Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 69  species 0  interactions 117  sequences 7  architectures

Family: ESR1_C (PF12743)

Summary: Oestrogen-type nuclear receptor final C-terminal

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Estrogen receptor". More...

Estrogen receptor Edit Wikipedia article

estrogen receptor 1 (ER-alpha)
PBB Protein ESR1 image.png
A dimer of the ligand-binding region of ERα (PDB rendering based on 3erd).
Identifiers
Symbol ESR1
Alt. symbols ER-α, NR3A1
Entrez 2099
HUGO 3467
OMIM 133430
PDB 1ERE (RCSB PDB PDBe PDBj)
RefSeq NM_000125
UniProt P03372
Other data
Locus Chr. 6 q24-q27
estrogen receptor 2 (ER-beta)
Estrogen receptor beta 1U3S.png
A dimer of the ligand-binding region of ERβ (PDB rendering based on 1u3s).
Identifiers
Symbol ESR2
Alt. symbols ER-β, NR3A2
Entrez 2100
HUGO 3468
OMIM 601663
PDB 1QKM (RCSB PDB PDBe PDBj)
RefSeq NM_001040275
UniProt Q92731
Other data
Locus Chr. 14 q21-q22

Estrogen receptors are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol).[1] Two classes of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and GPR30, which is a member of the rhodopsin-like family of G protein-coupled receptors. This article refers to the former (ER).

Once activated by estrogen, the ER is able to translocate into the nucleus and bind to DNA to regulate the activity of different genes (i.e. it is a DNA-binding transcription factor). However, it also has additional functions independent of DNA binding.[2]

Proteomics[edit]

There are two different forms of the estrogen receptor, usually referred to as α and β, each encoded by a separate gene (ESR1 and ESR2, respectively). Hormone-activated estrogen receptors form dimers, and, since the two forms are coexpressed in many cell types, the receptors may form ERα (αα) or ERβ (ββ) homodimers or ERαβ (αβ) heterodimers.[3] Estrogen receptor alpha and beta show significant overall sequence homology, and both are composed of five domains (listed from the N- to C-terminus; amino acid sequence numbers refer to human ER):(A-F domain)

The domain structures of ERα and ERβ, including some of the known phosphorylation sites involved in ligand-independent regulation.

The N-terminal A/B domain is able to transactivate gene transcription in the absence of bound ligand (e.g., the estrogen hormone). While this region is able to activate gene transcription without ligand, this activation is weak and more selective compared to the activation provided by the E domain. The C domain, also known as the DNA-binding domain, binds to estrogen response elements in DNA. The D domain is a hinge region that connects the C and E domains. The E domain contains the ligand binding cavity as well as binding sites for coactivator and corepressor proteins. The E-domain in the presence of bound ligand is able to activate gene transcription. The C-terminal F domain function is not entirely clear and is variable in length.

Estrogen receptor alpha
N-terminal AF1 domain
Identifiers
Symbol Oest_recep
Pfam PF02159
InterPro IPR001292
SCOP 1hcp
SUPERFAMILY 1hcp
Estrogen and estrogen related receptor C-terminal domain
Identifiers
Symbol ESR1_C
Pfam PF12743

Due to alternative RNA splicing, several ER isoforms are known to exist. At least three ERalpha and five ERbeta isoforms have been identified. The ERbeta isoforms receptor subtypes can transactivate transcription only when a heterodimer with the functional ERß1 receptor of 59 kDa is formed. The ERß3 receptor was detected at high levels in the testis. The two other ERalpha isoforms are 36 and 46kDa.[4][5]

Only in fish, but not in humans, an ERgamma receptor has been described.[6]

Genetics[edit]

In humans, the two forms of the estrogen receptor are encoded by different genes, ESR1 and ESR2 on the sixth and fourteenth chromosome (6q25.1 and 14q23.2), respectively.

Distribution[edit]

Both ERs are widely expressed in different tissue types, however there are some notable differences in their expression patterns:[7]

The ERs are regarded to be cytoplasmic receptors in their unliganded state, but visualization research has shown that a fraction of the ERs resides in the nucleus.[11] The "ERα" primary transcript gives rise to several alternatively spliced variants of unknown function.[12]

Binding and functional selectivity[edit]

The ER's helix 12 domain plays a crucial role in determining interactions with coactivators and corepressors and, therefore, the respective agonist or antagonist effect of the ligand.[13][14]

Different ligands may differ in their affinity for alpha and beta isoforms of the estrogen receptor:

Subtype selective estrogen receptor modulators preferentially bind to either the α- or the β-subtype of the receptor. In addition, the different estrogen receptor combinations may respond differently to various ligands, which may translate into tissue selective agonistic and antagonistic effects.[15] The ratio of α- to β- subtype concentration has been proposed to play a role in certain diseases.[16]

The concept of selective estrogen receptor modulators is based on the ability to promote ER interactions with different proteins such as transcriptional coactivator or corepressors. Furthermore, the ratio of coactivator to corepressor protein varies in different tissues.[17] As a consequence, the same ligand may be an agonist in some tissue (where coactivators predominate) while antagonistic in other tissues (where corepressors dominate). Tamoxifen, for example, is an antagonist in breast and is, therefore, used as a breast cancer treatment[18] but an ER agonist in bone (thereby preventing osteoporosis) and a partial agonist in the endometrium (increasing the risk of uterine cancer) .

Signal transduction[edit]

Since estrogen is a steroidal hormone, it can pass through the phospholipid membranes of the cell, and receptors therefore do not need to be membrane-bound in order to bind with estrogen.

Genomic[edit]

In the absence of hormone, estrogen receptors are largely located in the cytosol. Hormone binding to the receptor triggers a number of events starting with migration of the receptor from the cytosol into the nucleus, dimerization of the receptor, and subsequent binding of the receptor dimer to specific sequences of DNA known as hormone response elements. The DNA/receptor complex then recruits other proteins that are responsible for the transcription of downstream DNA into mRNA and finally protein that results in a change in cell function. Estrogen receptors also occur within the cell nucleus, and both estrogen receptor subtypes have a DNA-binding domain and can function as transcription factors to regulate the production of proteins.

The receptor also interacts with activator protein 1 and Sp-1 to promote transcription, via several coactivators such as PELP-1.[2]

Direct acetylation of the estrogen receptor alpha at the lysine residues in hinge region by p300 regulates transactivation and hormone sensitivity.[19]

Nongenomic[edit]

Some estrogen receptors associate with the cell surface membrane and can be rapidly activated by exposure of cells to estrogen.[20][21]

In addition, some ER may associate with cell membranes by attachment to caveolin-1 and form complexes with G proteins, striatin, receptor tyrosine kinases (e.g., EGFR and IGF-1), and non-receptor tyrosine kinases (e.g., Src).[2][20] Through striatin, some of this membrane bound ER may lead to increased levels of Ca2+ and nitric oxide (NO).[22] Through the receptor tyrosine kinases, signals are sent to the nucleus through the mitogen-activated protein kinase (MAPK/ERK) pathway and phosphoinositide 3-kinase (Pl3K/AKT) pathway.[23] Glycogen synthase kinase-3 (GSK)-3β inhibits transcription by nuclear ER by inhibiting phosphorylation of serine 118 of nuclear ERα. Phosphorylation of GSK-3β removes its inhibitory effect, and this can be achieved by the PI3K/AKT pathway and the MAPK/ERK pathway, via rsk.

17β-Estradiol has been shown to activate the G protein-coupled receptor GPR30.[24] However the subcellular localization and role of this receptor are still object of controversy.[25]

Disease[edit]

Nolvadex (tamoxifen) 20 mg
Arimidex (anastrozole) 1 mg

Cancer[edit]

Estrogen receptors are over-expressed in around 70% of breast cancer cases, referred to as "ER-positive", and can be demonstrated in such tissues using immunohistochemistry. Two hypotheses have been proposed to explain why this causes tumorigenesis, and the available evidence suggests that both mechanisms contribute:

  • Second, estrogen metabolism produces genotoxic waste.

The result of both processes is disruption of cell cycle, apoptosis and DNA repair, and, therefore, tumour formation. ERα is certainly associated with more differentiated tumours, while evidence that ERβ is involved is controversial. Different versions of the ESR1 gene have been identified (with single-nucleotide polymorphisms) and are associated with different risks of developing breast cancer.[18]

Estrogen and the ERs have also been implicated in breast cancer, ovarian cancer, colon cancer, prostate cancer, and endometrial cancer. Advanced colon cancer is associated with a loss of ERβ, the predominant ER in colon tissue, and colon cancer is treated with ERβ-specific agonists.[26]

Phytoestrogens such as quercetin can modulate estrogen receptor’s activities in such a way that it may prevent cancers including breasts, prostate, and colon all by promoting apoptosis.[27] Quercetin selectively binds to the estrogen receptor beta (ERβ).[28] This was tested in HeLa cells which were treated with a pure estrogen receptor antagonist which blocked both estradiol and quercetin from inducing the caspase-3 activation.[27] ERβ is expressed in the human colon and activates a specific signal transduction pathway that controls apoptosis in the colon and works by being activated by estradiol and more recently found to possibly be activated by quercetin.[27] Quercetin activates the ERβ along with the apoptotic cascade when caspase-3 is present by the phosphorylation of p38 kinase. In colon cancers and tumors ERβ and its pathway have been proven to be significantly decreased thus allowing the tumors to thrive.[29]

Endocrine therapy for breast cancer involves selective estrogen receptor modulators (SERMS), such as tamoxifen, which behave as ER antagonists in breast tissue, or aromatase inhibitors, such as anastrozole. ER status is used to determine sensitivity of breast cancer lesions to tamoxifen and aromatase inhibitors.[30] Another SERM, raloxifene, has been used as a preventive chemotherapy for women judged to have a high risk of developing breast cancer.[31] Another chemotherapeutic anti-estrogen, ICI 182,780 (Faslodex), which acts as a complete antagonist, also promotes degradation of the estrogen receptor.

However, de novo resistance to endocrine therapy undermines the efficacy of using competitive inhibitors like tamoxifen. Hormone deprivation through the use of aromatase inhibitors is also rendered futile.[32] Massively parallel genome sequencing has revealed the common presence of point mutations on ESR1 that are drivers for resistance, and promote the agonist conformation of ERα without the bound ligand. Such constitutive, estrogen-independent activity is driven by specific mutations, such as the D538G or Y537S/C/N mutations, in the ligand binding domain of ESR1 and promote cell proliferation and tumor progression without hormone stimulation.[33]

Aging[edit]

Studies in female mice have shown that estrogen receptor-alpha declines in the pre-optic hypothalamus as they grow old. Female mice that were given a calorically restricted diet during the majority of their lives maintained higher levels of ERα in the pre-optic hypothalamus than their non-calorically restricted counterparts.[8]

Obesity[edit]

A dramatic demonstration of the importance of estrogens in the regulation of fat deposition comes from transgenic mice that were genetically engineered to lack a functional aromatase gene. These mice have very low levels of estrogen and are obese.[34] Obesity was also observed in estrogen deficient female mice lacking the follicle-stimulating hormone receptor.[35] The effect of low estrogen on increased obesity has been linked to estrogen receptor alpha.[36]

Research history[edit]

Estrogen receptors were first identified by Elwood V. Jensen at the University of Chicago in 1958,[37][38] for which Jensen was awarded the Lasker Award.[39] The gene for a second estrogen receptor (ERβ) was identified in 1996 by Kuiper et al. in rat prostate and ovary using degenerate ERalpha primers.[40]

References[edit]

  1. ^ Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA (2006). "International Union of Pharmacology. LXIV. Estrogen receptors". Pharmacol. Rev. 58 (4): 773–81. doi:10.1124/pr.58.4.8. PMID 17132854. 
  2. ^ a b c Levin ER (2005). "Integration of the extranuclear and nuclear actions of estrogen". Mol. Endocrinol. 19 (8): 1951–9. doi:10.1210/me.2004-0390. PMC 1249516. PMID 15705661. 
  3. ^ Li X, Huang J, Yi P, Bambara RA, Hilf R, Muyan M (2004). "Single-chain estrogen receptors (ERs) reveal that the ERalpha/beta heterodimer emulates functions of the ERalpha dimer in genomic estrogen signaling pathways". Mol. Cell. Biol. 24 (17): 7681–94. doi:10.1128/MCB.24.17.7681-7694.2004. PMC 506997. PMID 15314175. 
  4. ^ Nilsson S, Mäkelä S, Treuter E, et al. (October 2001). "Mechanisms of estrogen action". Physiol Rev 81 (4): 1535–65. PMID 11581496. 
  5. ^ Leung YK, Mak P, Hassan S, Ho SM (August 2006). "Estrogen receptor (ER)-beta isoforms: a key to understanding ER-beta signaling". Proc Natl Acad Sci USA 103 (35): 13162–7. doi:10.1073/pnas.0605676103. PMC 1552044. PMID 16938840. 
  6. ^ Hawkins MB, Thornton JW, Crews D, Skipper JK, Dotte A, Thomas P (September 2000). "Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts". Proc Natl Acad Sci USA 97 (20): 10751–6. doi:10.1073/pnas.97.20.10751. PMC 27095. PMID 11005855. 
  7. ^ Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS (November 1997). "Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse". Endocrinology 138 (11): 4613–21. doi:10.1210/en.138.11.4613. PMID 9348186. 
  8. ^ a b Yaghmaie F, Saeed O, Garan SA, Freitag W, Timiras PS, Sternberg H (2005). "Caloric restriction reduces cell loss and maintains estrogen receptor-alpha immunoreactivity in the pre-optic hypothalamus of female B6D2F1 mice". Neuro Endocrinol. Lett. 26 (3): 197–203. PMID 15990721. 
  9. ^ Hess, RA (2003). "Estrogen in the adult male reproductive tract: A review". Reproductive Biology and Endocrinology 1 (52): 52. doi:10.1186/1477-7827-1-52. PMC 179885. PMID 12904263. 
  10. ^ Babiker FA, De Windt LJ, van Eickels M, Grohe C, Meyer R, Doevendans PA (2002). "Estrogenic hormone action in the heart: regulatory network and function". Cardiovasc. Res. 53 (3): 709–19. doi:10.1016/S0008-6363(01)00526-0. PMID 11861041. 
  11. ^ Htun H, Holth LT, Walker D, Davie JR, Hager GL (1 February 1999). "Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor". Mol Biol Cell 10 (2): 471–86. PMC 25181. PMID 9950689. 
  12. ^ Pfeffer U, Fecarotta E, Vidali G (15 May 1995). "Coexpression of multiple estrogen receptor variant messenger RNAs in normal and neoplastic breast tissues and in MCF-7 cells". Cancer Res 55 (10): 2158–65. PMID 7743517. 
  13. ^ Ascenzi P, Bocedi A, Marino M (August 2006). "Structure-function relationship of estrogen receptor alpha and beta: impact on human health". Mol Aspects Med 27 (4): 299–402. doi:10.1016/j.mam.2006.07.001. PMID 16914190. 
  14. ^ Bourguet W, Germain P, Gronemeyer H (October 2000). "Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications". Trends Pharmacol Sci 21 (10): 381–8. doi:10.1016/S0165-6147(00)01548-0. PMID 11050318. 
  15. ^ Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N (2005). "Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release". Mol. Cell. Endocrinol. 239 (1-2): 27–36. doi:10.1016/j.mce.2005.04.008. PMID 15950373. 
  16. ^ Bakas P, Liapis A, Vlahopoulos S, Giner M, Logotheti S, Creatsas G, Meligova AK, Alexis MN, Zoumpourlis V (December 2007). "Estrogen receptor alpha and beta in uterine fibroids: a basis for altered estrogen responsiveness". Fertil. Steril. 90 (5): 1878–85. doi:10.1016/j.fertnstert.2007.09.019. PMID 18166184. 
  17. ^ Shang Y, Brown M (2002). "Molecular determinants for the tissue specificity of SERMs". Science 295 (5564): 2465–8. doi:10.1126/science.1068537. PMID 11923541. 
  18. ^ a b Deroo BJ, Korach KS (2006). "Estrogen receptors and human disease". J. Clin. Invest. 116 (3): 561–7. doi:10.1172/JCI27987. PMC 2373424. PMID 16511588. 
  19. ^ Wang C, Fu M, Angeletti RH, Siconolfi-Baez L, Reutens AT, Albanese C, Lisanti MP, Katzenellenbogen BS, Kato S, Hopp T, Fuqua SA, Lopez GN, Kushner PJ, Pestell RG. (25 May 2001). "Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity.". J Biol Chem. 276 (21): 18375–83. PMID 11279135. 
  20. ^ a b Zivadinovic D, Gametchu B, Watson CS (2005). "Membrane estrogen receptor-alpha levels in MCF-7 breast cancer cells predict cAMP and proliferation responses". Breast Cancer Res. 7 (1): R101–12. doi:10.1186/bcr958. PMC 1064104. PMID 15642158. 
  21. ^ Björnström L, Sjöberg M (2004). "Estrogen receptor-dependent activation of AP-1 via non-genomic signalling". Nucl Recept 2 (1): 3. doi:10.1186/1478-1336-2-3. PMC 434532. PMID 15196329. 
  22. ^ Lu Q, Pallas DC, Surks HK, Baur WE, Mendelsohn ME, Karas RH (2004). "Striatin assembles a membrane signaling complex necessary for rapid, nongenomic activation of endothelial NO synthase by estrogen receptor alpha". Proc. Natl. Acad. Sci. U.S.A. 101 (49): 17126–31. doi:10.1073/pnas.0407492101. PMC 534607. PMID 15569929. 
  23. ^ Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D, Chambon P (1995). "Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase". Science 270 (5241): 1491–4. doi:10.1126/science.270.5241.1491. PMID 7491495. 
  24. ^ Prossnitz ER, Arterburn JB, Sklar LA (2007). "GPR30: A G protein-coupled receptor for estrogen". Mol. Cell. Endocrinol. 265-266: 138–42. doi:10.1016/j.mce.2006.12.010. PMC 1847610. PMID 17222505. 
  25. ^ Otto C, Rohde-Schulz B, Schwarz G, Fuchs I, Klewer M, Brittain D, Langer G, Bader B, Prelle K, Nubbemeyer R, Fritzemeier KH (2008). "G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol.". Endocrinology. 149 (10): 4846–56. doi:10.1210/en.2008-0269. PMID 18566127. 
  26. ^ Harris HA, Albert LM, Leathurby Y, Malamas MS, Mewshaw RE, Miller CP, Kharode YP, Marzolf J, Komm BS, Winneker RC, Frail DE, Henderson RA, Zhu Y, Keith JC (2003). "Evaluation of an estrogen receptor-beta agonist in animal models of human disease". Endocrinology 144 (10): 4241–9. doi:10.1210/en.2003-0550. PMID 14500559. 
  27. ^ a b c Bulzomi P, Galluzzo P, Bolli A, Leone S, Acconcia F, Marino M (May 2012). "The pro-apoptotic effect of quercetin in cancer cell lines requires ERβ-dependent signals". J. Cell. Physiol. 227 (5): 1891–8. doi:10.1002/jcp.22917. PMID 21732360. 
  28. ^ Ascenzi P, Bocedi A, Marino M (August 2006). "Structure-function relationship of estrogen receptor alpha and beta: impact on human health". Mol. Aspects Med. 27 (4): 299–402. doi:10.1016/j.mam.2006.07.001. PMID 16914190. 
  29. ^ Konstantinopoulos PA, Kominea A, Vandoros G, Sykiotis GP, Andricopoulos P, Varakis I, Sotiropoulou-Bonikou G, Papavassiliou AG (June 2003). "Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation". Eur. J. Cancer 39 (9): 1251–8. PMID 12763213. 
  30. ^ Clemons M, Danson S, Howell A (2002). "Tamoxifen ("Nolvadex"): a review". Cancer Treat. Rev. 28 (4): 165–80. PMID 12363457. 
  31. ^ Fabian CJ, Kimler BF (2005). "Selective estrogen-receptor modulators for primary prevention of breast cancer". J. Clin. Oncol. 23 (8): 1644–55. doi:10.1200/JCO.2005.11.005. PMID 15755972. 
  32. ^ Oesterreich, S; Davidson, N. E. (2013). "The search for ESR1 mutations in breast cancer". Nature Genetics 45 (12): 1415–6. doi:10.1038/ng.2831. PMID 24270445.  edit
  33. ^ Li, S; Shen, D; Shao, J; Crowder, R; Liu, W; Prat, A; He, X; Liu, S; Hoog, J; Lu, C; Ding, L; Griffith, O. L.; Miller, C; Larson, D; Fulton, R. S.; Harrison, M; Mooney, T; McMichael, J. F.; Luo, J; Tao, Y; Goncalves, R; Schlosberg, C; Hiken, J. F.; Saied, L; Sanchez, C; Giuntoli, T; Bumb, C; Cooper, C; Kitchens, R. T.; Lin, A (2013). "Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts". Cell Reports 4 (6): 1116–30. doi:10.1016/j.celrep.2013.08.022. PMC 3881975. PMID 24055055.  edit
  34. ^ Hewitt KN, Boon WC, Murata Y, Jones ME, Simpson ER (2003). "The aromatase knockout mouse presents with a sexually dimorphic disruption to cholesterol homeostasis". Endocrinology 144 (9): 3895–903. doi:10.1210/en.2003-0244. PMID 12933663. 
  35. ^ Danilovich N, Babu PS, Xing W, Gerdes M, Krishnamurthy H, Sairam MR (2000). "Estrogen deficiency, obesity, and skeletal abnormalities in follicle-stimulating hormone receptor knockout (FORKO) female mice". Endocrinology 141 (11): 4295–308. doi:10.1210/en.141.11.4295. PMID 11089565. 
  36. ^ Ohlsson C, Hellberg N, Parini P, Vidal O, Bohlooly-Y M, Bohlooly M, Rudling M, Lindberg MK, Warner M, Angelin B, Gustafsson JA (2000). "Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice". Biochem. Biophys. Res. Commun. 278 (3): 640–5. doi:10.1006/bbrc.2000.3827. PMID 11095962. 
  37. ^ Jensen EV, Jordan VC (1 June 2003). "The estrogen receptor: a model for molecular medicine" (abstract). Clin. Cancer Res. 9 (6): 1980–9. PMID 12796359. 
  38. ^ Moore DD (2011). "A Conversation with Elwood Jensen.". Annu Rev Physiol 74: 1–11. doi:10.1146/annurev-physiol-020911-153327. PMID 21888507. 
  39. ^ David Bracey, 2004 "UC Scientist Wins 'American Nobel' Research Award." University of Cincinnati press release.
  40. ^ Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996). "Cloning of a novel receptor expressed in rat prostate and ovary". Proc. Natl. Acad. Sci. U.S.A. 93 (12): 5925–30. doi:10.1073/pnas.93.12.5925. PMC 39164. PMID 8650195. 

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Oestrogen-type nuclear receptor final C-terminal Provide feedback

This is the very C-terminal region of a subfamily of nuclear receptors that includes oestrogen receptors and other subfamily 3 group A members. The actual function of this region is not known, but the domain is absent from all the other types of nuclear receptors. Oestrogen receptors modulate AP-1-dependent transcription [1] through two distinct mechanisms: via protein-protein interactions on DNA; and via non-genomic actions. The mechanism used depends on the cellular localisation of the receptor. In addition to the more extensively studied cross-talk on DNA, additional non-genomic actions might be very important in target tissues in which membrane-associated ERs are found. These non-genomic actions probably contribute to the overall physiological responses mediated by ligand-bound ERs [2] and might possibly be mediated via this C-terminal domain.

Literature references

  1. Klinge CM;, Steroids. 2000;65:227-251.: Estrogen receptor interaction with co-activators and co-repressors. PUBMED:10751636 EPMC:10751636

  2. Bjornstrom L, Sjoberg M;, Nucl Recept. 2004;2:3.: Estrogen receptor-dependent activation of AP-1 via non-genomic signalling. PUBMED:15196329 EPMC:15196329


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR024736

This entry represents C-terminal domain (also known as the F domain) of the estrogen-type receptors. The actual function of this domain is not known, but it is absent from all the other types of nuclear receptors. Oestrogen receptors modulate AP-1-dependent transcription [PUBMED:10751636] through two distinct mechanisms: via protein-protein interactions on DNA; and via non-genomic actions. The mechanism used depends on the cellular localisation of the receptor. In addition to the more extensively studied cross-talk on DNA, additional non-genomic actions might be very important in target tissues in which membrane-associated ERs are found. These non-genomic actions probably contribute to the overall physiological responses mediated by ligand-bound ERs [PUBMED:15196329] and might possibly be mediated via this C-terminal domain.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(17)
Full
(117)
Representative proteomes NCBI
(113)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(7)
RP75
(25)
Jalview View  View  View  View  View  View  View   
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(17)
Full
(117)
Representative proteomes NCBI
(113)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(7)
RP75
(25)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(17)
Full
(117)
Representative proteomes NCBI
(113)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(7)
RP75
(25)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Willis S
Previous IDs: none
Type: Domain
Author: Coggill P
Number in seed: 17
Number in full: 117
Average length of the domain: 42.60 aa
Average identity of full alignment: 53 %
Average coverage of the sequence by the domain: 8.76 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.0 22.0
Trusted cut-off 22.6 23.7
Noise cut-off 19.2 21.9
Model length: 43
Family (HMM) version: 2
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.