Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence-specific transcription factors. Plays a role in estrogen receptor (ER) genomic activity when present in the nuclear compartment by activating the ER target genes in a hormonal stimulation dependent manner. Can facilitate ER non-genomic signaling via SRC and PI3K interaction in the cytosol. Plays a role in E2-mediated cell cycle progression by interacting with RB1. May have important functional implications in ER/growth factor cross-talk. Interacts with several growth factor signaling components including EGFR and HRS. Involved in nuclear receptor signaling via its interaction with AR and NR3C1. May promote tumorigenesis via its interaction with and modulation of several oncogenes including SRC, PI3K, STAT3 and EGFR. Plays a role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes and cell migration via its interaction with SRC and PI3K.
Isoform 2 is expressed in breast cancer cell lines. Isoform 1 is widely expressed.
The Glu-rich region mediates histones interaction. The Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are required for the association with nuclear receptor ESR1.
Phosphorylated upon DNA damage, probably by ATM or ATR.
Nucleus. Cytoplasm. Also found associated with the plasma membrane. Mainly in cytoplasm in a subset of breast tumors. Localization is widely deregulated in endometrial cancers with predominantly cytoplasm localization in high-grade endometrial tumors.