Gene/Proteome Database (LMPD)

LMPD ID
LMP000383
Gene ID
2099
Species
Homo sapiens (Human)
Gene Name
estrogen receptor 1
Gene Symbol
ESR1
Synonyms
ER; ESR; ESRA; ESTRR; Era; NR3A1
Chromosome
6
Map Location
6q25.1
Summary
This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative promoter usage and alternative splicing result in dozens of transcript variants, but the full-length nature of many of these variants has not been determined. [provided by RefSeq, Mar 2014]
Orthologs
View orthologs and multiple alignments for ESR1

Proteins

estrogen receptor isoform 1
Refseq ID NP_001116212
Protein GI 170295800
UniProt ID Q9UBT1
mRNA ID NM_001122740
Length 595
RefSeq Status REVIEWED
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
estrogen receptor isoform 1
Refseq ID NP_001116214
Protein GI 170295804
UniProt ID P03372
mRNA ID NM_001122742
Length 595
RefSeq Status REVIEWED
Protein sequence is identical to GI:170295800 (mRNA isoform)
estrogen receptor isoform 1
Refseq ID NP_000116
Protein GI 62821794
UniProt ID P03372
mRNA ID NM_000125
Length 595
RefSeq Status REVIEWED
Protein sequence is identical to GI:170295800 (mRNA isoform)
estrogen receptor isoform 1
Refseq ID NP_001116213
Protein GI 170295802
UniProt ID P03372
mRNA ID NM_001122741
Length 595
RefSeq Status REVIEWED
Protein sequence is identical to GI:170295800 (mRNA isoform)
estrogen receptor isoform 2
Refseq ID NP_001278159
Protein GI 170295804
UniProt ID P03372
mRNA ID NM_001291230
Length 595
RefSeq Status REVIEWED
Protein sequence is identical to GI:170295800 (mRNA isoform)
estrogen receptor isoform 3
Refseq ID NP_001278170
Protein GI 170295804
UniProt ID P03372
mRNA ID NM_001291241
Length 595
RefSeq Status REVIEWED
Protein sequence is identical to GI:170295800 (mRNA isoform)

Gene Information

Entrez Gene ID
2099
Gene Name
estrogen receptor 1
Gene Symbol
ESR1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005794 IEA:UniProtKB-KW C Golgi apparatus
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0016021 IEA:UniProtKB-KW C integral component of membrane
GO:0016020 NAS:UniProtKB C membrane
GO:0005654 TAS:Reactome C nucleoplasm
GO:0005634 IDA:UniProtKB C nucleus
GO:0005886 IDA:UniProtKB C plasma membrane
GO:0035327 IDA:UniProtKB C transcriptionally active chromatin
GO:0000978 IDA:NTNU_SB F RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001077 IDA:NTNU_SB F RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0008013 IPI:BHF-UCL F beta-catenin binding
GO:0003682 IDA:UniProtKB F chromatin binding
GO:0001046 IDA:UniProtKB F core promoter sequence-specific DNA binding
GO:0019899 IPI:UniProtKB F enzyme binding
GO:0030284 NAS:UniProtKB F estrogen receptor activity
GO:0034056 IDA:UniProtKB F estrogen response element binding
GO:0038052 IGI:MGI F estrogen-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
GO:0042802 IPI:IntAct F identical protein binding
GO:0030235 NAS:UniProtKB F nitric-oxide synthase regulator activity
GO:0003700 NAS:BHF-UCL F sequence-specific DNA binding transcription factor activity
GO:0005496 ISS:UniProtKB F steroid binding
GO:0003707 TAS:ProtInc F steroid hormone receptor activity
GO:0008134 IPI:UniProtKB F transcription factor binding
GO:0008270 IEA:InterPro F zinc ion binding
GO:0008209 IEA:Ensembl P androgen metabolic process
GO:0001547 IEA:Ensembl P antral ovarian follicle growth
GO:0071392 ISS:UniProtKB P cellular response to estradiol stimulus
GO:0006338 NAS:UniProtKB P chromatin remodeling
GO:0002064 IEA:Ensembl P epithelial cell development
GO:0060750 IEA:Ensembl P epithelial cell proliferation involved in mammary gland duct elongation
GO:0010467 TAS:Reactome P gene expression
GO:0030520 NAS:UniProtKB P intracellular estrogen receptor signaling pathway
GO:0030518 ISS:UniProtKB P intracellular steroid hormone receptor signaling pathway
GO:0008584 IEA:Ensembl P male gonad development
GO:0060749 IEA:Ensembl P mammary gland alveolus development
GO:0060745 IEA:Ensembl P mammary gland branching involved in pregnancy
GO:0043124 IDA:UniProtKB P negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0010629 IDA:UniProtKB P negative regulation of gene expression
GO:0043433 IDA:UniProtKB P negative regulation of sequence-specific DNA binding transcription factor activity
GO:0007200 ISS:UniProtKB P phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0007204 ISS:UniProtKB P positive regulation of cytosolic calcium ion concentration
GO:0048146 IEA:Ensembl P positive regulation of fibroblast proliferation
GO:0045429 IDA:UniProtKB P positive regulation of nitric oxide biosynthetic process
GO:0051000 IDA:UniProtKB P positive regulation of nitric-oxide synthase activity
GO:0010863 ISS:UniProtKB P positive regulation of phospholipase C activity
GO:0048386 IDA:BHF-UCL P positive regulation of retinoic acid receptor signaling pathway
GO:0051091 IDA:UniProtKB P positive regulation of sequence-specific DNA binding transcription factor activity
GO:0045944 IDA:UniProtKB P positive regulation of transcription from RNA polymerase II promoter
GO:0060527 IEA:Ensembl P prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
GO:0060523 IEA:Ensembl P prostate epithelial cord elongation
GO:0042981 IEA:Ensembl P regulation of apoptotic process
GO:0060687 IEA:Ensembl P regulation of branching involved in prostate gland morphogenesis
GO:0006355 NAS:UniProtKB P regulation of transcription, DNA-templated
GO:0032355 IDA:BHF-UCL P response to estradiol
GO:0043627 IDA:UniProtKB P response to estrogen
GO:0007165 TAS:ProtInc P signal transduction
GO:0006367 TAS:Reactome P transcription initiation from RNA polymerase II promoter
GO:0006351 TAS:ProtInc P transcription, DNA-templated
GO:0060065 IEA:Ensembl P uterus development
GO:0060068 IEA:Ensembl P vagina development

KEGG Pathway Links

KEGG Pathway ID Description
hsa04915 Estrogen signaling pathway
hsa04917 Prolactin signaling pathway
hsa05205 Proteoglycans in cancer
hsa04919 Thyroid hormone signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR008946 Nuclear hormone receptor, ligand-binding
IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001292 Oestrogen receptor
IPR024178 Oestrogen receptor/oestrogen-related receptor
IPR024736 Oestrogen-type nuclear receptor final C-terminal domain
IPR001723 Steroid hormone receptor
IPR013088 Zinc finger, NHR/GATA-type
IPR001628 Zinc finger, nuclear hormone receptor-type

UniProt Annotations

Entry Information

Gene Name
estrogen receptor 1
Protein Entry
ESR1_HUMAN
UniProt ID
Q9UBT1
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative promoter usage, Alternative splicing; Named isoforms=4; Comment=Additional isoforms seem to exist.; Name=1; Synonyms=Long, hER-alpha66, ER66; IsoId=P03372-1; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=P03372-2; Sequence=VSP_003680; Name=3; Synonyms=hER-alpha46, ER46; IsoId=P03372-3; Sequence=VSP_042460; Note=Produced by alternative promoter usage.; Name=4; Synonyms=hER-alpha36, ER36; IsoId=P03372-4; Sequence=VSP_042460, VSP_042461; Note=Produced by alternative splicing of isoform 3.;
Disease Estrogen resistance (ESTRR) [MIM
Domain Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand- independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF- 2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner. AF-1 seems to provide the major transactivation function in differentiated cells.
Function Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA- binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF- kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA- binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1. {ECO
Interaction Self; NbExp=9; IntAct=EBI-78473, EBI-78473; Q12802:AKAP13; NbExp=3; IntAct=EBI-78473, EBI-1373806; Q9Y294:ASF1A; NbExp=2; IntAct=EBI-78473, EBI-749553; Q8IXJ9:ASXL1; NbExp=2; IntAct=EBI-78473, EBI-1646500; P59598:Asxl1 (xeno); NbExp=2; IntAct=EBI-78473, EBI-5743705; P62952:BLCAP; NbExp=2; IntAct=EBI-78473, EBI-3895726; P38398:BRCA1; NbExp=12; IntAct=EBI-78473, EBI-349905; P20290-2:BTF3; NbExp=5; IntAct=EBI-78473, EBI-1054703; Q86Y37:CACUL1; NbExp=5; IntAct=EBI-78473, EBI-8168227; Q99966:CITED1; NbExp=3; IntAct=EBI-78473, EBI-2624951; Q9H467:CUEDC2; NbExp=2; IntAct=EBI-78473, EBI-1248228; Q92841:DDX17; NbExp=7; IntAct=EBI-78473, EBI-746012; P17844:DDX5; NbExp=8; IntAct=EBI-78473, EBI-351962; O00429:DNM1L; NbExp=2; IntAct=EBI-78473, EBI-724571; P00533:EGFR; NbExp=4; IntAct=EBI-4309277, EBI-297353; Q09472:EP300; NbExp=2; IntAct=EBI-78473, EBI-447295; Q12778:FOXO1; NbExp=2; IntAct=EBI-78473, EBI-1108782; Q9Y3R0:GRIP1; NbExp=2; IntAct=EBI-78473, EBI-5349621; O00165:HAX1; NbExp=2; IntAct=EBI-78473, EBI-357001; P05627:Jun (xeno); NbExp=6; IntAct=EBI-78473, EBI-764369; O15054:KDM6B; NbExp=2; IntAct=EBI-78473, EBI-2831260; O14686:KMT2D; NbExp=3; IntAct=EBI-78473, EBI-996065; Q9BQ69:MACROD1; NbExp=4; IntAct=EBI-78473, EBI-5324932; Q00987:MDM2; NbExp=2; IntAct=EBI-78473, EBI-389668; Q13330:MTA1; NbExp=4; IntAct=EBI-78473, EBI-714236; O94776:MTA2; NbExp=3; IntAct=EBI-78473, EBI-1783035; Q9BTC8:MTA3; NbExp=3; IntAct=EBI-78473, EBI-2461787; P60660:MYL6; NbExp=3; IntAct=EBI-78473, EBI-300817; Q15788:NCOA1; NbExp=10; IntAct=EBI-78473, EBI-455189; Q15596:NCOA2; NbExp=8; IntAct=EBI-78473, EBI-81236; Q9Y6Q9:NCOA3; NbExp=2; IntAct=EBI-78473, EBI-81196; Q9JLI4:Ncoa6 (xeno); NbExp=2; IntAct=EBI-78473, EBI-286271; Q9UN36:NDRG2; NbExp=2; IntAct=EBI-78473, EBI-3895741; P19838:NFKB1; NbExp=3; IntAct=EBI-78473, EBI-697771; Q9BTK6:PAGR1; NbExp=5; IntAct=EBI-78473, EBI-2372223; Q96AQ6:PBXIP1; NbExp=9; IntAct=EBI-78473, EBI-740845; P62962:Pfn1 (xeno); NbExp=3; IntAct=EBI-78473, EBI-647096; Q99623:PHB2; NbExp=4; IntAct=EBI-78473, EBI-358348; P27986:PIK3R1; NbExp=6; IntAct=EBI-78473, EBI-79464; P53041:PPP5C; NbExp=4; IntAct=EBI-78473, EBI-716663; P55345:PRMT2; NbExp=9; IntAct=EBI-78473, EBI-78458; P60763:RAC3; NbExp=5; IntAct=EBI-78473, EBI-767084; O43251:RBFOX2; NbExp=4; IntAct=EBI-78473, EBI-746056; Q04206:RELA; NbExp=7; IntAct=EBI-78473, EBI-73886; Q14151:SAFB2; NbExp=2; IntAct=EBI-78473, EBI-352869; Q96HI0:SENP5; NbExp=2; IntAct=EBI-78473, EBI-3895753; P29353:SHC1; NbExp=2; IntAct=EBI-4309277, EBI-78835; P51532:SMARCA4; NbExp=3; IntAct=EBI-78473, EBI-302489; P08047:SP1; NbExp=2; IntAct=EBI-78473, EBI-298336; Q02447:SP3; NbExp=2; IntAct=EBI-78473, EBI-348158; P12931:SRC; NbExp=9; IntAct=EBI-78473, EBI-621482; Q16881-4:TXNRD1; NbExp=4; IntAct=EBI-78473, EBI-9080335; Q8N895:ZNF366; NbExp=6; IntAct=EBI-78473, EBI-2813661;
Miscellaneous Selective estrogen receptor modulators (SERMs), such as tamoxifen, raloxifene, toremifene, lasofoxifene, clomifene, femarelle and ormeloxifene, have tissue selective agonistic and antagonistic effects on the estrogen receptor (ER). They interfere with the ER association with coactivators or corepressors, mainly involving the AF-2 domain.
Polymorphism Genetic variations in ESR1 are correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disrutption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.
Ptm Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization.
Ptm Glycosylated; contains N-acetylglucosamine, probably O- linked.
Ptm Palmitoylated (isoform 3). Not biotinylated (isoform 3).
Ptm Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation, but not for signaling mediated by the nuclear hormone receptor.
Ptm Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Self-association induces phosphorylation. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity. {ECO
Ptm Ubiquitinated. Deubiquitinated by OTUB1.
Similarity Belongs to the nuclear hormone receptor family. NR3 subfamily.
Similarity Contains 1 nuclear receptor DNA-binding domain.
Subcellular Location Isoform 1: Nucleus {ECO
Subcellular Location Isoform 3: Nucleus. Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane; Single-pass type I membrane protein. Note=Associated with the inner membrane via palmitoylation (Probable). At least a subset exists as a transmembrane protein with a N-terminal extracellular domain.
Subcellular Location Nucleus. Golgi apparatus. Cell membrane. Note=Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably palmitoylation occurs. Associated with the plasma membrane when palmitoylated.
Subunit Binds DNA as a homodimer. Can form a heterodimer with ESR2. Isoform 3 can probably homodimerize or heterodimerize with isoform 1 and ESR2. Interacts with FOXC2, MAP1S, SLC30A9, UBE1C and NCOA3 coactivator (By similarity). Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent. Interacts with NCOA5 and NCOA6 coactivators. Interacts with NCOA7; the interaction is a ligand-inducible. Interacts with PHB2, PELP1 and UBE1C. Interacts with AKAP13. Interacts with CUEDC2. Interacts with KDM5A. Interacts with SMARD1. Interacts with HEXIM1. Interacts with PBXIP1. Interaction with MUC1 is stimulated by 7 beta-estradiol (E2) and enhances ERS1-mediated transcription. Interacts with DNTTIP2, FAM120B and UIMC1. Interacts with isoform 4 of TXNRD1. Interacts with KMT2D/MLL2. Interacts with ATAD2 and this interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interaction with SH2D4A blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes. Interacts with NR2C1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with DYX1C1. Interacts with PRMT2. Interacts with PI3KR1 or PI3KR2, SRC and PTK2/FAK1. Interacts with RBFOX2. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESR1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the interaction seems to require a self-association of N-terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3. Interacts with NRIP1 (By similarity). Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts with CLOCK and the interaction is stimulated by estrogen. Interacts with BCAS3. {ECO
Tissue Specificity Widely expressed. Isoform 3 is not expressed in the pituitary gland.
Web Resource Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/esr1/";
Web Resource Name=Wikipedia; Note=Estrogen receptor entry; URL="http://en.wikipedia.org/wiki/Estrogen_receptor";

Identical and Related Proteins

Unique RefSeq proteins for LMP000383 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
170295800 RefSeq NP_001116212 595 estrogen receptor isoform 1

Identical Sequences to LMP000383 proteins

Reference Database Accession Length Protein Name
GI:170295800 EMBL CEF39418.1 595 unnamed protein product [Homo sapiens]
GI:170295800 GenBank AFA66615.1 595 Sequence 3 from patent US 8101352
GI:170295800 GenBank AFD45319.1 595 Sequence 27 from patent US 8129125
GI:170295800 GenBank AGV91517.1 595 Sequence 73 from patent US 8530168
GI:170295800 GenBank AHD80269.1 595 Sequence 32085 from patent US 8586006
GI:170295800 GenBank AIC48713.1 595 ESR1, partial [synthetic construct]

Related Sequences to LMP000383 proteins

Reference Database Accession Length Protein Name
GI:170295800 GenBank AAX42995.1 596 estrogen receptor 1, partial [synthetic construct]
GI:170295800 GenBank ACW46744.1 595 Sequence 1 from patent US 7582476
GI:170295800 GenBank ACW46745.1 595 Sequence 2 from patent US 7582476
GI:170295800 GenBank ACW46747.1 595 Sequence 4 from patent US 7582476
GI:170295800 GenBank ACW46751.1 595 Sequence 8 from patent US 7582476
GI:170295800 GenBank ACW46752.1 595 Sequence 9 from patent US 7582476