MED15

Mediator complex subunit 15

PDB rendering based on 2gut.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2GUT

Identifiers

Symbols

MED15 ; ARC105; CAG7A; CTG7A; PCQAP; TIG-1; TIG1; TNRC7

External IDs

OMIM: 607372 MGI: 2137379 HomoloGene: 32283 GeneCards: MED15 Gene

Gene ontology
Molecular function	• RNA polymerase II transcription cofactor activity • protein binding
Cellular component	• nucleus • nucleoplasm • cytoplasm • membrane • mediator complex
Biological process	• regulation of transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • gene expression • stem cell maintenance
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 22:
20.5 – 20.59 Mb

Chr 16:
17.65 – 17.72 Mb

PubMed search

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.^[1]

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.^[2]

Most of these transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with KIX domain of the MED15.^[3]

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.^[1]

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.^[1]

References

1 2 3 "Entrez Gene: PCQAP PC2 (positive cofactor 2, multiprotein complex) glutamine/Q-rich-associated protein".
↑ 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. PMID 19056732.
↑ 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: Prepublication research and preliminary findings. 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. PMID 19056732. ; Piskacek M (November 2009). "9aaTAD Prediction result (2006)". Nature Precedings: Prepublication research and preliminary findings. 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: Prepublication research and preliminary findings. 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: Prepublication research and preliminary findings. doi:10.1038/npre.2009.3939.1.

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, Neuropsychiatric Genetics 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. Journal International Du 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.

PDB gallery

2gut: Solution structure of the trans-activation domain of the human co-activator ARC105

This article is issued from Wikipedia - version of the Tuesday, January 26, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

MED15

Function

Gene

References

Further reading