MED12

MED12
识别号
别名	MED12；, ARC240, CAGH45, FGS1, HOPA, MED12S, OHDOX, OKS, OPA1, TNRC11, TRAP230, mediator complex subunit 12, Kto, HDKR
外部ID	OMIM：300188 MGI：1926212 HomoloGene：68441 GeneCards：MED12
相关疾病
	FG syndrome、blepharophimosis-intellectual disability syndrome, MKB type
基因位置（人类）
染色体	X染色体
终止	71,144,103 bp
基因位置（小鼠）
染色体	小鼠X染色体
终止	100,341,071 bp
RNA表达模式
	; ; ; ;
	查阅更多表达数据
基因本体
分子功能	• RNA polymerase II cis-regulatory region sequence-specific DNA binding; • 转录共激活因子活性; • beta-catenin binding; • protein domain specific binding; • ubiquitin protein ligase activity; • transcription coregulator activity; • 转录因子结合; • chromatin binding; • thyroid hormone receptor binding; • protein C-terminus binding; • 血浆蛋白结合; • nuclear receptor coactivator activity; • vitamin D receptor binding; • signaling receptor activity;
细胞组分	• 膜; • ubiquitin ligase complex; • 中介体; • 细胞核; • 核质;
生物学过程	• 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; • 心脏发育; • 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
直系同源
	9968
	59024
	ENSG00000184634
	ENSMUSG00000079487
	Q93074
	A2AGH6
	NM_005120
	NM_021521
	NP_005111
	NP_067496
	维基数据
查看/编辑人类	查看/编辑小鼠

MED12（Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae)）是在X染色体发现的人类基因。^[6]

临床意义

已隐藏部分未翻译内容，欢迎参与翻译。

MED12基因上的突变与Lujan-Fryns综合症、FG综合症等X连锁显性遗传智能障碍，以及前列腺癌有关^[7]。

Mutations in MED12 are associated with uterine leiomyomas^[8] and breast fibroepithelial tumors (e.g. fibroadenoma and phyllodes tumors).^[9]

相互作用

MED12可与下列蛋白发生相互作用：

参考

^ 與MED12相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000184634 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000079487 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Entrez Gene: MED12 mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae). （原始内容存档于2010-03-07）.
^ 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. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer (PDF). Nature Genetics. Jun 2012, 44 (6): 685–9. PMC 3673022  . PMID 22610119. doi:10.1038/ng.2279.
^ 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. Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas. Human Mutation. Sep 2014, 35 (9): 1136–41. PMID 24980722. S2CID 13931280. doi:10.1002/humu.22612.
^ Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, Reis-Filho JS. MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast. Histopathology. Nov 2015, 67 (5): 719–29. PMC 4996373  . PMID 25855048. doi:10.1111/his.12712.
^ ^10.0 ^10.1 ^10.2 Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Molecular Cell. Mar 1999, 3 (3): 361–70. PMID 10198638. doi:10.1016/S1097-2765(00)80463-3  .
^ 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. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. Jun 2003, 113 (7): 905–17. PMID 12837248. doi:10.1016/S0092-8674(03)00436-7  .
^ ^12.0 ^12.1 Kang YK, Guermah M, Yuan CX, Roeder RG. 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. Mar 2002, 99 (5): 2642–7. Bibcode:2002PNAS...99.2642K. PMC 122401  . PMID 11867769. doi:10.1073/pnas.261715899  .
^ Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG. Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Molecular Cell. Nov 2003, 12 (5): 1137–49. PMID 14636573. doi:10.1016/S1097-2765(03)00391-5  .
^ 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. A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Molecular Cell. Jun 2004, 14 (5): 685–91. PMID 15175163. doi:10.1016/j.molcel.2004.05.006  .
^ Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S. SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex. Nucleic Acids Research. Jul 2002, 30 (14): 3245–52. PMC 135763  . PMID 12136106. doi:10.1093/nar/gkf443.

延伸阅读

Fondell JD, Ge H, Roeder RG. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proceedings of the National Academy of Sciences of the United States of America. Aug 1996, 93 (16): 8329–33. Bibcode:1996PNAS...93.8329F. PMC 38670  . PMID 8710870. doi:10.1073/pnas.93.16.8329  .
Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N. 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. Feb 1996, 3 (1): 17–24. PMID 8724849. doi:10.1093/dnares/3.1.17  .
Yamagata K, Takeda J, Menzel S, Chen X, Eng S, Lim LR, Concannon P, Hanis CL, Spielman RS, Cox NJ, Bell GI. Searching for NIDDM susceptibility genes: studies of genes with triplet repeats expressed in skeletal muscle. Diabetologia. Jun 1996, 39 (6): 725–30. PMID 8781769. S2CID 41411039. doi:10.1007/BF00418545.
Bonaldo MF, Lennon G, Soares MB. Normalization and subtraction: two approaches to facilitate gene discovery. Genome Research. Sep 1996, 6 (9): 791–806. PMID 8889548. doi:10.1101/gr.6.9.791  .
Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA. cDNAs with long CAG trinucleotide repeats from human brain. Human Genetics. Jul 1997, 100 (1): 114–22. PMID 9225980. S2CID 25999127. doi:10.1007/s004390050476.
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. Association of an X-chromosome dodecamer insertional variant allele with mental retardation. Molecular Psychiatry. Jul 1998, 3 (4): 303–9. PMID 9702738. doi:10.1038/sj.mp.4000442  .
Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Molecular Cell. Mar 1999, 3 (3): 361–70. PMID 10198638. doi:10.1016/S1097-2765(00)80463-3  .
Rachez C, Lemon BD, Suldan Z, Bromleigh V, Gamble M, Näär AM, Erdjument-Bromage H, Tempst P, Freedman LP. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature. Apr 1999, 398 (6730): 824–8. Bibcode:1999Natur.398..824R. PMID 10235266. S2CID 204992765. doi:10.1038/19783.
Näär AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature. Apr 1999, 398 (6730): 828–32. Bibcode:1999Natur.398..828N. PMID 10235267. S2CID 23646963. doi:10.1038/19789.
Philibert RA, Winfield SL, Damschroder-Williams P, Tengstrom C, Martin BM, Ginns EI. The genomic structure and developmental expression patterns of the human OPA-containing gene (HOPA). Human Genetics. 1999, 105 (1–2): 174–8. PMID 10480376. doi:10.1007/s004390051084.
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. Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. American Journal of Human Genetics. Oct 2001, 69 (4): 673–84. PMC 1226054  . PMID 11524702. doi:10.1086/323610.
Beyer KS, Klauck SM, Benner A, Poustka F, Poustka A. Association studies of the HOPA dodecamer duplication variant in different subtypes of autism. American Journal of Medical Genetics. Jan 2002, 114 (1): 110–5. PMID 11840515. doi:10.1002/ajmg.1613.
Tchernev VT, Mansfield TA, Giot L, Kumar AM, Nandabalan K, Li Y, Mishra VS, Detter JC, Rothberg JM, Wallace MR, Southwick FS, Kingsmore SF. The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins. Molecular Medicine. Jan 2002, 8 (1): 56–64. PMC 2039936  . PMID 11984006. doi:10.1007/BF03402003.
Ge K, Guermah M, Yuan CX, Ito M, Wallberg AE, Spiegelman BM, Roeder RG. Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Nature. May 2002, 417 (6888): 563–7. Bibcode:2002Natur.417..563G. PMID 12037571. S2CID 4432077. doi:10.1038/417563a.
Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S. SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex. Nucleic Acids Research. Jul 2002, 30 (14): 3245–52. PMC 135763  . PMID 12136106. doi:10.1093/nar/gkf443.
Wang Q, Sharma D, Ren Y, Fondell JD. A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression. The Journal of Biological Chemistry. Nov 2002, 277 (45): 42852–8. PMID 12218053. doi:10.1074/jbc.M206061200  .
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. Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3. The Journal of Biological Chemistry. Apr 2003, 278 (17): 15123–7. PMID 12584197. doi:10.1074/jbc.C300054200  .
Gwack Y, Baek HJ, Nakamura H, Lee SH, Meisterernst M, Roeder RG, Jung JU. Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation. Molecular and Cellular Biology. Mar 2003, 23 (6): 2055–67. PMC 149486  . PMID 12612078. doi:10.1128/MCB.23.6.2055-2067.2003.
Kitano T, Schwarz C, Nickel B, Pääbo S. Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees. Molecular Biology and Evolution. Aug 2003, 20 (8): 1281–9. PMID 12777533. doi:10.1093/molbev/msg134  .
Zhou H, Kim S, Ishii S, Boyer TG. Mediator modulates Gli3-dependent Sonic hedgehog signaling. Molecular and Cellular Biology. Dec 2006, 26 (23): 8667–82. PMC 1636813  . PMID 17000779. doi:10.1128/MCB.00443-06.
Zhou H, Spaeth JM, Kim NH, Xu X, Friez MJ, Schwartz CE, Boyer TG. 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. Nov 2012, 109 (48): 19763–8. PMC 3511715  . PMID 23091001. doi:10.1073/pnas.1121120109  .

外部链接

GeneReviews/NCBI/NIH/UW entry on MED12-Related Disorders （页面存档备份，存于互联网档案馆）

[1] 與MED12相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000184634 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000079487 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-6] Entrez Gene: MED12 mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae). （原始内容存档于2010-03-07）.

[pmid22610119-7] 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. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer (PDF). Nature Genetics. Jun 2012, 44 (6): 685–9. PMC 3673022  . PMID 22610119. doi:10.1038/ng.2279.

[8] 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. Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas. Human Mutation. Sep 2014, 35 (9): 1136–41. PMID 24980722. S2CID 13931280. doi:10.1002/humu.22612.

[9] Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, Reis-Filho JS. MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast. Histopathology. Nov 2015, 67 (5): 719–29. PMC 4996373  . PMID 25855048. doi:10.1111/his.12712.

[pmid10198638-10] 10.0 ^10.1 ^10.2 Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Molecular Cell. Mar 1999, 3 (3): 361–70. PMID 10198638. doi:10.1016/S1097-2765(00)80463-3  .

[pmid12837248-11] 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. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. Jun 2003, 113 (7): 905–17. PMID 12837248. doi:10.1016/S0092-8674(03)00436-7  .

[pmid11867769-12] 12.0 ^12.1 Kang YK, Guermah M, Yuan CX, Roeder RG. 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. Mar 2002, 99 (5): 2642–7. Bibcode:2002PNAS...99.2642K. PMC 122401  . PMID 11867769. doi:10.1073/pnas.261715899  .

[pmid14636573-13] Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG. Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Molecular Cell. Nov 2003, 12 (5): 1137–49. PMID 14636573. doi:10.1016/S1097-2765(03)00391-5  .

[pmid15175163-14] 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. A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Molecular Cell. Jun 2004, 14 (5): 685–91. PMID 15175163. doi:10.1016/j.molcel.2004.05.006  .

[pmid12136106-15] Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S. SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex. Nucleic Acids Research. Jul 2002, 30 (14): 3245–52. PMC 135763  . PMID 12136106. doi:10.1093/nar/gkf443.

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