MED12

MED12（Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae)）是在X染色體發現的人類基因。^[6]

MED12
識別號
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
相關疾病
FG syndrome、​blepharophimosis-intellectual disability syndrome, MKB type^[1]
基因位置（人类） 染色体 X染色體^[2] 基因座 Xq13.1 起始 71,118,543 bp^[2] 终止 71,144,103 bp^[2]
基因位置（小鼠） 染色体 小鼠X染色体^[3] 基因座 X|X D 起始 100,317,636 bp^[3] 终止 100,341,071 bp^[3]
RNA表达模式
查阅更多表达数据
基因本體 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 細胞組分 • 膜 • ubiquitin ligase complex • 仲介體 • 细胞核 • 核质 生物學過程 • 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
物種	人類	小鼠
Entrez	9968	59024
Ensembl	ENSG00000184634	ENSMUSG00000079487
UniProt	Q93074	A2AGH6
mRNA​序列	NM_005120	NM_021521
蛋白序列	NP_005111	NP_067496
基因位置​（UCSC）	Chr X: 71.12 – 71.14 Mb	Chr X: 100.32 – 100.34 Mb
PubMed​查找	^[4]	^[5]
維基數據
檢視/編輯人類 檢視/編輯小鼠

臨床意義

已隱藏部分未翻譯内容，歡迎參與翻譯。

MED12基因上的突变与Lujan-Fryns綜合症、FG综合征等X連鎖顯性遺傳智能障礙，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可與下列蛋白發生相互作用：

• 维生素D受体^[10][11]
• 周期蛋白依赖性激酶8^[10][12]
• 雌激素受体α^[12]
• Gli3、G9a、PPARGC1A^[13]
• MED26^[14]
• SOX9^[15]
• 甲状腺激素受体α^[10]

參考

1. 與MED12相關的疾病；在維基數據上查看/編輯參考. 
2. GRCh38: Ensembl release 89: ENSG00000184634 - Ensembl, May 2017
3. 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. 
6. Entrez Gene: MED12 mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae). （原始内容于2010-03-07）. 
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. 
10. 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  . 
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  . 
12. 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  . 
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  . 
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  . 
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. 

延伸閱讀

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• 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. 
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• 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. 
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• 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. 
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• 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  . 

外部鏈接

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