P06211 (ESR1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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, Estr, Nr3a1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	600 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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 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 withN NRIP1 By similarity. Ref.4 Ref.5 Ref.6
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	Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity By similarity. Ubiquitinated. Deubiquitinated by OTUB1 By similarity. Dimethylated by PRMT1 at Arg-265. The methylation may favor cytoplasmic localization By similarity. Palmitoylated at Cys-452 by ZDHHC7 and ZDHHC21. This modification 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.
Miscellaneous	In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity. The hormone-receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Steroid-binding Zinc
Molecular function	Activator Receptor
PTM	Glycoprotein Lipoprotein Methylation Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell proliferation Inferred from mutant phenotype PubMed 17928626. Source: RGD intracellular steroid hormone receptor signaling pathway Inferred from direct assay PubMed 17928626. Source: RGD negative regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of neuron death Inferred from direct assay PubMed 15126114. Source: RGD negative regulation of sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB osteoblast development Inferred from expression pattern PubMed 9528993. Source: RGD positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 17928626. Source: RGD positive regulation of epidermal growth factor receptor signaling pathway Inferred from mutant phenotype PubMed 17928626. Source: RGD 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 sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Traceable author statement PubMed 11562484. Source: RGD regulation of neuron apoptotic process Inferred from direct assay PubMed 15126114. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 9528993. Source: RGD transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell T-tubule Inferred from direct assay PubMed 16876190. Source: RGD mitochondrial part Inferred from direct assay PubMed 15994367. Source: RGD nucleus Inferred from direct assay PubMed 12372009PubMed 16122717PubMed 16869728PubMed 17928626. Source: RGD perikaryon Inferred from direct assay PubMed 16122717. Source: RGD perinuclear region of cytoplasm Inferred from direct assay PubMed 17928626. Source: RGD protein complex Inferred from direct assay PubMed 18434427. Source: RGD terminal bouton Inferred from direct assay PubMed 17314305. Source: RGD
Molecular_function	DNA binding Inferred from mutant phenotype PubMed 12372009. Source: RGD estrogen receptor activity Inferred from direct assay PubMed 15105439. Source: RGD hormone binding Inferred from direct assay PubMed 17928626. Source: RGD protein complex binding Inferred from direct assay PubMed 18434427. Source: RGD 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 direct assay PubMed 17928626. Source: RGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 600	600	Estrogen receptor		PRO_0000053623
Regions
	DNA binding	190 – 255	66	Nuclear receptor
	Zinc finger	190 – 210	21	NR C4-type
	Zinc finger	226 – 250	25	NR C4-type
	Region	1 – 189	189	Modulating (transactivation AF-1); mediates interaction with MACROD1 By similarity
	Region	35 – 179	145	Interaction with DDX5; self-association By similarity
	Region	35 – 47	13	Required for interaction with NCOA1 By similarity
	Region	190 – 315	126	Mediates interaction with DNTTIP2 By similarity
	Region	256 – 315	60	Hinge
	Region	267 – 600	334	Interaction with AKAP13 By similarity
	Region	269 – 600	332	Self-association By similarity
	Region	316 – 600	285	Transactivation AF-2 By similarity
	Region	316 – 556	241	Steroid-binding
	Compositional bias	64 – 71	8	Poly-Ala
	Compositional bias	171 – 174	4	Poly-Ser
Amino acid modifications
	Modified residue	109	1	Phosphoserine; by CDK2 By similarity
	Modified residue	111	1	Phosphoserine; by CDK2 By similarity
	Modified residue	123	1	Phosphoserine By similarity
	Modified residue	172	1	Phosphoserine; by CK2 By similarity
	Modified residue	265	1	Asymmetric dimethylarginine; by PRMT1 By similarity
	Modified residue	542	1	Phosphotyrosine; by Tyr-kinases By similarity
	Lipidation	452	1	S-palmitoyl cysteine By similarity
	Glycosylation	10	1	O-linked (GlcNAc) By similarity
	Glycosylation	576	1	O-linked (GlcNAc) By similarity
Experimental info
	Sequence conflict	488	1	N → T in CAA43411. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P06211 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: C9C7D8CACE0F57D8	FASTA	600	67,030
	10 20 30 40 50 60 MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKMPMERALG EVYVDNSKPA VFNYPEGAAY 70 80 90 100 110 120 EFNAAAAAAA AGASAPVYGQ SSITYGPGSE AAAFGANSLG AFPQLNSVSP SPLMLLHPPP 130 140 150 160 170 180 HVSPFLHPHG HQVPYYLENE PSAYAVRDTG PPAFYRSNSD NRRQNGRERL SSSSEKGNMI 190 200 210 220 230 240 MESAKETRYC AVCNDYASGY HYGVWSCEGC KAFFKRSIQG HNDYMCPATN QCTIDKNRRK 250 260 270 280 290 300 SCQACRLRKC YEVGMMKGGI RKDRRGGRML KHKRQRDDLE GRNEMGTSGD MRAANLWPSP 310 320 330 340 350 360 LVIKHTKKNS PALSLTADQM VSALLDAEPP LIYSEYDPSR PFSEASMMGL LTNLADRELV 370 380 390 400 410 420 HMINWAKRVP GFGDLNLHDQ VHLLECAWLE ILMIGLVWRS MEHPGKLLFA PNLLLDRNQG 430 440 450 460 470 480 KCVEGMVEIF DMLLATSSRF RMMNLQGEEF VCLKSIILLN SGVYTFLSST LKSLEEKDHI 490 500 510 520 530 540 HRVLDKINDT LIHLMAKAGL TLQQQHRRLA QLLLILSHIR HMSNKGMEHL YNMKCKNVVP 550 560 570 580 590 600 LYDLLLEMLD AHRLHAPASR MGVPPEEPSQ SQLTTTSSTS AHSLQTYYIP PEAEGFPNTI

References

[1]	Muramatsu M. Submitted (MAR-1987) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar.
[2]	"Molecular cloning and characterization of rat estrogen receptor cDNA." Koike S., Sakai M. Nucleic Acids Res. 15:2499-2513(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Maggi A.M.A. Submitted (JUN-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Uterus.
[4]	"The activating enzyme of NEDD8 inhibits steroid receptor function." Fan M., Long X., Bailey J.A., Reed C.A., Osborne E., Gize E.A., Kirk E.A., Bigsby R.M., Nephew K.P. Mol. Endocrinol. 16:315-330(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBE1C.
[5]	"The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain." Eriksson M., Samuelsson H., Samuelsson E.-B., Liu L., McKeehan W.L., Benedikz E., Sundstroem E. Biochem. Biophys. Res. Commun. 361:127-132(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP1S.
[6]	"Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia." Massinen S., Tammimies K., Tapia-Paez I., Matsson H., Hokkanen M.E., Soederberg O., Landegren U., Castren E., Gustafsson J.A., Treuter E., Kere J. Hum. Mol. Genet. 18:2802-2812(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DYX1C1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y00102 mRNA. Translation: CAA68287.1. X61098 mRNA. Translation: CAA43411.1.
IPI	IPI00201392.
PIR	QRRTE. S07379.
RefSeq	NP_036821.1. NM_012689.1.
UniGene	Rn.10595.
3D structure databases
ProteinModelPortal	P06211.
SMR	P06211. Positions 185-258, 306-555.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-234578.
STRING	10116.ENSRNOP00000026350.
PTM databases
PhosphoSite	P06211.
Proteomic databases
PaxDb	P06211.
PRIDE	P06211.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24890.
KEGG	rno:24890.
UCSC	RGD:2581. rat.
Organism-specific databases
CTD	2099.
RGD	2581. Esr1.
Phylogenomic databases
eggNOG	NOG320746.
HOGENOM	HOG000233468.
HOVERGEN	HBG108344.
InParanoid	P06211.
KO	K08550.
OrthoDB	EOG4JM7PP.
Gene expression databases
ArrayExpress	P06211.
Genevestigator	P06211.
Family and domain databases
Gene3D	1.10.565.10. 2 hits. 3.30.50.10. 1 hit.
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. [Graphical view]
Pfam	PF12743. ESR1_C. 1 hit. PF00104. Hormone_recep. 1 hit. PF02159. Oest_recep. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view]
PIRSF	PIRSF500101. ER-a. 1 hit. PIRSF002527. ER-like_NR. 1 hit.
PRINTS	PR00543. OESTROGENR. PR00398. STRDHORMONER. PR00047. STROIDFINGER.
SMART	SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. [Graphical view]
SUPFAM	SSF48508. Str_ncl_receptor. 1 hit.
PROSITE	PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P06211.
ChEMBL	CHEMBL2724.
NextBio	604756.

Entry information

Entry name

ESR1_RAT

Accession

Primary (citable) accession number: P06211

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	May 29, 2013
This is version 150 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program