ID MED1_HUMAN Reviewed; 1581 AA. AC Q15648; A2RRQ6; O43810; O75447; Q6P9H7; Q6PK58; Q9HD39; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 11-SEP-2007, sequence version 4. DT 05-OCT-2010, entry version 107. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 1; DE AltName: Full=Activator-recruited cofactor 205 kDa component; DE Short=ARC205; DE AltName: Full=Mediator complex subunit 1; DE AltName: Full=Peroxisome proliferator-activated receptor-binding protein; DE Short=PBP; DE Short=PPAR-binding protein; DE AltName: Full=Thyroid hormone receptor-associated protein complex 220 kDa component; DE Short=Trap220; DE AltName: Full=Thyroid receptor-interacting protein 2; DE Short=TR-interacting protein 2; DE Short=TRIP-2; DE AltName: Full=Vitamin D receptor-interacting protein complex component DRIP205; DE AltName: Full=p53 regulatory protein RB18A; GN Name=MED1; GN Synonyms=ARC205, CRSP1, CRSP200, DRIP205, DRIP230, PBP, PPARBP, GN PPARGBP, RB18A, TRAP220, TRIP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DNA-BINDING, INTERACTION WITH RP TP53, AND TISSUE SPECIFICITY. RC TISSUE=Heart; RX MEDLINE=98105695; PubMed=9444950; DOI=10.1038/sj.onc.1201492; RA Drane P., Barel M., Balbo M., Frade R.; RT "Identification of RB18A, a 205 kDa new p53 regulatory protein which RT shares antigenic and functional properties with p53."; RL Oncogene 15:3013-3024(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 157-168; RP 943-952 AND 1432-1442, FUNCTION, INTERACTION WITH ESR1; PPARA; PPARG; RP RARA; RXRA; THRA AND VDR, TISSUE SPECIFICITY, AND MUTAGENESIS OF RP 607-LEU-LEU-608 AND 648-LEU-LEU-649. RX MEDLINE=98318590; PubMed=9653119; DOI=10.1073/pnas.95.14.7939; RA Yuan C.-X., Ito M., Fondell J.D., Fu Z.-Y., Roeder R.G.; RT "The TRAP220 component of a thyroid hormone receptor-associated RT protein (TRAP) coactivator complex interacts directly with nuclear RT receptors in a ligand-dependent fashion."; RL Proc. Natl. Acad. Sci. U.S.A. 95:7939-7944(1998). RN [3] RP ERRATUM. RA Yuan C.-X., Ito M., Fondell J.D., Fu Z.-Y., Roeder R.G.; RL Proc. Natl. Acad. Sci. U.S.A. 95:14584-14584(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Colon, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 1-13 AND 1452-1464, AND IDENTIFICATION IN THE ARC RP COMPLEX. RX MEDLINE=99249346; PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., RA Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed RT transcriptional activation."; RL Nature 398:828-832(1999). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-1581 (ISOFORM 1), INTERACTION WITH RP VDR, AND MUTAGENESIS OF 607-LEU-LEU-608 AND 648-LEU-LEU-649. RX MEDLINE=20198455; PubMed=10733574; RX DOI=10.1128/MCB.20.8.2718-2726.2000; RA Rachez C., Gamble M., Chang C.-P.B., Atkins G.B., Lazar M.A., RA Freedman L.P.; RT "The DRIP complex and SRC-1/p160 coactivators share similar nuclear RT receptor binding determinants but constitute functionally distinct RT complexes."; RL Mol. Cell. Biol. 20:2718-2726(2000). RN [8] RP PROTEIN SEQUENCE OF 307-315 AND 584-597, IDENTIFICATION IN THE DRIP RP COMPLEX, AND INTERACTION WITH VDR. RC TISSUE=Cervix carcinoma; RX MEDLINE=99249345; PubMed=10235266; DOI=10.1038/19783; RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., RA Naeaer A.M., Erdjument-Bromage H., Tempst P., Freedman L.P.; RT "Ligand-dependent transcription activation by nuclear receptors RT requires the DRIP complex."; RL Nature 398:824-828(1999). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 622-711. RX MEDLINE=95295737; PubMed=7776974; DOI=10.1210/me.9.2.243; RA Lee J.W., Choi H.-S., Gyuris J., Brent R., Moore D.D.; RT "Two classes of proteins dependent on either the presence or absence RT of thyroid hormone for interaction with the thyroid hormone RT receptor."; RL Mol. Endocrinol. 9:243-254(1995). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SMCC RP COMPLEX. RX MEDLINE=99149022; PubMed=10024883; DOI=10.1016/S1097-2765(00)80178-1; RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., RA Martinez E., Qin J., Roeder R.G.; RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in RT transcription regulation."; RL Mol. Cell 3:97-108(1999). RN [11] RP ERRATUM. RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., RA Martinez E., Qin J., Roeder R.G.; RL Mol. Cell 3:541-541(1999). RN [12] RP FUNCTION, AND INTERACTION WITH MED24; THRA; THRB AND VDR. RX MEDLINE=99333122; PubMed=10406464; DOI=10.1210/me.13.7.1130; RA Zhang J., Fondell J.D.; RT "Identification of mouse TRAP100: a transcriptional coregulatory RT factor for thyroid hormone and vitamin D receptors."; RL Mol. Endocrinol. 13:1130-1140(1999). RN [13] RP INTERACTION WITH ESR1; ESR2 AND VDR, AND MUTAGENESIS OF RP 607-LEU-LEU-608 AND 648-LEU-LEU-649. RX PubMed=10770935; DOI=10.1074/jbc.M002013200; RA Burakov D., Wong C.-W., Rachez C., Cheskis B.J., Freedman L.P.; RT "Functional interactions between the estrogen receptor and DRIP205, a RT subunit of the heteromeric DRIP coactivator complex."; RL J. Biol. Chem. 275:20928-20934(2000). RN [14] RP INTERACTION WITH ESR1 AND ESR2, AND MUTAGENESIS OF 599-SER--GLY-612; RP LEU-604; LEU-607; LEU-645 AND LEU-648. RX PubMed=11303023; DOI=10.1074/jbc.M011651200; RA Waernmark A., Almloef T., Leers J., Gustafsson J.-A., Treuter E.; RT "Differential recruitment of the mammalian mediator subunit TRAP220 by RT estrogen receptors ERalpha and ERbeta."; RL J. Biol. Chem. 276:23397-23404(2001). RN [15] RP FUNCTION, INTERACTION WITH AR, AND ASSOCIATION WITH PROMOTER REGIONS. RX PubMed=12218053; DOI=10.1074/jbc.M206061200; RA Wang Q., Sharma D., Ren Y., Fondell J.D.; RT "A coregulatory role for the TRAP-mediator complex in androgen RT receptor-mediated gene expression."; RL J. Biol. Chem. 277:42852-42858(2002). RN [16] RP FUNCTION, AND INTERACTION OF THE MEDIATOR COMPLEX WITH PPARG. RX PubMed=12037571; DOI=10.1038/417563a; RA Ge K., Guermah M., Yuan C.-X., Ito M., Wallberg A.E., Spiegelman B.M., RA Roeder R.G.; RT "Transcription coactivator TRAP220 is required for PPAR gamma 2- RT stimulated adipogenesis."; RL Nature 417:563-567(2002). RN [17] RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE RP MEDIATOR COMPLEX, AND INTERACTION OF THE MEDIATOR COMPLEX WITH ESR1 RP AND ESR2. RX PubMed=11867769; DOI=10.1073/pnas.261715899; RA Kang Y.K., Guermah M., Yuan C.-X., Roeder R.G.; RT "The TRAP/Mediator coactivator complex interacts directly with RT estrogen receptors alpha and beta through the TRAP220 subunit and RT directly enhances estrogen receptor function in vitro."; RL Proc. Natl. Acad. Sci. U.S.A. 99:2642-2647(2002). RN [18] RP ASSOCIATION WITH PROMOTER REGIONS. RX PubMed=12034878; DOI=10.1073/pnas.122004799; RA Sharma D., Fondell J.D.; RT "Ordered recruitment of histone acetyltransferases and the RT TRAP/Mediator complex to thyroid hormone-responsive promoters in RT vivo."; RL Proc. Natl. Acad. Sci. U.S.A. 99:7934-7939(2002). RN [19] RP FUNCTION, INTERACTION WITH ESR1; PPARG; RARA; RXRA AND THRB, AND RP MUTAGENESIS OF 600-GLN--SER-612; 607-LEU-LEU-608; 639-THR--PRO-653 AND RP 648-LEU-LEU-649. RX PubMed=12556447; DOI=10.1074/jbc.M212950200; RA Coulthard V.H., Matsuda S., Heery D.M.; RT "An extended LXXLL motif sequence determines the nuclear receptor RT binding specificity of TRAP220."; RL J. Biol. Chem. 278:10942-10951(2003). RN [20] RP FUNCTION, INTERACTION WITH PPARGC1A, AND MUTAGENESIS OF RP 607-LEU-LEU-608 AND 648-LEU-LEU-649. RX PubMed=14636573; DOI=10.1016/S1097-2765(03)00391-5; RA Wallberg A.E., Yamamura S., Malik S., Spiegelman B.M., Roeder R.G.; RT "Coordination of p300-mediated chromatin remodeling and TRAP/mediator RT function through coactivator PGC-1alpha."; RL Mol. Cell 12:1137-1149(2003). RN [21] RP FUNCTION, INTERACTION WITH ESR1, AND SUBCELLULAR LOCATION. RX PubMed=15471764; DOI=10.1074/jbc.M409778200; RA Wu Q., Burghardt R., Safe S.; RT "Vitamin D-interacting protein 205 (DRIP205) coactivation of estrogen RT receptor alpha (ERalpha) involves multiple domains of both proteins."; RL J. Biol. Chem. 279:53602-53612(2004). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE RP MEDIATOR COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., RA Conaway J.W., Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [23] RP FUNCTION, INTERACTION OF THE MEDIATOR COMPLEX WITH THRA, AND RP MUTAGENESIS OF 607-LEU-LEU-608 AND 648-LEU-LEU-649. RX PubMed=15340084; DOI=10.1128/MCB.24.18.8244-8254.2004; RA Malik S., Guermah M., Yuan C.-X., Wu W., Yamamura S., Roeder R.G.; RT "Structural and functional organization of TRAP220, the TRAP/mediator RT subunit that is targeted by nuclear receptors."; RL Mol. Cell. Biol. 24:8244-8254(2004). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; THR-805 AND RP THR-1051, AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [25] RP FUNCTION, ASSOCIATION WITH PROMOTER REGIONS, INTERACTION WITH CCNC; RP MED6; MED10; MED11; MED12; MED13; MED14; MED15; MED16; MED17; MED18; RP MED19; MED20; MED21; MED23; MED24; MED25; MED26; MED28; MED29 AND RP MED30, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE RP MEDIATOR COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA RP POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [26] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-1032 AND THR-1457, AND RP MUTAGENESIS OF THR-1032 AND THR-1457. RX PubMed=16314496; DOI=10.1128/MCB.25.24.10695-10710.2005; RA Pandey P.K., Udayakumar T.S., Lin X., Sharma D., Shapiro P.S., RA Fondell J.D.; RT "Activation of TRAP/mediator subunit TRAP220/Med1 is regulated by RT mitogen-activated protein kinase-dependent phosphorylation."; RL Mol. Cell. Biol. 25:10695-10710(2005). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-770; SER-771; SER-772 RP AND SER-774, AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [28] RP FUNCTION, INTERACTION WITH GABPA, ASSOCIATION WITH PROMOTER REGIONS, RP AND SUBCELLULAR LOCATION. RX PubMed=16574658; DOI=10.1074/jbc.M600163200; RA Udayakumar T.S., Belakavadi M., Choi K.-H., Pandey P.K., Fondell J.D.; RT "Regulation of Aurora-A kinase gene expression via GABP recruitment of RT TRAP220/MED1."; RL J. Biol. Chem. 281:14691-14699(2006). RN [29] RP INTERACTION WITH CDK8. RX PubMed=17000779; DOI=10.1128/MCB.00443-06; RA Zhou H., Kim S., Ishii S., Boyer T.G.; RT "Mediator modulates Gli3-dependent Sonic hedgehog signaling."; RL Mol. Cell. Biol. 26:8667-8682(2006). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-795; THR-805; THR-1051 RP AND THR-1057, AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein RT phosphorylation analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-953 AND SER-1134, AND RP MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664; SER-770; SER-771; RP SER-772; THR-805; THR-1051; THR-1057; SER-1155; SER-1207; THR-1215; RP SER-1403 AND SER-1433, AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664; THR-1051; THR-1057; RP SER-1207; THR-1215; SER-1463; SER-1479; SER-1481 AND SER-1482, AND RP MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1049; THR-1051; RP THR-1057; SER-1207; THR-1215; SER-1223; SER-1252; SER-1433; SER-1439; RP THR-1440; SER-1463; SER-1479 AND SER-1482, AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664; SER-770; SER-771; RP SER-772; SER-774; THR-805; SER-1049; THR-1051; THR-1215; SER-1232; RP SER-1433; SER-1479; SER-1481 AND SER-1482, AND MASS SPECTROMETRY. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664; SER-1049; THR-1051; RP THR-1057; SER-1433; THR-1440; SER-1463; SER-1479; SER-1481 AND RP SER-1482, AND MASS SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [38] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-15; LYS-1177; LYS-1354 AND RP LYS-1529, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). CC -!- FUNCTION: Component of the Mediator complex, a coactivator CC involved in the regulated transcription of nearly all RNA CC polymerase II-dependent genes. Mediator functions as a bridge to CC convey information from gene-specific regulatory proteins to the CC basal RNA polymerase II transcription machinery. Mediator is CC recruited to promoters by direct interactions with regulatory CC proteins and serves as a scaffold for the assembly of a functional CC preinitiation complex with RNA polymerase II and the general CC transcription factors. CC -!- SUBUNIT: Interacts with GATA1 and YWHAH (By similarity). Component CC of the Mediator complex, which is composed of MED1, MED4, MED6, CC MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, CC MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a CC distinct module termed the CDK8 module. Mediator containing the CC CDK8 module is less active than Mediator lacking this module in CC supporting transcriptional activation. Individual preparations of CC the Mediator complex lacking one or more distinct subunits have CC been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. This CC subunit specifically interacts with a number of nuclear receptors CC in a ligand-dependent fashion including AR, ESR1, ESR2, PPARA, CC PPARG, RXRA, RXRG, THRA, THRB and VDR. Interacts with CTNNB1, CC GABPA, GLI3, PPARGC1A and TP53. Binds DNA. CC -!- INTERACTION: CC P37231:PPARG; NbExp=1; IntAct=EBI-394459, EBI-781384; CC P10827:THRA; NbExp=1; IntAct=EBI-394459, EBI-286285; CC -!- SUBCELLULAR LOCATION: Nucleus. Note=A subset of the protein may CC enter the nucleolus subsequent to phosphorylation by MAPK1 or CC MAPK3. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15648-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15648-3; Sequence=VSP_027906, VSP_027907; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC -!- PTM: Phosphorylated by MAPK1 or MAPK3 during G2/M phase which may CC enhance protein stability and promote entry into the nucleolus. CC Phosphorylated upon DNA damage, probably by ATM or ATR. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 1 family. CC -!- SEQUENCE CAUTION: CC Sequence=AAC39854.1; Type=Frameshift; Positions=543, 545; CC Sequence=AAH06517.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; CC Sequence=CAA73867.1; Type=Frameshift; Positions=4; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Y13467; CAA73867.1; ALT_FRAME; mRNA. DR EMBL; AF055994; AAC39854.1; ALT_FRAME; mRNA. DR EMBL; CH471152; EAW60575.1; -; Genomic_DNA. DR EMBL; BC006517; AAH06517.1; ALT_TERM; mRNA. DR EMBL; BC060758; AAH60758.1; -; mRNA. DR EMBL; BC131783; AAI31784.1; -; mRNA. DR EMBL; AF283812; AAF98352.1; -; mRNA. DR EMBL; L40366; AAC41736.1; -; mRNA. DR IPI; IPI00790747; -. DR IPI; IPI00829826; -. DR RefSeq; NP_004765.2; -. DR UniGene; Hs.643754; -. DR PDB; 1RJK; X-ray; 1.99 A; C=640-652. DR PDB; 1RK3; X-ray; 2.20 A; C=640-652. DR PDB; 1RKG; X-ray; 1.90 A; C=640-652. DR PDB; 1RKH; X-ray; 2.28 A; C=640-652. DR PDB; 2O4J; X-ray; 1.74 A; C=640-652. DR PDB; 2O4R; X-ray; 1.98 A; C=640-652. DR PDB; 2ZFX; X-ray; 1.99 A; C=640-652. DR PDB; 3A2H; X-ray; 2.50 A; B=640-652. DR PDBsum; 1RJK; -. DR PDBsum; 1RK3; -. DR PDBsum; 1RKG; -. DR PDBsum; 1RKH; -. DR PDBsum; 2O4J; -. DR PDBsum; 2O4R; -. DR PDBsum; 2ZFX; -. DR PDBsum; 3A2H; -. DR ProteinModelPortal; Q15648; -. DR DIP; DIP-24212N; -. DR IntAct; Q15648; 20. DR MINT; MINT-1345780; -. DR STRING; Q15648; -. DR PhosphoSite; Q15648; -. DR PRIDE; Q15648; -. DR Ensembl; ENST00000300651; ENSP00000300651; ENSG00000125686. DR GeneID; 5469; -. DR KEGG; hsa:5469; -. DR UCSC; uc002hru.2; human. DR UCSC; uc002hrv.2; human. DR CTD; 5469; -. DR GeneCards; GC17M037560; -. DR H-InvDB; HIX0039048; -. DR HGNC; HGNC:9234; MED1. DR HPA; CAB017696; -. DR MIM; 604311; gene. DR PharmGKB; PA33556; -. DR eggNOG; prNOG08550; -. DR HOVERGEN; HBG101127; -. DR InParanoid; Q15648; -. DR OMA; RNKKPSL; -. DR OrthoDB; EOG91RSDK; -. DR PhylomeDB; Q15648; -. DR Pathway_Interaction_DB; rxr_vdr_pathway; RXR and RAR hetrodimerization with other nuclear receptor. DR Reactome; REACT_22258; Metabolism of lipids and lipoproteins. DR Reactome; REACT_71; Gene Expression. DR NextBio; 21174; -. DR ArrayExpress; Q15648; -. DR Bgee; Q15648; -. DR CleanEx; HS_MED1; -. DR Genevestigator; Q15648; -. DR GermOnline; ENSG00000125686; Homo sapiens. DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0030331; F:estrogen receptor binding; IPI:UniProtKB. DR GO; GO:0016922; F:ligand-dependent nuclear receptor binding; IPI:UniProtKB. DR GO; GO:0030374; F:ligand-dependent nuclear receptor transcrip...; NAS:UniProtKB. DR GO; GO:0042975; F:peroxisome proliferator activated receptor ...; IPI:UniProtKB. DR GO; GO:0004872; F:receptor activity; IDA:UniProtKB. DR GO; GO:0042974; F:retinoic acid receptor binding; IPI:UniProtKB. DR GO; GO:0016455; F:RNA polymerase II transcription mediator ac...; IDA:UniProtKB. DR GO; GO:0046966; F:thyroid hormone receptor binding; IDA:UniProtKB. DR GO; GO:0042809; F:vitamin D receptor binding; IPI:UniProtKB. DR GO; GO:0006702; P:androgen biosynthetic process; IMP:UniProtKB. DR GO; GO:0030521; P:androgen receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0045444; P:fat cell differentiation; IDA:MGI. DR GO; GO:0045944; P:positive regulation of transcription from R...; IDA:UniProtKB. DR GO; GO:0006367; P:transcription initiation from RNA polymeras...; IDA:UniProtKB. DR InterPro; IPR019680; Mediator_Med1_met/fun. DR Pfam; PF10744; Med1-Trap220; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Complete proteome; Direct protein sequencing; DNA-binding; Nucleus; KW Phosphoprotein; Polymorphism; Repeat; Transcription; KW Transcription regulation. FT CHAIN 1 1581 Mediator of RNA polymerase II FT transcription subunit 1. FT /FTId=PRO_0000058552. FT REGION 1 670 Interaction with the Mediator complex and FT THRA. FT REGION 16 590 Interaction with ESR1. FT REGION 108 212 Interaction with the Mediator complex. FT REGION 215 390 Interaction with the Mediator complex. FT REGION 405 644 Interaction with THRA. FT REGION 542 789 Interaction with VDR. FT REGION 622 701 Interaction with PPARGC1A and THRA. FT REGION 637 716 Interaction with GATA1 (By similarity). FT REGION 656 1066 Interaction with ESR1. FT REGION 1249 1421 Interaction with TP53. FT MOTIF 604 608 LXXLL motif 1. FT MOTIF 645 649 LXXLL motif 2. FT COMPBIAS 1078 1482 Ser-rich. FT COMPBIAS 1496 1529 Lys-rich. FT MOD_RES 15 15 N6-acetyllysine. FT MOD_RES 18 18 Phosphoserine. FT MOD_RES 664 664 Phosphoserine. FT MOD_RES 770 770 Phosphoserine. FT MOD_RES 771 771 Phosphoserine. FT MOD_RES 772 772 Phosphoserine. FT MOD_RES 774 774 Phosphoserine. FT MOD_RES 795 795 Phosphoserine. FT MOD_RES 805 805 Phosphothreonine. FT MOD_RES 953 953 Phosphoserine. FT MOD_RES 1032 1032 Phosphothreonine; by MAPK1 or MAPK3. FT MOD_RES 1049 1049 Phosphoserine. FT MOD_RES 1051 1051 Phosphothreonine. FT MOD_RES 1057 1057 Phosphothreonine. FT MOD_RES 1134 1134 Phosphoserine. FT MOD_RES 1155 1155 Phosphoserine. FT MOD_RES 1177 1177 N6-acetyllysine. FT MOD_RES 1207 1207 Phosphoserine. FT MOD_RES 1215 1215 Phosphothreonine. FT MOD_RES 1223 1223 Phosphoserine. FT MOD_RES 1232 1232 Phosphoserine. FT MOD_RES 1252 1252 Phosphoserine. FT MOD_RES 1354 1354 N6-acetyllysine. FT MOD_RES 1403 1403 Phosphoserine. FT MOD_RES 1433 1433 Phosphoserine. FT MOD_RES 1439 1439 Phosphoserine. FT MOD_RES 1440 1440 Phosphothreonine. FT MOD_RES 1457 1457 Phosphothreonine; by MAPK1 or MAPK3. FT MOD_RES 1463 1463 Phosphoserine. FT MOD_RES 1479 1479 Phosphoserine. FT MOD_RES 1481 1481 Phosphoserine. FT MOD_RES 1482 1482 Phosphoserine. FT MOD_RES 1529 1529 N6-acetyllysine. FT VAR_SEQ 548 556 YGMTTGNNP -> SKNPELGSG (in isoform 2). FT /FTId=VSP_027906. FT VAR_SEQ 557 1581 Missing (in isoform 2). FT /FTId=VSP_027907. FT VARIANT 753 753 P -> T (in dbSNP:rs1139825). FT /FTId=VAR_053955. FT VARIANT 1240 1240 S -> G (in dbSNP:rs35668211). FT /FTId=VAR_034938. FT MUTAGEN 599 612 SQNPILTSLLQITG->EKHKILHRLLQDSS: Enhances FT interaction with ESR1. FT MUTAGEN 600 612 QNPILTSLLQITG->RHKILHRLLQEGS: Enhances FT interaction with ESR1. FT MUTAGEN 604 604 L->A: Impairs interaction with ESR2; when FT associated with A-607; A-645 and A-648. FT MUTAGEN 607 608 LL->AA: Impairs interaction with ESR1, FT PPARG, RXRA and THRB. Impairs interaction FT with THRA; when associated with 648-A-A- FT 649. FT MUTAGEN 607 607 L->A: Impairs interaction with ESR2; when FT associated with A-604; A-645 and A-648. FT MUTAGEN 639 653 TKNHPMLMNLLKDNP->VSRHKILHRLLQEGS: FT Enhances interaction with ESR1. FT MUTAGEN 645 645 L->A: Impairs interaction with ESR2; when FT associated with A-604; A-607 and A-648. FT MUTAGEN 648 649 LL->AA: Impairs interaction with ESR1, FT PPARG, THRB and VDR. Impairs interaction FT with THRA; when associated with 607-A-A- FT 608. FT MUTAGEN 648 648 L->A: Impairs interaction with ESR2; when FT associated with A-604; A-607 and A-645. FT MUTAGEN 1032 1032 T->A: Enhances protein stability; when FT associated with A-1457. FT MUTAGEN 1457 1457 T->A: Enhances protein stability; when FT associated with A-1032. FT CONFLICT 86 86 R -> G (in Ref. 1; CAA73867). FT CONFLICT 147 147 F -> S (in Ref. 1; CAA73867). FT CONFLICT 471 472 DS -> GL (in Ref. 1; CAA73867). FT CONFLICT 563 563 P -> S (in Ref. 1; CAA73867 and 7; FT AAF98352). FT CONFLICT 573 573 T -> A (in Ref. 1; CAA73867 and 7; FT AAF98352). FT CONFLICT 651 651 D -> N (in Ref. 5; AAH06517). FT CONFLICT 673 673 S -> F (in Ref. 9; AAC41736). FT CONFLICT 702 708 Missing (in Ref. 9; AAC41736). FT CONFLICT 721 721 N -> K (in Ref. 2; AAC39854). FT CONFLICT 728 728 M -> R (in Ref. 7; AAF98352). FT CONFLICT 756 761 VPHPQP -> FYLTPQ (in Ref. 5; AAH06517). FT CONFLICT 1388 1388 G -> S (in Ref. 2; AAC39854). FT HELIX 643 649 SQ SEQUENCE 1581 AA; 168478 MW; FCE0FE87EF08B887 CRC64; MKAQGETEES EKLSKMSSLL ERLHAKFNQN RPWSETIKLV RQVMEKRVVM SSGGHQHLVS CLETLQKALK VTSLPAMTDR LESIARQNGL GSHLSASGTE CYITSDMFYV EVQLDPAGQL CDVKVAHHGE NPVSCPELVQ QLREKNFDEF SKHLKGLVNL YNLPGDNKLK TKMYLALQSL EQDLSKMAIM YWKATNAGPL DKILHGSVGY LTPRSGGHLM NLKYYVSPSD LLDDKTASPI ILHENNVSRS LGMNASVTIE GTSAVYKLPI APLIMGSHPV DNKWTPSFSS ITSANSVDLP ACFFLKFPQP IPVSRAFVQK LQNCTGIPLF ETQPTYAPLY ELITQFELSK DPDPIPLNHN MRFYAALPGQ QHCYFLNKDA PLPDGRSLQG TLVSKITFQH PGRVPLILNL IRHQVAYNTL IGSCVKRTIL KEDSPGLLQF EVCPLSESRF SVSFQHPVND SLVCVVMDVQ DSTHVSCKLY KGLSDALICT DDFIAKVVQR CMSIPVTMRA IRRKAETIQA DTPALSLIAE TVEDMVKKNL PPASSPGYGM TTGNNPMSGT TTPTNTFPGG PITTLFNMSM SIKDRHESVG HGEDFSKVSQ NPILTSLLQI TGNGGSTIGS SPTPPHHTPP PVSSMAGNTK NHPMLMNLLK DNPAQDFSTL YGSSPLERQN SSSGSPRMEI CSGSNKTKKK KSSRLPPEKP KHQTEDDFQR ELFSMDVDSQ NPIFDVNMTA DTLDTPHITP APSQCSTPPT TYPQPVPHPQ PSIQRMVRLS SSDSIGPDVT DILSDIAEEA SKLPSTSDDC PAIGTPLRDS SSSGHSQSTL FDSDVFQTNN NENPYTDPAD LIADAAGSPS SDSPTNHFFH DGVDFNPDLL NSQSQSGFGE EYFDESSQSG DNDDFKGFAS QALNTLGVPM LGGDNGETKF KGNNQADTVD FSIISVAGKA LAPADLMEHH SGSQGPLLTT GDLGKEKTQK RVKEGNGTSN STLSGPGLDS KPGKRSRTPS NDGKSKDKPP KRKKADTEGK SPSHSSSNRP FTPPTSTGGS KSPGSAGRSQ TPPGVATPPI PKITIQIPKG TVMVGKPSSH SQYTSSGSVS SSGSKSHHSH SSSSSSSAST SGKMKSSKSE GSSSSKLSSS MYSSQGSSGS SQSKNSSQSG GKPGSSPITK HGLSSGSSST KMKPQGKPSS LMNPSLSKPN ISPSHSRPPG GSDKLASPMK PVPGTPPSSK AKSPISSGSG GSHMSGTSSS SGMKSSSGLG SSGSLSQKTP PSSNSCTASS SSFSSSGSSM SSSQNQHGSS KGKSPSRNKK PSLTAVIDKL KHGVVTSGPG GEDPLDGQMG VSTNSSSHPM SSKHNMSGGE FQGKREKSDK DKSKVSTSGS SVDSSKKTSE SKNVGSTGVA KIIISKHDGG SPSIKAKVTL QKPGESSGEG LRPQMASSKN YGSPLISGST PKHERGSPSH SKSPAYTPQN LDSESESGSS IAEKSYQNSP SSDDGIRPLP EYSTEKHKKH KKEKKKVKDK DRDRDRDKDR DKKKSHSIKP ESWSKSPISS DQSLSMTSNT ILSADRPSRL SPDFMIGEED DDLMDVALIG N //