, AP001040, AP001041

Conserved Domains (3) summary

cd08543
Location:225 → 313

SAM_PNT-ETS-2; Sterile alpha motif (SAM)/Pointed domain of ETS-2

smart00413
Location:502 → 586

ETS; erythroblast transformation specific domain

pfam05350
Location:39 → 143

GSK-3_bind; Glycogen synthase kinase-3 binding
NM_005239.6 → NP_005230.1 protein C-ets-2 isoform 1

See identical proteins and their annotated locations for NP_005230.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the shorter protein (isoform 1).

Source sequence(s)

AA452482, AK000535, BC042954, J04102

Consensus CDS

CCDS13659.1

UniProtKB/Swiss-Prot

P15036

Related

ENSP00000354194.3, ENST00000360938.7

Conserved Domains (2) summary

cd08543
Location:85 → 173

SAM_PNT-ETS-2; Sterile alpha motif (SAM)/Pointed domain of ETS-2

smart00413
Location:362 → 446

ETS; erythroblast transformation specific domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000021.9 Reference GRCh38.p12 Primary Assembly

Range

38805307..38824955

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005260935.1 → XP_005260992.1 protein C-ets-2 isoform X1

See identical proteins and their annotated locations for XP_005260992.1

UniProtKB/Swiss-Prot

P15036

Conserved Domains (2) summary

cd08543
Location:85 → 173

SAM_PNT-ETS-2; Sterile alpha motif (SAM)/Pointed domain of ETS-2

smart00413
Location:362 → 446

ETS; erythroblast transformation specific domain
XM_017028290.1 → XP_016883779.1 protein C-ets-2 isoform X1

UniProtKB/Swiss-Prot

P15036

Conserved Domains (2) summary

cd08543
Location:85 → 173

SAM_PNT-ETS-2; Sterile alpha motif (SAM)/Pointed domain of ETS-2

smart00413
Location:362 → 446

ETS; erythroblast transformation specific domain