NCOA2
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.
The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding.
Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.
Function
Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity).
Involvement in disease
Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
Post-translational modifications
Acetylated. Deacetylation at Lys-780 by SIRT6 stimulates its ability to coactivate PPARA.
Sequence Similarities
Belongs to the SRC/p160 nuclear receptor coactivator family.
Cellular localization
- Nucleus
Alternative names
BHLHE75, SRC2, TIF2, NCOA2, Nuclear receptor coactivator 2, NCoA-2, Class E basic helix-loop-helix protein 75, Transcriptional intermediary factor 2, bHLHe75, hTIF2