BioPAX pathway converted from "p-S MAPK6 phosphorylates NCOA3" in the Reactome database.LEFT-TO-RIGHT2.7.11p-S MAPK6 phosphorylates NCOA3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 29358nucleoplasmGENE ONTOLOGYGO:0005654ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 7529358Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29358ReactomeR-ALL-293583Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29358.3Reactomehttp://www.reactome.orgCOMPOUNDC00002additional informationMIMI:0361Ncoa3NCOA3O09000Reactome DB_ID: 9789377UniProt:O09000 Ncoa3Ncoa3Aib1PcipRac3Tram1FUNCTION 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).ACTIVITY 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 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). Interacts with NR4A3 (via AF-1 domain) (PubMed:12709428). Interacts with ESRRB; mediates the interaction between ESRRB and RNA polymerase II complexes and allows NCOA3 corecruitment to ESRRB, KLF4, NANOG, and SOX2 enhancer regions to trigger ESRRB-dependent gene activation involved in self-renewal and pluripotency (PubMed:23019124).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.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).PTM Acetylated by CREBBP. Acetylation occurs in the RID domain, and disrupts the interaction with nuclear receptors and regulates its function (By similarity).PTM Methylated by CARM1.PTM 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.SIMILARITY Belongs to the SRC/p160 nuclear receptor coactivator family.Mus musculusNCBI Taxonomy10090UniProtO090001EQUAL1424EQUALReactome Database ID Release 759789377Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9789377ReactomeR-MMU-4424881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-442488.1O09000phospho-Ncoa3p-S857 NCOA3Reactome DB_ID: 9789380857EQUALO-phospho-L-serineMODMOD:000461EQUAL1424EQUALReactome Database ID Release 759789380Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9789380ReactomeR-MMU-56870051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5687005.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 113582ADP(3-) [ChEBI:456216]ADP(3-)ADP5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 75113582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113582ReactomeR-ALL-1135823Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113582.3COMPOUNDC00008ACTIVATIONQ61532phospho-Mapk6p-S189 MAPK6Reactome DB_ID: 9789382UniProt:Q61532Mapk6UniProtQ61532189EQUAL1EQUAL721EQUALReactome Database ID Release 759789382Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9789382ReactomeR-MMU-56870151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5687015.1GENE ONTOLOGYGO:0004674gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 759789383Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9789383Reactome Database ID Release 759789385Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9789385ReactomeR-MMU-56870901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5687090.1MAPK6 is proposed to phosphorylate NCOA3 at serine 857. This phosphorylation is required for NCOA3 to interact with the transcription factor ETV4 (also known as PEA3). Together, ETV4 and NCOA3 bind to the promoters and regulate the expression of metalloprotease genes such as MMP2 and MMP10 and in this way contribute to cell motility and invasiveness in lung cancer (Long et al, 2012; Qin et al, 2008; Yan et al, 2008; Li et al, 2008; reviewed in Kostenko et al, 2012).22505454Pubmed2012ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasionLong, WFoulds, Charles EQin, JLiu, JDing, ChenLonard, David MSolis, Luisa MWistuba, Ignacio IQin, JTsai, Sophia YTsai, MJO'Malley, Bert WJ. Clin. Invest. 122:1869-8018644862Pubmed2008The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expressionQin, LiLiao, LanRedmond, AislingYoung, LeonieYuan, YuhuiChen, HongwuO'Malley, Bert WXu, JianmingMol. Cell. Biol. 28:5937-5018593949Pubmed2008Steroid receptor coactivator-3/AIB1 promotes cell migration and invasiveness through focal adhesion turnover and matrix metalloproteinase expressionYan, JunErdem, HalimeLi, RCai, YiAyala, GustavoIttmann, MYu-Lee, Li-yuanTsai, Sophia YTsai, MJCancer Res. 68:5460-818162290Pubmed2008Proto-oncogene ACTR/AIB1 promotes cancer cell invasion by up-regulating specific matrix metalloproteinase expressionLi, Li BLouie, Maggie CChen, H-WZou, June XCancer Lett. 261:64-7322800433Pubmed2012Tumour promoting and suppressing roles of the atypical MAP kinase signalling pathway ERK3/4-MK5Kostenko, SergiyDumitriu, GianinaMoens, UgoJ Mol Signal 7:9inferred from electronic annotationEVIDENCE CODEECO:0000203