MED15

Mediator of RNA polymerase II transcription subunit 15, also known as Gal11,Spt13 in yeast and PCQAP, ARC105, or TIG-1 in humans is a protein encoded by the MED15 gene.[5]

MED15
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2GUT
Identifiers
Aliases	MED15, ARC105, CAG7A, CTG7A, PCQAP, TIG-1, TIG1, TNRC7, mediator complex subunit 15
External IDs	OMIM: 607372 MGI: 2137379 GeneCards: MED15
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q11.21 Start 20,495,913 bp[1] End 20,587,632 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 A3|16 10.94 cM Start 17,651,208 bp[2] End 17,732,891 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001104 transcription cofactor activity • GO:0001948 protein binding Cellular component • cytoplasm • mediator complex • membrane • cell nucleus • nucleoplasm Biological process • regulation of transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • regulation of transcription, DNA-templated • transcription, DNA-templated • stem cell population maintenance Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	51586	94112
Ensembl	ENSG00000099917	ENSMUSG00000012114
UniProt	Q96RN5	Q924H2
RefSeq (mRNA)	NM_001003891 NM_001293234 NM_001293235 NM_001293236 NM_001293237 NM_015889	NM_001040683 NM_001285884 NM_001285886 NM_033609 NM_001358404
RefSeq (protein)	NP_001003891 NP_001280163 NP_001280164 NP_001280165 NP_001280166 NP_056973	NP_001035773 NP_001272813 NP_001272815 NP_001345333 NP_291087
Location (UCSC)	Chr 22: 20.5 – 20.59 Mb	Chr 16: 17.65 – 17.73 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

MED15 is a general transcriptional cofactor of the mediator complex involved in RNA polymerase II dependent transcription, originally called Gal11 and Spt13 and found in yeast as an essential factor for Gal4 dependent transactivation by T.Fukasawa and F.Winston labs. Transcription factors Gcn4, Pho4, Msn2, Ino2, members of the Gal4 family - Gal4, Oaf1, Pdr1, and viral VP16 have been reported to interact with yeast MED15.[6]

Most of these transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with KIX domain of the MED15.[7]

Furthermore, human MED15 cooperates in mediator complex (previously known as PC2, ARC, or DRIP) with transcription factors like VP16 and SREBP. Human SREBP regulates sterol responsive gene expression, and this regulatory action is conserved in the genetic model organism C. elegans, a roundworm (homologues MDT-15 and SBP-1). Also in C. elegans, MDT-15 is essential for the response to several stresses (fasting, heavy metal, toxin, and oxidative stress); at least in part the fasting response is conferred by interactions of MDT-15 with nuclear receptors, including NHR-49.[5]

Gene

The MED15 gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge's syndrome. Two transcript variants encoding different isoforms have been found for this gene.[5]

References

1. GRCh38: Ensembl release 89: ENSG00000099917 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000012114 - 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: PCQAP PC2 (positive cofactor 2, multiprotein complex) glutamine/Q-rich-associated protein".
6. Suzuki Y, Nogi Y, Abe A, Fukasawa T (Nov 1988). "GAL11 protein, an auxiliary transcription activator for genes encoding galactose-metabolizing enzymes in Saccharomyces cerevisiae". Molecular and Cellular Biology. 8 (11): 4991–9. doi:10.1128/mcb.8.11.4991. PMC 365593. PMID 3062377.; Fassler JS, Winston F (Dec 1989). "The Saccharomyces cerevisiae SPT13/GAL11 gene has both positive and negative regulatory roles in transcription". Molecular and Cellular Biology. 9 (12): 5602–9. doi:10.1128/mcb.9.12.5602. PMC 363730. PMID 2685570.; Swanson MJ, Qiu H, Sumibcay L, Krueger A, Kim SJ, Natarajan K, Yoon S, Hinnebusch AG (Apr 2003). "A multiplicity of coactivators is required by Gcn4p at individual promoters in vivo". Molecular and Cellular Biology. 23 (8): 2800–20. doi:10.1128/MCB.23.8.2800-2820.2003. PMC 152555. PMID 12665580.; Bryant GO, Ptashne M (May 2003). "Independent recruitment in vivo by Gal4 of two complexes required for transcription". Molecular Cell. 11 (5): 1301–9. doi:10.1016/S1097-2765(03)00144-8. PMID 12769853.; Jedidi I, Zhang F, Qiu H, Stahl SJ, Palmer I, Kaufman JD, Nadaud PS, Mukherjee S, Wingfield PT, Jaroniec CP, Hinnebusch AG (Jan 2010). "Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo". The Journal of Biological Chemistry. 285 (4): 2438–55. doi:10.1074/jbc.M109.071589. PMC 2807301. PMID 19940160.; Thakur JK, Arthanari H, Yang F, Chau KH, Wagner G, Näär AM (Feb 2009). "Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p". The Journal of Biological Chemistry. 284 (7): 4422–8. doi:10.1074/jbc.M808263200. PMC 3837390. PMID 19056732.
7. Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (Jun 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics. 89 (6): 756–68. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953.; Piskacek M (November 2009). "Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300". Nature Precedings. doi:10.1038/npre.2009.3488.2.; Thakur JK, Arthanari H, Yang F, Chau KH, Wagner G, Näär AM (Feb 2009). "Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p". The Journal of Biological Chemistry. 284 (7): 4422–8. doi:10.1074/jbc.M808263200. PMC 3837390. PMID 19056732.; Piskacek M (November 2009). "9aaTAD Prediction result (2006)". Nature Precedings. doi:10.1038/npre.2009.3984.1.; Piskacek M (November 2009). "Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300". Nature Precedings. doi:10.1038/npre.2009.3488.2.; Piskacek M (November 2009). "9aaTADs mimic DNA to interact with a pseudo-DNA Binding Domain KIX of Med15 (Molecular Chameleons)". Nature Precedings. doi:10.1038/npre.2009.3939.1.

Further reading

• Taubert S, Hansen M, Van Gilst MR, Cooper SB, Yamamoto KR (Feb 2008). Mango SE (ed.). "The Mediator subunit MDT-15 confers metabolic adaptation to ingested material". PLoS Genetics. 4 (2): e1000021. doi:10.1371/journal.pgen.1000021. PMC 2265483. PMID 18454197.
• 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.
• 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.
• Taubert S, Van Gilst MR, Hansen M, Yamamoto KR (May 2006). "A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans". Genes & Development. 20 (9): 1137–49. doi:10.1101/gad.1395406. PMC 1472473. PMID 16651656.
• Abraham S, Solomon WB (Sep 2000). "A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), preferentially expressed in placental and bone-marrow tissues". Gene. 255 (2): 389–400. doi:10.1016/S0378-1119(00)00292-4. PMID 11024300.
• Berti L, Mittler G, Przemeck GK, Stelzer G, Günzler B, Amati F, Conti E, Dallapiccola B, Hrabé de Angelis M, Novelli G, Meisterernst M (Jun 2001). "Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit". Genomics. 74 (3): 320–32. doi:10.1006/geno.2001.6566. PMID 11414760.
• Kato Y, Habas R, Katsuyama Y, Näär AM, He X (Aug 2002). "A component of the ARC/Mediator complex required for TGF beta/Nodal signalling". Nature. 418 (6898): 641–6. doi:10.1038/nature00969. PMID 12167862.
• De Luca A, Conti E, Grifone N, Amati F, Spalletta G, Caltagirone C, Bonaviri G, Pasini A, Gennarelli M, Stefano B, Berti L, Mittler G, Meisterernst M, Dallapiccola B, Novelli G (Jan 2003). "Association study between CAG trinucleotide repeats in the PCQAP gene (PC2 glutamine/Q-rich-associated protein) and schizophrenia". American Journal of Medical Genetics Part B. 116B (1): 32–5. doi:10.1002/ajmg.b.10008. PMID 12497610.
• Zhang J, Liu L, Pfeifer GP (Mar 2004). "Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene". Oncogene. 23 (12): 2241–9. doi:10.1038/sj.onc.1207328. PMID 14691453.
• Yang F, DeBeaumont R, Zhou S, Näär AM (Feb 2004). "The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator". Proceedings of the National Academy of Sciences of the United States of America. 101 (8): 2339–44. doi:10.1073/pnas.0308676100. PMC 356952. PMID 14983011.
• 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.
• Sandhu HK, Hollenbeck N, Wassink TH, Philibert RA (Sep 2004). "An association study of PCQAP polymorphisms and schizophrenia". Psychiatric Genetics. 14 (3): 169–72. doi:10.1097/00041444-200409000-00010. PMID 15318033.
• Kwong J, Lo KW, Chow LS, Chan FL, To KF, Huang DP (Jan 2005). "Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma". International Journal of Cancer. 113 (3): 386–92. doi:10.1002/ijc.20593. PMID 15455391.
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
• Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, Macol C, Iyer L, Tjian R, van den Heuvel S, Hart AC, Wagner G, Näär AM (Aug 2006). "An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis". Nature. 442 (7103): 700–4. doi:10.1038/nature04942. PMID 16799563.
• Ishikawa H, Tachikawa H, Miura Y, Takahashi N (Sep 2006). "TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system". FEBS Letters. 580 (20): 4784–92. doi:10.1016/j.febslet.2006.07.066. PMID 16904669.