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 05-FEB-2025, entry version 220. 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=12; 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 PDB; 8TQ2; EM; 3.80 A; C=1-2177. DR PDB; 8TQC; EM; 3.80 A; C=1-2177. DR PDB; 8TQW; EM; 8.20 A; c=1-2177. DR PDBsum; 8TQ2; -. DR PDBsum; 8TQC; -. DR PDBsum; 8TQW; -. DR AlphaFoldDB; Q93074; -. DR EMDB; EMD-41499; -. DR EMDB; EMD-41502; -. DR EMDB; EMD-41565; -. DR SMR; Q93074; -. DR BioGRID; 115293; 178. 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; 88. DR MINT; Q93074; -. DR STRING; 9606.ENSP00000363193; -. DR GlyGen; Q93074; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q93074; -. DR PhosphoSitePlus; Q93074; -. DR BioMuta; MED12; -. DR DMDM; 209572775; -. DR jPOST; Q93074; -. DR MassIVE; Q93074; -. DR PaxDb; 9606-ENSP00000363193; -. DR PeptideAtlas; Q93074; -. DR ProteomicsDB; 75701; -. [Q93074-1] DR ProteomicsDB; 75702; -. [Q93074-2] DR ProteomicsDB; 75703; -. [Q93074-3] DR Pumba; Q93074; -. DR Antibodypedia; 562; 290 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 AGR; HGNC:11957; -. 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; 2728; Blepharophimosis-intellectual disability syndrome, Ohdo type. DR Orphanet; 93932; FG syndrome type 1. DR Orphanet; 1415; Hardikar syndrome. 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; 20828at2759; -. 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 Reactome; R-HSA-9833110; RSV-host interactions. DR Reactome; R-HSA-9841922; MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis. DR SignaLink; Q93074; -. DR SIGNOR; Q93074; -. DR BioGRID-ORCS; 9968; 263 hits in 832 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 199 other cell types or tissues. DR ExpressionAtlas; Q93074; baseline and differential. DR GO; GO:1990508; C:CKM complex; IPI:ComplexPortal. 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: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:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. 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 by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl. DR GO; GO:0016567; P:protein ubiquitination; 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; IPR051647; Mediator_comp_sub12. DR InterPro; IPR019035; Mediator_Med12. DR InterPro; IPR021989; Mediator_Med12_catenin-bd. DR InterPro; IPR021990; Mediator_Med12_LCEWAV. DR PANTHER; PTHR46007; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 12; 1. DR PANTHER; PTHR46007:SF2; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 12; 1. 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 3D-structure; Acetylation; Activator; Alternative splicing; KW Direct protein sequencing; Disease variant; Intellectual disability; KW Methylation; Nucleus; Phosphoprotein; Proteomics identification; KW Reference proteome; Repressor; Transcription; 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 702..717 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1450..1469 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1758..1771 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1784..1793 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1927..1938 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; uncertain significance; 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 //