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O09000 (NCOA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1398 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Interacts with NPAS2 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 processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainRepeat
   Molecular functionActivator
Acyltransferase
Transferase
   PTMAcetylation
Methylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdevelopmental growth

Inferred from mutant phenotype PubMed 10751423. Source: MGI

labyrinthine layer morphogenesis

Inferred from genetic interaction PubMed 20685850. Source: MGI

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-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

vagina development

Inferred from mutant phenotype PubMed 10751423. Source: MGI

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 11555636. Source: MGI

   Molecular_functionchromatin binding

Inferred from direct assay PubMed 16109736. Source: MGI

histone acetyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

ligand-dependent nuclear receptor transcription coactivator activity

Inferred from electronic annotation. Source: InterPro

signal transducer activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 13981397Nuclear receptor coactivator 3
PRO_0000094407

Regions

Domain26 – 8358bHLH
Domain111 – 18171PAS
Region949 – 1113165Interaction with CREBBP By similarity
Region1104 – 1278175Acetyltransferase
Motif678 – 6825LXXLL motif 1
Motif730 – 7345LXXLL motif 2
Motif1041 – 10455LXXLL motif 3
Compositional bias429 – 664236Ser-rich
Compositional bias965 – 98723Poly-Gln

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue2151Phosphoserine Ref.6
Modified residue5441Phosphoserine Ref.6
Modified residue5941Phosphoserine; by CK1 By similarity
Modified residue6091N6-acetyllysine; alternate Ref.7
Modified residue6091N6-acetyllysine; by CREBBP; alternate By similarity
Modified residue6121N6-acetyllysine; alternate Ref.7
Modified residue6121N6-acetyllysine; by CREBBP; alternate By similarity
Modified residue6131N6-acetyllysine; alternate Ref.7
Modified residue6131N6-acetyllysine; by CREBBP; alternate By similarity
Modified residue6801N6-acetyllysine By similarity
Modified residue7201Phosphoserine Ref.6
Modified residue8471Phosphoserine Ref.6
Modified residue8501Phosphoserine Ref.6

Sequences

Sequence LengthMass (Da)Tools
O09000 [UniParc].

Last modified August 1, 1998. Version 2.
Checksum: EF44E92735816C24

FASTA1,398151,574
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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-850, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-609; LYS-612 AND LYS-613, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF000581 mRNA. Translation: AAC05020.1.
AK021229 mRNA. No translation available.
UniGeneMm.469663.

3D structure databases

ProteinModelPortalO09000.
SMRO09000. Positions 35-365, 1052-1098.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO09000. 12 interactions.
MINTMINT-1531012.
STRING10090.ENSMUSP00000085416.

PTM databases

PhosphoSiteO09000.

Proteomic databases

PaxDbO09000.
PRIDEO09000.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:1276535. Ncoa3.

Phylogenomic databases

eggNOGNOG315556.
HOGENOMHOG000230947.
HOVERGENHBG052583.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.
REACT_200794. Mus musculus biological processes.

Gene expression databases

CleanExMM_NCOA3.
MM_RAC3.
GenevestigatorO09000.

Family and domain databases

Gene3D4.10.630.10. 2 hits.
InterProIPR011598. bHLH_dom.
IPR010011. DUF1518.
IPR028818. NCOA3.
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]
PANTHERPTHR10684. PTHR10684. 1 hit.
PTHR10684:SF3. PTHR10684:SF3. 1 hit.
PfamPF07469. DUF1518. 1 hit.
PF08815. Nuc_rec_co-act. 1 hit.
PF00989. PAS. 1 hit.
PF08832. SRC-1. 1 hit.
[Graphical view]
PIRSFPIRSF038181. Nuclear_receptor_coactivator. 1 hit.
SMARTSM00353. HLH. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
SSF69125. SSF69125. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNCOA3. mouse.
PROO09000.
SOURCESearch...

Entry information

Entry nameNCOA3_MOUSE
AccessionPrimary (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: June 11, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot