ID NCO3_MOUSE STANDARD; PRT; 1398 AA. AC O09000; Q9CRD5; DT 28-FEB-2003 (Rel. 41, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 25-OCT-2004 (Rel. 45, Last annotation update) DE Nuclear receptor coactivator 3 (EC 2.3.1.48) (NCoA-3) (Thyroid hormone DE receptor activator molecule 1) (TRAM-1) (ACTR) (Receptor-associated DE coactivator 3) (RAC-3) (Amplified in breast cancer-1 protein homolog) DE (AIB-1) (Steroid receptor coactivator protein 3) (SRC-3) (CBP- DE interacting protein) (p/CIP) (pCIP). GN Name=Ncoa3; Synonyms=Aib1, Pcip, Rac3, Tram1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Rodentia; Sciurognathi; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP SEQUENCE FROM N.A., 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 SEQUENCE OF 1360-1398 FROM N.A. RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cells; RX MEDLINE=22354683; PubMed=12466851; DOI=10.1038/nature01266; RA Okazaki Y., Furuno M., Kasukawa T., Adachi J., Bono H., Kondo S., RA Nikaido I., Osato N., Saito R., Suzuki H., Yamanaka I., Kiyosawa H., RA Yagi K., Tomaru Y., Hasegawa Y., Nogami A., Schonbach C., Gojobori T., RA Baldarelli R., Hill D.P., Bult C., Hume D.A., Quackenbush J., RA Schriml L.M., Kanapin A., Matsuda H., Batalov S., Beisel K.W., RA Blake J.A., Bradt D., Brusic V., Chothia C., Corbani L.E., Cousins S., RA Dalla E., Dragani T.A., Fletcher C.F., Forrest A., Frazer K.S., RA Gaasterland T., Gariboldi M., Gissi C., Godzik A., Gough J., RA Grimmond S., Gustincich S., Hirokawa N., Jackson I.J., Jarvis E.D., RA Kanai A., Kawaji H., Kawasawa Y., Kedzierski R.M., King B.L., RA Konagaya A., Kurochkin I.V., Lee Y., Lenhard B., Lyons P.A., RA Maglott D.R., Maltais L., Marchionni L., McKenzie L., Miki H., RA Nagashima T., Numata K., Okido T., Pavan W.J., Pertea G., Pesole G., RA Petrovsky N., Pillai R., Pontius J.U., Qi D., Ramachandran S., RA Ravasi T., Reed J.C., Reed D.J., Reid J., Ring B.Z., Ringwald M., RA Sandelin A., Schneider C., Semple C.A., Setou M., Shimada K., RA Sultana R., Takenaka Y., Taylor M.S., Teasdale R.D., Tomita M., RA Verardo R., Wagner L., Wahlestedt C., Wang Y., Watanabe Y., Wells C., RA Wilming L.G., Wynshaw-Boris A., Yanagisawa M., Yang I., Yang L., RA Yuan Z., Zavolan M., Zhu Y., Zimmer A., Carninci P., Hayatsu N., RA Hirozane-Kishikawa T., Konno H., Nakamura M., Sakazume N., Sato K., RA Shiraki T., Waki K., Kawai J., Aizawa K., Arakawa T., Fukuda S., RA Hara A., Hashizume W., Imotani K., Ishii Y., Itoh M., Kagawa I., RA Miyazaki A., Sakai K., Sasaki D., Shibata K., Shinagawa A., RA Yasunishi A., Yoshino M., Waterston R., Lander E.S., Rogers J., RA Birney E., Hayashizaki Y.; RT "Analysis of the mouse transcriptome based on functional annotation of RT 60,770 full-length cDNAs."; RL Nature 420:563-573(2002). RN [3] RP FUNCTION, AND TISSUE SPECIFICITY. 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). 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 + acetyl-histone. 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 (By similarity). CC -!- SUBCELLULAR LOCATION: Mainly cytoplasmic and weakly nuclear. Upon CC TNF activation and subsequent phosphorylation, it translocates CC from 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 cerebrellum. 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: Phosphorylated by IKK complex and acetylated by CREBBP. CC Acetylation occurs in the RID domain, and disrupts the interaction CC with nuclear receptors. Both modifications regulate its function CC (By similarity). CC -!- MISCELLANEOUS: Defects in NCOA3 result in diverse phenotype of CC post natal 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) dimerization 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; -. DR EMBL; AK021229; -; NOT_ANNOTATED_CDS. DR HSSP; Q9Y6Q9; 1KBH. DR TRANSFAC; T04638; -. DR MGD; MGI:1276535; Ncoa3. DR GO; GO:0005634; C:nucleus; IDA. DR InterPro; IPR010011; DUF1518. DR InterPro; IPR001092; HLH_basic. DR InterPro; IPR009110; Nuc_recept_coact. DR InterPro; IPR000014; PAS. DR InterPro; IPR008955; Src1_receptcoact. DR Pfam; PF07469; DUF1518; 1. DR Pfam; PF00989; PAS; 1. DR SMART; SM00353; HLH; 1. DR SMART; SM00091; PAS; 1. DR PROSITE; PS50888; HLH; 1. DR PROSITE; PS50112; PAS; 1. KW Acetylation; Activator; Acyltransferase; Nuclear protein; KW Phosphorylation; Repeat; Transcription regulation; Transferase. FT DNA_BIND 36 44 Basic motif. FT DOMAIN 45 81 Helix-loop-helix motif (By similarity). FT DOMAIN 111 181 PAS. FT DOMAIN 949 1113 Interaction with CREBBP (By similarity). FT DOMAIN 1104 1278 Acetyltransferase (By similarity). FT DOMAIN 429 664 Ser-rich. FT DOMAIN 965 987 Poly-Gln. FT SITE 678 682 LXXLL motif 1. FT SITE 730 734 LXXLL motif 2. FT SITE 1041 1045 LXXLL motif 3. 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). SQ SEQUENCE 1398 AA; 151573 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 //