ID NCOA2_HUMAN Reviewed; 1464 AA. AC Q15596; Q14CD2; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 2. DT 11-NOV-2015, entry version 175. DE RecName: Full=Nuclear receptor coactivator 2; DE Short=NCoA-2; DE AltName: Full=Class E basic helix-loop-helix protein 75; DE Short=bHLHe75; DE AltName: Full=Transcriptional intermediary factor 2; DE Short=hTIF2; GN Name=NCOA2; Synonyms=BHLHE75, SRC2, TIF2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=8670870; RA Voegel J.J., Heine M.J.S., Zechel C., Chambon P., Gronemeyer H.; RT "TIF2, a 160 kDa transcriptional mediator for the ligand-dependent RT activation function AF-2 of nuclear receptors."; RL EMBO J. 15:3667-3675(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-1282. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 870-939, AND CHROMOSOMAL TRANSLOCATION RP WITH KAT6A. RX PubMed=9558366; RA Carapeti M., Aguiar R.C.T., Goldman J.M., Cross N.C.P.; RT "A novel fusion between MOZ and the nuclear receptor coactivator TIF2 RT in acute myeloid leukemia."; RL Blood 91:3127-3133(1998). RN [4] RP FUNCTION, INTERACTION WITH CREBBP; ESR1; RARA AND RXRA, DOMAIN, AND RP MUTAGENESIS OF 644-LEU-LEU-645; 693-LEU-LEU-694; 748-LEU-LEU-749; RP 1079-LEU--LEU-1083 AND 1081-ASP-GLN-1082. RX PubMed=9430642; DOI=10.1093/emboj/17.2.507; RA Voegel J.J., Heine M.J.S., Tini M., Vivat V., Chambon P., RA Gronemeyer H.; RT "The coactivator TIF2 contains three nuclear receptor-binding motifs RT and mediates transactivation through CBP binding-dependent and RT -independent pathways."; RL EMBO J. 17:507-519(1998). RN [5] RP INTERACTION WITH NR3C1. RX PubMed=9590696; DOI=10.1038/30032; RA Fryer C.J., Archer T.K.; RT "Chromatin remodelling by the glucocorticoid receptor requires the RT BRG1 complex."; RL Nature 393:88-91(1998). RN [6] RP INTERACTION WITH RORA. RX PubMed=10478845; DOI=10.1210/me.13.9.1550; RA Atkins G.B., Hu X., Guenther M.G., Rachez C., Freedman L.P., RA Lazar M.A.; RT "Coactivators for the orphan nuclear receptor RORalpha."; RL Mol. Endocrinol. 13:1550-1557(1999). RN [7] RP INTERACTION WITH HIF1A; NCOA1 AND APEX. RX PubMed=10594042; DOI=10.1128/MCB.20.1.402-415.2000; RA Carrero P., Okamoto K., Coumailleau P., O'Brien S., Tanaka H., RA Poellinger L.; RT "Redox-regulated recruitment of the transcriptional coactivators CREB- RT binding protein and SRC-1 to hypoxia-inducible factor 1alpha."; RL Mol. Cell. Biol. 20:402-415(2000). RN [8] RP INTERACTION WITH DDX5. RX PubMed=11250900; DOI=10.1093/emboj/20.6.1341; RA Watanabe M., Yanagisawa J., Kitagawa H., Takeyama K., Ogawa S., RA Arao Y., Suzawa M., Kobayashi Y., Yano T., Yoshikawa H., Masuhiro Y., RA Kato S.; RT "A subfamily of RNA-binding DEAD-box proteins acts as an estrogen RT receptor alpha coactivator through the N-terminal activation domain RT (AF-1) with an RNA coactivator, SRA."; RL EMBO J. 20:1341-1352(2001). RN [9] RP IDENTIFICATION IN A COACTIVATOR COMPLEX CONTAINING CREBBP; NCOA3; RP IKKA; IKKB AND IKBKG. RX PubMed=11971985; DOI=10.1128/MCB.22.10.3549-3561.2002; RA Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., RA O'Malley B.W.; RT "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator RT activity by I kappa B kinase."; RL Mol. Cell. Biol. 22:3549-3561(2002). RN [10] RP CHROMOSOMAL TRANSLOCATION WITH KAT6A. RX PubMed=12676584; DOI=10.1016/S1535-6108(03)00051-5; RA Deguchi K., Ayton P.M., Carapeti M., Kutok J.L., Snyder C.S., RA Williams I.R., Cross N.C.P., Glass C.K., Cleary M.L., Gilliland D.G.; RT "MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome RT binding motif and TIF2-mediated recruitment of CBP."; RL Cancer Cell 3:259-271(2003). RN [11] RP CHROMOSOMAL TRANSLOCATION WITH KAT6A. RX PubMed=15657427; DOI=10.1128/MCB.25.3.988-1002.2005; RA Kindle K.B., Troke P.J.F., Collins H.M., Matsuda S., Bossi D., RA Bellodi C., Kalkhoven E., Salomoni P., Pelicci P.G., Minucci S., RA Heery D.M.; RT "MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by RT impairment of CBP function."; RL Mol. Cell. Biol. 25:988-1002(2005). RN [12] RP INTERACTION WITH PSMB9. RX PubMed=16957778; DOI=10.1038/sj.emboj.7601306; RA Zhang H., Sun L., Liang J., Yu W., Zhang Y., Wang Y., Chen Y., Li R., RA Sun X., Shang Y.; RT "The catalytic subunit of the proteasome is engaged in the entire RT process of estrogen receptor-regulated transcription."; RL EMBO J. 25:4223-4233(2006). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein RT phosphorylation analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [14] RP INTERACTION WITH TTLL5. RC TISSUE=Testis; RX PubMed=17116691; DOI=10.1128/MCB.01360-06; RA He Y., Simons S.S. Jr.; RT "STAMP, a novel predicted factor assisting TIF2 actions in RT glucocorticoid receptor-mediated induction and repression."; RL Mol. Cell. Biol. 27:1467-1485(2007). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-640; LYS-780 AND LYS-785, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487; SER-493 AND RP SER-499, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] RP FUNCTION, AND INTERACTION WITH RWDD3 AND NR3C1. RX PubMed=23508108; DOI=10.1128/MCB.01470-12; RA Druker J., Liberman A.C., Antunica-Noguerol M., Gerez J., RA Paez-Pereda M., Rein T., Iniguez-Lluhi J.A., Holsboer F., Arzt E.; RT "RSUME enhances glucocorticoid receptor SUMOylation and RT transcriptional activity."; RL Mol. Cell. Biol. 33:2116-2127(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-493; SER-554; SER-565 RP AND SER-699, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-785, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). CC -!- FUNCTION: Transcriptional coactivator for steroid receptors and CC nuclear receptors. Coactivator of the steroid binding domain (AF- CC 2) but not of the modulating N-terminal domain (AF-1). Required CC with NCOA1 to control energy balance between white and brown CC adipose tissues. Critical regulator of glucose metabolism CC regulation, acts as RORA coactivator to specifically modulate G6PC CC expression. Involved in the positive regulation of the CC transcriptional activity of the glucocorticoid receptor NR3C1 by CC sumoylation enhancer RWDD3. Positively regulates the circadian CC clock by acting as a transcriptional coactivator for the CLOCK- CC ARNTL/BMAL1 heterodimer (By similarity). CC {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:23508108, CC ECO:0000269|PubMed:9430642}. CC -!- SUBUNIT: Present in a complex containing NCOA3, IKKA, IKKB, IKBKG CC and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with CC ESR1, HIF1A, NCOA1, APEX, NR3C1, NR3C2, CARM1, RARA, and RXRA. CC Present in a complex containing CARM1 and EP300/P300. Interacts CC with CASP8AP2 and TTLL5/STAMP. Interacts with PSMB9 and DDX5. CC Interacts (via LXXLL 1, 2 and 3 motifs) with RORA and RORC (via CC AF-2 motif). Interacts with RWDD3. Interacts with CLOCK and CC ARNTL/BMAL1 (By similarity). Interacts with NR4A3; potentiates the CC activity of the NR4A3 (By similarity). CC {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:10478845, CC ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11250900, CC ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:16957778, CC ECO:0000269|PubMed:17116691, ECO:0000269|PubMed:23508108, CC ECO:0000269|PubMed:9430642, ECO:0000269|PubMed:9590696}. CC -!- INTERACTION: CC P10275:AR; NbExp=2; IntAct=EBI-81236, EBI-608057; CC Q92841:DDX17; NbExp=2; IntAct=EBI-81236, EBI-746012; CC P03372:ESR1; NbExp=8; IntAct=EBI-81236, EBI-78473; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- DOMAIN: Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The CC LXXLL motifs are essential for the association with nuclear CC receptors and are, at least in part, functionally redundant. CC {ECO:0000269|PubMed:9430642}. CC -!- DOMAIN: The LLXXLXXXL motif is involved in transcriptional CC coactivation and CREBBP/CBP binding. {ECO:0000269|PubMed:9430642}. CC -!- DOMAIN: Contains 2 C-terminal transcription activation domains CC (AD1 and AD2) that can function independently. CC {ECO:0000269|PubMed:9430642}. CC -!- DISEASE: Note=Chromosomal aberrations involving NCOA2 may be a CC cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) CC generates the KAT6A-NCOA2 oncogene, which consists of the N- CC terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. CC KAT6A-NCOA2 binds to CREBBP and disrupts its function in CC transcription activation. CC -!- SIMILARITY: Belongs to the SRC/p160 nuclear receptor coactivator CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00981}. CC -!- SIMILARITY: Contains 1 PAS (PER-ARNT-SIM) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00140}. 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; X97674; CAA66263.1; -; mRNA. DR EMBL; BC114383; AAI14384.1; -; mRNA. DR CCDS; CCDS47872.1; -. DR RefSeq; NP_006531.1; NM_006540.2. DR RefSeq; XP_005251185.1; XM_005251128.3. DR RefSeq; XP_005251186.1; XM_005251129.3. DR RefSeq; XP_005251187.1; XM_005251130.3. DR RefSeq; XP_005251188.1; XM_005251131.3. DR RefSeq; XP_011515738.1; XM_011517436.1. DR RefSeq; XP_011515739.1; XM_011517437.1. DR RefSeq; XP_011515740.1; XM_011517438.1. DR RefSeq; XP_011515741.1; XM_011517439.1. DR UniGene; Hs.446678; -. DR UniGene; Hs.595378; -. DR PDB; 1GWQ; X-ray; 2.45 A; C/D=688-696. DR PDB; 1GWR; X-ray; 2.40 A; C/D=742-750. DR PDB; 1M2Z; X-ray; 2.50 A; B/E=734-754. DR PDB; 1MV9; X-ray; 1.90 A; B=686-698. DR PDB; 1MVC; X-ray; 1.90 A; B=686-698. DR PDB; 1MZN; X-ray; 1.90 A; B/D/F/H=686-698. DR PDB; 1P93; X-ray; 2.70 A; E/F/G/H=740-751. DR PDB; 1T63; X-ray; 2.07 A; B=740-753. DR PDB; 1T65; X-ray; 1.66 A; B=686-698. DR PDB; 1UHL; X-ray; 2.90 A; C/D=687-696. DR PDB; 1YOK; X-ray; 2.50 A; B/C=740-753. DR PDB; 1ZDT; X-ray; 2.10 A; P/Q=741-752. DR PDB; 1ZDU; X-ray; 2.50 A; P/Q=741-751. DR PDB; 1ZKY; X-ray; 2.25 A; C/D=686-698. DR PDB; 2AO6; X-ray; 1.89 A; B=740-753. DR PDB; 2B1V; X-ray; 1.80 A; C/D=686-698. DR PDB; 2B1Z; X-ray; 1.78 A; C/D=686-698. DR PDB; 2B23; X-ray; 2.10 A; C/D=686-698. DR PDB; 2FAI; X-ray; 2.10 A; C/D=686-698. DR PDB; 2G44; X-ray; 2.65 A; C/D=686-698. DR PDB; 2G5O; X-ray; 2.30 A; C/D=686-698. DR PDB; 2LDC; NMR; -; A=687-697. DR PDB; 2P15; X-ray; 1.94 A; C/D=686-698. DR PDB; 2P1T; X-ray; 1.80 A; B=686-698. DR PDB; 2P1U; X-ray; 2.20 A; B=686-698. DR PDB; 2P1V; X-ray; 2.20 A; B=686-698. DR PDB; 2Q7J; X-ray; 1.90 A; B=740-753. DR PDB; 2Q7L; X-ray; 1.92 A; B=740-753. DR PDB; 2YJD; X-ray; 1.93 A; C/D=687-697. DR PDB; 2ZXZ; X-ray; 3.00 A; B=686-698. DR PDB; 2ZY0; X-ray; 2.90 A; B/D=686-698. DR PDB; 3A9E; X-ray; 2.75 A; I=686-698. DR PDB; 3CLD; X-ray; 2.84 A; C/H=740-751. DR PDB; 3DZU; X-ray; 3.20 A; E/G=685-697. DR PDB; 3DZY; X-ray; 3.10 A; E/G=685-697. DR PDB; 3E00; X-ray; 3.10 A; E/G=685-697. DR PDB; 3E7C; X-ray; 2.15 A; D/H=741-751. DR PDB; 3E94; X-ray; 1.90 A; B=686-698. DR PDB; 3ERD; X-ray; 2.03 A; C/D=686-698. DR PDB; 3FUG; X-ray; 2.00 A; B=686-698. DR PDB; 3GN8; X-ray; 2.50 A; C/E=734-754. DR PDB; 3K22; X-ray; 2.10 A; D/H=740-751. DR PDB; 3K23; X-ray; 3.00 A; D/E/F=740-751. DR PDB; 3KWY; X-ray; 2.30 A; B=686-698. DR PDB; 3KYT; X-ray; 2.35 A; C=686-697. DR PDB; 3L0E; X-ray; 2.30 A; B=740-751. DR PDB; 3L0J; X-ray; 2.40 A; C=688-697. DR PDB; 3L0L; X-ray; 1.74 A; C/E=685-697. DR PDB; 3O1D; X-ray; 2.40 A; B=686-698. DR PDB; 3O1E; X-ray; 2.50 A; B=686-698. DR PDB; 3OAP; X-ray; 2.05 A; B=686-696. DR PDB; 3OZJ; X-ray; 2.10 A; B/D=686-696. DR PDB; 3PCU; X-ray; 2.00 A; B=687-696. DR PDB; 3PLZ; X-ray; 1.75 A; C/D=740-753. DR PDB; 3Q95; X-ray; 2.05 A; C/D=686-698. DR PDB; 3Q97; X-ray; 2.10 A; C/D=686-698. DR PDB; 3R5M; X-ray; 2.80 A; B/D=687-696. DR PDB; 3UP0; X-ray; 1.60 A; P/Q=740-753. DR PDB; 3UP3; X-ray; 1.25 A; P=741-754. DR PDB; 4CSJ; X-ray; 2.30 A; B=741-753. DR PDB; 4DOS; X-ray; 2.00 A; B/C=740-753. DR PDB; 4E2J; X-ray; 2.50 A; C/E=741-752. DR PDB; 4FHH; X-ray; 2.33 A; B=686-698. DR PDB; 4FHI; X-ray; 2.40 A; B=686-698. DR PDB; 4IA1; X-ray; 2.44 A; B=686-698. DR PDB; 4IA2; X-ray; 2.95 A; B=686-698. DR PDB; 4IA3; X-ray; 2.70 A; B=686-698. DR PDB; 4IA7; X-ray; 2.70 A; B=686-698. DR PDB; 4IQR; X-ray; 2.90 A; I/J/K/L=685-697. DR PDB; 4IU7; X-ray; 2.29 A; C/D=687-696. DR PDB; 4IUI; X-ray; 2.30 A; C/D=687-696. DR PDB; 4IV2; X-ray; 2.14 A; C/D=687-696. DR PDB; 4IV4; X-ray; 2.30 A; C/D=687-696. DR PDB; 4IVW; X-ray; 2.06 A; C/D=687-696. DR PDB; 4IVY; X-ray; 1.95 A; C/D=687-696. DR PDB; 4IW6; X-ray; 1.98 A; C/D=687-696. DR PDB; 4IW8; X-ray; 2.04 A; C/D=687-696. DR PDB; 4IWC; X-ray; 2.24 A; C/D=687-696. DR PDB; 4IWF; X-ray; 1.93 A; C/D=687-696. DR PDB; 4K4J; X-ray; 2.00 A; B=686-698. DR PDB; 4K6I; X-ray; 2.10 A; B=686-698. DR PDB; 4M8E; X-ray; 2.40 A; B=686-696. DR PDB; 4M8H; X-ray; 2.20 A; B=686-696. DR PDB; 4NIE; X-ray; 2.01 A; C/D=686-697. DR PDB; 4NQA; X-ray; 3.10 A; C/D/J/K=686-698. DR PDB; 4OC7; X-ray; 2.50 A; B=686-698. DR PDB; 4P6W; X-ray; 1.95 A; B=741-752. DR PDB; 4P6X; X-ray; 2.50 A; B/D/F/H/J/L=740-753. DR PDB; 4POH; X-ray; 2.30 A; B=686-698. DR PDB; 4POJ; X-ray; 2.00 A; B=686-698. DR PDB; 4PP3; X-ray; 2.00 A; B=686-698. DR PDB; 4PP5; X-ray; 2.00 A; B=686-698. DR PDB; 4PP6; X-ray; 2.20 A; C/D=688-696. DR PDB; 4PPP; X-ray; 2.69 A; C/D=688-696. DR PDB; 4PPS; X-ray; 1.93 A; C/D=687-698. DR PDB; 4PXM; X-ray; 1.90 A; C/D=686-698. DR PDB; 4Q0A; X-ray; 1.90 A; D=687-695. DR PDB; 4QE6; X-ray; 1.65 A; B=740-752. DR PDB; 4QE8; X-ray; 2.62 A; C/D=740-752. DR PDB; 4RFW; X-ray; 2.40 A; G=686-698. DR PDB; 4RMC; X-ray; 2.70 A; B=686-698. DR PDB; 4RMD; X-ray; 1.90 A; B=686-698. DR PDB; 4RME; X-ray; 2.30 A; B=686-698. DR PDB; 4WG0; X-ray; 1.82 A; A/B/C/D/E/F/G/H/I/J/K/L/M=742-752. DR PDB; 4ZN9; X-ray; 2.21 A; C/D=686-698. DR PDB; 4ZO1; X-ray; 3.22 A; A=686-694. DR PDBsum; 1GWQ; -. DR PDBsum; 1GWR; -. DR PDBsum; 1M2Z; -. DR PDBsum; 1MV9; -. DR PDBsum; 1MVC; -. DR PDBsum; 1MZN; -. DR PDBsum; 1P93; -. DR PDBsum; 1T63; -. DR PDBsum; 1T65; -. DR PDBsum; 1UHL; -. DR PDBsum; 1YOK; -. DR PDBsum; 1ZDT; -. DR PDBsum; 1ZDU; -. DR PDBsum; 1ZKY; -. DR PDBsum; 2AO6; -. DR PDBsum; 2B1V; -. DR PDBsum; 2B1Z; -. DR PDBsum; 2B23; -. DR PDBsum; 2FAI; -. DR PDBsum; 2G44; -. DR PDBsum; 2G5O; -. DR PDBsum; 2LDC; -. DR PDBsum; 2P15; -. DR PDBsum; 2P1T; -. DR PDBsum; 2P1U; -. DR PDBsum; 2P1V; -. DR PDBsum; 2Q7J; -. DR PDBsum; 2Q7L; -. DR PDBsum; 2YJD; -. DR PDBsum; 2ZXZ; -. DR PDBsum; 2ZY0; -. DR PDBsum; 3A9E; -. DR PDBsum; 3CLD; -. DR PDBsum; 3DZU; -. DR PDBsum; 3DZY; -. DR PDBsum; 3E00; -. DR PDBsum; 3E7C; -. DR PDBsum; 3E94; -. DR PDBsum; 3ERD; -. DR PDBsum; 3FUG; -. DR PDBsum; 3GN8; -. DR PDBsum; 3K22; -. DR PDBsum; 3K23; -. DR PDBsum; 3KWY; -. DR PDBsum; 3KYT; -. DR PDBsum; 3L0E; -. DR PDBsum; 3L0J; -. DR PDBsum; 3L0L; -. DR PDBsum; 3O1D; -. DR PDBsum; 3O1E; -. DR PDBsum; 3OAP; -. DR PDBsum; 3OZJ; -. DR PDBsum; 3PCU; -. DR PDBsum; 3PLZ; -. DR PDBsum; 3Q95; -. DR PDBsum; 3Q97; -. DR PDBsum; 3R5M; -. DR PDBsum; 3UP0; -. DR PDBsum; 3UP3; -. DR PDBsum; 4CSJ; -. DR PDBsum; 4DOS; -. DR PDBsum; 4E2J; -. DR PDBsum; 4FHH; -. DR PDBsum; 4FHI; -. DR PDBsum; 4IA1; -. DR PDBsum; 4IA2; -. DR PDBsum; 4IA3; -. DR PDBsum; 4IA7; -. DR PDBsum; 4IQR; -. DR PDBsum; 4IU7; -. DR PDBsum; 4IUI; -. DR PDBsum; 4IV2; -. DR PDBsum; 4IV4; -. DR PDBsum; 4IVW; -. DR PDBsum; 4IVY; -. DR PDBsum; 4IW6; -. DR PDBsum; 4IW8; -. DR PDBsum; 4IWC; -. DR PDBsum; 4IWF; -. DR PDBsum; 4K4J; -. DR PDBsum; 4K6I; -. DR PDBsum; 4M8E; -. DR PDBsum; 4M8H; -. DR PDBsum; 4NIE; -. DR PDBsum; 4NQA; -. DR PDBsum; 4OC7; -. DR PDBsum; 4P6W; -. DR PDBsum; 4P6X; -. DR PDBsum; 4POH; -. DR PDBsum; 4POJ; -. DR PDBsum; 4PP3; -. DR PDBsum; 4PP5; -. DR PDBsum; 4PP6; -. DR PDBsum; 4PPP; -. DR PDBsum; 4PPS; -. DR PDBsum; 4PXM; -. DR PDBsum; 4Q0A; -. DR PDBsum; 4QE6; -. DR PDBsum; 4QE8; -. DR PDBsum; 4RFW; -. DR PDBsum; 4RMC; -. DR PDBsum; 4RMD; -. DR PDBsum; 4RME; -. DR PDBsum; 4WG0; -. DR PDBsum; 4ZN9; -. DR PDBsum; 4ZO1; -. DR ProteinModelPortal; Q15596; -. DR SMR; Q15596; 1071-1115. DR BioGrid; 115761; 67. DR DIP; DIP-5997N; -. DR IntAct; Q15596; 12. DR MINT; MINT-122867; -. DR STRING; 9606.ENSP00000399968; -. DR ChEMBL; CHEMBL2095163; -. DR PhosphoSite; Q15596; -. DR BioMuta; NCOA2; -. DR DMDM; 13626594; -. DR MaxQB; Q15596; -. DR PaxDb; Q15596; -. DR PRIDE; Q15596; -. DR Ensembl; ENST00000452400; ENSP00000399968; ENSG00000140396. DR GeneID; 10499; -. DR KEGG; hsa:10499; -. DR UCSC; uc003xyn.1; human. DR CTD; 10499; -. DR GeneCards; NCOA2; -. DR HGNC; HGNC:7669; NCOA2. DR MIM; 601993; gene. DR neXtProt; NX_Q15596; -. DR PharmGKB; PA31471; -. DR eggNOG; ENOG410IQ5S; Eukaryota. DR eggNOG; ENOG410XPF9; LUCA. DR GeneTree; ENSGT00530000063109; -. DR HOGENOM; HOG000230947; -. DR HOVERGEN; HBG052583; -. DR InParanoid; Q15596; -. DR KO; K11255; -. DR OMA; PSDMNGW; -. DR OrthoDB; EOG72JWFB; -. DR PhylomeDB; Q15596; -. DR TreeFam; TF332652; -. DR Reactome; R-HSA-1368082; RORA activates gene expression. DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression. DR Reactome; R-HSA-159418; Recycling of bile acids and salts. DR Reactome; R-HSA-192105; Synthesis of bile acids and bile salts. DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol. DR Reactome; R-HSA-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression. DR Reactome; R-HSA-211976; Endogenous sterols. DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis. DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP). DR Reactome; R-HSA-3214847; HATs acetylate histones. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-400206; Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). DR Reactome; R-HSA-400253; Circadian Clock. DR Reactome; R-HSA-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. DR SignaLink; Q15596; -. DR ChiTaRS; NCOA2; human. DR EvolutionaryTrace; Q15596; -. DR GeneWiki; Nuclear_receptor_coactivator_2; -. DR GenomeRNAi; 10499; -. DR NextBio; 39840; -. DR PRO; PR:Q15596; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; Q15596; -. DR CleanEx; HS_NCOA2; -. DR ExpressionAtlas; Q15596; baseline and differential. DR Genevisible; Q15596; HS. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0004402; F:histone acetyltransferase activity; IEA:InterPro. DR GO; GO:0016922; F:ligand-dependent nuclear receptor binding; IPI:UniProtKB. DR GO; GO:0030374; F:ligand-dependent nuclear receptor transcription coactivator activity; IDA:BHF-UCL. DR GO; GO:0035257; F:nuclear hormone receptor binding; IPI:UniProtKB. DR GO; GO:0030375; F:thyroid hormone receptor coactivator activity; IEA:Ensembl. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0015721; P:bile acid and bile salt transport; TAS:Reactome. DR GO; GO:0008206; P:bile acid metabolic process; TAS:Reactome. DR GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome. DR GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central. DR GO; GO:0006325; P:chromatin organization; TAS:Reactome. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0045475; P:locomotor rhythm; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR GO; GO:0010906; P:regulation of glucose metabolic process; IEA:Ensembl. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 4.10.280.10; -; 1. DR Gene3D; 4.10.630.10; -; 2. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR010011; DUF1518. DR InterPro; IPR032565; DUF4927. DR InterPro; IPR028822; NCOA2. DR InterPro; IPR009110; Nuc_rcpt_coact. DR InterPro; IPR014920; Nuc_rcpt_coact_Ncoa-typ. DR InterPro; IPR017426; Nuclear_rcpt_coactivator. DR InterPro; IPR001610; PAC. DR InterPro; IPR000014; PAS. DR InterPro; IPR013767; PAS_fold. DR InterPro; IPR014935; SRC-1. DR InterPro; IPR008955; Src1_rcpt_coact. DR PANTHER; PTHR10684; PTHR10684; 2. DR PANTHER; PTHR10684:SF2; PTHR10684:SF2; 2. 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; SM00353; HLH; 1. DR SMART; SM00086; PAC; 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; KW Complete proteome; Isopeptide bond; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; Transcription; KW Transcription regulation; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330}. FT CHAIN 2 1464 Nuclear receptor coactivator 2. FT /FTId=PRO_0000094402. FT DOMAIN 26 83 bHLH. {ECO:0000255|PROSITE- FT ProRule:PRU00981}. FT DOMAIN 119 183 PAS. {ECO:0000255|PROSITE- FT ProRule:PRU00140}. FT REGION 691 743 CASP8AP2-binding. {ECO:0000250}. FT REGION 730 1121 Interaction with ARNTL. FT {ECO:0000250|UniProtKB:Q61026}. FT MOTIF 641 645 LXXLL motif 1. FT MOTIF 690 694 LXXLL motif 2. FT MOTIF 745 749 LXXLL motif 3. FT MOTIF 878 882 LXXLL motif 4. FT MOTIF 1079 1087 LLXXLXXXL motif. FT COMPBIAS 1254 1260 Poly-Gln. FT SITE 869 870 Breakpoint for translocation to form FT KAT6A-NCOA2. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:19413330}. FT MOD_RES 487 487 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 493 493 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 499 499 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 554 554 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 565 565 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 636 636 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q61026}. FT MOD_RES 640 640 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 699 699 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 771 771 Phosphoserine. FT {ECO:0000250|UniProtKB:Q61026}. FT MOD_RES 780 780 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 785 785 N6-acetyllysine; alternate. FT {ECO:0000244|PubMed:19608861}. FT CROSSLNK 785 785 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447}. FT VARIANT 1282 1282 M -> I (in dbSNP:rs2228591). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_024546. FT MUTAGEN 644 645 LL->AA: By itself, does not affect FT nuclear receptor binding or FT transcriptional coactivation. Abrogates FT ligand-induced nuclear receptor binding FT and transactivation; when associated with FT 693-A-A-694 and 748-A-A-749. FT {ECO:0000269|PubMed:9430642}. FT MUTAGEN 693 694 LL->AA: By itself, does not affect FT nuclear receptor binding or FT transcriptional coactivation. Abrogates FT ligand-induced nuclear receptor binding FT and transactivation; when associated with FT 644-A-A-665 and 748-A-A-749. FT {ECO:0000269|PubMed:9430642}. FT MUTAGEN 748 749 LL->AA: By itself, does not affect FT nuclear receptor binding or FT transcriptional coactivation. Abrogates FT ligand-induced nuclear receptor binding FT and transactivation; when associated with FT 644-A-A-665 and 693-A-A-694. FT {ECO:0000269|PubMed:9430642}. FT MUTAGEN 1079 1083 LLDQL->AADQA: Reduces transcriptional FT coactivation and disrupts interaction FT with CREBBP/CBP. FT {ECO:0000269|PubMed:9430642}. FT MUTAGEN 1081 1082 DQ->AA: Has little effect on FT transcriptional coactivation. FT {ECO:0000269|PubMed:9430642}. FT HELIX 688 694 {ECO:0000244|PDB:3L0L}. FT STRAND 739 741 {ECO:0000244|PDB:1M2Z}. FT HELIX 743 750 {ECO:0000244|PDB:3UP3}. SQ SEQUENCE 1464 AA; 159157 MW; 0A61AA5D1878304B CRC64; MSGMGENTSD PSRAETRKRK ECPDQLGPSP KRNTEKRNRE QENKYIEELA ELIFANFNDI DNFNFKPDKC AILKETVKQI RQIKEQEKAA AANIDEVQKS DVSSTGQGVI DKDALGPMML EALDGFFFVV NLEGNVVFVS ENVTQYLRYN QEELMNKSVY SILHVGDHTE FVKNLLPKSI VNGGSWSGEP PRRNSHTFNC RMLVKPLPDS EEEGHDNQEA HQKYETMQCF AVSQPKSIKE EGEDLQSCLI CVARRVPMKE RPVLPSSESF TTRQDLQGKI TSLDTSTMRA AMKPGWEDLV RRCIQKFHAQ HEGESVSYAK RHHHEVLRQG LAFSQIYRFS LSDGTLVAAQ TKSKLIRSQT TNEPQLVISL HMLHREQNVC VMNPDLTGQT MGKPLNPISS NSPAHQALCS GNPGQDMTLS SNINFPINGP KEQMGMPMGR FGGSGGMNHV SGMQATTPQG SNYALKMNSP SQSSPGMNPG QPTSMLSPRH RMSPGVAGSP RIPPSQFSPA GSLHSPVGVC SSTGNSHSYT NSSLNALQAL SEGHGVSLGS SLASPDLKMG NLQNSPVNMN PPPLSKMGSL DSKDCFGLYG EPSEGTTGQA ESSCHPGEQK ETNDPNLPPA VSSERADGQS RLHDSKGQTK LLQLLTTKSD QMEPSPLASS LSDTNKDSTG SLPGSGSTHG TSLKEKHKIL HRLLQDSSSP VDLAKLTAEA TGKDLSQESS STAPGSEVTI KQEPVSPKKK ENALLRYLLD KDDTKDIGLP EITPKLERLD SKTDPASNTK LIAMKTEKEE MSFEPGDQPG SELDNLEEIL DDLQNSQLPQ LFPDTRPGAP AGSVDKQAII NDLMQLTAEN SPVTPVGAQK TALRISQSTF NNPRPGQLGR LLPNQNLPLD ITLQSPTGAG PFPPIRNSSP YSVIPQPGMM GNQGMIGNQG NLGNSSTGMI GNSASRPTMP SGEWAPQSSA VRVTCAATTS AMNRPVQGGM IRNPAASIPM RPSSQPGQRQ TLQSQVMNIG PSELEMNMGG PQYSQQQAPP NQTAPWPESI LPIDQASFAS QNRQPFGSSP DDLLCPHPAA ESPSDEGALL DQLYLALRNF DGLEEIDRAL GIPELVSQSQ AVDPEQFSSQ DSNIMLEQKA PVFPQQYASQ AQMAQGSYSP MQDPNFHTMG QRPSYATLRM QPRPGLRPTG LVQNQPNQLR LQLQHRLQAQ QNRQPLMNQI SNVSNVNLTL RPGVPTQAPI NAQMLAQRQR EILNQHLRQR QMHQQQQVQQ RTLMMRGQGL NMTPSMVAPS GMPATMSNPR IPQANAQQFP FPPNYGISQQ PDPGFTGATT PQSPLMSPRM AHTQSPMMQQ SQANPAYQAP SDINGWAQGN MGGNSMFSQQ SPPHFGQQAN TSMYSNNMNI NVSMATNTGG MSSMNQMTGQ ISMTSVTSVP TSGLSSMGPE QVNDPALRGG NLFPNQLPGM DMIKQEGDTT RKYC //