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nuclear receptor coactivator 2; NCoA-2; transcriptional intermediary factor 2; hTIF2; class E basic helix-loop-helix protein 75; bHLHe75 (NCOA2, BHLHE75, TIF2)
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: nucleus
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
Related
nuclear hormone receptor family
General
DNA-binding protein
nuclear (steroid) receptor coactivator (NRC, SRC, NCoA)
phosphoprotein
Properties
SIZE: entity length = 1464 aa
MW = 159 kD
COMPARTMENT: cell nucleus
MOTIF: helix-loop-helix
NAME: helix-loop-helix
SITE: 17-20
FOR-BINDING-VIA: helix-loop-helix
DNA-binding motif
SITE: 21-84
MOTIF: Ser phosphorylation site {S29}
PAS domain {119-183}
Ser phosphorylation site {S493}
Ser phosphorylation site {S565}
LXXLL motif 1 {641-645}
LXXLL motif 2 {690-694}
binding site
SITE: 691-743
FOR-BINDING-OF: CASP8-associated protein 2
MOTIF: Ser phosphorylation site {S699}
Ser phosphorylation site {S716}
Ser phosphorylation site {S736}
LXXLL motif 3 {745-749}
breakpoint {869-870}
LXXLL motif 4 {878-882}
LLXXLXXXL {1079-1087}
glutamine-rich region {1254-1260}
MOTIF: glutamine residue (SEVERAL)
Database Correlations
OMIM 601993
UniProt Q15596
PFAM correlations
Entrez Gene 10499
Kegg hsa:10499
References
- UniProt :accession Q15596
- OMIM :accession 601993