nuclear receptor coactivator 2; NCoA-2; transcriptional intermediary factor 2; hTIF2; class E basic helix-loop-helix protein 75; bHLHe75 (NCOA2, BHLHE75, TIF2)
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Function
- transcriptional coactivator for steroid receptors & 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 & brown adipose tissues
- phosphorylated upon DNA damage, probably by ATM or ATR
- present in a complex containing CARM1 & EP300/P300, & interacts with CARM1 & NR3C2 (putative)
- present in a complex containing NCOA3, IKKA, IKKB, IKBKG & CREBBP
- interacts (via C-terminus) with CREBBP
- interacts with HIF1A, NCOA1, APEX & NR3C1
- interacts with CASP8AP2 & TTLL5/STAMP
- interacts with ESR1, RARA & RXRA
- interacts with PSMB9
Structure
- contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs
- the LXXLL motifs are essential for the association with nuclear receptors & are, at least in part, functionally redundant
- the LLXXLXXXL motif is involved in transcriptional coactivation & CREBBP/CBP binding
- contains 2 C-terminal transcription activation domains (AD1 & AD2) that can function independently
- belongs to the SRC/p160 nuclear receptor coactivator family
- contains 1 basic helix-loop-helix (bHLH) domain
- contains 1 PAS (PER-ARNT-SIM) domain
Compartment
Pathology
- chromosomal inversion inv(8)(p11;q13) involving NCOA2 may be a cause of acute myeloid leukemias
- the inversion generates the MYST3-NCOA2 oncogene, which consists of the N-terminus part of MYST3/MOZ & the C-terminus part of NCOA2/TIF2
- MYST3-NCOA2 binds to CREBBP & disrupts its function in transcription activation