LOCUS       NM_000125               6327 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens estrogen receptor 1 (ESR1), transcript variant 1,
            mRNA.
ACCESSION   NM_000125
VERSION     NM_000125.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 6327)
  AUTHORS   Liu,X., Matsuyama,Y., Sugiyama,M., Suyama,K., Nose,T.,
            Shimohigashi,M. and Shimohigashi,Y.
  TITLE     The N-terminal activation function AF-1 domain of ERalpha interacts
            directly with the C-terminal AF-2-holding ligand-binding domain to
            recruit the coactivator proteins
  JOURNAL   PLoS One 19 (10), e0312276 (2024)
   PUBMED   39432505
  REMARK    GeneRIF: The N-terminal activation function AF-1 domain of ERalpha
            interacts directly with the C-terminal AF-2-holding ligand-binding
            domain to recruit the coactivator proteins.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 6327)
  AUTHORS   Aboelroos,S.A., Segaey,D.G.E., Elgawad,A.K.A., Orabi,M.,
            Mohamed,M.H. and Hassan,N.R.
  TITLE     Association of Estrogen Receptor-alpha and Aryl Hydrocarbon
            Receptor Gene Polymorphisms with Ischemic Stroke in an Egyptian
            Population: A Pilot Study
  JOURNAL   J Mol Neurosci 74 (3), 85 (2024)
   PUBMED   39264466
  REMARK    GeneRIF: Association of Estrogen Receptor-alpha and Aryl
            Hydrocarbon Receptor Gene Polymorphisms with Ischemic Stroke in an
            Egyptian Population: A Pilot Study.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 6327)
  AUTHORS   Zhuang,T., Zhang,S., Liu,D., Li,Z., Li,X., Li,J., Yang,P.,
            Zhang,C., Cui,J., Fu,M., Shen,F., Yuan,L., Zhang,Z., Su,P., Zhu,J.
            and Yang,H.
  TITLE     USP36 promotes tumorigenesis and tamoxifen resistance in breast
            cancer by deubiquitinating and stabilizing ERalpha
  JOURNAL   J Exp Clin Cancer Res 43 (1), 249 (2024)
   PUBMED   39215346
  REMARK    GeneRIF: USP36 promotes tumorigenesis and tamoxifen resistance in
            breast cancer by deubiquitinating and stabilizing ERalpha.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 6327)
  AUTHORS   Ishii,H., Kobayashi,M., Munetomo,A., Miyamoto,T. and Sakuma,Y.
  TITLE     Novel splicing events and post-transcriptional regulation of human
            estrogen receptor alpha E isoforms
  JOURNAL   J Steroid Biochem Mol Biol 133, 120-128 (2013)
   PUBMED   23032375
  REMARK    GeneRIF: the 5'-UTRs of the E isoforms post-transcriptionally
            control ERalpha expression mainly through translational repression
REFERENCE   5  (bases 1 to 6327)
  AUTHORS   Pentecost,B.T., Song,R., Luo,M., DePasquale,J.A. and Fasco,M.J.
  TITLE     Upstream regions of the estrogen receptor alpha proximal promoter
            transcript regulate ER protein expression through a translational
            mechanism
  JOURNAL   Mol Cell Endocrinol 229 (1-2), 83-94 (2005)
   PUBMED   15607532
REFERENCE   6  (bases 1 to 6327)
  AUTHORS   Kos,M., Denger,S., Reid,G. and Gannon,F.
  TITLE     Upstream open reading frames regulate the translation of the
            multiple mRNA variants of the estrogen receptor alpha
  JOURNAL   J Biol Chem 277 (40), 37131-37138 (2002)
   PUBMED   12147702
  REMARK    GeneRIF: Upstream open reading frames regulate the translation of
            the multiple mRNA variants
REFERENCE   7  (bases 1 to 6327)
  AUTHORS   Ing,N.H., Beekman,J.M., Tsai,S.Y., Tsai,M.J. and O'Malley,B.W.
  TITLE     Members of the steroid hormone receptor superfamily interact with
            TFIIB (S300-II)
  JOURNAL   J Biol Chem 267 (25), 17617-17623 (1992)
   PUBMED   1517211
REFERENCE   8  (bases 1 to 6327)
  AUTHORS   Piva,R., Gambari,R., Zorzato,F., Kumar,L. and del Senno,L.
  TITLE     Analysis of upstream sequences of the human estrogen receptor gene
  JOURNAL   Biochem Biophys Res Commun 183 (3), 996-1002 (1992)
   PUBMED   1567414
REFERENCE   9  (bases 1 to 6327)
  AUTHORS   Keaveney,M., Klug,J. and Gannon,F.
  TITLE     Sequence analysis of the 5' flanking region of the human estrogen
            receptor gene
  JOURNAL   DNA Seq 2 (6), 347-358 (1992)
   PUBMED   1476547
  REMARK    Erratum:[DNA Seq 1992;3(3):201]
REFERENCE   10 (bases 1 to 6327)
  AUTHORS   Keaveney,M., Klug,J., Dawson,M.T., Nestor,P.V., Neilan,J.G.,
            Forde,R.C. and Gannon,F.
  TITLE     Evidence for a previously unidentified upstream exon in the human
            oestrogen receptor gene
  JOURNAL   J Mol Endocrinol 6 (1), 111-115 (1991)
   PUBMED   2015052
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL356311.6, BC128573.1,
            AL590993.14, BE084831.1 and AL078582.13.
            
            On Dec 27, 2019 this sequence version replaced NM_000125.3.
            
            Summary: This gene encodes an estrogen receptor and
            ligand-activated transcription factor. The canonical protein
            contains an N-terminal ligand-independent transactivation domain, a
            central DNA binding domain, a hinge domain, and a C-terminal
            ligand-dependent transactivation domain. The protein localizes to
            the nucleus where it may form either a homodimer or a heterodimer
            with estrogen receptor 2. The protein encoded by this gene
            regulates the transcription of many estrogen-inducible genes that
            play a role in growth, metabolism, sexual development, gestation,
            and other reproductive functions and is expressed in many
            non-reproductive tissues. The receptor encoded by this gene plays a
            key role in breast cancer, endometrial cancer, and osteoporosis.
            This gene is reported to have dozens of transcript variants due to
            the use of alternate promoters and alternative splicing, however,
            the full-length nature of many of these variants remain uncertain.
            [provided by RefSeq, Jul 2020].
            
            Transcript Variant: This variant (1) uses the most proximal
            promoter, and encodes isoform 1. Variants 1-4 and 8-9 encode the
            same isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X03635.1, SRR14038197.2033366.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000206249.8/ ENSP00000206249.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            regulatory uORF        :: PMID: 12147702
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-126               AL356311.6         49381-49506
            127-959             BC128573.1         1-833
            960-960             AL590993.14        57093-57093
            961-1205            BC128573.1         835-1079
            1206-1206           AL590993.14        120740-120740
            1207-3005           BC128573.1         1081-2879
            3006-3049           BE084831.1         171-214
            3050-6327           AL078582.13        51058-54335
FEATURES             Location/Qualifiers
     source          1..6327
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q25.1-q25.2"
     gene            1..6327
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /note="estrogen receptor 1"
                     /db_xref="GeneID:2099"
                     /db_xref="HGNC:HGNC:3467"
                     /db_xref="MIM:133430"
     exon            1..683
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     CDS             232..2019
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     ER-alpha; estradiol receptor; nuclear receptor subfamily 3
                     group A member 1; estrogen nuclear receptor alpha;
                     estrogen receptor alpha E1-E2-1-2; estrogen receptor alpha
                     E1-N2-E2-1-2; oestrogen receptor alpha; E2 receptor alpha"
                     /codon_start=1
                     /product="estrogen receptor isoform 1"
                     /protein_id="NP_000116.2"
                     /db_xref="CCDS:CCDS5234.1"
                     /db_xref="GeneID:2099"
                     /db_xref="HGNC:HGNC:3467"
                     /db_xref="MIM:133430"
                     /translation="MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYL
                     DSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNS
                     VSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQG
                     GRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHND
                     YMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEG
                     RGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPT
                     RPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLV
                     WRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKS
                     IILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLL
                     LILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQS
                     HLATAGSTSSHSLQKYYITGEAEGFPATV"
     exon            684..874
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     exon            875..991
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     exon            992..1327
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1328..1466
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1467..1600
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1601..1784
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     exon            1785..6327
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6309..6314
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /note="hexamer: AATAAA"
     polyA_site      6327
                     /gene="ESR1"
                     /gene_synonym="ER; Era; ESR; ESRA; ESTRR; NR3A1"
                     /note="major polyA site"
ORIGIN      
        1 agctggcgga gggcgttcgt cctgggactg cacttgctcc cgtcgggtcg cccggcttca
       61 ccggacccgc aggctcccgg ggcagggccg gggccagagc tcgcgtgtcg gcgggacatg
      121 cgctgcgtcg cctctaacct cgggctgtgc tctttttcca ggtggcccgc cggtttctga
      181 gccttctgcc ctgcggggac acggtctgca ccctgcccgc ggccacggac catgaccatg
      241 accctccaca ccaaagcatc tgggatggcc ctactgcatc agatccaagg gaacgagctg
      301 gagcccctga accgtccgca gctcaagatc cccctggagc ggcccctggg cgaggtgtac
      361 ctggacagca gcaagcccgc cgtgtacaac taccccgagg gcgccgccta cgagttcaac
      421 gccgcggccg ccgccaacgc gcaggtctac ggtcagaccg gcctccccta cggccccggg
      481 tctgaggctg cggcgttcgg ctccaacggc ctggggggtt tccccccact caacagcgtg
      541 tctccgagcc cgctgatgct actgcacccg ccgccgcagc tgtcgccttt cctgcagccc
      601 cacggccagc aggtgcccta ctacctggag aacgagccca gcggctacac ggtgcgcgag
      661 gccggcccgc cggcattcta caggccaaat tcagataatc gacgccaggg tggcagagaa
      721 agattggcca gtaccaatga caagggaagt atggctatgg aatctgccaa ggagactcgc
      781 tactgtgcag tgtgcaatga ctatgcttca ggctaccatt atggagtctg gtcctgtgag
      841 ggctgcaagg ccttcttcaa gagaagtatt caaggacata acgactatat gtgtccagcc
      901 accaaccagt gcaccattga taaaaacagg aggaagagct gccaggcctg ccggctccgt
      961 aaatgctacg aagtgggaat gatgaaaggt gggatacgaa aagaccgaag aggagggaga
     1021 atgttgaaac acaagcgcca gagagatgat ggggagggca ggggtgaagt ggggtctgct
     1081 ggagacatga gagctgccaa cctttggcca agcccgctca tgatcaaacg ctctaagaag
     1141 aacagcctgg ccttgtccct gacggccgac cagatggtca gtgccttgtt ggatgctgag
     1201 cccccgatac tctattccga gtatgatcct accagaccct tcagtgaagc ttcgatgatg
     1261 ggcttactga ccaacctggc agacagggag ctggttcaca tgatcaactg ggcgaagagg
     1321 gtgccaggct ttgtggattt gaccctccat gatcaggtcc accttctaga atgtgcctgg
     1381 ctagagatcc tgatgattgg tctcgtctgg cgctccatgg agcacccagg gaagctactg
     1441 tttgctccta acttgctctt ggacaggaac cagggaaaat gtgtagaggg catggtggag
     1501 atcttcgaca tgctgctggc tacatcatct cggttccgca tgatgaatct gcagggagag
     1561 gagtttgtgt gcctcaaatc tattattttg cttaattctg gagtgtacac atttctgtcc
     1621 agcaccctga agtctctgga agagaaggac catatccacc gagtcctgga caagatcaca
     1681 gacactttga tccacctgat ggccaaggca ggcctgaccc tgcagcagca gcaccagcgg
     1741 ctggcccagc tcctcctcat cctctcccac atcaggcaca tgagtaacaa aggcatggag
     1801 catctgtaca gcatgaagtg caagaacgtg gtgcccctct atgacctgct gctggagatg
     1861 ctggacgccc accgcctaca tgcgcccact agccgtggag gggcatccgt ggaggagacg
     1921 gaccaaagcc acttggccac tgcgggctct acttcatcgc attccttgca aaagtattac
     1981 atcacggggg aggcagaggg tttccctgcc acggtctgag agctccctgg ctcccacacg
     2041 gttcagataa tccctgctgc attttaccct catcatgcac cactttagcc aaattctgtc
     2101 tcctgcatac actccggcat gcatccaaca ccaatggctt tctagatgag tggccattca
     2161 tttgcttgct cagttcttag tggcacatct tctgtcttct gttgggaaca gccaaaggga
     2221 ttccaaggct aaatctttgt aacagctctc tttccccctt gctatgttac taagcgtgag
     2281 gattcccgta gctcttcaca gctgaactca gtctatgggt tggggctcag ataactctgt
     2341 gcatttaagc tacttgtaga gacccaggcc tggagagtag acattttgcc tctgataagc
     2401 actttttaaa tggctctaag aataagccac agcaaagaat ttaaagtggc tcctttaatt
     2461 ggtgacttgg agaaagctag gtcaagggtt tattatagca ccctcttgta ttcctatggc
     2521 aatgcatcct tttatgaaag tggtacacct taaagctttt atatgactgt agcagagtat
     2581 ctggtgattg tcaattcatt ccccctatag gaatacaagg ggcacacagg gaaggcagat
     2641 cccctagttg gcaagactat tttaacttga tacactgcag attcagatgt gctgaaagct
     2701 ctgcctctgg ctttccggtc atgggttcca gttaattcat gcctcccatg gacctatgga
     2761 gagcagcaag ttgatcttag ttaagtctcc ctatatgagg gataagttcc tgatttttgt
     2821 ttttattttt gtgttacaaa agaaagccct ccctccctga acttgcagta aggtcagctt
     2881 caggacctgt tccagtgggc actgtacttg gatcttcccg gcgtgtgtgt gccttacaca
     2941 ggggtgaact gttcactgtg gtgatgcatg atgagggtaa atggtagttg aaaggagcag
     3001 gggccctggt gttgcattta gccctggggc atggagctga acagtacttg tgcaggattg
     3061 ttgtggctac tagagaacaa gagggaaagt agggcagaaa ctggatacag ttctgaggca
     3121 cagccagact tgctcagggt ggccctgcca caggctgcag ctacctagga acattccttg
     3181 cagaccccgc attgcccttt gggggtgccc tgggatccct ggggtagtcc agctcttctt
     3241 catttcccag cgtggccctg gttggaagaa gcagctgtca cagctgctgt agacagctgt
     3301 gttcctacaa ttggcccagc accctggggc acgggagaag ggtggggacc gttgctgtca
     3361 ctactcaggc tgactggggc ctggtcagat tacgtatgcc cttggtggtt tagagataat
     3421 ccaaaatcag ggtttggttt ggggaagaaa atcctccccc ttcctccccc gccccgttcc
     3481 ctaccgcctc cactcctgcc agctcatttc cttcaatttc ctttgaccta taggctaaaa
     3541 aagaaaggct cattccagcc acagggcagc cttccctggg cctttgcttc tctagcacaa
     3601 ttatgggtta cttccttttt cttaacaaaa aagaatgttt gatttcctct gggtgacctt
     3661 attgtctgta attgaaaccc tattgagagg tgatgtctgt gttagccaat gacccaggtg
     3721 agctgctcgg gcttctcttg gtatgtcttg tttggaaaag tggatttcat tcatttctga
     3781 ttgtccagtt aagtgatcac caaaggactg agaatctggg agggcaaaaa aaaaaaaaaa
     3841 gtttttatgt gcacttaaat ttggggacaa ttttatgtat ctgtgttaag gatatgttta
     3901 agaacataat tcttttgttg ctgtttgttt aagaagcacc ttagtttgtt taagaagcac
     3961 cttatatagt ataatatata tttttttgaa attacattgc ttgtttatca gacaattgaa
     4021 tgtagtaatt ctgttctgga tttaatttga ctgggttaac atgcaaaaac caaggaaaaa
     4081 tatttagttt tttttttttt ttttgtatac ttttcaagct accttgtcat gtatacagtc
     4141 atttatgcct aaagcctggt gattattcat ttaaatgaag atcacatttc atatcaactt
     4201 ttgtatccac agtagacaaa atagcactaa tccagatgcc tattgttgga tactgaatga
     4261 cagacaatct tatgtagcaa agattatgcc tgaaaaggaa aattattcag ggcagctaat
     4321 tttgctttta ccaaaatatc agtagtaata tttttggaca gtagctaatg ggtcagtggg
     4381 ttctttttaa tgtttatact tagattttct tttaaaaaaa ttaaaataaa acaaaaaaaa
     4441 atttctagga ctagacgatg taataccagc taaagccaaa caattataca gtggaaggtt
     4501 ttacattatt catccaatgt gtttctattc atgttaagat actactacat ttgaagtggg
     4561 cagagaacat cagatgattg aaatgttcgc ccaggggtct ccagcaactt tggaaatctc
     4621 tttgtatttt tacttgaagt gccactaatg gacagcagat attttctggc tgatgttggt
     4681 attgggtgta ggaacatgat ttaaaaaaaa actcttgcct ctgctttccc ccactctgag
     4741 gcaagttaaa atgtaaaaga tgtgatttat ctggggggct caggtatggt ggggaagtgg
     4801 attcaggaat ctggggaatg gcaaatatat taagaagagt attgaaagta tttggaggaa
     4861 aatggttaat tctgggtgtg caccagggtt cagtagagtc cacttctgcc ctggagacca
     4921 caaatcaact agctccattt acagccattt ctaaaatggc agcttcagtt ctagagaaga
     4981 aagaacaaca tcagcagtaa agtccatgga atagctagtg gtctgtgttt cttttcgcca
     5041 ttgcctagct tgccgtaatg attctataat gccatcatgc agcaattatg agaggctagg
     5101 tcatccaaag agaagaccct atcaatgtag gttgcaaaat ctaaccccta aggaagtgca
     5161 gtctttgatt tgatttccct agtaaccttg cagatatgtt taaccaagcc atagcccatg
     5221 ccttttgagg gctgaacaaa taagggactt actgataatt tacttttgat cacattaagg
     5281 tgttctcacc ttgaaatctt atacactgaa atggccattg atttaggcca ctggcttaga
     5341 gtactccttc ccctgcatga cactgattac aaatactttc ctattcatac tttccaatta
     5401 tgagatggac tgtgggtact gggagtgatc actaacacca tagtaatgtc taatattcac
     5461 aggcagatct gcttggggaa gctagttatg tgaaaggcaa atagagtcat acagtagctc
     5521 aaaaggcaac cataattctc tttggtgcag gtcttgggag cgtgatctag attacactgc
     5581 accattccca agttaatccc ctgaaaactt actctcaact ggagcaaatg aactttggtc
     5641 ccaaatatcc atcttttcag tagcgttaat tatgctctgt ttccaactgc atttcctttc
     5701 caattgaatt aaagtgtggc ctcgttttta gtcatttaaa attgttttct aagtaattgc
     5761 tgcctctatt atggcacttc aattttgcac tgtcttttga gattcaagaa aaatttctat
     5821 tctttttttt gcatccaatt gtgcctgaac ttttaaaata tgtaaatgct gccatgttcc
     5881 aaacccatcg tcagtgtgtg tgtttagagc tgtgcaccct agaaacaaca tattgtccca
     5941 tgagcaggtg cctgagacac agaccccttt gcattcacag agaggtcatt ggttatagag
     6001 acttgaatta ataagtgaca ttatgccagt ttctgttctc tcacaggtga taaacaatgc
     6061 tttttgtgca ctacatactc ttcagtgtag agctcttgtt ttatgggaaa aggctcaaat
     6121 gccaaattgt gtttgatgga ttaatatgcc cttttgccga tgcatactat tactgatgtg
     6181 actcggtttt gtcgcagctt tgctttgttt aatgaaacac acttgtaaac ctcttttgca
     6241 ctttgaaaaa gaatccagcg ggatgctcga gcacctgtaa acaattttct caacctattt
     6301 gatgttcaaa taaagaatta aactaaa
//
