ID:NCOA2_HUMAN DESCRIPTION: RecName: Full=Nuclear receptor coactivator 2; Short=NCoA-2; AltName: Full=Class E basic helix-loop-helix protein 75; Short=bHLHe75; AltName: Full=Transcriptional intermediary factor 2; Short=hTIF2; 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. SUBUNIT: Present in a complex containing CARM1 and EP300/P300, and interacts with CARM1 and NR3C2 (By similarity). Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with HIF1A, NCOA1, APEX and NR3C1. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with ESR1, RARA and RXRA. Interacts with PSMB9 and DDX5. INTERACTION: P10275:AR; NbExp=2; IntAct=EBI-81236, EBI-608057; Q92841:DDX17; NbExp=2; IntAct=EBI-81236, EBI-746012; P03372:ESR1; NbExp=8; IntAct=EBI-81236, EBI-78473; 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. 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: Phosphorylated upon DNA damage, probably by ATM or ATR (By similarity). 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. SIMILARITY: Belongs to the SRC/p160 nuclear receptor coactivator family. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. SIMILARITY: Contains 1 PAS (PER-ARNT-SIM) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00989 - PAS fold PF07469 - Domain of unknown function (DUF1518) PF08815 - Nuclear receptor coactivator PF08832 - Steroid receptor coactivator PF13426 - PAS domain PF14598 - PAS domain PF16279 - Domain of unknown function (DUF4927) PF16665 - Unstructured region on nuclear receptor coactivator protein
ModBase Predicted Comparative 3D Structure on Q15596
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001162 RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding GO:0003682 chromatin binding GO:0003713 transcription coactivator activity GO:0005102 receptor binding GO:0005515 protein binding GO:0008134 transcription factor binding GO:0016922 ligand-dependent nuclear receptor binding GO:0017162 aryl hydrocarbon receptor binding GO:0019904 protein domain specific binding GO:0030374 ligand-dependent nuclear receptor transcription coactivator activity GO:0030375 thyroid hormone receptor coactivator activity GO:0035257 nuclear hormone receptor binding GO:0046983 protein dimerization activity
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0007623 circadian rhythm GO:0010468 regulation of gene expression GO:0010906 regulation of glucose metabolic process GO:0015721 bile acid and bile salt transport GO:0019216 regulation of lipid metabolic process GO:0030522 intracellular receptor signaling pathway GO:0032570 response to progesterone GO:0032870 cellular response to hormone stimulus GO:0032922 circadian regulation of gene expression GO:0045475 locomotor rhythm GO:0045892 negative regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048511 rhythmic process GO:1904017 cellular response to Thyroglobulin triiodothyronine
X97674 - H.sapiens mRNA for transcriptional intermediary factor 2. AK308426 - Homo sapiens cDNA, FLJ98374. BC092442 - Homo sapiens nuclear receptor coactivator 2, mRNA (cDNA clone IMAGE:30716806), complete cds. BC114383 - Homo sapiens nuclear receptor coactivator 2, mRNA (cDNA clone MGC:138808 IMAGE:40082387), complete cds. AK298528 - Homo sapiens cDNA FLJ51272 complete cds, highly similar to Nuclear receptor coactivator 2. AB384685 - Synthetic construct DNA, clone: pF1KB0150, Homo sapiens NCOA2 gene for nuclear receptor coactivator 2, complete cds, without stop codon, in Flexi system. BC047111 - Homo sapiens cDNA clone IMAGE:5314178. JD167736 - Sequence 148760 from Patent EP1572962. JD500990 - Sequence 482014 from Patent EP1572962. JD454794 - Sequence 435818 from Patent EP1572962. JD565957 - Sequence 546981 from Patent EP1572962. JD410637 - Sequence 391661 from Patent EP1572962. JD218605 - Sequence 199629 from Patent EP1572962. JD298295 - Sequence 279319 from Patent EP1572962. JD250369 - Sequence 231393 from Patent EP1572962. JD244867 - Sequence 225891 from Patent EP1572962. JD552045 - Sequence 533069 from Patent EP1572962. JD299386 - Sequence 280410 from Patent EP1572962. JD240334 - Sequence 221358 from Patent EP1572962. JD082902 - Sequence 63926 from Patent EP1572962. JD245228 - Sequence 226252 from Patent EP1572962. JD287638 - Sequence 268662 from Patent EP1572962. JD561565 - Sequence 542589 from Patent EP1572962. JD184890 - Sequence 165914 from Patent EP1572962. JD553709 - Sequence 534733 from Patent EP1572962. JD326097 - Sequence 307121 from Patent EP1572962. JD070839 - Sequence 51863 from Patent EP1572962. JD105372 - Sequence 86396 from Patent EP1572962. JD333822 - Sequence 314846 from Patent EP1572962. JD291978 - Sequence 273002 from Patent EP1572962. JD149776 - Sequence 130800 from Patent EP1572962. JD299282 - Sequence 280306 from Patent EP1572962. JD410277 - Sequence 391301 from Patent EP1572962. JD432037 - Sequence 413061 from Patent EP1572962. JD316325 - Sequence 297349 from Patent EP1572962. JD075332 - Sequence 56356 from Patent EP1572962. JD151749 - Sequence 132773 from Patent EP1572962. JD051635 - Sequence 32659 from Patent EP1572962. JD459207 - Sequence 440231 from Patent EP1572962. EF374064 - Homo sapiens MYST3/NCOA2 fusion protein (MYST3/NCOA2 fusion) mRNA, partial cds. LN607830 - Homo sapiens partial mRNA for nuclear receptor coactivator 2 (NCOA2 gene). AK021838 - Homo sapiens cDNA FLJ11776 fis, clone HEMBA1005894. DL492464 - Novel nucleic acids. JD187238 - Sequence 168262 from Patent EP1572962. DL490941 - Novel nucleic acids. JD211208 - Sequence 192232 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q15596 (Reactome details) participates in the following event(s):
R-HSA-381309 PPARG:RXRA heterodimer binds to fatty acid-like ligands R-HSA-5340251 NR1H4:DCA,CDCA,LCHA binds RXRA and NCOA1,2 R-HSA-5625745 PKN1 stimulates association of AR with NCOA2 R-HSA-5579023 NCOA2(869-1464) binds KAT6A(1-1118) R-HSA-400143 Fatty acid ligands activate PPARA R-HSA-9023840 HATs and coactivators are recruited to the CTSD gene R-HSA-381340 Transcriptional regulation of white adipocyte differentiation R-HSA-159418 Recycling of bile acids and salts R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 R-HSA-3214847 HATs acetylate histones R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) R-HSA-9018519 Estrogen-dependent gene expression R-HSA-1266738 Developmental Biology R-HSA-194068 Bile acid and bile salt metabolism R-HSA-5625740 RHO GTPases activate PKNs R-HSA-3247509 Chromatin modifying enzymes R-HSA-556833 Metabolism of lipids R-HSA-8939211 ESR-mediated signaling R-HSA-8957322 Metabolism of steroids R-HSA-195258 RHO GTPase Effectors R-HSA-4839726 Chromatin organization R-HSA-1430728 Metabolism R-HSA-9006931 Signaling by Nuclear Receptors R-HSA-194315 Signaling by Rho GTPases R-HSA-162582 Signal Transduction
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
