MED12

MED12
Identifiers
Aliases	MED12 , ARC240, CAGH45, FGS1, HOPA, MED12S, OHDOX, OKS, OPA1, TNRC11, TRAP230, mediator complex subunit 12, Kto, HDKR
External IDs	OMIM: 300188; MGI: 1926212; HomoloGene: 68441; GeneCards: MED12; OMA:MED12 - orthologs
Gene location (Human) Chr. X chromosome (human) [1] Band Xq13.1 Start 71,118,543 bp [1] End 71,144,103 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X|X D Start 100,317,636 bp [2] End 100,341,071 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left ovary right ovary left adrenal gland left adrenal cortex body of uterus right uterine tube spleen canal of the cervix right lobe of thyroid gland Top expressed in bone marrow tail of embryo islet of Langerhans spleen genital tubercle neural layer of retina thymus adrenal gland cerebellar cortex granulocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function RNA polymerase II cis-regulatory region sequence-specific DNA binding transcription coactivator activity beta-catenin binding protein domain specific binding ubiquitin protein ligase activity transcription coregulator activity transcription factor binding chromatin binding thyroid hormone receptor binding protein C-terminus binding protein binding nuclear receptor coactivator activity vitamin D receptor binding signaling receptor activity Cellular component membrane ubiquitin ligase complex mediator complex nucleus nucleoplasm Biological process somitogenesis androgen receptor signaling pathway endoderm development regulation of transcription, DNA-templated embryonic organ development embryonic neurocranium morphogenesis axis elongation involved in somitogenesis regulation of transcription by RNA polymerase II Schwann cell development negative regulation of Wnt signaling pathway intracellular steroid hormone receptor signaling pathway transcription, DNA-templated stem cell population maintenance positive regulation of transcription, DNA-templated Wnt signaling pathway, planar cell polarity pathway heart development neural tube closure embryonic brain development protein ubiquitination neural tube development spinal cord development post-anal tail morphogenesis canonical Wnt signaling pathway oligodendrocyte development transcription initiation from RNA polymerase II promoter positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
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: 100.32 – 100.34 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome. ^[5]

Clinical significance

Mutations in MED12 are responsible for at least two different forms of X-linked dominant Intellectual disability, Lujan-Fryns syndrome and FG syndrome, as well as instances of prostate cancer. ^[6]

Mutations in MED12 are associated with uterine leiomyomas ^[7] and breast fibroepithelial tumors (e.g. fibroadenoma and phyllodes tumors). ^[8]

Interactions

MED12 has been shown to interact with:

• Calcitriol receptor, ^[9]
• Cyclin-dependent kinase 8 ^{[9] [10]}
• Estrogen receptor alpha, ^[10]
• Gli3, G9a, PPARGC1A, ^[11]
• MED26, ^[12]
• SOX9, ^[13] and
• Thyroid hormone receptor alpha. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000184634 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000079487 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: MED12 mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae)".
6. 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" (PDF). Nature Genetics. 44 (6): 685–9. doi:10.1038/ng.2279. PMC   3673022 . PMID   22610119.
7. 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. S2CID   13931280.
8. 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. PMC   4996373 . PMID   25855048.
9. 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.
10. 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. Bibcode:2002PNAS...99.2642K. doi: 10.1073/pnas.261715899 . PMC   122401 . PMID   11867769.
11. 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.
12. 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.
13. 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. Bibcode:1996PNAS...93.8329F. 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. S2CID   41411039.
• 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. S2CID   25999127.
• 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. Bibcode:1999Natur.398..824R. doi:10.1038/19783. PMID   10235266. S2CID   204992765.
• 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. Bibcode:1999Natur.398..828N. doi:10.1038/19789. PMID   10235267. S2CID   23646963.
• 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/s004399900084. 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. doi:10.1007/BF03402003. 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. Bibcode:2002Natur.417..563G. doi:10.1038/417563a. PMID   12037571. S2CID   4432077.
• 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