NCOA2_MOUSE
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 03-AUG-2022, entry version 205.
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 ARNTL.
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 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-ARNTL/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. Interacts (via C-terminus) with CREBBP. Interacts with ESR1,
CC HIF1A, NCOA1, APEX1, NR3C1, NR3C2, CARM1, RARA, and RXRA. Present in a
CC complex containing CARM1 and EP300/P300. Interacts with CASP8AP2 and
CC TTLL5/STAMP. Interacts with PSMB9 and DDX5. Interacts (via LXXLL 1, 2
CC and 3 motifs) with RORA and RORC (via AF-2 motif). Interacts with
CC RWDD3. Interacts with CLOCK and ARNTL/BMAL1. Interacts with NR4A3;
CC potentiates the activity of the NR4A3 (PubMed:12709428). Interacts with
CC NR1H3 (By similarity). {ECO:0000250|UniProtKB:Q15596,
CC ECO:0000269|PubMed:10381882, ECO:0000269|PubMed:11997499,
CC ECO:0000269|PubMed:12477726, ECO:0000269|PubMed:12709428,
CC ECO:0000269|PubMed:16148126, ECO:0000269|PubMed:19039140,
CC ECO:0000269|PubMed:24529706, 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};
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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 iPTMnet; Q61026; -.
DR PhosphoSitePlus; Q61026; -.
DR SwissPalm; Q61026; -.
DR EPD; Q61026; -.
DR jPOST; Q61026; -.
DR MaxQB; Q61026; -.
DR PaxDb; Q61026; -.
DR PRIDE; Q61026; -.
DR ProteomicsDB; 287453; -.
DR Antibodypedia; 6252; 322 antibodies from 32 providers.
DR DNASU; 17978; -.
DR Ensembl; ENSMUST00000006037; ENSMUSP00000006037; ENSMUSG00000005886.
DR GeneID; 17978; -.
DR KEGG; mmu:17978; -.
DR UCSC; uc007aim.2; mouse.
DR CTD; 10499; -.
DR MGI; MGI:1276533; Ncoa2.
DR VEuPathDB; HostDB:ENSMUSG00000005886; -.
DR eggNOG; KOG3561; Eukaryota.
DR GeneTree; ENSGT00950000183021; -.
DR InParanoid; Q61026; -.
DR OMA; DSNMPPV; -.
DR OrthoDB; 59971at2759; -.
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; 3 hits in 77 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 228 other tissues.
DR ExpressionAtlas; Q61026; baseline and differential.
DR Genevisible; Q61026; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; 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:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0048786; C:presynaptic active zone; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IC:ComplexPortal.
DR GO; GO:0005791; C:rough endoplasmic reticulum; 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:0033142; F:nuclear progesterone 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:0030165; F:PDZ domain 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; IC:ComplexPortal.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0035357; P:peroxisome proliferator activated receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; IC: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; IC:ComplexPortal.
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:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0032570; P:response to progesterone; IMP:MGI.
DR CDD; cd00130; PAS; 1.
DR Gene3D; 4.10.280.10; -; 1.
DR Gene3D; 6.10.140.20; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR010011; NCO_DUF1518.
DR InterPro; IPR028822; NCOA2.
DR InterPro; IPR032565; NCOA2/3_DUF4927.
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; PTHR10684; 1.
DR PANTHER; PTHR10684:SF2; PTHR10684:SF2; 1.
DR Pfam; PF07469; DUF1518; 1.
DR Pfam; PF16279; DUF4927; 1.
DR Pfam; PF08815; Nuc_rec_co-act; 1.
DR Pfam; PF00989; PAS; 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; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR SUPFAM; SSF69125; SSF69125; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 1.
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 ARNTL"
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
