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Q9TV98 (ESR1_HORSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Estrogen receptor

Short name=ER
Alternative name(s):
ER-alpha
Estradiol receptor
Nuclear receptor subfamily 3 group A member 1
Gene names
Name:ESR1
Synonyms:ESR, NR3A1
OrganismEquus caballus (Horse) [Reference proteome]
Taxonomic identifier9796 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus

Protein attributes

Sequence length594 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 By similarity.

Subunit structure

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.

Subcellular location

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.

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 By similarity.

Post-translational modification

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.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCell membrane
Cytoplasm
Golgi apparatus
Membrane
Nucleus
   DomainZinc-finger
   LigandDNA-binding
Lipid-binding
Metal-binding
Steroid-binding
Zinc
   Molecular functionActivator
Receptor
   PTMGlycoprotein
Lipoprotein
Methylation
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to estradiol stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular steroid hormone receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of nitric oxide biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of nitric-oxide synthase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phospholipase C activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionestrogen receptor activity

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

steroid binding

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 594594Estrogen receptor
PRO_0000053617

Regions

DNA binding185 – 25066Nuclear receptor
Zinc finger185 – 20521NR C4-type
Zinc finger221 – 24525NR C4-type
Region1 – 184184Modulating (transactivation AF-1); mediates interaction with MACROD1 By similarity
Region35 – 174140Interaction with DDX5; self-association By similarity
Region35 – 4713Required for interaction with NCOA1 By similarity
Region185 – 310126Mediates interaction with DNTTIP2 By similarity
Region251 – 31060Hinge
Region262 – 594333Interaction with AKAP13 By similarity
Region264 – 594331Self-association By similarity
Region311 – 594284Transactivation AF-2 By similarity
Region311 – 550240Steroid-binding
Compositional bias64 – 707Poly-Ala

Amino acid modifications

Modified residue1041Phosphoserine; by CDK2 By similarity
Modified residue1061Phosphoserine; by CDK2 By similarity
Modified residue1181Phosphoserine By similarity
Modified residue1671Phosphoserine; by CK2 By similarity
Modified residue2601Asymmetric dimethylarginine; by PRMT1 By similarity
Modified residue5361Phosphotyrosine; by Tyr-kinases By similarity
Lipidation4471S-palmitoyl cysteine By similarity
Glycosylation101O-linked (GlcNAc) By similarity
Glycosylation5701O-linked (GlcNAc) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9TV98 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: DD36CA7C24C74B95

FASTA59466,104
        10         20         30         40         50         60 
MTMTLHTKAS GMALLHQIQG NELETLNLPQ FKIPLERPLG EVYVESSKPP VYDYPEGAAY 

        70         80         90        100        110        120 
DFNAAAAASA SVYGQSGLAY GPGSEAAAFG ANGLGGFPPL NSVSPSQLML LHPPPQLSPY 

       130        140        150        160        170        180 
LHPPGQQVPY YLENEPSGYS VCEAGPQAFY RPNADNRRQG GRERLASSGD KGSMAMESAK 

       190        200        210        220        230        240 
ETRYCAVCND YASGYHYGVW SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC 

       250        260        270        280        290        300 
RLRKCYEVGM MKGGIRKDRR GGRMLKHKRQ RDDGEGRNEA GPSGDRRPAN FWPSPLLIKH 

       310        320        330        340        350        360 
TKKISPVLSL TAEQMISALL DAEPPVLYSE YDATRPFNEA SMMGLLTNLA DRELVHMINW 

       370        380        390        400        410        420 
AKRVPGFVDL SLHDQVHLLE CAWLEILMIG LVWRSMEHPG KLLFAPNLLL DRNQGKCVEG 

       430        440        450        460        470        480 
MVEIFDMLLA TSSRLRMMNL QGEEFVCLKS IILLNSGVYT FLSSTLKSLE EKDHIHRVLD 

       490        500        510        520        530        540 
KMTDTLIHLM AKAGLTLQQH RRLAQLLLIL SHIRHMSNKG MEHLYSMKCK NVVPLYDLLL 

       550        560        570        580        590 
EMLDAHRLHA PANHGGAPME ETNQSQLATT GSTSPHSMQT YYITGEAEGF PNTI 

« Hide

References

[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].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF124093 mRNA. Translation: AAD17316.1.
RefSeqNP_001075241.1. NM_001081772.1.
UniGeneEca.13034.
Eca.21644.

3D structure databases

ProteinModelPortalQ9TV98.
SMRQ9TV98. Positions 180-253, 301-549.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID791249.
KEGGecb:791249.

Organism-specific databases

CTD2099.

Phylogenomic databases

eggNOGNOG320746.
HOGENOMHOG000233468.
HOVERGENHBG108344.
InParanoidQ9TV98.
KOK08550.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR008946. 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]
PfamPF12743. ESR1_C. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFPIRSF500101. ER-a. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSPR00543. OESTROGENR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameESR1_HORSE
AccessionPrimary (citable) accession number: Q9TV98
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families