在Reactome数据库中，BioPAX途径由“ESR1结合到TGFA基因启动子”转化而来。 ESR1与TGFA基因启动子结合 ESR1与TGFA基因启动子结合 激素激活的雌激素受体(ER)与特定的DNA序列，雌激素反应元件(EREs)紧密结合，发现在雌激素反应基因的调节区域(Klinge CM 2001)。大多数已知的雌激素应答基因都含有不完全的EREs，与一致的ERE序列5 ' -GGTCAnnnTGACC-3 '有一个或多个碱基对的不同。研究发现，单个ERE序列会不同程度地诱导ER构象的变化，从而影响特异性共激活蛋白的募集(Wood JR et al. 2001)。TGFA基因的启动子有两个在-252到-200之间的不完善的EREs和一个在-623到-549之间的额外的上游序列。这些元素赋予启动子雌激素响应性，并通过电泳迁移移位检测被ESR1所结合(Vyhidal et al, 2000)。 作者:Shamovsky, Veronica, 2017-06-20 马格纳尼，卢卡，2018-02-23 编辑:Karen Rothfels, 2017-11-13 Reactome DB_ID: 9008284 1 核浆 去 0005654 ESR1二聚体:雌激素(核浆) ESR1二聚体:雌激素 从Reactome中的EntitySet转换而来 Reactome DB_ID: 9008257 2 E1, EST17b，雌三醇，酯[核质] 从Reactome中的EntitySet转换而来。每个同义词是一个PhysicalEntity的名称，每个XREF指向一个PhysicalEntity 雌三醇(核浆) E1(核浆) estetrol(核浆) EST17b(核浆) Reactome //www.joaskin.com ChEBI 27974 ChEBI 17263 ChEBI 142773 ChEBI 16469 Reactome DB_ID: 446168 2 UniProt: P03372 ESR1 ESR1 ESR ESR1 NR3A1 功能核激素受体。类固醇激素及其受体参与了真核基因表达的调节，影响靶组织中的细胞增殖和分化。依赖性核转移涉及直接同型二聚体与回文雌激素响应元件（ORE）序列或与其他DNA结合转录因子结合，例如AP-1 / C-Jun，C-FOS，ATF-2，SP1和SP3，用于介绍无关的信令。配体结合诱导构象变化，允许随后或组合与多液蛋白共粘膜复合物的组合结合通过它们各自组分的LxxLL基序。在雌激素受体（ER）和NF-Kappa-B以细胞型特异性方式发生相互转型。降低NF-Kappa-B DNA结合活性，并抑制来自IL6启动子的NF-Kappa-B介导的转录，并从启动子移位Rela / P65和相关的核核试剂。募集到CCL2和IL8启动子的NF-Kappa-B响应元件，可以取代CREBBP。含有NF-Kappa-B分量Rela / P65和ERE序列的NFKB1 / P50。还可以用NF-Kappa-B协同作用，激活涉及相应招聘响应元素的转录; 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.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 DNAAF4. 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. Interacts with TRIP4 (ufmylated); estrogen dependent. Interacts with LMTK3; the interaction phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with ZFHX3. Interacts with SFR1 in a ligand-dependent and -independent manner (PubMed:23874500). Interacts with DCAF13, LATS1 and DCAF1; regulates ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:28068668). Interacts (via DNA-binding domain) with POU4F2 (C-terminus); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (By similarity). Interacts with ESRRB isoform 1 (PubMed:19755138). Interacts with UBE3A and WBP2 (PubMed:16772533). Interacts with GTF2B (PubMed:1517211). Interacts with RBM39 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).TISSUE SPECIFICITY Widely expressed. Isoform 3 is not expressed in the pituitary gland.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.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. Phosphorylated by LMTK3 in vitro.PTM Glycosylated; contains N-acetylglucosamine, probably O-linked.PTM Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation (PubMed:21602804, PubMed:28068668). Deubiquitinated by OTUB1 (PubMed:19383985).PTM Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization (PubMed:18657504, PubMed:24498420). Demethylated by JMJD6 at Arg-260 (PubMed:24498420).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.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, disruption 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.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.SIMILARITY Belongs to the nuclear hormone receptor family. NR3 subfamily. 智人 NCBI分类法 9606 UniProt P03372 链坐标 1 平等的 595 平等的 Reactome数据库ID Release 77 9008284 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9008284 Reactome r - hsa - 9008284 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9008284.1 Reactome DB_ID: 8864987 1 运用:ENSG00000163235 TGFA TGFA 运用 ENSG00000163235 Reactome DB_ID: 9008287 1 ESR1二聚体:雌激素:TGFA基因启动子[核质] ESR1二聚体:雌激素:TGFA基因启动子 Reactome DB_ID: 9008284 1 Reactome DB_ID: 8864987 1 Reactome数据库ID Release 77 9008287 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9008287 Reactome r - hsa - 9008287 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9008287.1 Reactome数据库ID Release 77 9008267 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9008267 Reactome r - hsa - 9008267 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9008267.1 11581164 Pubmed 2001 通过CITED1 CBP/p300结合蛋白选择性共激活雌激素依赖的转录 以T 邵,W Endoh H 户珥,J 因为,K R 太阳,H 建筑师,Y 加藤,年代 Isselbacher K J 布朗,米 Shioda T 基因Dev。15:2598 - 612 11452016 Pubmed 2001 雌激素受体与雌激素反应元件的相互作用 Klinge C M 核酸Res. 29:2905-19 10828826 Pubmed 2000 通过雌二醇转录激活转化生长因子:需要一个富含gc的位点和一个雌激素反应元件的半位点 Vyhlidal C Samudio, Ismael Kladde, M P 安全,斯蒂芬 《内分泌》24:329-38 11435612 Pubmed 2001 不同雌激素反应元件对雌激素受体构象的变构调节 木材、J R Likhite V年代 Loven,米 Nardulli,米 15:1114-26摩尔。性