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Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (PubMed:10406464, PubMed:11867769, PubMed:12037571, PubMed:12218053, PubMed:12556447, PubMed:14636573, PubMed:15340084, PubMed:15471764, PubMed:15989967, PubMed:16574658, PubMed:9653119). Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q925J9"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10024883"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10235266"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10235267"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10406464"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10478845"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10733574"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10770935"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11303023"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11867769"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12037571"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12218053"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12556447"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14636573"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15175163"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15340084"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15471764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15989967"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16574658"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17000779"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19786558"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24245781"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29997176"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9444950"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9653119"}],"value":"Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. This subunit specifically interacts with a number of nuclear receptors in a ligand-dependent fashion including AR, ESR1, ESR2, PPARA, PPARG, RORA, RXRA, RXRG, THRA, THRB and VDR. Interacts with CTNNB1, GABPA, GLI3, PPARGC1A and TP53. Interacts with YWHAH. Interacts with CLOCK; this interaction requires the presence of THRAP3 (By similarity). Interacts with GATA1 and CCAR1. Interacts with NR4A3 (By similarity). Interacts (via IBM motif) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (PubMed:29997176). Interacts with USP22 (By similarity). Interacts with PRDM16; promoting recruitment of the Mediator complex to chromatin and activation of genes that are highly expressed in brown adipocytes (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"P03372","geneName":"ESR1","intActId":"EBI-78473"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"P15976","geneName":"GATA1","intActId":"EBI-3909284"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"Q13503","geneName":"MED21","intActId":"EBI-394678"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"O43513","geneName":"MED7","intActId":"EBI-394632"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"P10276","geneName":"RARA","intActId":"EBI-413374"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"P19793","geneName":"RXRA","intActId":"EBI-78598"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"P10827","geneName":"THRA","intActId":"EBI-286285"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15648","intActId":"EBI-394459"},"interactantTwo":{"uniProtKBAccession":"P11473","geneName":"VDR","intActId":"EBI-286357"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"value":"A subset of the protein may enter the nucleolus subsequent to phosphorylation by MAPK1 or MAPK3"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15471764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16314496"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16574658"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q15648-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q15648-3"],"sequenceIds":["VSP_027906","VSP_027907"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9444950"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9653119"}],"value":"Ubiquitously expressed"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16314496"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29997176"}],"value":"Phosphorylated by MAPK1 or MAPK3 during G2/M phase which may enhance protein stability and promote entry into the nucleolus (PubMed:16314496). 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