ID NCOA2_MOUSE Reviewed; 1462 AA. AC Q61026; E9QMH9; O09001; P97759; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 24-JAN-2024, entry version 213. DE RecName: Full=Nuclear receptor coactivator 2; DE Short=NCoA-2; DE AltName: Full=Glucocorticoid receptor-interacting protein 1 {ECO:0000303|PubMed:9111344}; DE Short=GRIP-1 {ECO:0000303|PubMed:9111344}; DE AltName: Full=Steroid receptor coactivator 2; DE Short=SRC-2; DE AltName: Full=Transcriptional intermediary factor 2; GN Name=Ncoa2; Synonyms=Grip1 {ECO:0000303|PubMed:9111344}, Src2, Tif2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH NR3C2. RC STRAIN=ICR; TISSUE=Brain; RX PubMed=9111344; DOI=10.1128/mcb.17.5.2735; RA Hong H., Kohli K., Garabedian M.J., Stallcup M.R.; RT "GRIP1, a transcriptional coactivator for the AF-2 transactivation domain RT of steroid, thyroid, retinoid, and vitamin D receptors."; RL Mol. Cell. Biol. 17:2735-2744(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9192892; DOI=10.1038/42652; RA Torchia J., Rose D.W., Inostroza J., Kamei Y., Westin S., Glass C.K., RA Rosenfeld M.G.; RT "The transcriptional co-activator p/CIP binds CBP and mediates nuclear- RT receptor function."; RL Nature 387:677-684(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 322-1119. RC STRAIN=ICR; TISSUE=Embryo; RX PubMed=8643509; DOI=10.1073/pnas.93.10.4948; RA Hong H., Kohli K., Trivedi A., Johnson D.L., Stallcup M.R.; RT "GRIP1, a novel mouse protein that serves as a transcriptional coactivator RT in yeast for the hormone binding domains of steroid receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 93:4948-4952(1996). RN [5] RP INTERACTION WITH CARM1. RX PubMed=10381882; DOI=10.1126/science.284.5423.2174; RA Chen D., Ma H., Hong H., Koh S.S., Huang S.-M., Schurter B.T., Aswad D.W., RA Stallcup M.R.; RT "Regulation of transcription by a protein methyltransferase."; RL Science 284:2174-2177(1999). RN [6] RP FUNCTION. RX PubMed=12507421; DOI=10.1016/s0092-8674(02)01169-8; RA Picard F., Gehin M., Annicotte J.-S., Rocchi S., Champy M.-F., RA O'Malley B.W., Chambon P., Auwerx J.; RT "SRC-1 and TIF2 control energy balance between white and brown adipose RT tissues."; RL Cell 111:931-941(2002). RN [7] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH EP300 AND NCOA2. RX PubMed=11997499; DOI=10.1128/mcb.22.11.3621-3632.2002; RA Lee Y.-H., Koh S.S., Zhang X., Cheng X., Stallcup M.R.; RT "Synergy among nuclear receptor coactivators: selective requirement for RT protein methyltransferase and acetyltransferase activities."; RL Mol. Cell. Biol. 22:3621-3632(2002). RN [8] RP INTERACTION WITH CASP8AP2. RX PubMed=12477726; DOI=10.1074/jbc.m209234200; RA Kino T., Chrousos G.P.; RT "Tumor necrosis factor alpha receptor- and Fas-associated FLASH inhibit RT transcriptional activity of the glucocorticoid receptor by binding to and RT interfering with its interaction with p160 type nuclear receptor RT coactivators."; RL J. Biol. Chem. 278:3023-3029(2003). RN [9] RP INTERACTION WITH NR4A3. RX PubMed=12709428; DOI=10.1074/jbc.m300088200; RA Wansa K.D., Harris J.M., Yan G., Ordentlich P., Muscat G.E.; RT "The AF-1 domain of the orphan nuclear receptor NOR-1 mediates trans- RT activation, coactivator recruitment, and activation by the purine anti- RT metabolite 6-mercaptopurine."; RL J. Biol. Chem. 278:24776-24790(2003). RN [10] RP FUNCTION AS COACTIVATOR, INTERACTION WITH RORC, DOMAIN, AND MUTAGENESIS OF RP 644-L-L-645; 689-L--L-694; 744-L--L-749. RX PubMed=16148126; DOI=10.4049/jimmunol.175.6.3800; RA Xie H., Sadim M.S., Sun Z.; RT "RORgammat recruits steroid receptor coactivators to ensure thymocyte RT survival."; RL J. Immunol. 175:3800-3809(2005). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [13] RP FUNCTION IN GLUCOSE METABOLISM REGULATION, INTERACTION WITH RORA, AND RP DISRUPTION PHENOTYPE. RX PubMed=19039140; DOI=10.1126/science.1164847; RA Chopra A.R., Louet J.F., Saha P., An J., Demayo F., Xu J., York B., RA Karpen S., Finegold M., Moore D., Chan L., Newgard C.B., O'Malley B.W.; RT "Absence of the SRC-2 coactivator results in a glycogenopathy resembling RT Von Gierke's disease."; RL Science 322:1395-1399(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-493; SER-699 AND SER-771, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487; SER-565 AND SER-699, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Kidney, Lung, Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [16] RP INTERACTS WITH RORA AND RORC. RX PubMed=21499262; DOI=10.1038/nature10075; RA Solt L.A., Kumar N., Nuhant P., Wang Y., Lauer J.L., Liu J., Istrate M.A., RA Kamenecka T.M., Roush W.R., Vidovic D., Schuerer S.C., Xu J., Wagoner G., RA Drew P.D., Griffin P.R., Burris T.P.; RT "Suppression of TH17 differentiation and autoimmunity by a synthetic ROR RT ligand."; RL Nature 472:491-494(2011). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-636; LYS-640; LYS-780 AND RP LYS-785, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [18] RP FUNCTION, INDUCTION, AND INTERACTION WITH CLOCK AND BMAL1. RX PubMed=24529706; DOI=10.1016/j.celrep.2014.01.027; RA Stashi E., Lanz R.B., Mao J., Michailidis G., Zhu B., Kettner N.M., RA Putluri N., Reineke E.L., Reineke L.C., Dasgupta S., Dean A., RA Stevenson C.R., Sivasubramanian N., Sreekumar A., Demayo F., York B., RA Fu L., O'Malley B.W.; RT "SRC-2 is an essential coactivator for orchestrating metabolism and RT circadian rhythm."; RL Cell Rep. 6:633-645(2014). RN [19] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-338; ARG-864; ARG-874; ARG-1173; RP ARG-1177; ARG-1190; ARG-1203; ARG-1221 AND ARG-1240, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, and Embryo; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [20] RP FUNCTION, ACETYLATION AT LYS-780, AND DEACETYLATION BY SIRT6. RX PubMed=31851938; DOI=10.1016/j.celrep.2019.11.067; RA Naiman S., Huynh F.K., Gil R., Glick Y., Shahar Y., Touitou N., Nahum L., RA Avivi M.Y., Roichman A., Kanfi Y., Gertler A.A., Doniger T., Ilkayeva O.R., RA Abramovich I., Yaron O., Lerrer B., Gottlieb E., Harris R.A., Gerber D., RA Hirschey M.D., Cohen H.Y.; RT "SIRT6 promotes hepatic beta-oxidation via activation of PPARalpha."; RL Cell Rep. 29:4127-4143(2019). CC -!- FUNCTION: Transcriptional coactivator for steroid receptors and nuclear CC receptors (PubMed:11997499, PubMed:12507421, PubMed:16148126, CC PubMed:19039140, PubMed:31851938). Coactivator of the steroid binding CC domain (AF-2) but not of the modulating N-terminal domain (AF-1) CC (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140). CC Required with NCOA1 to control energy balance between white and brown CC adipose tissues (PubMed:11997499, PubMed:12507421, PubMed:16148126, CC PubMed:19039140). Critical regulator of glucose metabolism regulation, CC acts as a RORA coactivator to specifically modulate G6PC1 expression CC (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140). CC Involved in the positive regulation of the transcriptional activity of CC the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 CC (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140). CC Positively regulates the circadian clock by acting as a transcriptional CC coactivator for the CLOCK-BMAL1 heterodimer (PubMed:24529706). CC {ECO:0000269|PubMed:11997499, ECO:0000269|PubMed:12507421, CC ECO:0000269|PubMed:16148126, ECO:0000269|PubMed:19039140, CC ECO:0000269|PubMed:24529706, ECO:0000269|PubMed:31851938}. CC -!- SUBUNIT: Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CC CREBBP (By similarity). Present in a complex containing CARM1 and CC EP300/P300 (PubMed:11997499, PubMed:10381882). Interacts (via C- CC terminus) with CREBBP (By similarity). Interacts (via LXXLL 1, 2 and 3 CC motifs) with RORA (via AF-2 motif) (PubMed:19039140). Interacts (via CC LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif) (PubMed:16148126). CC Interacts with APEX1 (By similarity). Interacts with BMAL1 CC (PubMed:24529706). Interacts with CARM1 (PubMed:10381882). Interacts CC with CASP8AP2 (PubMed:12477726). Interacts with CLOCK CC (PubMed:24529706). Interacts with DDX5 (By similarity). Interacts with CC ESR1 (By similarity). Interacts with HIF1A (By similarity). Interacts CC with NCOA1 (By similarity). Interacts with NR4A1/Nur77 (By similarity). CC Interacts with NR4A3; potentiates the activity of the NR4A3 CC (PubMed:12709428). Interacts with NR1H3 (By similarity). Interacts with CC NR3C1 (By similarity). Interacts with NR3C2 (PubMed:9111344). Interacts CC with PSMB9 (By similarity). Interacts with RARA (By similarity). CC Interacts with RXRA (By similarity). Interacts with RWDD3 (By CC similarity). Interacts with TTLL5/STAMP (By similarity). CC {ECO:0000250|UniProtKB:Q15596, ECO:0000269|PubMed:10381882, CC ECO:0000269|PubMed:11997499, ECO:0000269|PubMed:12477726, CC ECO:0000269|PubMed:12709428, ECO:0000269|PubMed:16148126, CC ECO:0000269|PubMed:19039140, ECO:0000269|PubMed:24529706, CC ECO:0000269|PubMed:9111344}. CC -!- INTERACTION: CC Q61026; Q4FZB7-1: KMT5B; Xeno; NbExp=4; IntAct=EBI-688662, EBI-15746366; CC Q61026; P04150-1: NR3C1; Xeno; NbExp=3; IntAct=EBI-688662, EBI-15750116; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q15596}. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- INDUCTION: Expressed in a circadian manner in the liver, brown adipose CC tissue (BAT), white adipose tissue (WAT), heart, skeletal muscle and CC suprachiasmatic nucleus (SCN) of the brain. Shows a higher expression CC during the light phase compared with the dark phase. CC {ECO:0000269|PubMed:24529706}. CC -!- DOMAIN: Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL CC motifs are essential for the association with nuclear receptors and CC are, at least in part, functionally redundant. CC {ECO:0000250|UniProtKB:Q15596}. CC -!- DOMAIN: The LLXXLXXXL motif is involved in transcriptional coactivation CC and CREBBP/CBP binding. {ECO:0000250|UniProtKB:Q15596}. CC -!- DOMAIN: Contains 2 C-terminal transcription activation domains (AD1 and CC AD2) that can function independently. {ECO:0000250|UniProtKB:Q15596}. CC -!- PTM: Acetylated (PubMed:31851938). Deacetylation at Lys-780 by SIRT6 CC stimulates its ability to coactivate PPARA (PubMed:31851938). CC {ECO:0000269|PubMed:31851938}. CC -!- DISRUPTION PHENOTYPE: Animals show a glycogenopathy resembling to Von CC Gierke's disease with impaired growth, fasting hypoglycemia, and an CC increase in concentrations of triglycerides, cholesterol, free fatty CC acids, ketone bodies, uric acid and lactic acid in the plasma during CC fating. They also have increased liver glycogen stores and hepatic CC steatosis. {ECO:0000269|PubMed:19039140}. CC -!- SIMILARITY: Belongs to the SRC/p160 nuclear receptor coactivator CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB61575.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U39060; AAC53151.1; -; mRNA. DR EMBL; AF000582; AAB61575.1; ALT_FRAME; mRNA. DR EMBL; AC091248; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC121538; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS35515.1; -. DR PIR; T30193; T30193. DR PIR; T42639; T42639. DR RefSeq; NP_032704.2; NM_008678.3. DR RefSeq; XP_006495528.1; XM_006495465.3. DR PDB; 1L2I; X-ray; 1.95 A; C/D=686-698. DR PDB; 1OSV; X-ray; 2.50 A; C/D/E=741-752. DR PDB; 1WM0; X-ray; 2.90 A; Y=684-697. DR PDB; 2Q6J; X-ray; 2.70 A; C/D=686-698. DR PDB; 2QA6; X-ray; 2.60 A; C/D=686-698. DR PDB; 2QA8; X-ray; 1.85 A; C/D=686-698. DR PDB; 2QAB; X-ray; 1.89 A; C/D=686-698. DR PDB; 2QGT; X-ray; 2.15 A; C/D=686-698. DR PDB; 2QGW; X-ray; 2.39 A; C/D=686-698. DR PDB; 2QH6; X-ray; 2.70 A; C/D=686-698. DR PDB; 2QPY; X-ray; 2.50 A; B=744-753. DR PDB; 2QR9; X-ray; 2.00 A; C/D=686-698. DR PDB; 2QSE; X-ray; 1.85 A; C/D=686-698. DR PDB; 2QXM; X-ray; 2.30 A; C/D=686-698. DR PDB; 2QZO; X-ray; 1.72 A; C/D=686-698. DR PDB; 3MNE; X-ray; 1.96 A; B=740-752. DR PDB; 3MNO; X-ray; 1.55 A; B=740-752. DR PDB; 3MNP; X-ray; 1.50 A; B=740-752. DR PDBsum; 1L2I; -. DR PDBsum; 1OSV; -. DR PDBsum; 1WM0; -. DR PDBsum; 2Q6J; -. DR PDBsum; 2QA6; -. DR PDBsum; 2QA8; -. DR PDBsum; 2QAB; -. DR PDBsum; 2QGT; -. DR PDBsum; 2QGW; -. DR PDBsum; 2QH6; -. DR PDBsum; 2QPY; -. DR PDBsum; 2QR9; -. DR PDBsum; 2QSE; -. DR PDBsum; 2QXM; -. DR PDBsum; 2QZO; -. DR PDBsum; 3MNE; -. DR PDBsum; 3MNO; -. DR PDBsum; 3MNP; -. DR AlphaFoldDB; Q61026; -. DR SMR; Q61026; -. DR BioGRID; 201708; 18. DR ComplexPortal; CPX-643; RXRalpha-NCOA2 activated retinoic acid receptor complex. DR ComplexPortal; CPX-668; RARalpha-NCOA2 activated retinoic acid receptor complex. DR ComplexPortal; CPX-703; PPARgamma-NCOA2 activated nuclear receptor complex. DR ComplexPortal; CPX-818; RXRalpha-RARalpha-NCOA2 retinoic acid receptor complex. DR DIP; DIP-5979N; -. DR IntAct; Q61026; 12. DR MINT; Q61026; -. DR STRING; 10090.ENSMUSP00000006037; -. DR GlyGen; Q61026; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; Q61026; -. DR PhosphoSitePlus; Q61026; -. DR SwissPalm; Q61026; -. DR EPD; Q61026; -. DR jPOST; Q61026; -. DR MaxQB; Q61026; -. DR PaxDb; 10090-ENSMUSP00000006037; -. DR ProteomicsDB; 287453; -. DR Pumba; Q61026; -. DR Antibodypedia; 6252; 381 antibodies from 32 providers. DR DNASU; 17978; -. DR Ensembl; ENSMUST00000006037.13; ENSMUSP00000006037.7; ENSMUSG00000005886.15. DR GeneID; 17978; -. DR KEGG; mmu:17978; -. DR UCSC; uc007aim.2; mouse. DR AGR; MGI:1276533; -. DR CTD; 10499; -. DR MGI; MGI:1276533; Ncoa2. DR VEuPathDB; HostDB:ENSMUSG00000005886; -. DR eggNOG; KOG3561; Eukaryota. DR GeneTree; ENSGT00950000183021; -. DR InParanoid; Q61026; -. DR OMA; PIMPNAQ; -. DR OrthoDB; 4230728at2759; -. DR PhylomeDB; Q61026; -. DR TreeFam; TF332652; -. DR Reactome; R-MMU-159418; Recycling of bile acids and salts. DR Reactome; R-MMU-192105; Synthesis of bile acids and bile salts. DR Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol. DR Reactome; R-MMU-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol. DR Reactome; R-MMU-211976; Endogenous sterols. DR Reactome; R-MMU-3214847; HATs acetylate histones. DR Reactome; R-MMU-400206; Regulation of lipid metabolism by PPARalpha. DR Reactome; R-MMU-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression. DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1. DR BioGRID-ORCS; 17978; 4 hits in 83 CRISPR screens. DR ChiTaRS; Ncoa2; mouse. DR EvolutionaryTrace; Q61026; -. DR PRO; PR:Q61026; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; Q61026; Protein. DR Bgee; ENSMUSG00000005886; Expressed in substantia nigra and 231 other cell types or tissues. DR ExpressionAtlas; Q61026; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0043197; C:dendritic spine; ISO:MGI. DR GO; GO:0016604; C:nuclear body; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI. DR GO; GO:0005667; C:transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0017162; F:aryl hydrocarbon receptor binding; ISO:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0070182; F:DNA polymerase binding; ISO:MGI. DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI. DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; ISO:MGI. DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI. DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:UniProtKB. DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; ISO:MGI. DR GO; GO:0046965; F:nuclear retinoid X receptor binding; ISO:MGI. DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; ISO:MGI. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0001162; F:RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IDA:MGI. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central. DR GO; GO:1904017; P:cellular response to Thyroglobulin triiodothyronine; IDA:MGI. DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB. DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB. DR GO; GO:0045475; P:locomotor rhythm; IMP:UniProtKB. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISS:ComplexPortal. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0035357; P:peroxisome proliferator activated receptor signaling pathway; NAS:ComplexPortal. DR GO; GO:1904179; P:positive regulation of adipose tissue development; NAS:ComplexPortal. DR GO; GO:0045925; P:positive regulation of female receptivity; ISO:MGI. DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI. DR GO; GO:1900076; P:regulation of cellular response to insulin stimulus; NAS:ComplexPortal. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI. DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB. DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA:UniProtKB. DR GO; GO:0032570; P:response to progesterone; IMP:MGI. DR CDD; cd18950; bHLH-PAS_NCoA2_SRC2; 1. DR CDD; cd00130; PAS; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR Gene3D; 6.10.140.20; Nuclear receptor coactivator, Ncoa-type, interlocking domain; 1. DR Gene3D; 3.30.450.20; PAS domain; 2. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR010011; NCO_DUF1518. DR InterPro; IPR032565; NCOA2/3_DUF4927. DR InterPro; IPR028822; NCOA2_bHLH. DR InterPro; IPR009110; Nuc_rcpt_coact. DR InterPro; IPR014920; Nuc_rcpt_coact_Ncoa-typ. DR InterPro; IPR037077; Nuc_rcpt_coact_Ncoa_int_sf. DR InterPro; IPR017426; Nuclear_rcpt_coactivator. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR013767; PAS_fold. DR InterPro; IPR014935; SRC/p160_LXXLL. DR PANTHER; PTHR10684; NUCLEAR RECEPTOR COACTIVATOR; 1. DR PANTHER; PTHR10684:SF2; NUCLEAR RECEPTOR COACTIVATOR 2; 1. DR Pfam; PF07469; DUF1518; 1. DR Pfam; PF16279; DUF4927; 1. DR Pfam; PF16665; NCOA_u2; 1. DR Pfam; PF08815; Nuc_rec_co-act; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF14598; PAS_11; 1. DR Pfam; PF08832; SRC-1; 1. DR PIRSF; PIRSF038181; Nuclear_receptor_coactivator; 1. DR SMART; SM01151; DUF1518; 1. DR SMART; SM00353; HLH; 1. DR SMART; SM00091; PAS; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR SUPFAM; SSF69125; Nuclear receptor coactivator interlocking domain; 1. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS50112; PAS; 1. DR Genevisible; Q61026; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Biological rhythms; Isopeptide bond; KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Transcription; Transcription regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT CHAIN 2..1462 FT /note="Nuclear receptor coactivator 2" FT /id="PRO_0000094403" FT DOMAIN 26..83 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT DOMAIN 119..183 FT /note="PAS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT REGION 1..40 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 467..513 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 557..636 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 648..742 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 691..743 FT /note="CASP8AP2-binding" FT /evidence="ECO:0000269|PubMed:12477726" FT REGION 730..1121 FT /note="Interaction with BMAL1" FT /evidence="ECO:0000269|PubMed:24529706" FT REGION 1051..1071 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1309..1328 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 641..645 FT /note="LXXLL motif 1" FT MOTIF 690..694 FT /note="LXXLL motif 2" FT MOTIF 745..749 FT /note="LXXLL motif 3" FT MOTIF 878..882 FT /note="LXXLL motif 4" FT MOTIF 1079..1087 FT /note="LLXXLXXXL motif" FT COMPBIAS 11..40 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 467..490 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 557..572 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 596..620 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 648..678 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 712..729 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 29 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 338 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 487 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 493 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT MOD_RES 499 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 554 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 565 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 636 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 640 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 682 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 699 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319, FT ECO:0007744|PubMed:21183079" FT MOD_RES 736 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 771 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT MOD_RES 780 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31851938, FT ECO:0007744|PubMed:23806337" FT MOD_RES 785 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 864 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 874 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 1173 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 1177 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 1190 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 1196 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 1203 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 1221 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 1240 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 1259 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MOD_RES 1264 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT CROSSLNK 239 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT CROSSLNK 648 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT CROSSLNK 705 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT CROSSLNK 731 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT CROSSLNK 785 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT CROSSLNK 1452 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q15596" FT MUTAGEN 644..645 FT /note="LL->AA: Abolishes interaction with RORC; when FT associated with 689-A--A-694 and 744-A--A-749." FT /evidence="ECO:0000269|PubMed:16148126" FT MUTAGEN 689..694 FT /note="ILHRLL->AAHRAA: Abolishes interaction with RORC; FT when associated with 644-A-A-645 and 744-A--A-749." FT /evidence="ECO:0000269|PubMed:16148126" FT MUTAGEN 744..749 FT /note="LLRYLL->AARAA: Abolishes interaction with RORC; when FT associated with 644-A-A-645 and 689-A--A-694." FT /evidence="ECO:0000269|PubMed:16148126" FT CONFLICT 51 FT /note="E -> D (in Ref. 1; AAC53151)" FT /evidence="ECO:0000305" FT CONFLICT 140..141 FT /note="SE -> FR (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 194 FT /note="S -> T (in Ref. 1; AAC53151)" FT /evidence="ECO:0000305" FT CONFLICT 256 FT /note="V -> I (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 286 FT /note="S -> T (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 420 FT /note="G -> S (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 512 FT /note="S -> N (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 594 FT /note="E -> K (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 607..608 FT /note="EE -> KK (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 864 FT /note="R -> C (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 869 FT /note="T -> S (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 884 FT /note="N -> Y (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 972 FT /note="M -> K (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 980 FT /note="M -> K (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 991 FT /note="R -> G (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 996 FT /note="P -> L (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT CONFLICT 1407 FT /note="G -> C (in Ref. 1; AAC53151)" FT /evidence="ECO:0000305" FT CONFLICT 1446 FT /note="P -> L (in Ref. 2; AAB61575)" FT /evidence="ECO:0000305" FT HELIX 689..694 FT /evidence="ECO:0007829|PDB:2QZO" FT HELIX 743..749 FT /evidence="ECO:0007829|PDB:3MNP" SQ SEQUENCE 1462 AA; 158466 MW; 619462FF1ACC6067 CRC64; MSGMGENTSD PSRAETRKRK ECPDQLGPSP KRSTEKRNRE QENKYIEELA ELIFANFNDI DNFNFKPDKC AILKETVKQI RQIKEQEKAA AANIDEVQKS DVSSTGQGVI DKDALGPMML EALDGFFFVV NLEGSVVFVS ENVTQYLRYN QEELMNKSVY SILHVGDHTE FVKNLLPKSM VNGGSWSGEP PRRSSHTFNC RMLVKPLPDS EEEGHDSQEA HQKYEAMQCF AVSQPKSIKE EGEDLQSCLI CVARRVPMKE RPTLPSSESF TTRQDLQGKI TSLDTSTMRA AMKPGWEDLV RRCIQKFHTQ HEGESLSYAK RHHHEVLRQG LAFSQIYRFS LSDGTLVAAQ TKSKLIRSQT TNEPQLVISL HMLHREQNVC VMNPDLTGQA MGKPLNPISS SSPAHQALCS GNPGQDMTLG SNINFPMNGP KEQMGMPMGR FGGSGGMNHV SGMQATTPQG SNYALKMNSP SQSSPGMNPG QASSVLSPRQ RMSPGVAGSP RIPPSQFSPA GSLHSPVGVC SSTGNSHSYT NSSLNALQAL SEGHGVSLGS SLASPDLKMG NLQNSPVNMN PPPLSKMGSL DSKDCFGLYG EPSEGTTGQA EASCHPEEQK GPNDSSMPQA ASGDRAEGHS RLHDSKGQTK LLQLLTTKSD QMEPSPLPSS LSDTNKDSTG SLPGPGSTHG TSLKEKHKIL HRLLQDSSSP VDLAKLTAEA TGKELSQESS STAPGSEVTV KQEPASPKKK ENALLRYLLD KDDTKDIGLP EITPKLERLD SKTDPASNTK LIAMKTVKEE VSFEPSDQPG SELDNLEEIL DDLQNSQLPQ LFPDTRPGAP TGSVDKQAII NDLMQLTADS SPVPPAGAQK AALRMSQSTF NNPRPGQLGR LLPNQNLPLD ITLQSPTGAG PFPPIRNSSP YSVIPQPGMM GNQGMLGSQG NLGNNSTGMI GSSTSRPSMP SGEWAPQSPA VRVTCAATTG AMNRPVQGGM IRNPTASIPM RANSQPGQRQ MLQSQVMNIG PSELEMNMGG PQYNQQQAPP NQTAPWPESI LPIDQASFAS QNRQPFGSSP DDLLCPHPAA ESPSDEGALL DQLYLALRNF DGLEEIDRAL GIPELVSQSQ AVDAEQFSSQ ESSIMLEQKP PVFPQQYASQ AQMAQGGYNP MQDPNFHTMG QRPNYTTLRM QPRPGLRPTG IVQNQPNQLR LQLQHRLQAQ QNRQPLMNQI SSVSNVNLTL RPGVPTQAPI NAQMLAQRQR EILNQHLRQR QMQQQVQQRT LMMRGQGLNV TPSMVAPAGL PAAMSNPRIP QANAQQFPFP PNYGISQQPD PGFTGATTPQ SPLMSPRMAH TQSPMMQQSQ ANPAYQPTSD MNGWAQGSMG GNSMFSQQSP PHFGQQANTS MYSNNMNISV SMATNTGGLS SMNQMTGQMS MTSVTSVPTS GLPSMGPEQV NDPALRGGNL FPNQLPGMDM IKQEGDASRK YC //