Human Gene ESR2 (ENST00000267525.10) from GENCODE V44
  Description: Homo sapiens estrogen receptor 2 (ESR2), transcript variant g, mRNA. (from RefSeq NM_001271877)
RefSeq Summary (NM_001271877): This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000267525.10
Gencode Gene: ENSG00000140009.19
Transcript (Including UTRs)
   Position: hg38 chr14:64,233,029-64,283,075 Size: 50,047 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg38 chr14:64,233,137-64,282,985 Size: 49,849 Coding Exon Count: 6 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr14:64,233,029-64,283,075)mRNA (may differ from genome)Protein (439 aa)
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-  Comments and Description Text from UniProtKB
  ID: ESR2_HUMAN
DESCRIPTION: RecName: Full=Estrogen receptor beta; Short=ER-beta; AltName: Full=Nuclear receptor subfamily 3 group A member 2;
FUNCTION: Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
SUBUNIT: Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with PELP1 and UBE1C. Isoform beta-2/cx preferentially forms a heterodimer with ESR1 rather than ESR2 and inhibits DNA-binding by ESR1. Interacts with AKAP13. Interacts with DNTTIP2. Interacts with isoform 4 of TXNRD1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes, including cyclin-D1/CCND1 AP-1 promoter. Interacts with DYX1C1 (By similarity). Interacts with PRMT2.
INTERACTION: P53041:PPP5C; NbExp=4; IntAct=EBI-78505, EBI-716663;
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Isoform beta-1 is expressed in testis and ovary, and at a lower level in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland and uterus. Also found in uterine bone, breast, and ovarian tumor cell lines, but not in colon and liver tumors. Isoform beta-2 is expressed in spleen, thymus, testis and ovary and at a lower level in skeletal muscle, prostate, colon, small intestine, leukocytes, bone marrow, mammary gland and uterus. Isoform beta-3 is found in testis. Isoform beta-4 is expressed in testis, and at a lower level in spleen, thymus, ovary, mammary gland and uterus. Isoform beta-5 is expressed in testis, placenta, skeletal muscle, spleen and leukocytes, and at a lower level in heart, lung, liver, kidney, pancreas, thymus, prostate, colon, small intestine, bone marrow, mammary gland and uterus. Not expressed in brain.
DOMAIN: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 subfamily.
SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
SEQUENCE CAUTION: Sequence=CAA67555.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/ESR2ID40500ch14q23.html";
WEB RESOURCE: Name=Wikipedia; Note=Estrogen receptor entry; URL="http://en.wikipedia.org/wiki/Estrogen_receptor";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: ESR2
Diseases sorted by gene-association score: medullary thyroid carcinoma, familial* (202), de quervain disease (18), transsexualism (16), gender identity disorder (16), endometrial cancer (15), breast cancer (14), lobular neoplasia (13), endometriosis (12), progesterone resistance (12), testicular germ cell cancer (11), breast disease (11), progesterone-receptor positive breast cancer (11), endometriosis of ovary (11), serous cystadenocarcinoma (11), vaginitis (10), endometrial adenocarcinoma (8), dental fluorosis (8), leiomyoma (8), cystadenocarcinoma (8), ovarian clear cell adenocarcinoma (7), uterine carcinosarcoma (7), seminoma (7), idiopathic scoliosis (7), postmenopausal atrophic vaginitis (6), infertility (6), sporadic breast cancer (6), prostate adenocarcinoma (6), diffuse glomerulonephritis (6), primary pigmented nodular adrenocortical disease (5), ovarian serous cystadenocarcinoma (5), estrogen excess (5), testicular germ cell tumor (5), osteoporosis (5), cerebellopontine angle tumor (5), plexopathy (4), in situ pulmonary adenocarcinoma (4), parotid gland cancer (4), prostate cancer (3), colorectal cancer (3), cryptorchidism (2), intrahepatic cholestasis (2), ovarian cancer, somatic (2), lung cancer (2), female reproductive system disease (1), reproductive system disease (1), reproductive organ cancer (1), male reproductive organ cancer (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.54 RPKM in Testis
Total median expression: 16.56 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -12.8090-0.142 Picture PostScript Text
3' UTR -35.50108-0.329 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR021064 - Estrogen_rcpt_beta_N
IPR008946 - Nucl_hormone_rcpt_ligand-bd
IPR000536 - Nucl_hrmn_rcpt_lig-bd_core
IPR024178 - Oestrogen_rcpt-rel
IPR001723 - Str_hrmn_rcpt
IPR001628 - Znf_hrmn_rcpt
IPR013088 - Znf_NHR/GATA

Pfam Domains:
PF12497 - Estrogen receptor beta
PF00104 - Ligand-binding domain of nuclear hormone receptor
PF00105 - Zinc finger, C4 type (two domains)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1L2J - X-ray MuPIT 1NDE - X-ray MuPIT 1QKM - X-ray MuPIT 1U3Q - X-ray MuPIT 1U3R - X-ray MuPIT 1U3S - X-ray MuPIT 1U9E - X-ray MuPIT 1X76 - X-ray MuPIT 1X78 - X-ray MuPIT 1X7B - X-ray MuPIT 1X7J - X-ray MuPIT 1YY4 - X-ray MuPIT 1YYE - X-ray MuPIT 1ZAF - X-ray MuPIT 2FSZ - X-ray MuPIT 2GIU - X-ray MuPIT 2I0G - X-ray MuPIT 2JJ3 - X-ray MuPIT 2NV7 - X-ray MuPIT 2QTU - X-ray MuPIT 2YJD - X-ray MuPIT 2YLY - X-ray MuPIT 2Z4B - X-ray MuPIT 3OLL - X-ray MuPIT 3OLS - X-ray MuPIT 3OMO - X-ray MuPIT 3OMP - X-ray MuPIT 3OMQ - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q92731
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001046 core promoter sequence-specific DNA binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003707 steroid hormone receptor activity
GO:0003713 transcription coactivator activity
GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
GO:0005496 steroid binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0008289 lipid binding
GO:0019899 enzyme binding
GO:0030284 estrogen receptor activity
GO:0034056 estrogen response element binding
GO:0038052 RNA polymerase II transcription factor activity, estrogen-activated sequence-specific DNA binding
GO:0042802 identical protein binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
GO:0048019 receptor antagonist activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007165 signal transduction
GO:0007267 cell-cell signaling
GO:0030308 negative regulation of cell growth
GO:0030520 intracellular estrogen receptor signaling pathway
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0071392 cellular response to estradiol stimulus
GO:1900116 extracellular negative regulation of signal transduction

Cellular Component:
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005739 mitochondrion


-  Descriptions from all associated GenBank mRNAs
  AF060555 - Homo sapiens estrogen receptor beta 3 isoform mRNA, complete cds.
AB006589 - Homo sapiens mRNA for estrogen receptor beta cx, complete cds.
BC024181 - Homo sapiens estrogen receptor 2 (ER beta), mRNA (cDNA clone MGC:26496 IMAGE:4825937), complete cds.
AF051428 - Homo sapiens estrogen receptor beta2 splice variant mRNA, complete cds.
LC122965 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbeta2delta7, complete cds.
LC122966 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbeta4delta7, complete cds.
LC122967 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbeta6, complete cds.
LC122968 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbeta6delta7, complete cds.
AK292370 - Homo sapiens cDNA FLJ77184 complete cds, highly similar to Homo sapiens estrogen receptor beta2 splice variant mRNA.
AF061054 - Homo sapiens estrogen receptor beta 4 splice variant mRNA, partial cds.
DQ838582 - Homo sapiens estrogen receptor beta isoform 4 (ESR2) mRNA, complete cds.
AF061055 - Homo sapiens estrogen receptor beta 5 splice variant mRNA, partial cds.
DQ838583 - Homo sapiens estrogen receptor beta isoform 5 (ESR2) mRNA, complete cds.
AF124790 - Homo sapiens estrogen receptor beta2 splice variant mRNA, complete cds.
HQ692821 - Homo sapiens estrogen nuclear receptor beta variant b (NR3A2) mRNA, complete cds.
DQ777076 - Homo sapiens estrogen receptor beta 4 mRNA, complete cds.
LC122969 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbeta7, complete cds.
LC122970 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbeta7delta7, complete cds.
AB209620 - Homo sapiens mRNA for estrogen receptor 2 (ER beta) variant protein.
AY438022 - Homo sapiens estrogen receptor beta mRNA, partial sequence.
X99101 - H.sapiens mRNA for estrogen receptor.
AF074599 - Homo sapiens estrogen receptor beta isoform 5/6 mRNA, partial cds.
AB006590 - Homo sapiens mRNA for estrogen receptor beta, complete cds.
HQ692820 - Homo sapiens estrogen nuclear receptor beta variant a (NR3A2) mRNA, complete cds.
AF051427 - Homo sapiens estrogen receptor beta mRNA, complete cds.
KJ534833 - Homo sapiens clone ESR2_iso-A_fetal-F02 estrogen receptor 2 isoform A (ESR2) mRNA, partial cds, alternatively spliced.
DQ777077 - Homo sapiens estrogen receptor beta 5-like mRNA, complete sequence.
AF074598 - Homo sapiens estrogen receptor beta isoform 6 mRNA, partial cds.
LC122972 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbetaEx. 6L, complete cds.
KJ901413 - Synthetic construct Homo sapiens clone ccsbBroadEn_10807 ESR2 gene, encodes complete protein.
KR709495 - Synthetic construct Homo sapiens clone CCSBHm_00002792 ESR2 (ESR2) mRNA, encodes complete protein.
LC122971 - Homo sapiens ESR2 mRNA for human estrogen receptor beta splice variant, ERbetaEx. 4L, complete cds.
AF047463 - Homo sapiens estrogen receptor beta mRNA, partial cds.
LC515463 - Homo sapiens ESR2 mRNA for human estrogen receptor beta, partial cds.
LC515464 - Homo sapiens ESR2 mRNA for human estrogen receptor beta, partial cds.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q92731 (Reactome details) participates in the following event(s):

R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-9038029 27-hydroxysterol binds ESR1, ESR2
R-HSA-8939201 ESR dimerizes
R-HSA-8939203 HSP90-dependent ATP hydrolysis promotes release of ESR:ESTG from chaperone complex
R-HSA-8939204 ESTG binds the ESR:chaperone complex
R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity
R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-8939211 ESR-mediated signaling
R-HSA-212436 Generic Transcription Pathway
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-162582 Signal Transduction
R-HSA-74160 Gene expression (Transcription)
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-199418 Negative regulation of the PI3K/AKT network
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: A8K8K5, ENST00000267525.1, ENST00000267525.2, ENST00000267525.3, ENST00000267525.4, ENST00000267525.5, ENST00000267525.6, ENST00000267525.7, ENST00000267525.8, ENST00000267525.9, ESR2_HUMAN, ESTRB, NM_001271877, NR3A2, O60608, O60685, O60702, O60703, O75583, O75584, Q0MWT5, Q0MWT6, Q86Z31, Q92731, Q9UEV6, Q9UHD3, Q9UQK9, uc010aqc.1
UCSC ID: ENST00000267525.10
RefSeq Accession: NM_001271877
Protein: Q92731 (aka ESR2_HUMAN)
CCDS: CCDS61469.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.