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The protein encoded by this gene functions as a transcriptional coactivator for nuclear hormone receptors, including steroid, thyroid, retinoid, and vitamin D receptors. The encoded protein acts as an intermediary factor for the ligand-dependent activity of these nuclear receptors, which regulate their target genes upon binding of cognate response elements. This gene has been found to be involved in translocations that result in fusions with other genes in various cancers, including the lysine acetyltransferase 6A (KAT6A) gene in acute myeloid leukemia, the ETS variant 6 (ETV6) gene in acute lymphoblastic leukemia, and the hes related family bHLH transcription factor with YRPW motif 1 (HEY1) gene in mesenchymal chondrosarcoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016],disease:Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the MYST3-NCOA2 oncogene, which consists of the N-terminus part of MYST3/MOZ and the C-terminus part of NCOA2/TIF2. MYST3-NCOA2 binds to CREBBP and disrupts its function in transcription activation.,domain:Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.,domain:Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant.,domain:The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding.,function:Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.,PTM:Phosphorylated upon DNA damage, probably by ATM or ATR.,similarity:Belongs to the SRC/p160 nuclear receptor coactivator family.,similarity:Contains 1 basic helix-loop-helix (bHLH) domain.,similarity:Contains 1 PAS (PER-ARNT-SIM) domain.,subunit:Present in a complex containing CARM1 and EP300/P300, and interacts with CARM1 and NR3C2 (By similarity). Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with HIF1A, NCOA1, APEX and NR3C1. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with ESR1, RARA and RXRA.,

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