UniProt Accession

 ESR1_HUMAN; P03372; Q13511; Q14276; Q5T5H7; Q6MZQ9; Q9NU51; Q9UDZ7; Q9UIS7 

Genbank Protein ID

 X03635; M12674; U47678; AY425004; BX640939; AL356311; AL049821; AL078582; AL590993; AL049821; AL078582; AL356311; AL590993; AL590993; AL049821; AL078582; AL356311; AL078582; AL356311; AL590993; CH471051; BC128573; BC128574; AH008151; X73067; Z75126 

Genbank Nucleotide ID

 CAA27284.1; AAA52399.1; AAB00115.1; AAQ91815.1; CAE45969.1; CAI21012.1; CAI21012.1; CAI21012.1; CAI21012.1; CAI22123.1; CAI22123.1; CAI22123.1; CAI22123.1; CAI14237.1; CAI14237.1; CAI14237.1; CAI14237.1; CAI42285.1; CAI42285.1; CAI42285.1; EAW47740.1; AAI28574.1; AAI28575.1; AAD52984.1; CAA51528.1; CAA99436.1 

Protein Name

 Estrogen receptor 

Protein Synonyms/Alias

 ER; ER-alpha; Estradiol receptor; Nuclear receptor subfamily 3 group A member 1 

Gene Name

 ESR1 

Gene Synonyms/Alias

 ESR; NR3A1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
8	MTMTLHTKASGMALL	acetylation	[1]
266	RRGGRMLKHKRQRDD	acetylation	[2, 3]
266	RRGGRMLKHKRQRDD	sumoylation	[4]
268	GGRMLKHKRQRDDGE	acetylation	[2]
268	GGRMLKHKRQRDDGE	sumoylation	[4]
299	WPSPLMIKRSKKNSL	acetylation	[5]
299	WPSPLMIKRSKKNSL	sumoylation	[4]
302	PLMIKRSKKNSLALS	acetylation	[5]
302	PLMIKRSKKNSLALS	methylation	[6]
302	PLMIKRSKKNSLALS	sumoylation	[4, 7]
302	PLMIKRSKKNSLALS	ubiquitination	[8]
303	LMIKRSKKNSLALSL	acetylation	[5]
303	LMIKRSKKNSLALSL	sumoylation	[4, 7, 9]
472	TLKSLEEKDHIHRVL	acetylation	[1]

Reference

 [1] Systematic mapping of posttranslational modifications in human estrogen receptor-alpha with emphasis on novel phosphorylation sites.
 Atsriku C, Britton DJ, Held JM, Schilling B, Scott GK, Gibson BW, Benz CC, Baldwin MA.
 Mol Cell Proteomics. 2009 Mar;8(3):467-80. [PMID: 18984578]
 [2] Acetylation of estrogen receptor alpha by p300 at lysines 266 and 268 enhances the deoxyribonucleic acid binding and transactivation activities of the receptor.
 Kim MY, Woo EM, Chong YT, Homenko DR, Kraus WL.
 Mol Endocrinol. 2006 Jul;20(7):1479-93. [PMID: 16497729]
 [3] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [4] Sumoylation of the estrogen receptor alpha hinge region regulates its transcriptional activity.
 Sentis S, Le Romancer M, Bianchin C, Rostan MC, Corbo L.
 Mol Endocrinol. 2005 Nov;19(11):2671-84. [PMID: 15961505]
 [5] Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity.
 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.
 J Biol Chem. 2001 May 25;276(21):18375-83. [PMID: 11279135]
 [6] Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase.
 Subramanian K, Jia D, Kapoor-Vazirani P, Powell DR, Collins RE, Sharma D, Peng J, Cheng X, Vertino PM.
 Mol Cell. 2008 May 9;30(3):336-47. [PMID: 18471979]
 [7] 17β-Estradiol-induced cell proliferation requires estrogen receptor (ER) α monoubiquitination.
 La Rosa P, Pesiri V, Marino M, Acconcia F.
 Cell Signal. 2011 Jul;23(7):1128-35. [PMID: 21356307]
 [8] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [9] Phosphorylation of estrogen receptor alpha blocks its acetylation and regulates estrogen sensitivity.
 Cui Y, Zhang M, Pestell R, Curran EM, Welshons WV, Fuqua SA.
 Cancer Res. 2004 Dec 15;64(24):9199-208. [PMID: 15604293] 

Functional Description

 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. Isoform 3 can bind to ERE and inhibit isoform 1. 

Sequence Annotation

 DNA_BIND 185 250 Nuclear receptor.
 ZN_FING 185 205 NR C4-type.
 ZN_FING 221 245 NR C4-type.
 REGION 1 184 Modulating (transactivation AF-1);
 REGION 35 174 Interaction with DDX5; self-association.
 REGION 35 47 Required for interaction with NCOA1.
 REGION 185 310 Mediates interaction with DNTTIP2.
 REGION 251 310 Hinge.
 REGION 262 595 Interaction with AKAP13.
 REGION 264 595 Self-association.
 REGION 311 595 Transactivation AF-2.
 REGION 311 551 Steroid-binding.
 MOD_RES 104 104 Phosphoserine; by CDK2.
 MOD_RES 106 106 Phosphoserine; by CDK2.
 MOD_RES 118 118 Phosphoserine.
 MOD_RES 167 167 Phosphoserine; by CK2.
 MOD_RES 260 260 Asymmetric dimethylarginine; by PRMT1.
 MOD_RES 537 537 Phosphotyrosine; by Tyr-kinases.
 LIPID 447 447 S-palmitoyl cysteine (By similarity).
 CARBOHYD 10 10 O-linked (GlcNAc) (By similarity).  

Keyword

 3D-structure; Activator; Alternative promoter usage; Alternative splicing; Cell membrane; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; Glycoprotein; Golgi apparatus; Lipid-binding; Lipoprotein; Membrane; Metal-binding; Methylation; Nucleus; Palmitate; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Transmembrane; Ubl conjugation; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 595 AA 

Protein Sequence

Gene Ontology

 GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0003682; F:chromatin binding; IEA:Compara.
 GO:0001046; F:core promoter sequence-specific DNA binding; IDA:UniProtKB.
 GO:0034056; F:estrogen response element binding; IDA:UniProtKB.
 GO:0038052; F:estrogen-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; IGI:MGI.
 GO:0030235; F:nitric-oxide synthase regulator activity; NAS:UniProtKB.
 GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0008209; P:androgen metabolic process; IEA:Compara.
 GO:0001547; P:antral ovarian follicle growth; IEA:Compara.
 GO:0071391; P:cellular response to estrogen stimulus; IEA:Compara.
 GO:0002064; P:epithelial cell development; IEA:Compara.
 GO:0060750; P:epithelial cell proliferation involved in mammary gland duct elongation; IEA:Compara.
 GO:0008584; P:male gonad development; IEA:Compara.
 GO:0060749; P:mammary gland alveolus development; IEA:Compara.
 GO:0060745; P:mammary gland branching involved in pregnancy; IEA:Compara.
 GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
 GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
 GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
 GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Compara.
 GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:UniProtKB.
 GO:0051000; P:positive regulation of nitric-oxide synthase activity; IDA:UniProtKB.
 GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IDA:BHF-UCL.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IEA:Compara.
 GO:0060523; P:prostate epithelial cord elongation; IEA:Compara.
 GO:0042981; P:regulation of apoptotic process; IEA:Compara.
 GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IEA:Compara.
 GO:0032355; P:response to estradiol stimulus; IDA:BHF-UCL.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
 GO:0060065; P:uterus development; IEA:Compara.
 GO:0060068; P:vagina development; IEA:Compara. 

Interpro

 IPR008946; Nucl_hormone_rcpt_ligand-bd.
 IPR000536; Nucl_hrmn_rcpt_lig-bd_core.
 IPR024178; Oest_rcpt/oest-rel_rcp.
 IPR001292; Oestr_rcpt.
 IPR024736; Oestrogen-typ_rcpt_final_C_dom.
 IPR001723; Str_hrmn_rcpt.
 IPR001628; Znf_hrmn_rcpt.
 IPR013088; Znf_NHR/GATA. 

Pfam

 PF12743; ESR1_C
 PF00104; Hormone_recep
 PF02159; Oest_recep
 PF00105; zf-C4 

SMART

 SM00430; HOLI
 SM00399; ZnF_C4 

PROSITE

 PS00031; NUCLEAR_REC_DBD_1
 PS51030; NUCLEAR_REC_DBD_2 

PRINTS

 PR00543; OESTROGENR.
 PR00398; STRDHORMONER.
 PR00047; STROIDFINGER.