MED12

Mediator complex subunit 12
Identifiers
Symbols	MED12 ; ARC240; CAGH45; FGS1; HOPA; MED12S; OHDOX; OKS; OPA1; TNRC11; TRAP230
External IDs	OMIM: 300188 MGI: 1926212 HomoloGene: 68441 GeneCards: MED12 Gene
Gene ontology Molecular function • RNA polymerase II distal enhancer sequence-specific DNA binding • RNA polymerase II transcription cofactor activity • RNA polymerase II transcription coactivator activity • chromatin binding • transcription cofactor activity • transcription coactivator activity • receptor activity • protein binding • beta-catenin binding • protein C-terminus binding • protein domain specific binding • ligand-dependent nuclear receptor transcription coactivator activity • vitamin D receptor binding • thyroid hormone receptor binding • ubiquitin protein ligase activity Cellular component • ubiquitin ligase complex • nucleus • nucleoplasm • nucleolus • centrosome • membrane • mediator complex Biological process • neural tube closure • transcription initiation from RNA polymerase II promoter • heart development • gene expression • oligodendrocyte development • Schwann cell development • protein ubiquitination • stem cell maintenance • negative regulation of Wnt signaling pathway • intracellular steroid hormone receptor signaling pathway • androgen receptor signaling pathway • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • canonical Wnt signaling pathway • Wnt signaling pathway, planar cell polarity pathway • axis elongation involved in somitogenesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9968	59024
Ensembl	ENSG00000184634	ENSMUSG00000079487
UniProt	Q93074	A2AGH6
RefSeq (mRNA)	NM_005120	NM_021521
RefSeq (protein)	NP_005111	NP_067496
Location (UCSC)	Chr X: 71.12 – 71.14 Mb	Chr X: 101.27 – 101.3 Mb
PubMed search

Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome.^[1]

Clinical significance

Mutations in MED12 are responsible for at least two different forms of X-linked dominant mental retardation, Lujan-Fryns syndrome and FG syndrome, as well as instances of prostate cancer.^[2]

Mutations in MED12 are associated to uterine leiomyomas ^[3] and breast fibroepithelial tumors (e.g. fibroadenoma and phyllodes tumors).^[4]

Interactions

MED12 has been shown to interact with:

• Calcitriol receptor,^[5][6]
• Cyclin-dependent kinase 8^[5][7]
• Estrogen receptor alpha,^[7]
• Gli3, G9a, PPARGC1A,^[8]
• MED26,^[9]
• SOX9,^[10] and
• Thyroid hormone receptor alpha.^[5]

References

1. "Entrez Gene: MED12 mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae)".
2. Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA (Jun 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nature Genetics 44 (6): 685–9. doi:10.1038/ng.2279. PMC 3673022. PMID 22610119.
3. Kämpjärvi K, Park MJ, Mehine M, Kim NH, Clark AD, Bützow R, Böhling T, Böhm J, Mecklin JP, Järvinen H, Tomlinson IP, van der Spuy ZM, Sjöberg J, Boyer TG, Vahteristo P (Sep 2014). "Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas". Human Mutation 35 (9): 1136–41. doi:10.1002/humu.22612. PMID 24980722.
4. Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, Reis-Filho JS (Nov 2015). "MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast". Histopathology 67 (5): 719–29. doi:10.1111/his.12712. PMID 25855048.
5. Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (Mar 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Molecular Cell 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. PMID 10198638.
6. Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (Jun 2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell 113 (7): 905–17. doi:10.1016/S0092-8674(03)00436-7. PMID 12837248.
7. Kang YK, Guermah M, Yuan CX, Roeder RG (Mar 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proceedings of the National Academy of Sciences of the United States of America 99 (5): 2642–7. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
8. Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (Nov 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Molecular Cell 12 (5): 1137–49. doi:10.1016/S1097-2765(03)00391-5. PMID 14636573.
9. Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, Banks CA, Jin J, Cai Y, Washburn MP, Conaway JW, Conaway RC (Jun 2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Molecular Cell 14 (5): 685–91. doi:10.1016/j.molcel.2004.05.006. PMID 15175163.
10. Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S (Jul 2002). "SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex". Nucleic Acids Research 30 (14): 3245–52. doi:10.1093/nar/gkf443. PMC 135763. PMID 12136106.

Further reading

• Fondell JD, Ge H, Roeder RG (Aug 1996). "Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex". Proceedings of the National Academy of Sciences of the United States of America 93 (16): 8329–33. doi:10.1073/pnas.93.16.8329. PMC 38670. PMID 8710870.
• Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N (Feb 1996). "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research 3 (1): 17–24. doi:10.1093/dnares/3.1.17. PMID 8724849.
• Yamagata K, Takeda J, Menzel S, Chen X, Eng S, Lim LR, Concannon P, Hanis CL, Spielman RS, Cox NJ, Bell GI (Jun 1996). "Searching for NIDDM susceptibility genes: studies of genes with triplet repeats expressed in skeletal muscle". Diabetologia 39 (6): 725–30. doi:10.1007/BF00418545. PMID 8781769.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (Jul 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Human Genetics 100 (1): 114–22. doi:10.1007/s004390050476. PMID 9225980.
• Philibert RA, King BH, Winfield S, Cook EH, Lee YH, Stubblefield B, Damschroder-Williams P, Dea C, Palotie A, Tengstrom C, Martin BM, Ginns EI (Jul 1998). "Association of an X-chromosome dodecamer insertional variant allele with mental retardation". Molecular Psychiatry 3 (4): 303–9. doi:10.1038/sj.mp.4000442. PMID 9702738.
• Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (Mar 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Molecular Cell 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. PMID 10198638.
• Rachez C, Lemon BD, Suldan Z, Bromleigh V, Gamble M, Näär AM, Erdjument-Bromage H, Tempst P, Freedman LP (Apr 1999). "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature 398 (6730): 824–8. doi:10.1038/19783. PMID 10235266.
• Näär AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R (Apr 1999). "Composite co-activator ARC mediates chromatin-directed transcriptional activation". Nature 398 (6730): 828–32. doi:10.1038/19789. PMID 10235267.
• Philibert RA, Winfield SL, Damschroder-Williams P, Tengstrom C, Martin BM, Ginns EI (1999). "The genomic structure and developmental expression patterns of the human OPA-containing gene (HOPA)". Human Genetics 105 (1-2): 174–8. doi:10.1007/s004390051084. PMID 10480376.
• Joensuu T, Hämäläinen R, Yuan B, Johnson C, Tegelberg S, Gasparini P, Zelante L, Pirvola U, Pakarinen L, Lehesjoki AE, de la Chapelle A, Sankila EM (Oct 2001). "Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3". American Journal of Human Genetics 69 (4): 673–84. doi:10.1086/323610. PMC 1226054. PMID 11524702.
• Beyer KS, Klauck SM, Benner A, Poustka F, Poustka A (Jan 2002). "Association studies of the HOPA dodecamer duplication variant in different subtypes of autism". American Journal of Medical Genetics 114 (1): 110–5. doi:10.1002/ajmg.1613. PMID 11840515.
• Tchernev VT, Mansfield TA, Giot L, Kumar AM, Nandabalan K, Li Y, Mishra VS, Detter JC, Rothberg JM, Wallace MR, Southwick FS, Kingsmore SF (Jan 2002). "The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins". Molecular Medicine 8 (1): 56–64. PMC 2039936. PMID 11984006.
• Ge K, Guermah M, Yuan CX, Ito M, Wallberg AE, Spiegelman BM, Roeder RG (May 2002). "Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis". Nature 417 (6888): 563–7. doi:10.1038/417563a. PMID 12037571.
• Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S (Jul 2002). "SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex". Nucleic Acids Research 30 (14): 3245–52. doi:10.1093/nar/gkf443. PMC 135763. PMID 12136106.
• Wang Q, Sharma D, Ren Y, Fondell JD (Nov 2002). "A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression". The Journal of Biological Chemistry 277 (45): 42852–8. doi:10.1074/jbc.M206061200. PMID 12218053.
• Sato S, Tomomori-Sato C, Banks CA, Sorokina I, Parmely TJ, Kong SE, Jin J, Cai Y, Lane WS, Brower CS, Conaway RC, Conaway JW (Apr 2003). "Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3". The Journal of Biological Chemistry 278 (17): 15123–7. doi:10.1074/jbc.C300054200. PMID 12584197.
• Gwack Y, Baek HJ, Nakamura H, Lee SH, Meisterernst M, Roeder RG, Jung JU (Mar 2003). "Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation". Molecular and Cellular Biology 23 (6): 2055–67. doi:10.1128/MCB.23.6.2055-2067.2003. PMC 149486. PMID 12612078.
• Kitano T, Schwarz C, Nickel B, Pääbo S (Aug 2003). "Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees". Molecular Biology and Evolution 20 (8): 1281–9. doi:10.1093/molbev/msg134. PMID 12777533.
• Zhou H, Kim S, Ishii S, Boyer TG (Dec 2006). "Mediator modulates Gli3-dependent Sonic hedgehog signaling". Molecular and Cellular Biology 26 (23): 8667–82. doi:10.1128/MCB.00443-06. PMC 1636813. PMID 17000779.
• Zhou H, Spaeth JM, Kim NH, Xu X, Friez MJ, Schwartz CE, Boyer TG (Nov 2012). "MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling". Proceedings of the National Academy of Sciences of the United States of America 109 (48): 19763–8. doi:10.1073/pnas.1121120109. PMC 3511715. PMID 23091001.

External links

• GeneReviews/NCBI/NIH/UW entry on MED12-Related Disorders