Reviewed, UniProtKB/Swiss-Prot P03372 (ESR1_HUMAN)

Names and origin

Protein names

Recommended name:
    Estrogen receptor
      Short name=ER
Alternative name(s):
    Estradiol receptor
    ER-alpha
    Nuclear receptor subfamily 3 group A member 1

Gene names

Name:	ESR1
Synonyms:	ESR, NR3A1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	595 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Subunit structure	Interacts with SLC30A9 By similarity. Binds DNA as a homodimer. Can form a heterodimer with ESR2. Interacts with NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with NCOA7 in a ligand-inducible manner. Interacts with PHB2, PELP1 and UBE1C. Interacts with AKAP13. Interacts with CUEDC2. Interacts with KDM5A. Interacts with SMARD1. Interacts with HEXIM1 and MAP1S. 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 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.
Subcellular location	Nucleus. Ref.32
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal steroid-binding domain.
Post-translational modification	Phosphorylated by cyclin A/CDK2. Phosphorylation probably enhances transcriptional activity. Ref.6 Ref.10 Ref.12 Ref.15 Ref.35 Glycosylated; contains N-acetylglucosamine, probably O-linked. Ref.13
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, disrutption 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.
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	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Steroid-binding Zinc
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	estrogen receptor signaling pathway Ref.2 Non-traceable author statement. Source: UniProtKB positive regulation of retinoic acid receptor signaling pathway Inferred from direct assay. Source: UniProtKB regulation of transcription, DNA-dependent Ref.2 Non-traceable author statement. Source: UniProtKB transcription, DNA-dependent Traceable author statement. Source: ProtInc
Cellular component	chromatin remodeling complex Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from direct assay. Source: UniProtKB
Molecular function	estrogen receptor activity Ref.2 Non-traceable author statement. Source: UniProtKB estrogen response element binding Inferred from direct assay. Source: UniProtKB nitric-oxide synthase regulator activity Non-traceable author statement. Source: UniProtKB protein N-terminus binding Ref.23 Inferred from physical interaction. Source: UniProtKB steroid binding Inferred from electronic annotation. Source: UniProtKB-KW transcription factor activity Non-traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRCA1	P38398	4	EBI-78473,EBI-349905
BTF3	P20290-2	4	EBI-78473,EBI-1054703
CHD9	Q3L8U1-3	1	EBI-78473,EBI-960730
CRIPAK	Q8N1N5	1	EBI-78473,EBI-1205846
CUEDC2	Q9H467	2	EBI-78473,EBI-1248228
FOXO1	Q12778	1	EBI-78473,EBI-1108782
MDM2	Q00987	1	EBI-78473,EBI-389668
MLL2	O14686	1	EBI-78473,EBI-996065
NCOA3	Q9Y6Q9	1	EBI-78473,EBI-81196
Ncoa6	Q9JLI4	1	EBI-78473,EBI-286271	From a different organism.
NR1H4	Q96RI1	1	EBI-78473,EBI-1250177
PPP1CC	P36873	1	EBI-78473,EBI-356283
PPP5C	P53041	3	EBI-78473,EBI-716663
PRMT2	P55345	2	EBI-78473,EBI-78458
SAFB2	Q14151	2	EBI-78473,EBI-352869
SMARCD1	Q96GM5	1	EBI-78473,EBI-358489
VAV3	Q9UKW4	1	EBI-78473,EBI-297568

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P03372-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P03372-2)

The sequence of this isoform differs from the canonical sequence as follows:
     255-366: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 595

595

Estrogen receptor

PRO_0000053618

Regions

DNA binding

185 – 250

66

Nuclear receptor

Zinc finger

185 – 205

21

NR C4-type

Zinc finger

221 – 245

25

NR C4-type

Region

1 – 184

184

Modulating; mediates interaction with MACROD1

Region

185 – 310

126

Mediates interaction with DNTTIP2

Region

251 – 310

60

Hinge

Region

262 – 595

334

Interaction with AKAP13

Region

311 – 551

241

Steroid-binding

Amino acid modifications

Modified residue

7

1

Phosphothreonine Ref.35

Modified residue

10

1

Phosphoserine Ref.35

Modified residue

104

1

Phosphoserine; by CDK2 Ref.15

Modified residue

106

1

Phosphoserine; by CDK2 Ref.15

Modified residue

118

1

Phosphoserine

Modified residue

167

1

Phosphoserine; by CK2

Modified residue

537

1

Phosphotyrosine; by Tyr-kinases

Glycosylation

10

1

O-linked (GlcNAc) By similarity

Natural variations

Alternative sequence

255 – 366

112

Missing in isoform Short.

VSP_003680

Natural variant

6

1

H → Y in a breast cancer sample; somatic mutation. Ref.48

VAR_033028

Natural variant

77

1

G → S: dbSNP rs9340773. Ref.4

VAR_018905

Natural variant

160

1

G → C

VAR_004671

Natural variant

264

1

M → I in a breast cancer sample; somatic mutation. Ref.48

VAR_033029

Natural variant

364

1

V → E in estrogen resistance; dominant-negative inhibitor of the wild-type ESR. Ref.45

VAR_004672

Natural variant

400

1

G → V Destabilizes the receptor and decreases its affinity for estradiol at 25 degrees Celsius, but not at 4 degrees Celsius. Ref.44

VAR_004673

Natural variant

411

1

D → RNQGKCVEGMVEIFDMLLAT SSRFRMMNLQGEEFVCLKSI ILLNSGVYTFLSSTLKSLEE KDHIHRVLDKITDTLIHLMA KAGLTLQQQHQRLAQLLLIL SHIRHM in a 80 kDa form found in a breast cancer line; contains an in-frame duplication of exons 6 and 7.

VAR_010143

Experimental info

Mutagenesis

104

1

S → A: Loss of cyclin A-dependent induction of transcriptional activation.

Mutagenesis

106

1

S → A: Loss of cyclin A-dependent induction of transcriptional activation.

Mutagenesis

118

1

S → A: Decrease in phosphorylation.

Mutagenesis

447

1

C → A: Loss of hormone binding capacity and temperature-sensitive loss in DNA-binding. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

595

Helix Strand Turn

Details...

Turn

186 – 188

3

Beta strand

194 – 196

3

Beta strand

199 – 201

3

Helix

203 – 213

11

Beta strand

222 – 225

4

Turn

231 – 236

6

Helix

238 – 248

11

Helix

306 – 308

3

Helix

312 – 322

11

Helix

339 – 363

25

Helix

367 – 369

3

Helix

372 – 395

24

Beta strand

401 – 405

5

Beta strand

408 – 411

4

Helix

412 – 417

6

Helix

421 – 438

18

Helix

442 – 455

14

Helix

466 – 492

27

Helix

497 – 530

34

Helix

538 – 545

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified June 1, 1994. Version 2. Checksum: 5455C57AB0CCCAA7	FASTA	595	66,216
	10 20 30 40 50 60 MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKIPLERPLG EVYLDSSKPA VYNYPEGAAY 70 80 90 100 110 120 EFNAAAAANA QVYGQTGLPY GPGSEAAAFG SNGLGGFPPL NSVSPSPLML LHPPPQLSPF 130 140 150 160 170 180 LQPHGQQVPY YLENEPSGYT VREAGPPAFY RPNSDNRRQG GRERLASTND KGSMAMESAK 190 200 210 220 230 240 ETRYCAVCND YASGYHYGVW SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC 250 260 270 280 290 300 RLRKCYEVGM MKGGIRKDRR GGRMLKHKRQ RDDGEGRGEV GSAGDMRAAN LWPSPLMIKR 310 320 330 340 350 360 SKKNSLALSL TADQMVSALL DAEPPILYSE YDPTRPFSEA SMMGLLTNLA DRELVHMINW 370 380 390 400 410 420 AKRVPGFVDL TLHDQVHLLE CAWLEILMIG LVWRSMEHPG KLLFAPNLLL DRNQGKCVEG 430 440 450 460 470 480 MVEIFDMLLA TSSRFRMMNL QGEEFVCLKS IILLNSGVYT FLSSTLKSLE EKDHIHRVLD 490 500 510 520 530 540 KITDTLIHLM AKAGLTLQQQ HQRLAQLLLI LSHIRHMSNK GMEHLYSMKC KNVVPLYDLL 550 560 570 580 590 LEMLDAHRLH APTSRGGASV EETDQSHLAT AGSTSSHSLQ KYYITGEAEG FPATV
	Isoform Short. Checksum: 449BC03EF22E80A5	FASTA	483	53,687
	10 20 30 40 50 60 MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKIPLERPLG EVYLDSSKPA VYNYPEGAAY 70 80 90 100 110 120 EFNAAAAANA QVYGQTGLPY GPGSEAAAFG SNGLGGFPPL NSVSPSPLML LHPPPQLSPF 130 140 150 160 170 180 LQPHGQQVPY YLENEPSGYT VREAGPPAFY RPNSDNRRQG GRERLASTND KGSMAMESAK 190 200 210 220 230 240 ETRYCAVCND YASGYHYGVW SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC 250 260 270 280 290 300 RLRKCYEVGM MKGGFVDLTL HDQVHLLECA WLEILMIGLV WRSMEHPGKL LFAPNLLLDR 310 320 330 340 350 360 NQGKCVEGMV EIFDMLLATS SRFRMMNLQG EEFVCLKSII LLNSGVYTFL SSTLKSLEEK 370 380 390 400 410 420 DHIHRVLDKI TDTLIHLMAK AGLTLQQQHQ RLAQLLLILS HIRHMSNKGM EHLYSMKCKN 430 440 450 460 470 480 VVPLYDLLLE MLDAHRLHAP TSRGGASVEE TDQSHLATAG STSSHSLQKY YITGEAEGFP ATV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A." Green S., Walter P., Kumar V., Krust A., Bornert J.-M., Argos P., Chambon P. Nature 320:134-139(1986) [PubMed: 3754034] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[2]	"Sequence and expression of human estrogen receptor complementary DNA." Greene G.L., Gilna P., Waterfield M., Baker A., Hort Y., Shine J. Science 231:1150-1154(1986) [PubMed: 3753802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[3]	"A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7." Pink J.J., Wu S.Q., Wolf D.M., Bilimoria M.M., Jordan V.C. Nucleic Acids Res. 24:962-969(1996) [PubMed: 8600466] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANT ASP-411 INS. Tissue: Mammary gland.
[4]	NIEHS SNPs program Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-77.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor." Joel P.B., Traish A.M., Lannigan D.A. Mol. Endocrinol. 9:1041-1052(1995) [PubMed: 7476978] [Abstract] Cited for: PROTEIN SEQUENCE OF 110-117, PHOSPHORYLATION, MUTAGENESIS.
[7]	"Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility." Schubert E.L., Lee M.K., Newman B., King M.C. J. Steroid Biochem. Mol. Biol. 71:21-27(1999) [PubMed: 10619354] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 152-595 (ISOFORM LONG).
[8]	"Estrogen receptor variant messenger RNA lacking exon 4 in estrogen-responsive human breast cancer cell lines." Pfeffer U., Fecarotta E., Castagnetta L., Vidali G. Cancer Res. 53:741-743(1993) [PubMed: 7916651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 216-434, ALTERNATIVE SPLICING. Tissue: Mammary carcinoma.
[9]	"Mechanisms of acquired tamoxifen resistance in a xenotransplanted human breast carcinoma." Naundorf H., Becker M., Fiebig C., Buettner B., Fichtner I. Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 354-548. Tissue: Mammary carcinoma.
[10]	"Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro." Arnold S.F., Obourn J.D., Jaffe H., Notides A.C. Mol. Endocrinol. 9:24-33(1995) [PubMed: 7539106] [Abstract] Cited for: PROTEIN SEQUENCE OF 532-542, PHOSPHORYLATION.
[11]	"Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation." Reese J.C., Katzenellenbogen B.S. J. Biol. Chem. 267:9868-9873(1992) [PubMed: 1577818] [Abstract] Cited for: MUTAGENESIS OF CYS-447.
[12]	"Serine 167 is the major estradiol-induced phosphorylation site on the human estrogen receptor." Arnold S.F., Obourn J.D., Jaffe H., Notides A.C. Mol. Endocrinol. 8:1208-1214(1994) [PubMed: 7838153] [Abstract] Cited for: PHOSPHORYLATION.
[13]	"A subpopulation of estrogen receptors are modified by O-linked N-acetylglucosamine." Jiang M.S., Hart G.W. J. Biol. Chem. 272:2421-2428(1997) [PubMed: 8999954] [Abstract] Cited for: GLYCOSYLATION.
[14]	"Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action." Rubino D., Driggers P., Arbit D., Kemp L., Miller B., Coso O., Pagliai K., Gray K., Gutkind S., Segars J. Oncogene 16:2513-2526(1998) [PubMed: 9627117] [Abstract] Cited for: INTERACTION WITH AKAP13.
[15]	"Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex." Rogatsky I., Trowbridge J.M., Garabedian M.J. J. Biol. Chem. 274:22296-22302(1999) [PubMed: 10428798] [Abstract] Cited for: PHOSPHORYLATION AT SER-104 AND SER-106, MUTAGENESIS.
[16]	"A nuclear factor ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo." Lee S.-K., Anzick S.L., Choi J.-E., Bubendorf L., Guan X.-Y., Jung Y.-K., Kallioniemi O.-P., Kononen J., Trent J.M., Azorsa D., Jhun B.-H., Cheong J.H., Lee Y.C., Meltzer P.S., Lee J.W. J. Biol. Chem. 274:34283-34293(1999) [PubMed: 10567404] [Abstract] Cited for: INTERACTION WITH NCOA6.
[17]	"An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens." Montano M.M., Ekena K., Delage-Mourroux R., Chang W., Martini P., Katzenellenbogen B.S. Proc. Natl. Acad. Sci. U.S.A. 96:6947-6952(1999) [PubMed: 10359819] [Abstract] Cited for: INTERACTION WITH PHB2.
[18]	"Functional cloning and characterization of a novel nonhomeodomain protein that inhibits the binding of PBX1-HOX complexes to DNA." Abramovich C., Shen W.-F., Pineault N., Imren S., Montpetit B., Largman C., Humphries R.K. J. Biol. Chem. 275:26172-26177(2000) [PubMed: 10825160] [Abstract] Cited for: INTERACTION WITH PBXIP1.
[19]	"Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription." Chan S.W., Hong W. J. Biol. Chem. 276:28402-28412(2001) [PubMed: 11358960] [Abstract] Cited for: INTERACTION WITH KDM5A.
[20]	"CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant." Sauve F., McBroom L.D.B., Gallant J., Moraitis A.N., Labrie F., Giguere V. Mol. Cell. Biol. 21:343-353(2001) [PubMed: 11113208] [Abstract] Cited for: INTERACTION WITH NCOA5.
[21]	"ERAP140, a conserved tissue-specific nuclear receptor coactivator." Shao W., Halachmi S., Brown M. Mol. Cell. Biol. 22:3358-3372(2002) [PubMed: 11971969] [Abstract] Cited for: INTERACTION WITH NCOA7.
[22]	"Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade." Wong C.-W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J. Proc. Natl. Acad. Sci. U.S.A. 99:14783-14788(2002) [PubMed: 12415108] [Abstract] Cited for: INTERACTION WITH PELP1.
[23]	"BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation." Hsiao P.W., Fryer C.J., Trotter K.W., Wang W., Archer T.K. Mol. Cell. Biol. 23:6210-6220(2003) [PubMed: 12917342] [Abstract] Cited for: INTERACTION WITH SMARD1.
[24]	"ERBP, a novel estrogen receptor binding protein enhancing the activity of estrogen receptor." Bu H., Kashireddy P., Chang J., Zhu Y.T., Zhang Z., Zheng W., Rao S.M., Zhu Y.-J. Biochem. Biophys. Res. Commun. 317:54-59(2004) [PubMed: 15047147] [Abstract] Cited for: INTERACTION WITH DNTTIP2.
[25]	"An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling." Damdimopoulos A.E., Miranda-Vizuete A., Treuter E., Gustafsson J.-A., Spyrou G. J. Biol. Chem. 279:38721-38729(2004) [PubMed: 15199063] [Abstract] Cited for: INTERACTION WITH TXNRD1.
[26]	"The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1." Wittmann B.M., Fujinaga K., Deng H., Ogba N., Montano M.M. Oncogene 24:5576-5588(2005) [PubMed: 15940264] [Abstract] Cited for: INTERACTION WITH HEXIM1.
[27]	"Identification of the MLL2 complex as a coactivator for estrogen receptor alpha." Mo R., Rao S.M., Zhu Y.-J. J. Biol. Chem. 281:15714-15720(2006) [PubMed: 16603732] [Abstract] Cited for: INTERACTION WITH MLL2.
[28]	"MUC1 oncoprotein stabilizes and activates estrogen receptor alpha." Wei X., Xu H., Kufe D. Mol. Cell 21:295-305(2006) [PubMed: 16427018] [Abstract] Cited for: INTERACTION WITH MUC1.
[29]	"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: 17658481] [Abstract] Cited for: INTERACTION WITH MAP1S.
[30]	"CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome." Zhang P.-J., Zhao J., Li H.-Y., Man J.-H., He K., Zhou T., Pan X., Li A.-L., Gong W.-L., Jin B.-F., Xia Q., Yu M., Shen B.-F., Zhang X.-M. EMBO J. 26:1831-1842(2007) [PubMed: 17347654] [Abstract] Cited for: INTERACTION WITH CUEDC2.
[31]	"Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity." Han W.-D., Zhao Y.-L., Meng Y.G., Zang L., Wu Z.-Q., Li Q., Si Y.-L., Huang K., Ba J.-M., Morinaga H., Nomura M., Mu Y.-M. Endocr. Relat. Cancer 14:741-753(2007) [PubMed: 17914104] [Abstract] Cited for: INTERACTION WITH MACROD1.
[32]	"MS-KIF18A, a kinesin, is associated with estrogen receptor." Luboshits G., Benayahu D. J. Cell. Biochem. 100:693-702(2007) [PubMed: 17006958] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH KIF18A.
[33]	"Ubiquitin-interaction motifs of RAP80 are critical in its regulation of estrogen receptor alpha." Yan J., Kim Y.S., Yang X.-P., Albers M., Koegl M., Jetten A.M. Nucleic Acids Res. 35:1673-1686(2007) [PubMed: 17311814] [Abstract] Cited for: INTERACTION WITH UIMC1.
[34]	"ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification." Zou J.X., Revenko A.S., Li L.B., Gemo A.T., Chen H.-W. Proc. Natl. Acad. Sci. U.S.A. 104:18067-18072(2007) [PubMed: 17998543] [Abstract] Cited for: INTERACTION WITH ATAD2.
[35]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-7 AND SER-10, MASS SPECTROMETRY.
[36]	"Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer." Johnsen S.A., Guengoer C., Prenzel T., Riethdorf S., Riethdorf L., Taniguchi-Ishigaki N., Rau T., Tursun B., Furlow J.D., Sauter G., Scheffner M., Pantel K., Gannon F., Bach I. Cancer Res. 69:128-136(2009) [PubMed: 19117995] [Abstract] Cited for: INTERACTION WITH LDB1 AND RLIM.
[37]	"The regulation of MS-KIF18A expression and cross talk with estrogen receptor." Zusev M., Benayahu D. PLoS ONE 4:E6407-E6407(2009) [PubMed: 19636373] [Abstract] Cited for: INTERACTION WITH KIF18A.
[38]	"Solution structure of the DNA-binding domain of the oestrogen receptor." Schwabe J.W.E., Neuhaus D., Rhodes D. Nature 348:458-461(1990) [PubMed: 2247153] [Abstract] Cited for: STRUCTURE BY NMR OF 180-262.
[39]	"The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements." Schwabe J.W.E., Chapman L., Finch J.T., Rhodes D. Cell 75:567-578(1993) [PubMed: 8221895] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 180-262.
[40]	"Molecular basis of agonism and antagonism in the oestrogen receptor." Brzozowski A.M., Pike A.C.W., Dauter Z., Hubbard R.E., Bonn T., Engstroem O., Oehman L., Greene G.L., Gustafsson J.-A., Carlquist M. Nature 389:753-758(1997) [PubMed: 9338790] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 305-548.
[41]	"Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains." Tanenbaum D.M., Wang Y., Williams S.P., Sigler P.B. Proc. Natl. Acad. Sci. U.S.A. 95:5998-6003(1998) [PubMed: 9600906] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 306-544.
[42]	"The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen." Shiau A.K., Barstad D., Loria P.M., Cheng L., Kushner P.J., Agard D.A., Greene G.L. Cell 95:927-937(1998) [PubMed: 9875847] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 294-554.
[43]	"Homology model for the ligand-binding domain of the human estrogen receptor." Maalouf G.J., Xu W., Smith T., Mohr S.C. J. Biomol. Struct. Dyn. 15:841-850(1998) [PubMed: 9619507] [Abstract] Cited for: 3D-STRUCTURE MODELING OF 311-547.
[44]	"The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties." Tora L., Mullick A., Metzger D., Ponglikitmongkol M., Park I., Chambon P. EMBO J. 8:1981-1986(1989) [PubMed: 2792078] [Abstract] Cited for: VARIANT VAL-400.
[45]	"A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action." McInerney E.M., Ince B.A., Shapiro D.J., Katzenellenbogen B.S. Mol. Endocrinol. 10:1519-1526(1996) [PubMed: 8961262] [Abstract] Cited for: VARIANT GLU-364.
[46]	"Screening for ESR mutations in breast and ovarian cancer patients." Anderson T.I., Wooster R., Laake K., Collins N., Warren W., Skrede M., Eeles R., Tveit K.M., Johnston S.R.D., Dowsett M., Olsen A.O., Moeller P., Stratton M.R., Boerresen-Dale A.-L. Hum. Mutat. 9:531-536(1997) [PubMed: 9195227] [Abstract] Cited for: VARIANT CYS-160.
[47]	"Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women." Becherini L., Gennari L., Masi L., Mansani R., Massart F., Morelli A., Falchetti A., Gonnelli S., Fiorelli G., Tanini A., Brandi M.L. Hum. Mol. Genet. 9:2043-2050(2000) [PubMed: 10942433] [Abstract] Cited for: INVOLVEMENT IN BMD.
[48]	"Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas." Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., Boerresen-Dale A.-L. Breast Cancer Res. 9:R5-R5(2007) [PubMed: 17224074] [Abstract] Cited for: VARIANTS TYR-6 AND ILE-264.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Estrogen receptor entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X03635 mRNA. Translation: CAA27284.1.
M12674 mRNA. Translation: AAA52399.1.
U47678 mRNA. Translation: AAB00115.1.
AY425004 Genomic DNA. Translation: AAQ91815.1.
AL078582, AL356311, AL590993 Genomic DNA. Translation: CAI42285.1.
AF123500 , AF123494, AF123495, AF123496, AF123497, AF123498, AF123499 Genomic DNA. Translation: AAD52984.1.
X73067 mRNA. Translation: CAA51528.1.
Z75126 mRNA. Translation: CAA99436.1.

IPI

IPI00218352.
IPI00294982.

PIR

S64737.

RefSeq

NP_000116.2.
NP_001116212.1.
NP_001116213.1.
NP_001116214.1.

UniGene

Hs.208124

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A52	X-ray	2.80	A/B	297-554	[»]
1AKF	model	-	A	309-547	[»]
1ERE	X-ray	3.10	A/B/C/D/E/F	301-553	[»]
1ERR	X-ray	2.60	A/B	301-553	[»]
1G50	X-ray	2.90	A/B/C	304-550	[»]
1GWQ	X-ray	2.45	A/B	301-548	[»]
1GWR	X-ray	2.40	A/B	305-549	[»]
1HCP	NMR	-	A	180-254	[»]
1HCQ	X-ray	2.40	A/B/E/F	180-262	[»]
1L2I	X-ray	1.95	A/B	297-554	[»]
1PCG	X-ray	2.70	A/B	304-547	[»]
1QKT	X-ray	2.20	A	304-551	[»]
1QKU	X-ray	3.20	A/B/C	301-550	[»]
1R5K	X-ray	2.70	A/B/C	297-554	[»]
1SJ0	X-ray	1.90	A	307-554	[»]
1UOM	X-ray	2.28	A	301-553	[»]
1X7E	X-ray	2.80	A/B	305-549	[»]
1X7R	X-ray	2.00	A	305-549	[»]
1XP1	X-ray	1.80	A	307-554	[»]
1XP6	X-ray	1.70	A	307-554	[»]
1XP9	X-ray	1.80	A	307-554	[»]
1XPC	X-ray	1.60	A	307-554	[»]
1XQC	X-ray	2.05	A/B/C/D	301-553	[»]
1YIM	X-ray	1.90	A	307-554	[»]
1YIN	X-ray	2.20	A	307-554	[»]
1ZKY	X-ray	2.25	A/B	298-554	[»]
2AYR	X-ray	1.90	A	304-551	[»]
2B1V	X-ray	1.80	A/B	298-554	[»]
2B1Z	X-ray	1.78	A/B	298-554	[»]
2B23	X-ray	2.10	A/B	298-554	[»]
2BJ4	X-ray	2.00	A/B	305-533	[»]
2FAI	X-ray	2.10	A/B	298-554	[»]
2G44	X-ray	2.65	A/B	298-554	[»]
2G5O	X-ray	2.30	A/B	298-554	[»]
2I0J	X-ray	2.90	A/B/C/D	304-547	[»]
2IOG	X-ray	1.60	A	309-554	[»]
2IOK	X-ray	2.40	A/B	301-554	[»]
2JF9	X-ray	2.10	A/B/C	304-533	[»]
2JFA	X-ray	2.55	A/B	304-533	[»]
2OCF	X-ray	2.95	A	298-595	[»]
2OUZ	X-ray	2.00	A	301-553	[»]
2P15	X-ray	1.94	A/B	298-554	[»]
2POG	X-ray	1.84	A/B	304-551	[»]
2Q6J	X-ray	2.70	A/B	298-554	[»]
2Q70	X-ray	1.95	A/B	304-551	[»]
2QA6	X-ray	2.60	A/B	298-554	[»]
2QA8	X-ray	1.85	A/B	298-554	[»]
2QAB	X-ray	1.89	A/B	298-554	[»]
2QE4	X-ray	2.40	A/B	304-551	[»]
2QGT	X-ray	2.15	A/B	298-554	[»]
2QGW	X-ray	2.39	A/B	298-554	[»]
2QH6	X-ray	2.70	A/B	298-554	[»]
2QR9	X-ray	2.00	A/B	298-554	[»]
2QSE	X-ray	1.85	A/B	298-554	[»]
2QXM	X-ray	2.30	A/B	298-554	[»]
2QXS	X-ray	1.70	A/B	298-554	[»]
2QZO	X-ray	1.72	A/B	298-554	[»]
2R6W	X-ray	2.00	A/B	304-551	[»]
2R6Y	X-ray	2.00	A/B	304-551	[»]
3CBM	X-ray	1.69	B	298-307	[»]
3CBO	X-ray	1.65	B	298-307	[»]
3CBP	X-ray	1.42	B	298-307	[»]
3DT3	X-ray	2.40	A/B	299-551	[»]
3ERD	X-ray	2.03	A/B	297-554	[»]
3ERT	X-ray	1.90	A	297-554	[»]

DisProt

DP00074.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5965N.

IntAct

P03372. 21 interactions.

STRING

P03372.

PTM databases

GlycoSuiteDB

P03372.

PhosphoSite

P03372.

Proteomic databases

PRIDE

P03372.

Genome annotation databases

Ensembl

ENST00000206249; ENSP00000206249; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000338799; ENSP00000342630; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000347491; ENSP00000306312; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000404742; ENSP00000385373; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000406599; ENSP00000384064; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000412296; ENSP00000411930; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000415488; ENSP00000401995; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000427531; ENSP00000394721; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000431219; ENSP00000396350; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000431590; ENSP00000410047; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000440973; ENSP00000405330; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000443427; ENSP00000387500; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000446550; ENSP00000411105; ENSG00000091831; Homo sapiens. [Genome view]
ENST00000456483; ENSP00000415934; ENSG00000091831; Homo sapiens. [Genome view]

GeneID

2099.

KEGG

hsa:2099.

UCSC

uc003qom.2. human.

Organism-specific databases

CTD

2099.

GeneCards

GC06P152023.

HGNC

HGNC:3467. ESR1.

HPA

CAB000037.
HPA000449.
HPA000450.

MIM

133430. gene.

Orphanet

785. Estrogen resistance syndrome.

PharmGKB

PA156.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P03372.

HOVERGEN

P03372.

OMA

ENEPSGY.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3apathway. FOXA1 transcription factor network.
foxm1pathway. FOXM1 transcription factor network.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
telomerasepathway. Regulation of Telomerase.
hdac_classii_pathway. Signaling events mediated by HDAC Class II.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Gene expression databases

ArrayExpress

P03372.

Bgee

P03372.

CleanEx

HS_ESR1.

Genevestigator

P03372.

GermOnline

ENSG00000091831. Homo sapiens.

Family and domain databases

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001292. Oestr_rcpt_AF1.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Gene3D

G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit.
G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.

Pfam

PF00104. Hormone_recep. 1 hit.
PF02159. Oest_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00543. OESTROGENR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

ProDom

PD000035. Znf_C4steroid. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00269. Chlorotrianisene.
DB00882. Clomifene.
DB00286. Conjugated Estrogens.
DB01406. Danazol.
DB00304. Desogestrel.
DB00890. Dienestrol.
DB00255. Diethylstilbestrol.
DB00858. Dromostanolone.
DB01395. Drospirenone.
DB00783. Estradiol.
DB01196. Estramustine.
DB04573. Estriol.
DB00655. Estrone.
DB00977. Ethinyl Estradiol.
DB00823. Ethynodiol Diacetate.
DB00294. Etonogestrel.
DB01185. Fluoxymesterone.
DB00947. Fulvestrant.
DB01006. Letrozole.
DB00367. Levonorgestrel.
DB00603. Medroxyprogesterone.
DB00351. Megestrol.
DB01065. Melatonin.
DB01357. Mestranol.
DB01183. Naloxone.
DB00957. Norgestimate.
DB00506. Norgestrel.
DB00396. Progesterone.
DB04575. Quinestrol.
DB00481. Raloxifene.
DB00675. Tamoxifen.
DB00539. Toremifene.

NextBio

8491.

SOURCE

Search...

Entry information

Entry name

ESR1_HUMAN

Accession

Primary (citable) accession number: P03372
Secondary accession number(s): Q13511 , Q14276, Q9NU51, Q9UDZ7, Q9UIS7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	June 1, 1994
Last modified:	November 3, 2009
This is version 154 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.