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Details on Person UniProt:Q15596 NCOA2

Class:Id	ReferenceGeneProduct:59977
_chainChangeLog	initiator methionine:1 added on Fri February 6 2015;chain:2-1464 added on Fri February 6 2015;initiator methionine:1 for 59977 removed on Fri Nov 03 2023;initiator methionine: for 59977 added on Fri Nov 03 2023;initiator methionine: for 59977 removed on Fri Aug 15 2025;initiator methionine:1 for 59977 added on Fri Aug 15 2025
_displayName	UniProt:Q15596 NCOA2
_timestamp	2025-08-15 21:47:02
chain	initiator methionine:1 chain:2-1464
checksum	0A61AA5D1878304B
comment	FUNCTION Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642, PubMed:22504882, PubMed:26553876). 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).SUBUNIT Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP (PubMed:11971985, PubMed:9430642). Present in a complex containing CARM1 and EP300/P300. Interacts (via C-terminus) with CREBBP (PubMed:11971985, PubMed:9430642). Interacts (via LXXLL 1, 2 and 3 motifs) with RORA (via AF-2 motif) (PubMed:10478845). Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif). Interacts with APEX1 (PubMed:10594042). Interacts with BMAL1 (By similarity). Interacts with CARM1. Interacts with CASP8AP2. Interacts with CLOCK. Interacts with DDX5 (PubMed:11250900). Interacts with ESR1 (PubMed:9430642). Interacts with HIF1A (PubMed:10594042). Interacts with NCOA1 (PubMed:10594042). Interacts with NR4A1/Nur77 (PubMed:18690216). Interacts with NR4A3; potentiates the activity of the NR4A3 (By similarity). Interacts with NR1H3 (PubMed:19481530). Interacts with NR3C1 (PubMed:23508108, PubMed:9590696). Interacts with NR3C2. Interacts with PSMB9 (PubMed:16957778). Interacts with RARA (PubMed:21152046, PubMed:9430642). Interacts with RXRA (PubMed:21152046, PubMed:9430642). Interacts with RWDD3 (PubMed:23508108). Interacts with TTLL5/STAMP (PubMed:17116691). Interacts with NR5A2 (PubMed:22504882, PubMed:26553876, PubMed:27694446, PubMed:31419141, PubMed:33335203, PubMed:32631515, PubMed:35503419).INTERACTION 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.DOMAIN Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.PTM Acetylated. Deacetylation at Lys-780 by SIRT6 stimulates its ability to coactivate PPARA.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.SIMILARITY Belongs to the SRC/p160 nuclear receptor coactivator family.
description	recommendedName: Nuclear receptor coactivator 2 shortName: NCoA-2 alternativeName: Class E basic helix-loop-helix protein 75 shortName: bHLHe75 alternativeName: fullName evidence="29"Transcriptional intermediary factor 2 shortName evidence="29"hTIF2
geneName	NCOA2 BHLHE75 SRC2 TIF2
identifier	Q15596
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Activator Biological rhythms Isopeptide bond Methylation Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Transcription Transcription regulation Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	NCOA2
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:9004258] ENSEMBL:ENSG00000140396 NCOA2 [Homo sapiens]
secondaryIdentifier	NCOA2_HUMAN Q14CD2
sequenceLength	1464
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:376398] NCOA2 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:4085305] monoSUMO1-K239,K731,K788-NCOA2 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:5603186] NCOA2 (869-1464) [nucleoplasm] [Homo sapiens]
(referenceSequence)	[GroupModifiedResidue:4085283] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 788 [GroupModifiedResidue:4085302] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 239 [GroupModifiedResidue:4085314] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 731
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No pathways have been reviewed or authored by UniProt:Q15596 NCOA2 (59977)