BioPAX pathway converted from "Runx3:Cbfb binds the Rorc gene promoter" in the Reactome database.Runx3:Cbfb binds the Rorc gene promoterRunx3:Cbfb binds the Rorc gene promoterMouse Runx3, in complex with its heterodimerization partner Cbfb, binds the promoter of the Rorc (Ror-gamma) gene, encoding nuclear retinoid-related orphan receptor-gamma. The Runx binding site in the mouse Rorc promoter, TGTGGT, is conserved in the human RORC promoter. Human RUNX3 protein can also bind the mouse Rorc promoter. Mouse Runx3 is expressed in innate lymphoid cell lineages ILC1 and ILC3, but not ILC2 (Ebihara et al. 2015). Authored: Orlic-Milacic, Marija, 2016-12-12Reviewed: Ito, Yoshiaki, 2017-01-31Reviewed: Chuang, Linda Shyue Huey, 2017-01-31Edited: Orlic-Milacic, Marija, 2017-01-31Reactome DB_ID: 89492871nucleoplasmGO0005654ENSEMBL:ENSMUSG00000028150 RorcRorcReactomehttp://www.reactome.orgMus musculusNCBI Taxonomy10090ENSEMBLENSMUSG00000028150Reactome DB_ID: 89492891Runx3:Cbfb [nucleoplasm]Runx3:CbfbReactome DB_ID: 89492881UniProt:Q64131 Runx3Runx3Pebp2a3Cbfa3Runx3Aml2FUNCTION Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). May be involved in the control of cellular proliferation and/or differentiation. In association with ZFHX3, upregulates CDKN1A promoter activity following TGF-beta stimulation (By similarity). CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation (PubMed:18258917). CBF complexes binding to the transcriptional silencer is essential for recruitment of nuclear protein complexes that catalyze epigenetic modifications to establish epigenetic ZBTB7B silencing (PubMed:23481257).SUBUNIT Heterodimer with CBFB. RUNX3 binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization (Probable). Interacts with TLE1 and SUV39H1. The tyrosine phosphorylated form (via runt domain) interacts with SRC (via protein kinase domain). Interacts with FYN and LCK. Interacts with FOXP3. Interacts with ZFHX3. Interacts with TBX21 (PubMed:21151104).DOMAIN A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes.PTM Phosphorylated on tyrosine residues by SRC. Phosphorylated by LCK and FYN (By similarity).UniProtQ64131Chain Coordinates1EQUAL409EQUALReactome DB_ID: 88654181UniProt:Q08024 CbfbCbfbPebp2bPebpb2CbfbFUNCTION Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation (PubMed:18258917).SUBUNIT Heterodimer with RUNX1, RUNX2 and RUNX3 (Probable). Interacts with COPRS. Found in a complex with PRMT5 and RUNX1 (PubMed:22193545).TISSUE SPECIFICITY Expressed in all tissues tested. Highest level in thymus, but also abundantly expressed in muscle, lung and brain.SIMILARITY Belongs to the CBF-beta family.UniProtQ080241EQUAL187EQUALReactome Database ID Release 758949289Database 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=8949289ReactomeR-MMU-89492891Reactome 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-8949289.1Reactome DB_ID: 89492861Runx3:Cbfb:Rorc gene [nucleoplasm]Runx3:Cbfb:Rorc geneReactome DB_ID: 89492871Reactome DB_ID: 89492891Reactome Database ID Release 758949286Database 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=8949286ReactomeR-MMU-89492861Reactome 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-8949286.1Reactome Database ID Release 758949284Database 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=8949284ReactomeR-MMU-89492841Reactome 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-8949284.126414766Pubmed2015Runx3 specifies lineage commitment of innate lymphoid cellsEbihara, TakashiSong, ChristinaRyu, Stacy HPlougastel-Douglas, BeatriceYang, LipingLevanon, DitsaGroner, YoramBern, Michael DStappenbeck, Thaddeus SColonna, MEgawa, TakeshiYokoyama, Wayne MNat. Immunol. 16:1124-33