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Q9TV98

- ESR1_HORSE

UniProt

Q9TV98 - ESR1_HORSE

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Protein

Estrogen receptor

Gene
ESR1, ESR, NR3A1
Organism
Equus caballus (Horse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

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 By similarity.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi185 – 25066Nuclear receptorAdd
BLAST
Zinc fingeri185 – 20521NR C4-typeAdd
BLAST
Zinc fingeri221 – 24525NR C4-typeAdd
BLAST

GO - Molecular functioni

  1. estrogen receptor activity Source: InterPro
  2. sequence-specific DNA binding Source: InterPro
  3. sequence-specific DNA binding transcription factor activity Source: InterPro
  4. steroid binding Source: UniProtKB
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. cellular response to estradiol stimulus Source: UniProtKB
  2. intracellular steroid hormone receptor signaling pathway Source: UniProtKB
  3. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  4. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  5. phospholipase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  6. positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  7. positive regulation of nitric oxide biosynthetic process Source: UniProtKB
  8. positive regulation of nitric-oxide synthase activity Source: UniProtKB
  9. positive regulation of phospholipase C activity Source: UniProtKB
  10. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  11. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding, Steroid-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Estrogen receptor
Short name:
ER
Alternative name(s):
ER-alpha
Estradiol receptor
Nuclear receptor subfamily 3 group A member 1
Gene namesi
Name:ESR1
Synonyms:ESR, NR3A1
OrganismiEquus caballus (Horse)
Taxonomic identifieri9796 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus
ProteomesiUP000002281: Unplaced

Subcellular locationi

Nucleus By similarity. Cytoplasm By similarity. Golgi apparatus By similarity. Cell membrane By similarity
Note: Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably palmitoylation occurs By similarity. Associated with the plasma membrane when palmitoylated By similarity.

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB-SubCell
  2. nucleus Source: UniProtKB
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 594594Estrogen receptorPRO_0000053617Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi10 – 101O-linked (GlcNAc) By similarity
Modified residuei104 – 1041Phosphoserine; by CDK2 By similarity
Modified residuei106 – 1061Phosphoserine; by CDK2 By similarity
Modified residuei118 – 1181Phosphoserine By similarity
Modified residuei167 – 1671Phosphoserine; by CK2 By similarity
Modified residuei260 – 2601Asymmetric dimethylarginine; by PRMT1 By similarity
Lipidationi447 – 4471S-palmitoyl cysteine By similarity
Modified residuei536 – 5361Phosphotyrosine; by Tyr-kinases By similarity
Glycosylationi570 – 5701O-linked (GlcNAc) By similarity

Post-translational modificationi

Ubiquitinated. Deubiquitinated by OTUB1 By similarity.
Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization By similarity.
Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity By similarity.
Palmitoylated at Cys-447 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 By similarity.

Keywords - PTMi

Glycoprotein, Lipoprotein, Methylation, Palmitate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Binds DNA as a homodimer By similarity. Can form a heterodimer with ESR2 By similarity. Interacts with coactivator NCOA5. Interacts with NCOA7; the interaction is ligand-inducible. Interacts with AKAP13, CUEDC2, HEXIM1, KDM5A, MAP1S, PELP1, SMARD1, and UBE1C. Interacts with MUC1; the interaction is stimulated by 7 beta-estradiol (E2) and enhances ERS1-mediated transcription. Interacts with DNTTIP2, and UIMC1. Interacts with KMT2D/MLL2. Interacts with ATAD2; the interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via its C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interacts with SH2D4A; the interaction blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62; the interaction requires estradiol and appears 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 PIK3R2, SRC and PTK2/FAK1. Interacts with RBFOX2. Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent By similarity. Interacts with FAM120B, FOXL2, PHB2 and SLC30A9. Interacts with coactivators NCOA3 and NCOA6. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESE1 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. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts with CLOCK and the interaction is stimulated by estrogen By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ9TV98.
SMRiQ9TV98. Positions 180-253, 301-549.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 184184Modulating (transactivation AF-1); mediates interaction with MACROD1 By similarityAdd
BLAST
Regioni35 – 174140Interaction with DDX5; self-association By similarityAdd
BLAST
Regioni35 – 4713Required for interaction with NCOA1 By similarityAdd
BLAST
Regioni185 – 310126Mediates interaction with DNTTIP2 By similarityAdd
BLAST
Regioni251 – 31060HingeAdd
BLAST
Regioni262 – 594333Interaction with AKAP13 By similarityAdd
BLAST
Regioni264 – 594331Self-association By similarityAdd
BLAST
Regioni311 – 594284Transactivation AF-2 By similarityAdd
BLAST
Regioni311 – 550240Steroid-bindingAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi64 – 707Poly-Ala

Domaini

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 By similarity.

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri185 – 20521NR C4-typeAdd
BLAST
Zinc fingeri221 – 24525NR C4-typeAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG320746.
HOGENOMiHOG000233468.
HOVERGENiHBG108344.
InParanoidiQ9TV98.
KOiK08550.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR008946. 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.
[Graphical view]
PfamiPF12743. ESR1_C. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFiPIRSF500101. ER-a. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSiPR00543. OESTROGENR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9TV98-1 [UniParc]FASTAAdd to Basket

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MTMTLHTKAS GMALLHQIQG NELETLNLPQ FKIPLERPLG EVYVESSKPP    50
VYDYPEGAAY DFNAAAAASA SVYGQSGLAY GPGSEAAAFG ANGLGGFPPL 100
NSVSPSQLML LHPPPQLSPY LHPPGQQVPY YLENEPSGYS VCEAGPQAFY 150
RPNADNRRQG GRERLASSGD KGSMAMESAK ETRYCAVCND YASGYHYGVW 200
SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC RLRKCYEVGM 250
MKGGIRKDRR GGRMLKHKRQ RDDGEGRNEA GPSGDRRPAN FWPSPLLIKH 300
TKKISPVLSL TAEQMISALL DAEPPVLYSE YDATRPFNEA SMMGLLTNLA 350
DRELVHMINW AKRVPGFVDL SLHDQVHLLE CAWLEILMIG LVWRSMEHPG 400
KLLFAPNLLL DRNQGKCVEG MVEIFDMLLA TSSRLRMMNL QGEEFVCLKS 450
IILLNSGVYT FLSSTLKSLE EKDHIHRVLD KMTDTLIHLM AKAGLTLQQH 500
RRLAQLLLIL SHIRHMSNKG MEHLYSMKCK NVVPLYDLLL EMLDAHRLHA 550
PANHGGAPME ETNQSQLATT GSTSPHSMQT YYITGEAEGF PNTI 594
Length:594
Mass (Da):66,104
Last modified:May 1, 2000 - v1
Checksum:iDD36CA7C24C74B95
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF124093 mRNA. Translation: AAD17316.1.
RefSeqiNP_001075241.1. NM_001081772.1.
UniGeneiEca.13034.
Eca.21644.

Genome annotation databases

GeneIDi791249.
KEGGiecb:791249.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF124093 mRNA. Translation: AAD17316.1 .
RefSeqi NP_001075241.1. NM_001081772.1.
UniGenei Eca.13034.
Eca.21644.

3D structure databases

ProteinModelPortali Q9TV98.
SMRi Q9TV98. Positions 180-253, 301-549.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 791249.
KEGGi ecb:791249.

Organism-specific databases

CTDi 2099.

Phylogenomic databases

eggNOGi NOG320746.
HOGENOMi HOG000233468.
HOVERGENi HBG108344.
InParanoidi Q9TV98.
KOi K08550.

Family and domain databases

Gene3Di 1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProi 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.
[Graphical view ]
Pfami PF12743. ESR1_C. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PIRSFi PIRSF500101. ER-a. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSi PR00543. OESTROGENR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 1 hit.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. McDowell K.J., Adams M.H., Green M.L., Cleaver B.D., Sharp D.C.
    Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiESR1_HORSE
AccessioniPrimary (citable) accession number: Q9TV98
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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