NCOA2

NCOA2 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.

Full Name

Nuclear Receptor Coactivator 2

Function

Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:8670870, PubMed:23508108, PubMed:9430642).

Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:8670870, PubMed:23508108, PubMed:9430642).

Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:8670870, PubMed:23508108, PubMed:9430642).

Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC1 expression (PubMed:8670870, PubMed:23508108, 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-ARNTL/BMAL1 heterodimer (By similarity).

Biological Process

Cellular response to hormone stimulus Source: GO_Central
Cellular response to Thyroglobulin triiodothyronine Source: Ensembl
Circadian regulation of gene expression Source: UniProtKB
Locomotor rhythm Source: Ensembl
mRNA transcription by RNA polymerase II Source: ComplexPortal
Negative regulation of transcription by RNA polymerase II Source: Ensembl
Peroxisome proliferator activated receptor signaling pathway Source: ComplexPortal
Positive regulation of adipose tissue development Source: ComplexPortal
Positive regulation of transcription by RNA polymerase II Source: ComplexPortal
Regulation of cellular response to insulin stimulus Source: ComplexPortal
Regulation of glucose metabolic process Source: Ensembl
Regulation of transcription, DNA-templated Source: UniProtKB
Response to progesterone Source: Ensembl

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.

PTM

Acetylated. Deacetylation at Lys-780 by SIRT6 stimulates its ability to coactivate PPARA.