UniProtKB - Q92731 (ESR2_HUMAN)
(max 400 entries)x
Your basket is currently empty.
Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)
Protein
Estrogen receptor beta
Gene
ESR2
Organism
Homo sapiens (Human)
Status
Functioni
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 (PubMed:20074560). 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.1 Publication
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| DNA bindingi | 149 – 214 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 66 | |
| Zinc fingeri | 149 – 169 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
| Zinc fingeri | 185 – 209 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- core promoter sequence-specific DNA binding Source: UniProtKB
- DNA binding Source: ProtInc
- enzyme binding Source: UniProtKB
- estrogen receptor activity Source: CAFA
- estrogen response element binding Source: CAFA
- receptor antagonist activity Source: UniProtKB
- RNA polymerase II transcription factor activity, estrogen-activated sequence-specific DNA binding Source: ParkinsonsUK-UCL
- RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: UniProtKB
- steroid binding Source: UniProtKB
- steroid hormone receptor activity Source: ProtInc
- transcription coactivator activity Source: ProtInc
- transcription factor activity, sequence-specific DNA binding Source: ProtInc
- zinc ion binding Source: InterPro
GO - Biological processi
- cell-cell signaling Source: ProtInc
- cellular response to estradiol stimulus Source: CAFA
- intracellular estrogen receptor signaling pathway Source: CAFA
- negative regulation of cell growth Source: UniProtKB
- negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
- positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter Source: CAFA
- regulation of transcription, DNA-templated Source: UniProtKB
- signal transduction Source: ProtInc
- transcription initiation from RNA polymerase II promoter Source: Reactome
Keywordsi
| Molecular function | Activator, DNA-binding, Receptor |
| Biological process | Transcription, Transcription regulation |
| Ligand | Lipid-binding, Metal-binding, Steroid-binding, Zinc |
Enzyme and pathway databases
| Reactomei | R-HSA-383280. Nuclear Receptor transcription pathway. |
| SignaLinki | Q92731. |
| SIGNORi | Q92731. |
Names & Taxonomyi
| Protein namesi | Recommended name: Estrogen receptor betaShort name: ER-beta Alternative name(s): Nuclear receptor subfamily 3 group A member 2 |
| Gene namesi | Name:ESR2 Synonyms:ESTRB, NR3A2 |
| 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:3468. ESR2. |
Subcellular locationi
- Nucleus PROSITE-ProRule annotation2 Publications
GO - Cellular componenti
- extracellular region Source: GOC
- mitochondrion Source: MGI
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 87 | S → A: Enhances repression by activated ErbB2/ErbB3; when associated with A-105. 1 Publication | 1 | |
| Mutagenesisi | 87 | S → D: Abolishes repression by activated ErbB2/ErbB3; when associated with D-105. 1 Publication | 1 | |
| Mutagenesisi | 105 | S → A: Enhances repression by activated ErbB2/ErbB3; when associated with A-87. 1 Publication | 1 | |
| Mutagenesisi | 105 | S → D: Abolishes repression by activated ErbB2/ErbB3; when associated with D-87. 1 Publication | 1 |
Organism-specific databases
| DisGeNETi | 2100. |
| OpenTargetsi | ENSG00000140009. |
| PharmGKBi | PA27886. |
Chemistry databases
| ChEMBLi | CHEMBL242. |
| DrugBanki | DB07119. 1-CHLORO-6-(4-HYDROXYPHENYL)-2-NAPHTHOL. DB07032. 2-(4-HYDROXY-PHENYL)BENZOFURAN-5-OL. DB06875. 3-(3-FLUORO-4-HYDROXYPHENYL)-7-HYDROXY-1-NAPHTHONITRILE. DB07236. 3-(6-HYDROXY-NAPHTHALEN-2-YL)-BENZO[D]ISOOXAZOL-6-OL. DB07230. 3-BROMO-6-HYDROXY-2-(4-HYDROXYPHENYL)-1H-INDEN-1-ONE. DB07150. 4-(4-HYDROXYPHENYL)-1-NAPHTHALDEHYDE OXIME. DB07198. 5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFURAN-7-CARBONITRILE. DB06927. [5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFURAN-7-YL]ACETONITRILE. DB04468. Afimoxifene. DB05882. CHF 4227. DB00255. Diethylstilbestrol. DB00783. Estradiol. DB01196. Estramustine. DB04573. Estriol. DB04574. Estrone sulfate. DB01645. Genistein. DB06202. Lasofoxifene. DB05052. MF101. DB02983. Para-Mercury-Benzenesulfonic Acid. DB01708. Prasterone. DB00481. Raloxifene. DB00675. Tamoxifen. DB01108. Trilostane. |
| GuidetoPHARMACOLOGYi | 621. |
Polymorphism and mutation databases
| BioMutai | ESR2. |
| DMDMi | 6166154. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000053642 | 1 – 530 | Estrogen receptor betaAdd BLAST | 530 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 87 | Phosphoserine1 Publication | 1 | |
| Modified residuei | 105 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
Phosphorylation at Ser-87 and Ser-105 recruits NCOA1.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
| PaxDbi | Q92731. |
| PeptideAtlasi | Q92731. |
| PRIDEi | Q92731. |
PTM databases
| iPTMneti | Q92731. |
| PhosphoSitePlusi | Q92731. |
| SwissPalmi | Q92731. |
Miscellaneous databases
| PMAP-CutDBi | A8K8K5. |
Expressioni
Tissue specificityi
Isoform 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 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 4 is found in testis. Isoform 5 is expressed in testis, and at a lower level in spleen, thymus, ovary, mammary gland and uterus. Isoform 6 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.
Gene expression databases
| Bgeei | ENSG00000140009. |
| ExpressionAtlasi | Q92731. baseline and differential. |
| Genevisiblei | Q92731. HS. |
Organism-specific databases
| HPAi | CAB022544. |
Interactioni
Subunit structurei
Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA1, NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with PELP1 and UBE1C. Isoform 2 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 DNAAF4 (By similarity). Interacts with PRMT2. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner.By similarity10 Publications
Binary interactionsi
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- receptor antagonist activity Source: UniProtKB
Protein-protein interaction databases
| BioGridi | 108404. 100 interactors. |
| DIPi | DIP-5966N. |
| IntActi | Q92731. 430 interactors. |
| STRINGi | 9606.ENSP00000343925. |
Chemistry databases
| BindingDBi | Q92731. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Helixi | 257 – 260 | Combined sources | 4 | |
| Helixi | 261 – 263 | Combined sources | 3 | |
| Helixi | 265 – 275 | Combined sources | 11 | |
| Beta strandi | 286 – 288 | Combined sources | 3 | |
| Helixi | 291 – 314 | Combined sources | 24 | |
| Helixi | 319 – 321 | Combined sources | 3 | |
| Helixi | 324 – 347 | Combined sources | 24 | |
| Beta strandi | 348 – 350 | Combined sources | 3 | |
| Beta strandi | 353 – 357 | Combined sources | 5 | |
| Beta strandi | 359 – 363 | Combined sources | 5 | |
| Helixi | 364 – 369 | Combined sources | 6 | |
| Helixi | 373 – 389 | Combined sources | 17 | |
| Helixi | 394 – 406 | Combined sources | 13 | |
| Beta strandi | 407 – 409 | Combined sources | 3 | |
| Helixi | 411 – 413 | Combined sources | 3 | |
| Helixi | 417 – 419 | Combined sources | 3 | |
| Helixi | 421 – 442 | Combined sources | 22 | |
| Turni | 443 – 445 | Combined sources | 3 | |
| Helixi | 448 – 481 | Combined sources | 34 | |
| Beta strandi | 482 – 484 | Combined sources | 3 | |
| Helixi | 489 – 497 | Combined sources | 9 | |
| Helixi | 498 – 501 | Combined sources | 4 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1L2J | X-ray | 2.95 | A/B | 256-505 | [»] | |
| 1NDE | X-ray | 3.00 | A | 256-501 | [»] | |
| 1QKM | X-ray | 1.80 | A | 255-509 | [»] | |
| 1U3Q | X-ray | 2.40 | A/B/C/D | 261-500 | [»] | |
| 1U3R | X-ray | 2.21 | A/B | 261-501 | [»] | |
| 1U3S | X-ray | 2.50 | A/B | 261-500 | [»] | |
| 1U9E | X-ray | 2.40 | A/B | 261-501 | [»] | |
| 1X76 | X-ray | 2.20 | A/B | 261-500 | [»] | |
| 1X78 | X-ray | 2.30 | A/B | 261-500 | [»] | |
| 1X7B | X-ray | 2.30 | A/B | 261-500 | [»] | |
| 1X7J | X-ray | 2.30 | A/B | 261-500 | [»] | |
| 1YY4 | X-ray | 2.70 | A/B | 263-530 | [»] | |
| 1YYE | X-ray | 2.03 | A/B | 263-530 | [»] | |
| 1ZAF | X-ray | 2.20 | A/B | 263-500 | [»] | |
| 2FSZ | X-ray | 2.20 | A/B | 257-502 | [»] | |
| 2GIU | X-ray | 2.20 | A | 260-500 | [»] | |
| 2I0G | X-ray | 2.50 | A/B | 256-505 | [»] | |
| 2JJ3 | X-ray | 2.28 | A/B | 256-505 | [»] | |
| 2NV7 | X-ray | 2.10 | A/B | 263-500 | [»] | |
| 2QTU | X-ray | 2.53 | A/B | 256-505 | [»] | |
| 2YJD | X-ray | 1.93 | A/B | 261-500 | [»] | |
| 2YLY | X-ray | 3.20 | A/B | 260-500 | [»] | |
| 2Z4B | X-ray | 2.34 | A/B | 256-505 | [»] | |
| 3OLL | X-ray | 1.50 | A/B | 261-500 | [»] | |
| 3OLS | X-ray | 2.20 | A/B | 261-500 | [»] | |
| 3OMO | X-ray | 2.21 | A/B | 261-500 | [»] | |
| 3OMP | X-ray | 2.05 | A/B | 261-500 | [»] | |
| 3OMQ | X-ray | 1.97 | A/B | 261-500 | [»] | |
| 4J24 | X-ray | 2.10 | A/B/C/D | 261-500 | [»] | |
| 4J26 | X-ray | 2.30 | A/B | 261-500 | [»] | |
| 4ZI1 | X-ray | 2.10 | A | 262-509 | [»] | |
| DisProti | DP00079. | |||||
| ProteinModelPortali | Q92731. | |||||
| SMRi | Q92731. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | Q92731. |
Family & Domainsi
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 1 – 148 | ModulatingAdd BLAST | 148 | |
| Regioni | 215 – 530 | Steroid-bindingAdd BLAST | 316 |
Domaini
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Sequence similaritiesi
Zinc finger
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Zinc fingeri | 149 – 169 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
| Zinc fingeri | 185 – 209 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
| eggNOGi | KOG3575. Eukaryota. ENOG410XRZC. LUCA. |
| GeneTreei | ENSGT00760000118887. |
| HOVERGENi | HBG108344. |
| InParanoidi | Q92731. |
| KOi | K08551. |
| OMAi | VKCGSRR. |
| OrthoDBi | EOG091G03V4. |
| PhylomeDBi | Q92731. |
| TreeFami | TF323751. |
Family and domain databases
| Gene3Di | 3.30.50.10. 1 hit. |
| InterProi | View protein in InterPro IPR028355. ER-beta/gamma. IPR021064. Estrogen_rcpt_beta_N. IPR000536. Nucl_hrmn_rcpt_lig-bd. IPR001723. Nuclear_hrmn_rcpt. IPR024178. Oest_rcpt/oest-rel_rcp. IPR001628. Znf_hrmn_rcpt. IPR013088. Znf_NHR/GATA. |
| Pfami | View protein in Pfam PF12497. ERbeta_N. 1 hit. PF00104. Hormone_recep. 1 hit. PF00105. zf-C4. 1 hit. |
| PIRSFi | PIRSF500102. ER-b. 1 hit. PIRSF002527. ER-like_NR. 1 hit. |
| PRINTSi | PR00398. STRDHORMONER. PR00047. STROIDFINGER. |
| SMARTi | View protein in SMART SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. |
| SUPFAMi | SSF48508. SSF48508. 1 hit. |
| PROSITEi | View protein in PROSITE PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. |
Sequences (9)i
Sequence statusi: Complete.
This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q92731-1) [UniParc]FASTAAdd to basket
Also known as: Beta-1
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
MDIKNSPSSL NSPSSYNCSQ SILPLEHGSI YIPSSYVDSH HEYPAMTFYS
60 70 80 90 100
PAVMNYSIPS NVTNLEGGPG RQTTSPNVLW PTPGHLSPLV VHRQLSHLYA
110 120 130 140 150
EPQKSPWCEA RSLEHTLPVN RETLKRKVSG NRCASPVTGP GSKRDAHFCA
160 170 180 190 200
VCSDYASGYH YGVWSCEGCK AFFKRSIQGH NDYICPATNQ CTIDKNRRKS
210 220 230 240 250
CQACRLRKCY EVGMVKCGSR RERCGYRLVR RQRSADEQLH CAGKAKRSGG
260 270 280 290 300
HAPRVRELLL DALSPEQLVL TLLEAEPPHV LISRPSAPFT EASMMMSLTK
310 320 330 340 350
LADKELVHMI SWAKKIPGFV ELSLFDQVRL LESCWMEVLM MGLMWRSIDH
360 370 380 390 400
PGKLIFAPDL VLDRDEGKCV EGILEIFDML LATTSRFREL KLQHKEYLCV
410 420 430 440 450
KAMILLNSSM YPLVTATQDA DSSRKLAHLL NAVTDALVWV IAKSGISSQQ
460 470 480 490 500
QSMRLANLLM LLSHVRHASN KGMEHLLNMK CKNVVPVYDL LLEMLNAHVL
510 520 530
RGCKSSITGS ECSPAEDSKS KEGSQNPQSQ
Isoform 3 (identifier: Q92731-3) [UniParc]FASTAAdd to basket
Also known as: Beta-2A
The sequence of this isoform differs from the canonical sequence as follows:
319-323: FVELS → MRGNA
324-530: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »Sequence cautioni
The sequence CAA67555 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_003685 | 319 – 409 | Missing in isoform 7. 1 PublicationAdd BLAST | 91 | |
| Alternative sequenceiVSP_003684 | 319 – 323 | FVELS → MRGNA in isoform 3. 2 Publications | 5 | |
| Alternative sequenceiVSP_003686 | 324 – 530 | Missing in isoform 3. 2 PublicationsAdd BLAST | 207 | |
| Alternative sequenceiVSP_003687 | 365 – 375 | DEGKCVEGILE → YVPSGHSDPGC in isoform 8. 1 PublicationAdd BLAST | 11 | |
| Alternative sequenceiVSP_003688 | 376 – 530 | Missing in isoform 8. 1 PublicationAdd BLAST | 155 | |
| Alternative sequenceiVSP_003689 | 469 – 530 | SNKGM…NPQSQ → RAEKASQTLTSFGMKMETLL PEATMEQ in isoform 2. 3 PublicationsAdd BLAST | 62 | |
| Alternative sequenceiVSP_003690 | 469 – 530 | SNKGM…NPQSQ → SSLSLSWRLFMLREASCHGV RQTPGGAHMSVSRSRSFEAC QQPRE in isoform 4. 1 PublicationAdd BLAST | 62 | |
| Alternative sequenceiVSP_003691 | 469 – 530 | SNKGM…NPQSQ → RWGEKQFIHLKLS in isoform 5. 2 PublicationsAdd BLAST | 62 | |
| Alternative sequenceiVSP_003692 | 469 – 530 | SNKGM…NPQSQ → RYAP in isoform 6. 2 PublicationsAdd BLAST | 62 | |
| Alternative sequenceiVSP_055746 | 469 – 474 | SNKGME → RSCVYK in isoform 9. Curated | 6 | |
| Alternative sequenceiVSP_055747 | 475 – 530 | Missing in isoform 9. CuratedAdd BLAST | 56 |
Sequence databases
Genome annotation databases
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 | ESR2_HUMAN | |
| Accessioni | Q92731Primary (citable) accession number: Q92731 Secondary accession number(s): A8K8K5 Q9UQK9 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
| Last sequence update: | July 15, 1999 | |
| Last modified: | June 7, 2017 | |
| This is version 202 of the entry and version 2 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 14
Human chromosome 14: 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
