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estrogen receptor-2; estrogen receptor beta; ER-beta; nuclear receptor subfamily 3 group A member 2 (ESR2, ESTRB, NR3A2)
Function:
- nuclear hormone receptor
- binds estrogens with an affinity similar to that of ESR1, & activates expression of genes containing estrogen response elements (ERE)
- binds DNA as a homodimer
- can form a heterodimer with ESR1
- interacts with NCOA3, NCOA5 & NCOA6 coactivators, leading to activation of gene transcription
- interacts with PELP1 & UBE1C
- interacts with AKAP13
- interacts with DNTTIP2
- interacts with isoform 4 of TXNRD1
- isoform beta-2/cx preferentially forms a hetereodimer with ESR1 rather than ESR2 & inhibits DNA-binding by ESR1
- isoform beta-cx lacks ligand binding ability & has no or only very low ERE binding activity
Structure:
- composed of three domains:
a) modulating N-terminal domain
b) DNA-binding domain
c) C-terminal steroid-binding domain
- belongs to the nuclear hormone receptor family, NR3 subfamily
- contains 1 nuclear receptor DNA-binding domain
Compartment: nucleus
Alternative splicing:
- named isoforms=8
- some isoform(s) may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay
Expression:
- isoform beta-1 is expressed in testis & ovary > heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland & uterus
- expressed in uterine bone, breast, & ovarian tumor cell lines, but not in colon & liver tumors
- isoform beta-2 is expressed in spleen, thymus, testis & ovary > skeletal muscle, prostate, colon, small intestine, leukocytes, bone marrow, mammary gland & uterus
- isoform beta-3 is found in testis
- isoform beta-4 is expressed in testis > spleen, thymus, ovary, mammary gland & uterus
- isoform beta-5 is expressed in testis, placenta, skeletal muscle, spleen & leukocytes > heart, lung, liver, kidney, pancreas, thymus, prostate, colon, small intestine, bone marrow, mammary gland & uterus
- not expressed in brain
Notes:
- DNA-binding by ESR1 & ESR2 is rapidly lost at 37 C in the absence of ligand; in the presence of 17 beta-estradiol & 4-hydroxy-tamoxifen, loss in DNA-binding at elevated temperature is more gradual
General
estrogen receptor
phosphoprotein
Properties
SIZE: entity length = 530 aa
MW = 59 kD
COMPARTMENT: cell nucleus
MOTIF: Modulating {1-148}
MOTIF: Ser phosphorylation site {S87}
DNA-binding motif
SITE: 149-214
MOTIF: Zn finger C4-type
SITE: 149-169
EFFECTOR-BOUND: Zn+2
Zn finger C4-type
SITE: 185-209
EFFECTOR-BOUND: Zn+2
binding site
SITE: 215-530
FOR-BINDING-OF: steroid
MOTIF: Tyr phosphorylation site {Y488}
Database Correlations
OMIM 601663
UniProt Q92731
PFAM correlations
Kegg hsa:2100
References
- UniProt :accession Q9UEV6
- Wikipedia; Note: estrogen receptor entry
http://en.wikipedia.org/wiki/estrogen_receptor