MED12_HUMAN
ID MED12_HUMAN Reviewed; 2177 AA.
AC Q93074; O15410; O75557; Q9UHV6; Q9UND7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 4.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 12;
DE AltName: Full=Activator-recruited cofactor 240 kDa component;
DE Short=ARC240;
DE AltName: Full=CAG repeat protein 45;
DE AltName: Full=Mediator complex subunit 12;
DE AltName: Full=OPA-containing protein;
DE AltName: Full=Thyroid hormone receptor-associated protein complex 230 kDa component;
DE Short=Trap230;
DE AltName: Full=Trinucleotide repeat-containing gene 11 protein;
GN Name=MED12; Synonyms=ARC240, CAGH45, HOPA, KIAA0192, TNRC11, TRAP230;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 788-802
RP (ISOFORMS 1/2/3), IDENTIFICATION IN THE TRAP COMPLEX, TISSUE SPECIFICITY,
RP AND VARIANT ARG-1392.
RC TISSUE=Cervix carcinoma;
RX PubMed=10198638; DOI=10.1016/s1097-2765(00)80463-3;
RA Ito M., Yuan C.-X., Malik S., Gu W., Fondell J.D., Yamamura S., Fu Z.-Y.,
RA Zhang X., Qin J., Roeder R.G.;
RT "Identity between TRAP and SMCC complexes indicates novel pathways for the
RT function of nuclear receptors and diverse mammalian activators.";
RL Mol. Cell 3:361-370(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-2177 (ISOFORM 1), AND VARIANT
RP ARG-1392.
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 154-2177 (ISOFORM 3).
RX PubMed=9702738; DOI=10.1038/sj.mp.4000442;
RA Philibert R.A., King B.H., Cook E.H., Lee Y.-H., Stubblefield B.,
RA Damschroder-Williams P., Dea C., Palotie A., Tengstrom C., Martin B.M.,
RA Ginns E.I.;
RT "Association of an X-chromosome dodecamer insertional variant allele with
RT mental retardation.";
RL Mol. Psychiatry 3:303-309(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 154-2177 (ISOFORM 3).
RX PubMed=10480376; DOI=10.1007/s004399900084;
RA Philibert R.A., Winfield S.L., Damschroder-Williams P., Tengstrom C.,
RA Martin B.M., Ginns E.I.;
RT "The genomic structure and developmental expression patterns of the human
RT OPA-containing gene (HOPA).";
RL Hum. Genet. 105:174-178(1999).
RN [6]
RP PROTEIN SEQUENCE OF 386-418 (ISOFORMS 1/2/3), AND IDENTIFICATION IN THE ARC
RP COMPLEX.
RC TISSUE=Cervix carcinoma;
RX PubMed=10235266; DOI=10.1038/19783;
RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M.,
RA Erdjument-Bromage H., Tempst P., Freedman L.P.;
RT "Ligand-dependent transcription activation by nuclear receptors requires
RT the DRIP complex.";
RL Nature 398:824-828(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1529-2177 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9225980; DOI=10.1007/s004390050476;
RA Margolis R.L., Abraham M.R., Gatchell S.B., Li S.-H., Kidwai A.S.,
RA Breschel T.S., Stine O.C., Callahan C., McInnis M.G., Ross C.A.;
RT "cDNAs with long CAG trinucleotide repeats from human brain.";
RL Hum. Genet. 100:114-122(1997).
RN [8]
RP PROTEIN SEQUENCE OF 1674-1682 AND 1771-1782 (ISOFORMS 1/2/3), AND
RP IDENTIFICATION IN THE ARC COMPLEX.
RX PubMed=10235267; DOI=10.1038/19789;
RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.;
RT "Composite co-activator ARC mediates chromatin-directed transcriptional
RT activation.";
RL Nature 398:828-832(1999).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR
RP COMPLEX, AND INTERACTION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
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., Conaway J.W.,
RA 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 [10]
RP INTERACTION WITH MED1; MED18; MED21; MED28; MED29 AND MED30, IDENTIFICATION
RP BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND
RP ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION, AND INTERACTION WITH CTNNB1 AND MED30.
RX PubMed=16565090; DOI=10.1074/jbc.m602696200;
RA Kim S., Xu X., Hecht A., Boyer T.G.;
RT "Mediator is a transducer of Wnt/beta-catenin signaling.";
RL J. Biol. Chem. 281:14066-14075(2006).
RN [13]
RP FUNCTION, AND INTERACTION WITH MED1 AND MED10.
RX PubMed=16595664; DOI=10.1074/jbc.m601983200;
RA Baek H.J., Kang Y.K., Roeder R.G.;
RT "Human Mediator enhances basal transcription by facilitating recruitment of
RT transcription factor IIB during preinitiation complex assembly.";
RL J. Biol. Chem. 281:15172-15181(2006).
RN [14]
RP FUNCTION, AND INTERACTION WITH CDK8; CTNNB1 AND GLI3.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635 AND SER-1258, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635; SER-1258 AND SER-1269,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635; SER-698 AND SER-700, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635; SER-665 AND SER-698, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1994 AND ARG-2015, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [23]
RP VARIANT MRXSLF SER-1007.
RX PubMed=17369503; DOI=10.1136/jmg.2006.048637;
RA Schwartz C.E., Tarpey P.S., Lubs H.A., Verloes A., May M.M., Risheg H.,
RA Friez M.J., Futreal P.A., Edkins S., Teague J., Briault S., Skinner C.,
RA Bauer-Carlin A., Simensen R.J., Joseph S.M., Jones J.R., Gecz J.,
RA Stratton M.R., Raymond F.L., Stevenson R.E.;
RT "The original Lujan syndrome family has a novel missense mutation
RT (p.N1007S) in the MED12 gene.";
RL J. Med. Genet. 44:472-477(2007).
RN [24]
RP VARIANT OKS TRP-961.
RX PubMed=17334363; DOI=10.1038/ng1992;
RA Risheg H., Graham J.M. Jr., Clark R.D., Rogers R.C., Opitz J.M.,
RA Moeschler J.B., Peiffer A.P., May M., Joseph S.M., Jones J.R.,
RA Stevenson R.E., Schwartz C.E., Friez M.J.;
RT "A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia
RT syndrome.";
RL Nat. Genet. 39:451-453(2007).
RN [25]
RP VARIANTS OHDOX HIS-1148; PRO-1165 AND ASN-1729.
RX PubMed=23395478; DOI=10.1016/j.ajhg.2013.01.007;
RA Vulto-van Silfhout A.T., de Vries B.B., van Bon B.W., Hoischen A.,
RA Ruiterkamp-Versteeg M., Gilissen C., Gao F., van Zwam M., Harteveld C.L.,
RA van Essen A.J., Hamel B.C., Kleefstra T., Willemsen M.A., Yntema H.G.,
RA van Bokhoven H., Brunner H.G., Boyer T.G., de Brouwer A.P.;
RT "Mutations in MED12 cause X-linked Ohdo syndrome.";
RL Am. J. Hum. Genet. 92:401-406(2013).
RN [26]
RP VARIANT HIS-1974.
RX PubMed=26273451; DOI=10.1002/ccr3.301;
RA Bouazzi H., Lesca G., Trujillo C., Alwasiyah M.K., Munnich A.;
RT "Nonsyndromic X-linked intellectual deficiency in three brothers with a
RT novel MED12 missense mutation [c.5922G>T (p.Glu1974His)].";
RL Clin. Case Rep. 3:604-609(2015).
RN [27]
RP VARIANTS HDKR 108-ARG--TYR-2177 DEL; 1704-TRP--TYR-2177 DEL AND
RP 1874-TYR--TYR-2177 DEL, AND INVOLVEMENT IN HDKR.
RX PubMed=33244166; DOI=10.1038/s41436-020-01031-7;
RA Li D., Strong A., Shen K.M., Cassiman D., Van Dyck M., Linhares N.D.,
RA Valadares E.R., Wang T., Pena S.D.J., Jaeken J., Vergano S., Zackai E.,
RA Hing A., Chow P., Ganguly A., Scholz T., Bierhals T., Philipp D.,
RA Hakonarson H., Bhoj E.;
RT "De novo loss-of-function variants in X-linked MED12 are associated with
RT Hardikar syndrome in females.";
RL Genet. Med. 23:637-644(2021).
CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in
CC the regulated transcription of nearly all RNA polymerase II-dependent
CC genes. Mediator functions as a bridge to convey information from gene-
CC specific regulatory proteins to the basal RNA polymerase II
CC transcription machinery. Mediator is recruited to promoters by direct
CC interactions with regulatory proteins and serves as a scaffold for the
CC assembly of a functional pre-initiation complex with RNA polymerase II
CC and the general transcription factors. This subunit may specifically
CC regulate transcription of targets of the Wnt signaling pathway and SHH
CC signaling pathway. {ECO:0000269|PubMed:16565090,
CC ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:17000779}.
CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1,
CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L,
CC MED14, 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 distinct
CC module termed the CDK8 module. Mediator containing the CDK8 module is
CC less active than Mediator lacking this module in supporting
CC transcriptional activation. Individual preparations of the Mediator
CC complex lacking one or more distinct subunits have been variously
CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Also interacts with CTNNB1
CC and GLI3. {ECO:0000269|PubMed:10198638, ECO:0000269|PubMed:10235266,
CC ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:15175163,
CC ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:16565090,
CC ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:17000779}.
CC -!- INTERACTION:
CC Q93074; P51693: APLP1; NbExp=2; IntAct=EBI-394357, EBI-74648;
CC Q93074; Q06481: APLP2; NbExp=2; IntAct=EBI-394357, EBI-79306;
CC Q93074; P05067: APP; NbExp=2; IntAct=EBI-394357, EBI-77613;
CC Q93074; Q9NPJ6: MED4; NbExp=8; IntAct=EBI-394357, EBI-394607;
CC Q93074; P37173: TGFBR2; NbExp=3; IntAct=EBI-394357, EBI-296151;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q93074-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q93074-2; Sequence=VSP_035520;
CC Name=3;
CC IsoId=Q93074-3; Sequence=VSP_035521;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10198638}.
CC -!- DISEASE: Opitz-Kaveggia syndrome (OKS) [MIM:305450]: X-linked disorder
CC characterized by intellectual disability, relative macrocephaly,
CC hypotonia and constipation. {ECO:0000269|PubMed:17334363}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic,
CC Lujan-Fryns type (MRXSLF) [MIM:309520]: A disorder characterized by
CC tall stature with asthenic habitus, macrocephaly, a tall narrow face,
CC maxillary hypoplasia, a high narrow palate with dental crowding, a
CC small or receding chin, long hands with hyperextensible digits,
CC hypernasal speech, hypotonia, mild-to-moderate intellectual disability,
CC behavioral aberrations and dysgenesis of the corpus callosum.
CC {ECO:0000269|PubMed:17369503}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Ohdo syndrome, X-linked (OHDOX) [MIM:300895]: A syndrome
CC characterized by intellectual disability, feeding problems, and
CC distinctive facial appearance with coarse facial features, severe
CC blepharophimosis, ptosis, a bulbous nose, micrognathia and a small
CC mouth. Dental hypoplasia and deafness can be considered as common
CC manifestations of the syndrome. Male patients show cryptorchidism and
CC scrotal hypoplasia. {ECO:0000269|PubMed:23395478}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Hardikar syndrome (HDKR) [MIM:301068]: An X-linked dominant,
CC multiple congenital anomaly syndrome characterized by foregut
CC malformations, intestinal malrotation, liver and biliary tract disease,
CC genitourinary abnormalities, facial clefting, and pigmentary
CC retinopathy. Some patients may have congenital cardiac defects or
CC vascular abnormalities, including aortic coarctation and
CC carotid/intracranial aneurysms. Neurodevelopment and cognition is
CC normal. {ECO:0000269|PubMed:33244166}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 12 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD22033.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF117755; AAD22033.1; ALT_INIT; mRNA.
DR EMBL; AL590764; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; D83783; BAA12112.1; -; mRNA.
DR EMBL; AF071309; AAC83163.1; -; mRNA.
DR EMBL; AF132033; AAD44162.1; -; Genomic_DNA.
DR EMBL; U80742; AAB91440.1; -; mRNA.
DR CCDS; CCDS43970.1; -. [Q93074-1]
DR RefSeq; NP_005111.2; NM_005120.2. [Q93074-1]
DR AlphaFoldDB; Q93074; -.
DR BioGRID; 115293; 161.
DR ComplexPortal; CPX-3232; CKM complex variant 1.
DR ComplexPortal; CPX-3263; CKM complex variant 2.
DR CORUM; Q93074; -.
DR DIP; DIP-31459N; -.
DR IntAct; Q93074; 80.
DR MINT; Q93074; -.
DR STRING; 9606.ENSP00000363193; -.
DR iPTMnet; Q93074; -.
DR PhosphoSitePlus; Q93074; -.
DR BioMuta; MED12; -.
DR DMDM; 209572775; -.
DR EPD; Q93074; -.
DR jPOST; Q93074; -.
DR MassIVE; Q93074; -.
DR MaxQB; Q93074; -.
DR PaxDb; Q93074; -.
DR PeptideAtlas; Q93074; -.
DR PRIDE; Q93074; -.
DR ProteomicsDB; 75701; -. [Q93074-1]
DR ProteomicsDB; 75702; -. [Q93074-2]
DR ProteomicsDB; 75703; -. [Q93074-3]
DR Antibodypedia; 562; 242 antibodies from 32 providers.
DR DNASU; 9968; -.
DR Ensembl; ENST00000374080.8; ENSP00000363193.3; ENSG00000184634.17. [Q93074-1]
DR Ensembl; ENST00000374102.6; ENSP00000363215.2; ENSG00000184634.17. [Q93074-2]
DR Ensembl; ENST00000692304.1; ENSP00000508427.1; ENSG00000184634.17. [Q93074-3]
DR GeneID; 9968; -.
DR KEGG; hsa:9968; -.
DR MANE-Select; ENST00000374080.8; ENSP00000363193.3; NM_005120.3; NP_005111.2.
DR UCSC; uc004dyy.4; human. [Q93074-1]
DR CTD; 9968; -.
DR DisGeNET; 9968; -.
DR GeneCards; MED12; -.
DR GeneReviews; MED12; -.
DR HGNC; HGNC:11957; MED12.
DR HPA; ENSG00000184634; Low tissue specificity.
DR MalaCards; MED12; -.
DR MIM; 300188; gene.
DR MIM; 300895; phenotype.
DR MIM; 301068; phenotype.
DR MIM; 305450; phenotype.
DR MIM; 309520; phenotype.
DR neXtProt; NX_Q93074; -.
DR OpenTargets; ENSG00000184634; -.
DR Orphanet; 293707; Blepharophimosis-intellectual disability syndrome, MKB type.
DR Orphanet; 93932; FG syndrome type 1.
DR Orphanet; 776; Lujan-Fryns syndrome.
DR Orphanet; 777; X-linked non-syndromic intellectual disability.
DR PharmGKB; PA36645; -.
DR VEuPathDB; HostDB:ENSG00000184634; -.
DR eggNOG; KOG3598; Eukaryota.
DR GeneTree; ENSGT00440000037505; -.
DR HOGENOM; CLU_000904_1_0_1; -.
DR InParanoid; Q93074; -.
DR OMA; YQQSHDK; -.
DR OrthoDB; 15873at2759; -.
DR PhylomeDB; Q93074; -.
DR TreeFam; TF324178; -.
DR PathwayCommons; Q93074; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR SignaLink; Q93074; -.
DR SIGNOR; Q93074; -.
DR BioGRID-ORCS; 9968; 237 hits in 734 CRISPR screens.
DR ChiTaRS; MED12; human.
DR GeneWiki; MED12; -.
DR GenomeRNAi; 9968; -.
DR Pharos; Q93074; Tbio.
DR PRO; PR:Q93074; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q93074; protein.
DR Bgee; ENSG00000184634; Expressed in right adrenal gland cortex and 197 other tissues.
DR ExpressionAtlas; Q93074; baseline and differential.
DR Genevisible; Q93074; HS.
DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl.
DR GO; GO:0008013; F:beta-catenin binding; IEA:InterPro.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; NAS:UniProtKB.
DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IDA:UniProtKB.
DR GO; GO:0042809; F:nuclear vitamin D receptor binding; NAS:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0090245; P:axis elongation involved in somitogenesis; IEA:Ensembl.
DR GO; GO:1990403; P:embryonic brain development; IEA:Ensembl.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0007492; P:endoderm development; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR GO; GO:0014044; P:Schwann cell development; IEA:Ensembl.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IEA:Ensembl.
DR InterPro; IPR019035; Mediator_Med12.
DR InterPro; IPR021989; Mediator_Med12_catenin-bd.
DR InterPro; IPR021990; Mediator_Med12_LCEWAV.
DR Pfam; PF09497; Med12; 1.
DR Pfam; PF12145; Med12-LCEWAV; 1.
DR Pfam; PF12144; Med12-PQL; 1.
DR SMART; SM01281; Med12; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Direct protein sequencing;
KW Disease variant; Intellectual disability; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..2177
FT /note="Mediator of RNA polymerase II transcription subunit
FT 12"
FT /id="PRO_0000096359"
FT REGION 12..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 323..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 627..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 690..717
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1241..1266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1394..1415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1450..1474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1616..2051
FT /note="Interaction with CTNNB1 and GLI3"
FT /evidence="ECO:0000269|PubMed:17000779"
FT REGION 1738..1829
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1919..1938
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1967..1989
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2115..2149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2158..2177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 638..654
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..716
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1450..1471
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1738..1760
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2134..2149
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 80
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:A2AGH6"
FT MOD_RES 166
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 635
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 665
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 698
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 700
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1258
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 1269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 1798
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:A2AGH6"
FT MOD_RES 1899
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:A2AGH6"
FT MOD_RES 1899
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:A2AGH6"
FT MOD_RES 1910
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:A2AGH6"
FT MOD_RES 1994
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 2015
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1916
FT /note="Q -> QAKI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9225980"
FT /id="VSP_035520"
FT VAR_SEQ 1916
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10480376,
FT ECO:0000303|PubMed:9702738"
FT /id="VSP_035521"
FT VARIANT 108..2177
FT /note="Missing (in HDKR)"
FT /evidence="ECO:0000269|PubMed:33244166"
FT /id="VAR_086496"
FT VARIANT 961
FT /note="R -> W (in OKS; dbSNP:rs80338758)"
FT /evidence="ECO:0000269|PubMed:17334363"
FT /id="VAR_033112"
FT VARIANT 1007
FT /note="N -> S (in MRXSLF; dbSNP:rs80338759)"
FT /evidence="ECO:0000269|PubMed:17369503"
FT /id="VAR_037534"
FT VARIANT 1148
FT /note="R -> H (in OHDOX; dbSNP:rs387907360)"
FT /evidence="ECO:0000269|PubMed:23395478"
FT /id="VAR_069770"
FT VARIANT 1165
FT /note="S -> P (in OHDOX; dbSNP:rs387907361)"
FT /evidence="ECO:0000269|PubMed:23395478"
FT /id="VAR_069771"
FT VARIANT 1392
FT /note="Q -> R (in dbSNP:rs1139013)"
FT /evidence="ECO:0000269|PubMed:10198638,
FT ECO:0000269|PubMed:8724849"
FT /id="VAR_046672"
FT VARIANT 1704..2177
FT /note="Missing (in HDKR)"
FT /evidence="ECO:0000269|PubMed:33244166"
FT /id="VAR_086497"
FT VARIANT 1729
FT /note="H -> N (in OHDOX; dbSNP:rs387907362)"
FT /evidence="ECO:0000269|PubMed:23395478"
FT /id="VAR_069772"
FT VARIANT 1874..2177
FT /note="Missing (in HDKR)"
FT /evidence="ECO:0000269|PubMed:33244166"
FT /id="VAR_086498"
FT VARIANT 1974
FT /note="Q -> H (found in a family with X-linked intellectual
FT disability; unknown pathological significance;
FT dbSNP:rs879255528)"
FT /evidence="ECO:0000269|PubMed:26273451"
FT /id="VAR_074018"
FT CONFLICT 16
FT /note="R -> RPR (in Ref. 1; AAD22033)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="Missing (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1166
FT /note="E -> V (in Ref. 5; AAD44162)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2177 AA; 243081 MW; 7492B07BA0F6EA9D CRC64;
MAAFGILSYE HRPLKRPRLG PPDVYPQDPK QKEDELTALN VKQGFNNQPA VSGDEHGSAK
NVSFNPAKIS SNFSSIIAEK LRCNTLPDTG RRKPQVNQKD NFWLVTARSQ SAINTWFTDL
AGTKPLTQLA KKVPIFSKKE EVFGYLAKYT VPVMRAAWLI KMTCAYYAAI SETKVKKRHV
DPFMEWTQII TKYLWEQLQK MAEYYRPGPA GSGGCGSTIG PLPHDVEVAI RQWDYTEKLA
MFMFQDGMLD RHEFLTWVLE CFEKIRPGED ELLKLLLPLL LRYSGEFVQS AYLSRRLAYF
CTRRLALQLD GVSSHSSHVI SAQSTSTLPT TPAPQPPTSS TPSTPFSDLL MCPQHRPLVF
GLSCILQTIL LCCPSALVWH YSLTDSRIKT GSPLDHLPIA PSNLPMPEGN SAFTQQVRAK
LREIEQQIKE RGQAVEVRWS FDKCQEATAG FTIGRVLHTL EVLDSHSFER SDFSNSLDSL
CNRIFGLGPS KDGHEISSDD DAVVSLLCEW AVSCKRSGRH RAMVVAKLLE KRQAEIEAER
CGESEAADEK GSIASGSLSA PSAPIFQDVL LQFLDTQAPM LTDPRSESER VEFFNLVLLF
CELIRHDVFS HNMYTCTLIS RGDLAFGAPG PRPPSPFDDP ADDPEHKEAE GSSSSKLEDP
GLSESMDIDP SSSVLFEDME KPDFSLFSPT MPCEGKGSPS PEKPDVEKEV KPPPKEKIEG
TLGVLYDQPR HVQYATHFPI PQEESCSHEC NQRLVVLFGV GKQRDDARHA IKKITKDILK
VLNRKGTAET DQLAPIVPLN PGDLTFLGGE DGQKRRRNRP EAFPTAEDIF AKFQHLSHYD
QHQVTAQVSR NVLEQITSFA LGMSYHLPLV QHVQFIFDLM EYSLSISGLI DFAIQLLNEL
SVVEAELLLK SSDLVGSYTT SLCLCIVAVL RHYHACLILN QDQMAQVFEG LCGVVKHGMN
RSDGSSAERC ILAYLYDLYT SCSHLKNKFG ELFSDFCSKV KNTIYCNVEP SESNMRWAPE
FMIDTLENPA AHTFTYTGLG KSLSENPANR YSFVCNALMH VCVGHHDPDR VNDIAILCAE
LTGYCKSLSA EWLGVLKALC CSSNNGTCGF NDLLCNVDVS DLSFHDSLAT FVAILIARQC
LLLEDLIRCA AIPSLLNAAC SEQDSEPGAR LTCRILLHLF KTPQLNPCQS DGNKPTVGIR
SSCDRHLLAA SQNRIVDGAV FAVLKAVFVL GDAELKGSGF TVTGGTEELP EEEGGGGSGG
RRQGGRNISV ETASLDVYAK YVLRSICQQE WVGERCLKSL CEDSNDLQDP VLSSAQAQRL
MQLICYPHRL LDNEDGENPQ RQRIKRILQN LDQWTMRQSS LELQLMIKQT PNNEMNSLLE
NIAKATIEVF QQSAETGSSS GSTASNMPSS SKTKPVLSSL ERSGVWLVAP LIAKLPTSVQ
GHVLKAAGEE LEKGQHLGSS SRKERDRQKQ KSMSLLSQQP FLSLVLTCLK GQDEQREGLL
TSLYSQVHQI VNNWRDDQYL DDCKPKQLMH EALKLRLNLV GGMFDTVQRS TQQTTEWAML
LLEIIISGTV DMQSNNELFT TVLDMLSVLI NGTLAADMSS ISQGSMEENK RAYMNLAKKL
QKELGERQSD SLEKVRQLLP LPKQTRDVIT CEPQGSLIDT KGNKIAGFDS IFKKEGLQVS
TKQKISPWDL FEGLKPSAPL SWGWFGTVRV DRRVARGEEQ QRLLLYHTHL RPRPRAYYLE
PLPLPPEDEE PPAPTLLEPE KKAPEPPKTD KPGAAPPSTE ERKKKSTKGK KRSQPATKTE
DYGMGPGRSG PYGVTVPPDL LHHPNPGSIT HLNYRQGSIG LYTQNQPLPA GGPRVDPYRP
VRLPMQKLPT RPTYPGVLPT TMTGVMGLEP SSYKTSVYRQ QQPAVPQGQR LRQQLQQSQG
MLGQSSVHQM TPSSSYGLQT SQGYTPYVSH VGLQQHTGPA GTMVPPSYSS QPYQSTHPST
NPTLVDPTRH LQQRPSGYVH QQAPTYGHGL TSTQRFSHQT LQQTPMISTM TPMSAQGVQA
GVRSTAILPE QQQQQQQQQQ QQQQQQQQQQ QQQQQQYHIR QQQQQQILRQ QQQQQQQQQQ
QQQQQQQQQQ QQQQQHQQQQ QQQAAPPQPQ PQSQPQFQRQ GLQQTQQQQQ TAALVRQLQQ
QLSNTQPQPS TNIFGRY
