ID NCOA3_MOUSE Reviewed; 1398 AA. AC O09000; Q9CRD5; DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 2. DT 13-OCT-2009, entry version 91. DE RecName: Full=Nuclear receptor coactivator 3; DE Short=NCoA-3; DE EC=2.3.1.48; DE AltName: Full=Thyroid hormone receptor activator molecule 1; DE Short=TRAM-1; DE Short=ACTR; DE AltName: Full=Receptor-associated coactivator 3; DE Short=RAC-3; DE AltName: Full=Amplified in breast cancer-1 protein homolog; DE Short=AIB-1; DE AltName: Full=Steroid receptor coactivator protein 3; DE Short=SRC-3; DE AltName: Full=CBP-interacting protein; DE Short=p/CIP; DE Short=pCIP; GN Name=Ncoa3; Synonyms=Aib1, Pcip, Rac3, Tram1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH CREBBP; ESR AND RARA. RX MEDLINE=97336097; 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 RT nuclear-receptor function."; RL Nature 387:677-684(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1360-1398. RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX MEDLINE=20300909; PubMed=10823921; DOI=10.1073/pnas.120166297; RA Xu J., Liao L., Ning G., Yoshida-Komiya H., Deng C., O'Malley B.W.; RT "The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) RT is required for normal growth, puberty, female reproductive function, RT and mammary gland development."; RL Proc. Natl. Acad. Sci. U.S.A. 97:6379-6384(2000). RN [4] RP INTERACTION WITH CARM1. RX MEDLINE=99316081; 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., RA Aswad D.W., Stallcup M.R.; RT "Regulation of transcription by a protein methyltransferase."; RL Science 284:2174-2177(1999). RN [5] RP METHYLATION BY CARM1. RX MEDLINE=21625315; PubMed=11701890; DOI=10.1126/science.1065961; RA Xu W., Chen H., Du K., Asahara H., Tini M., Emerson B.M., Montminy M., RA Evans R.M.; RT "A transcriptional switch mediated by cofactor methylation."; RL Science 294:2507-2511(2001). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-544; SER-720; RP SER-847 AND SER-1049, AND MASS SPECTROMETRY. RC TISSUE=Macrophage; 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). CC -!- FUNCTION: Nuclear receptor coactivator that directly binds nuclear CC receptors and stimulates the transcriptional activities in a CC hormone-dependent fashion. Plays a central role in creating a CC multisubunit coactivator complex, probably via remodeling of CC chromatin. Involved in the coactivation of different nuclear CC receptors, such as for steroids (GR and ER), retinoids (RARs and CC RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids CC (PPARs). Displays histone acetyltransferase activity. Also CC involved in the coactivation of the NF-kappa-B pathway via its CC interaction with the NFKB1 subunit (By similarity). CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + histone = CoA + acetylhistone. CC -!- ENZYME REGULATION: Coactivator activity on nuclear receptors and CC NF-kappa-B pathways is enhanced by various hormones, and the TNF CC cytokine, respectively. TNF stimulation probably enhances CC phosphorylation, which in turn activates coactivator function. In CC contrast, acetylation by CREBBP apparently suppresses coactivation CC of target genes by disrupting its association with nuclear CC receptors (By similarity). CC -!- SUBUNIT: Interacts with the histone acetyltransferase protein CC CREBBP. These two proteins are present in a complex containing CC NCOA2, IKKA, IKKB and IKBKG. Interacts with PCAF and NR3C1 (By CC similarity). Interacts with CARM1. Interacts with CASP8AP2. CC Interacts with ATAD2 and this interaction is enhanced by estradiol CC (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By CC similarity). Note=Mainly cytoplasmic and weakly nuclear. Upon TNF CC activation and subsequent phosphorylation, it translocates from CC the cytoplasm to the nucleus (By similarity). CC -!- TISSUE SPECIFICITY: Not expressed in all steroid sensitive CC tissues. Highly expressed in the female reproductive system, in CC both oocyte and smooth muscle cells of the oviduct, but not CC expressed in the uterine endometrium. Highly expressed in mammary CC glands. Expressed moderately in smooth muscle cells of both blood CC vessels and intestines, and weakly expressed in hepatocytes. In CC brain, highly expressed in neurons of the hyppocampus, and in CC mitral cell and granule layers of the olfactory bulb. Expressed CC moderately in the internal layer of cerebellum. Not expressed in CC the spinal chord, cardiac muscle, skeletal muscle, thymus and CC pancreas. CC -!- DOMAIN: Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Motifs CC 1 and 2 are essential for the association with nuclear receptors, CC and constitute the RID domain (Receptor-interacting domain) (By CC similarity). CC -!- PTM: Acetylated by CREBBP. Acetylation occurs in the RID domain, CC and disrupts the interaction with nuclear receptors and regulates CC its function (By similarity). CC -!- PTM: Methylated by CARM1. CC -!- PTM: Phosphorylated by IKK complex. Regulated its function (By CC similarity). CC -!- DISRUPTION PHENOTYPE: Defects result in diverse phenotype of CC postnatal growth retardation, such as dwarfism, delayed puberty, CC abnormal reproductive fucntion and mammary gland growth CC retardation. CC -!- SIMILARITY: Belongs to the SRC/p160 nuclear receptor coactivator CC family. CC -!- SIMILARITY: Contains 1 basic helix-loop-helix (bHLH) domain. CC -!- SIMILARITY: Contains 1 PAS (PER-ARNT-SIM) domain. 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; AF000581; AAC05020.1; -; mRNA. DR EMBL; AK021229; -; NOT_ANNOTATED_CDS; mRNA. DR IPI; IPI00761976; -. DR UniGene; Mm.1011; -. DR HSSP; Q9Y6Q9; 1KBH. DR SMR; O09000; 1052-1098. DR STRING; O09000; -. DR PhosphoSite; O09000; -. DR PRIDE; O09000; -. DR Ensembl; ENSMUST00000088095; ENSMUSP00000085416; ENSMUSG00000027678; Mus musculus. DR Ensembl; ENSMUST00000099082; ENSMUSP00000096681; ENSMUSG00000027678; Mus musculus. DR MGI; MGI:1276535; Ncoa3. DR HOVERGEN; O09000; -. DR BRENDA; 2.3.1.48; 244. DR ArrayExpress; O09000; -. DR Bgee; O09000; -. DR CleanEx; MM_NCOA3; -. DR CleanEx; MM_RAC3; -. DR Genevestigator; O09000; -. DR GermOnline; ENSMUSG00000027678; Mus musculus. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0004402; F:histone acetyltransferase activity; IEA:EC. DR GO; GO:0035257; F:nuclear hormone receptor binding; IEA:InterPro. DR GO; GO:0004871; F:signal transducer activity; IEA:InterPro. DR GO; GO:0003713; F:transcription coactivator activity; IEA:InterPro. DR GO; GO:0048589; P:developmental growth; IMP:MGI. DR GO; GO:0060744; P:mammary gland branching involved in thelarche; IMP:MGI. DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:InterPro. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR GO; GO:0006350; P:transcription; IEA:UniProtKB-KW. DR GO; GO:0060068; P:vagina development; IMP:MGI. DR InterPro; IPR010011; DUF1518. DR InterPro; IPR001092; HLH_basic. DR InterPro; IPR014920; Nuc_rcpt_coact_Ncoa-typ. DR InterPro; IPR017426; Nuclear_rcpt_coactivator. DR InterPro; IPR000014; PAS. DR InterPro; IPR013767; PAS_fold. DR InterPro; IPR014935; SRC-1. DR Pfam; PF07469; DUF1518; 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; SM00091; PAS; 1. DR PROSITE; PS50888; HLH; 1. DR PROSITE; PS50112; PAS; 1. PE 1: Evidence at protein level; KW Acetylation; Activator; Acyltransferase; Cytoplasm; Methylation; KW Nucleus; Phosphoprotein; Repeat; Transcription; KW Transcription regulation; Transferase. FT CHAIN 1 1398 Nuclear receptor coactivator 3. FT /FTId=PRO_0000094407. FT DOMAIN 45 81 Helix-loop-helix motif. FT DOMAIN 111 181 PAS. FT DOMAIN 1104 1278 Acetyltransferase. FT DNA_BIND 36 44 Basic motif. FT REGION 949 1113 Interaction with CREBBP (By similarity). FT MOTIF 678 682 LXXLL motif 1. FT MOTIF 730 734 LXXLL motif 2. FT MOTIF 1041 1045 LXXLL motif 3. FT COMPBIAS 429 664 Ser-rich. FT COMPBIAS 965 987 Poly-Gln. FT MOD_RES 215 215 Phosphoserine. FT MOD_RES 544 544 Phosphoserine. FT MOD_RES 609 609 N6-acetyllysine; by CREBBP (By FT similarity). FT MOD_RES 612 612 N6-acetyllysine; by CREBBP (By FT similarity). FT MOD_RES 613 613 N6-acetyllysine; by CREBBP (By FT similarity). FT MOD_RES 680 680 N6-acetyllysine (By similarity). FT MOD_RES 720 720 Phosphoserine. FT MOD_RES 847 847 Phosphoserine. FT MOD_RES 1049 1049 Phosphoserine. SQ SEQUENCE 1398 AA; 151574 MW; EF44E92735816C24 CRC64; MSGLGESSLD PLAAESRKRK LPCDAPGQGL VYSGEKWRRE QESKYIEELA ELISANLSDI DNFNVKPDKC AILKETVRQI RQIKEQGKTI SSDDDVQKAD VSSTGQGVID KDSLGPLLLQ ALDGFLFVVN RDGNIVFVSE NVTQYLQYKQ EDLVNTSVYS ILHEPRRKDF LNTYQNPQLM EFLGLMRTRD KKAPYILIVR MLMKTHDILE DVNASPETRQ RYETMQCFAL SQPRAMLEEG EDLQCCMICV ARRVTAPFPS SPESFITRHD LSGKVVNIDT NSLRSSMRPG FEDIIRRCIQ RFFSLNDGQS WSQKRHYQEA YVHGHAETPV YRFSLADGTI VSAQTKSKLF RNPVTNDRHG FISTHFLQRE QNGYRPNPIP QDKGIRPPAA GCGVSMSPNQ NVQMMGSRTY GVPDPSNTGQ MGGARYGASS SVASLTPGQS LQSPSSYQNS SYGLSMSSPP HGSPGLGPNQ QNIMISPRNR GSPKMASHQF SPAAGAHSPM GPSGNTGSHS FSSSSLSALQ AISEGVGTSL LSTLSSPGPK LDNSPNMNIS QPSKVSGQDS KSPLGLYCEQ NPVESSVCQS NSRDPQVKKE SKESSGEVSE TPRGPLESKG HKKLLQLLTC SSDDRGHSSL TNSPLDPNCK DSSVSVTSPS GVSSSTSGTV SSTSNVHGSL LQEKHRILHK LLQNGNSPAE VAKITAEATG KDTSSTASCG EGTTRQEQLS PKKKENNALL RYLLDRDDPS DVLAKELQPQ ADSGDSKLSQ CSCSTNPSSG QEKDPKIKTE TNDEVSGDLD NLDAILGDLT SSDFYNNPTN GGHPGAKQQM FAGPSSLGLR SPQPVQSVRP PYNRAVSLDS PVSVGSGPPV KNVSAFPGLP KQPILAGNPR MMDSQENYGA NMGPNRNVPV NPTSSPGDWG LANSRASRME PLASSPLGRT GADYSATLPR PAMGGSVPTL PLRSNRLPGA RPSLQQQQQQ QQQQQQQQQQ QQQQQQQMLQ MRTGEIPMGM GVNPYSPAVQ SNQPGSWPEG MLSMEQGPHG SQNRPLLRNS LDDLLGPPSN AEGQSDERAL LDQLHTFLSN TDATGLEEID RALGIPELVN QGQALESKQD VFQGQEAAVM MDQKAALYGQ TYPAQGPPLQ GGFNLQGQSP SFNSMMGQIS QQGSFPLQGM HPRAGLVRPR TNTPKQLRMQ LQQRLQGQQF LNQSRQALEM KMENPAGTAV MRPMMPQAFF NAQMAAQQKR ELMSHHLQQQ RMAMMMSQPQ PQAFSPPPNV TASPSMDGVL AGSAMPQAPP QQFPYPANYG MGQPPEPAFG RGSSPPSAMM SSRMGPSQNA MVQHPQPTPM YQPSDMKGWP SGNLARNGSF PQQQFAPQGN PAAYNMVHMN SSGGHLGQMA MTPMPMSGMP MGPDQKYC //