MED15

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; OMA:MED15 - orthologs
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 17,469,072 bp [2] End 17,550,755 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve granulocyte left adrenal gland right adrenal gland left adrenal cortex upper lobe of left lung popliteal artery tibial arteries right adrenal cortex body of uterus Top expressed in zygote secondary oocyte genital tubercle tail of embryo superior frontal gyrus neural layer of retina primary visual cortex dentate gyrus of hippocampal formation granule cell granulocyte lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transcription coregulator activity protein binding Cellular component cytoplasm mediator complex membrane nucleus nucleoplasm Biological process regulation of transcription by RNA polymerase II 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: 17.47 – 17.55 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

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. S2CID   25999127.
• 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.
• 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. Bibcode:2002Natur.418..641K. doi:10.1038/nature00969. PMID   12167862. S2CID   4330754.
• 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. S2CID   28657663.
• 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. Bibcode:2004PNAS..101.2339Y. 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. S2CID   45479038.
• 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. S2CID   11628354.
• 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. Bibcode:2006Natur.442..700Y. doi:10.1038/nature04942. PMID   16799563. S2CID   4396081.
• 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. S2CID   33550003.