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 22-JUL-2008, entry version 81.
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, 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).
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).
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 -!- 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 -!- MISCELLANEOUS: Defects in NCOA3 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.
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DR EMBL; AF000581; AAC05020.1; -; mRNA.
DR EMBL; AK021229; -; NOT_ANNOTATED_CDS; mRNA.
DR UniGene; Mm.1011; -.
DR HSSP; Q9Y6Q9; 1KBH.
DR SMR; O09000; 1052-1098.
DR PhosphoSite; O09000; -.
DR Ensembl; ENSMUSG00000027678; Mus musculus.
DR MGI; MGI:1276535; Ncoa3.
DR HOVERGEN; O09000; -.
DR ArrayExpress; O09000; -.
DR CleanEx; MM_NCOA3; -.
DR CleanEx; MM_RAC3; -.
DR GermOnline; ENSMUSG00000027678; Mus musculus.
DR GO; GO:0005634; C:nucleus; IDA: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 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 847 847 Phosphoserine (By similarity).
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
//