O09000 (NCOA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor coactivator 3
Short name=NCoA-3
EC=2.3.1.48

Alternative name(s):
Amplified in breast cancer-1 protein homolog
Short name=AIB-1
CBP-interacting protein
Short name=p/CIP
Short name=pCIP
Receptor-associated coactivator 3
Short name=RAC-3
Steroid receptor coactivator protein 3
Short name=SRC-3
Thyroid hormone receptor activator molecule 1
Short name=ACTR
Short name=TRAM-1

Gene names

Name:	Ncoa3
Synonyms:	Aib1, Pcip, Rac3, Tram1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1398 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, probably via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit By similarity. Ref.3
Catalytic activity	Acetyl-CoA + [histone] = CoA + acetyl-[histone].
Enzyme regulation	Coactivator activity on nuclear receptors and NF-kappa-B pathways is enhanced by various hormones, and the TNF cytokine, respectively. TNF stimulation probably enhances phosphorylation, which in turn activates coactivator function. In contrast, acetylation by CREBBP apparently suppresses coactivation of target genes by disrupting its association with nuclear receptors By similarity.
Subunit structure	Interacts with the histone acetyltransferase protein CREBBP. These two proteins are present in a complex containing NCOA2, IKKA, IKKB and IKBKG. Interacts with PCAF and NR3C1 By similarity. Interacts with CARM1. Interacts with CASP8AP2. Interacts with ATAD2 and this interaction is enhanced by estradiol By similarity. Interacts with PSMB9. Binds to CSNK1D By similarity. Found in a complex containing NCOA3, AR and MAK. Interacts with DDX5 By similarity. Ref.1 Ref.4
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Mainly cytoplasmic and weakly nuclear. Upon TNF activation and subsequent phosphorylation, it translocates from the cytoplasm to the nucleus By similarity.
Tissue specificity	Not expressed in all steroid sensitive tissues. Highly expressed in the female reproductive system, in both oocyte and smooth muscle cells of the oviduct, but not expressed in the uterine endometrium. Highly expressed in mammary glands. Expressed moderately in smooth muscle cells of both blood vessels and intestines, and weakly expressed in hepatocytes. In brain, highly expressed in neurons of the hyppocampus, and in mitral cell and granule layers of the olfactory bulb. Expressed moderately in the internal layer of cerebellum. Not expressed in the spinal chord, cardiac muscle, skeletal muscle, thymus and pancreas. Ref.3
Domain	Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Motifs 1 and 2 are essential for the association with nuclear receptors, and constitute the RID domain (Receptor-interacting domain) By similarity.
Post-translational modification	Acetylated by CREBBP. Acetylation occurs in the RID domain, and disrupts the interaction with nuclear receptors and regulates its function By similarity. Methylated by CARM1. Ref.5 Phosphorylated by IKK complex. Regulated its function By similarity.
Disruption phenotype	Defects result in diverse phenotype of postnatal growth retardation, such as dwarfism, delayed puberty, abnormal reproductive function and mammary gland growth retardation. Ref.3
Sequence similarities	Belongs to the SRC/p160 nuclear receptor coactivator family. Contains 1 bHLH (basic helix-loop-helix) domain. Contains 1 PAS (PER-ARNT-SIM) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Repeat
Molecular function	Activator Acyltransferase Transferase
PTM	Acetylation Methylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	developmental growth Inferred from mutant phenotype PubMed 10751423. Source: MGI histone acetylation Inferred from electronic annotation. Source: GOC mammary gland branching involved in thelarche Inferred from mutant phenotype PubMed 11015591. Source: MGI multicellular organism growth Inferred from mutant phenotype Ref.3. Source: MGI regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW vagina development Inferred from mutant phenotype PubMed 10751423. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	chromatin binding Inferred from direct assay PubMed 16109736. Source: MGI histone acetyltransferase activity Inferred from electronic annotation. Source: EC signal transducer activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1398	1398	Nuclear receptor coactivator 3		PRO_0000094407
Regions
	Domain	26 – 83	58	bHLH
	Domain	111 – 181	71	PAS
	Region	949 – 1113	165	Interaction with CREBBP By similarity
	Region	1104 – 1278	175	Acetyltransferase
	Motif	678 – 682	5	LXXLL motif 1
	Motif	730 – 734	5	LXXLL motif 2
	Motif	1041 – 1045	5	LXXLL motif 3
	Compositional bias	429 – 664	236	Ser-rich
	Compositional bias	965 – 987	23	Poly-Gln
Amino acid modifications
	Modified residue	215	1	Phosphoserine Ref.6
	Modified residue	544	1	Phosphoserine Ref.6
	Modified residue	594	1	Phosphoserine; by CK1 By similarity
	Modified residue	609	1	N6-acetyllysine; by CREBBP By similarity
	Modified residue	612	1	N6-acetyllysine; by CREBBP By similarity
	Modified residue	613	1	N6-acetyllysine; by CREBBP By similarity
	Modified residue	680	1	N6-acetyllysine By similarity
	Modified residue	720	1	Phosphoserine Ref.6
	Modified residue	847	1	Phosphoserine Ref.6
	Modified residue	1049	1	Phosphoserine Ref.6

Sequences

	Sequence		Length	Mass (Da)
	O09000 [UniParc]. Last modified August 1, 1998. Version 2. Checksum: EF44E92735816C24	FASTA	1,398	151,574
	10 20 30 40 50 60 MSGLGESSLD PLAAESRKRK LPCDAPGQGL VYSGEKWRRE QESKYIEELA ELISANLSDI 70 80 90 100 110 120 DNFNVKPDKC AILKETVRQI RQIKEQGKTI SSDDDVQKAD VSSTGQGVID KDSLGPLLLQ 130 140 150 160 170 180 ALDGFLFVVN RDGNIVFVSE NVTQYLQYKQ EDLVNTSVYS ILHEPRRKDF LNTYQNPQLM 190 200 210 220 230 240 EFLGLMRTRD KKAPYILIVR MLMKTHDILE DVNASPETRQ RYETMQCFAL SQPRAMLEEG 250 260 270 280 290 300 EDLQCCMICV ARRVTAPFPS SPESFITRHD LSGKVVNIDT NSLRSSMRPG FEDIIRRCIQ 310 320 330 340 350 360 RFFSLNDGQS WSQKRHYQEA YVHGHAETPV YRFSLADGTI VSAQTKSKLF RNPVTNDRHG 370 380 390 400 410 420 FISTHFLQRE QNGYRPNPIP QDKGIRPPAA GCGVSMSPNQ NVQMMGSRTY GVPDPSNTGQ 430 440 450 460 470 480 MGGARYGASS SVASLTPGQS LQSPSSYQNS SYGLSMSSPP HGSPGLGPNQ QNIMISPRNR 490 500 510 520 530 540 GSPKMASHQF SPAAGAHSPM GPSGNTGSHS FSSSSLSALQ AISEGVGTSL LSTLSSPGPK 550 560 570 580 590 600 LDNSPNMNIS QPSKVSGQDS KSPLGLYCEQ NPVESSVCQS NSRDPQVKKE SKESSGEVSE 610 620 630 640 650 660 TPRGPLESKG HKKLLQLLTC SSDDRGHSSL TNSPLDPNCK DSSVSVTSPS GVSSSTSGTV 670 680 690 700 710 720 SSTSNVHGSL LQEKHRILHK LLQNGNSPAE VAKITAEATG KDTSSTASCG EGTTRQEQLS 730 740 750 760 770 780 PKKKENNALL RYLLDRDDPS DVLAKELQPQ ADSGDSKLSQ CSCSTNPSSG QEKDPKIKTE 790 800 810 820 830 840 TNDEVSGDLD NLDAILGDLT SSDFYNNPTN GGHPGAKQQM FAGPSSLGLR SPQPVQSVRP 850 860 870 880 890 900 PYNRAVSLDS PVSVGSGPPV KNVSAFPGLP KQPILAGNPR MMDSQENYGA NMGPNRNVPV 910 920 930 940 950 960 NPTSSPGDWG LANSRASRME PLASSPLGRT GADYSATLPR PAMGGSVPTL PLRSNRLPGA 970 980 990 1000 1010 1020 RPSLQQQQQQ QQQQQQQQQQ QQQQQQQMLQ MRTGEIPMGM GVNPYSPAVQ SNQPGSWPEG 1030 1040 1050 1060 1070 1080 MLSMEQGPHG SQNRPLLRNS LDDLLGPPSN AEGQSDERAL LDQLHTFLSN TDATGLEEID 1090 1100 1110 1120 1130 1140 RALGIPELVN QGQALESKQD VFQGQEAAVM MDQKAALYGQ TYPAQGPPLQ GGFNLQGQSP 1150 1160 1170 1180 1190 1200 SFNSMMGQIS QQGSFPLQGM HPRAGLVRPR TNTPKQLRMQ LQQRLQGQQF LNQSRQALEM 1210 1220 1230 1240 1250 1260 KMENPAGTAV MRPMMPQAFF NAQMAAQQKR ELMSHHLQQQ RMAMMMSQPQ PQAFSPPPNV 1270 1280 1290 1300 1310 1320 TASPSMDGVL AGSAMPQAPP QQFPYPANYG MGQPPEPAFG RGSSPPSAMM SSRMGPSQNA 1330 1340 1350 1360 1370 1380 MVQHPQPTPM YQPSDMKGWP SGNLARNGSF PQQQFAPQGN PAAYNMVHMN SSGGHLGQMA 1390 MTPMPMSGMP MGPDQKYC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function." Torchia J., Rose D.W., Inostroza J., Kamei Y., Westin S., Glass C.K., Rosenfeld M.G. Nature 387:677-684(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CREBBP; ESR AND RARA.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1360-1398. Strain: C57BL/6J. Tissue: Embryonic stem cell.
[3]	"The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development." Xu J., Liao L., Ning G., Yoshida-Komiya H., Deng C., O'Malley B.W. Proc. Natl. Acad. Sci. U.S.A. 97:6379-6384(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[4]	"Regulation of transcription by a protein methyltransferase." Chen D., Ma H., Hong H., Koh S.S., Huang S.-M., Schurter B.T., Aswad D.W., Stallcup M.R. Science 284:2174-2177(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CARM1.
[5]	"A transcriptional switch mediated by cofactor methylation." Xu W., Chen H., Du K., Asahara H., Tini M., Emerson B.M., Montminy M., Evans R.M. Science 294:2507-2511(2001) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION BY CARM1.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-544; SER-720; SER-847 AND SER-1049, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF000581 mRNA. Translation: AAC05020.1. AK021229 mRNA. No translation available.
IPI	IPI00761976.
UniGene	Mm.469663.
3D structure databases
ProteinModelPortal	O09000.
SMR	O09000. Positions 35-365, 1052-1098.
ModBase	Search...
Protein-protein interaction databases
IntAct	O09000. 12 interactions.
STRING	10090.ENSMUSP00000085416.
PTM databases
PhosphoSite	O09000.
Proteomic databases
PaxDb	O09000.
PRIDE	O09000.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:1276535. Ncoa3.
Phylogenomic databases
eggNOG	NOG315556.
HOGENOM	HOG000230947.
HOVERGEN	HBG052583.
Enzyme and pathway databases
Reactome	REACT_127416. Developmental Biology. REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
Gene expression databases
CleanEx	MM_NCOA3. MM_RAC3.
Genevestigator	O09000.
GermOnline	ENSMUSG00000027678. Mus musculus.
Family and domain databases
Gene3D	4.10.630.10. 2 hits.
InterPro	IPR011598. bHLH_dom. IPR010011. DUF1518. IPR009110. Nuc_rcpt_coact. IPR014920. Nuc_rcpt_coact_Ncoa-typ. IPR017426. Nuclear_rcpt_coactivator. IPR000014. PAS. IPR013767. PAS_fold. IPR014935. SRC-1. IPR008955. Src1_rcpt_coact. [Graphical view]
Pfam	PF07469. DUF1518. 1 hit. PF08815. Nuc_rec_co-act. 1 hit. PF00989. PAS. 1 hit. PF08832. SRC-1. 1 hit. [Graphical view]
PIRSF	PIRSF038181. Nuclear_receptor_coactivator. 1 hit.
SMART	SM00353. HLH. 1 hit. SM00091. PAS. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit. SSF69125. Nuc_recept_coact. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. PS50112. PAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NCOA3. mouse.
SOURCE	Search...

Entry information

Entry name

NCOA3_MOUSE

Accession

Primary (citable) accession number: O09000
Secondary accession number(s): Q9CRD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program