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:
  • modulating N-terminal domain
  • DNA-binding domain
  • 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

More general terms

• estrogen receptor
• phosphoprotein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2100
• OMIM: https://mirror.omim.org/entry/601663
• UniProt: http://www.uniprot.org/uniprot/Q92731.html