UniProt functional annotation for Q15596



	UniProt functional annotation for Q15596

UniProt code: Q15596.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC1 expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-ARNTL/BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:9430642}.

Subunit: Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with ESR1, HIF1A, NCOA1, APEX1, NR3C1, NR3C2, CARM1, RARA, and RXRA. Present in a complex containing CARM1 and EP300/P300. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with PSMB9 and DDX5. Interacts (via LXXLL 1, 2 and 3 motifs) with RORA and RORC (via AF-2 motif). Interacts with RWDD3. Interacts with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with NR4A3; potentiates the activity of the NR4A3 (By similarity). Interacts with NR1H3 (PubMed:19481530). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:10478845, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11250900, ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:16957778, ECO:0000269|PubMed:17116691, ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:9430642, ECO:0000269|PubMed:9590696}.

Subcellular location: Nucleus.

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. {ECO:0000269|PubMed:9430642}.

Domain: The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding. {ECO:0000269|PubMed:9430642}.

Domain: Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently. {ECO:0000269|PubMed:9430642}.

Disease: Note=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. {ECO:0000269|PubMed:12676584, ECO:0000269|PubMed:15657427, ECO:0000269|PubMed:9558366}.

Similarity: Belongs to the SRC/p160 nuclear receptor coactivator family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC1 expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-ARNTL/BMAL1 heterodimer (By similarity). {ECO:0000250\|UniProtKB:Q61026, ECO:0000269\|PubMed:23508108, ECO:0000269\|PubMed:9430642}.


Subunit:		Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with ESR1, HIF1A, NCOA1, APEX1, NR3C1, NR3C2, CARM1, RARA, and RXRA. Present in a complex containing CARM1 and EP300/P300. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with PSMB9 and DDX5. Interacts (via LXXLL 1, 2 and 3 motifs) with RORA and RORC (via AF-2 motif). Interacts with RWDD3. Interacts with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with NR4A3; potentiates the activity of the NR4A3 (By similarity). Interacts with NR1H3 (PubMed:19481530). {ECO:0000250\|UniProtKB:Q61026, ECO:0000269\|PubMed:10478845, ECO:0000269\|PubMed:10594042, ECO:0000269\|PubMed:11250900, ECO:0000269\|PubMed:11971985, ECO:0000269\|PubMed:16957778, ECO:0000269\|PubMed:17116691, ECO:0000269\|PubMed:19481530, ECO:0000269\|PubMed:23508108, ECO:0000269\|PubMed:9430642, ECO:0000269\|PubMed:9590696}.
Subcellular location:		Nucleus.
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. {ECO:0000269\|PubMed:9430642}.
Domain:		The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding. {ECO:0000269\|PubMed:9430642}.
Domain:		Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently. {ECO:0000269\|PubMed:9430642}.
Disease:		Note=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. {ECO:0000269\|PubMed:12676584, ECO:0000269\|PubMed:15657427, ECO:0000269\|PubMed:9558366}.
Similarity:		Belongs to the SRC/p160 nuclear receptor coactivator family. {ECO:0000305}.