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12  structures 1420  species 0  interactions 2056  sequences 22  architectures

Family: Med14 (PF08638)

Summary: Mediator complex subunit MED14

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "MED14". More...

MED14 Edit Wikipedia article

AliasesMED14, CRSP150, CRSP2, CSRP, CXorf4, DRIP150, EXLM1, RGR1, TRAP170, mediator complex subunit 14
External IDsOMIM: 300182 MGI: 1349442 HomoloGene: 22082 GeneCards: MED14
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr X: 40.65 – 40.74 MbChr X: 12.68 – 12.76 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene.[5][6][7]

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation.[7]


MED14 has been shown to interact with PPARGC1A,[8] Estrogen receptor alpha,[9] STAT2,[10] Cyclin-dependent kinase 8,[11][12] Glucocorticoid receptor[13] and Hepatocyte nuclear factor 4 alpha.[14][15]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000180182 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064127 - 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. ^ Ryu S, Zhou S, Ladurner AG, Tjian R (Feb 1999). "The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1". Nature. 397 (6718): 446–50. Bibcode:1999Natur.397..446R. doi:10.1038/17141. PMID 9989412. S2CID 4405569.
  6. ^ Yoshikawa H, Fujiyama A, Nakai K, Inazawa J, Matsubara K (Aug 1998). "Detection and isolation of a novel human gene located on Xp11.2-p11.4 that escapes X-inactivation using a two-dimensional DNA mapping method". Genomics. 49 (2): 237–46. doi:10.1006/geno.1998.5246. PMID 9598311.
  7. ^ a b "Entrez Gene: CRSP2 cofactor required for Sp1 transcriptional activation, subunit 2, 150kDa".
  8. ^ Wallberg, Annika E; Yamamura Soichiro; Malik Sohail; Spiegelman Bruce M; Roeder Robert G (Nov 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell. 12 (5): 1137–49. doi:10.1016/S1097-2765(03)00391-5. ISSN 1097-2765. PMID 14636573.
  9. ^ Kang, Yun Kyoung; Guermah Mohamed; Yuan Chao-Xing; Roeder Robert G (Mar 2002). "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". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2642–7. Bibcode:2002PNAS...99.2642K. doi:10.1073/pnas.261715899. ISSN 0027-8424. PMC 122401. PMID 11867769.
  10. ^ Lau, Joe F; Nusinzon Inna; Burakov Darya; Freedman Leonard P; Horvath Curt M (Jan 2003). "Role of metazoan mediator proteins in interferon-responsive transcription". Mol. Cell. Biol. 23 (2): 620–8. doi:10.1128/MCB.23.2.620-628.2003. ISSN 0270-7306. PMC 151539. PMID 12509459.
  11. ^ Wang, G; Cantin G T; Stevens J L; Berk A J (Jul 2001). "Characterization of mediator complexes from HeLa cell nuclear extract". Mol. Cell. Biol. 21 (14): 4604–13. doi:10.1128/MCB.21.14.4604-4613.2001. ISSN 0270-7306. PMC 87123. PMID 11416138.
  12. ^ Ito, M; Yuan C X; Malik S; Gu W; Fondell J D; Yamamura S; Fu Z Y; Zhang X; Qin J; Roeder R G (Mar 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Mol. Cell. 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. ISSN 1097-2765. PMID 10198638.
  13. ^ Hittelman, A B; Burakov D; Iñiguez-Lluhí J A; Freedman L P; Garabedian M J (Oct 1999). "Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins". EMBO J. 18 (19): 5380–8. doi:10.1093/emboj/18.19.5380. ISSN 0261-4189. PMC 1171607. PMID 10508170.
  14. ^ Maeda, Yutaka; Rachez Christophe; Hawel Leo; Byus Craig V; Freedman Leonard P; Sladek Frances M (Jul 2002). "Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205". Mol. Endocrinol. 16 (7): 1502–10. doi:10.1210/mend.16.7.0883. ISSN 0888-8809. PMID 12089346.
  15. ^ Malik, Sohail; Wallberg Annika E; Kang Yun Kyoung; Roeder Robert G (Aug 2002). "TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4". Mol. Cell. Biol. 22 (15): 5626–37. doi:10.1128/MCB.22.15.5626-5637.2002. ISSN 0270-7306. PMC 133960. PMID 12101254.

Further reading

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This is the Wikipedia entry entitled "Mediator (coactivator)". More...

Mediator (coactivator) Edit Wikipedia article

Diagram of mediator with cyclin-dependent kinase module

Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered in 1990 in the lab of Roger D. Kornberg, recipient of the 2006 Nobel Prize in Chemistry.[1][2] Mediator[a] complexes interact with transcription factors and RNA polymerase II. The main function of mediator complexes is to transmit signals from the transcription factors to the polymerase.[3]

Mediator complexes are variable at the evolutionary, compositional and conformational levels.[3] The first image shows only one "snapshot" of what a particular mediator complex might be composed of,[b] but it certainly does not accurately depict the conformation of the complex in vivo. During evolution, mediator has become more complex. The yeast Saccharomyces cerevisiae (a simple eukaryote) is thought to have up to 21 subunits in the core mediator (exclusive of the CDK module), while mammals have up to 26.

Individual subunits can be absent or replaced by other subunits under different conditions. Also, there are many intrinsically disordered regions in mediator proteins, which may contribute to the conformational flexibility seen both with and without other bound proteins or protein complexes. A more realistic model of a mediator complex without the CDK module is shown in the second figure.[4]

The mediator complex is required for the successful transcription by RNA polymerase II. Mediator has been shown to make contacts with the polymerase in the transcription preinitiation complex.[3] A recent model showing the association of the polymerase with mediator in the absence of DNA is shown in the figure to the left.[4] In addition to RNA polymerase II, mediator must also associate with transcription factors and DNA. A model of such interactions is shown in the figure to the right.[5] Note that the different morphologies of mediator do not necessarily mean that one of the models is correct; rather those differences may reflect the flexibility of mediator as it interacts with other molecules.[c] For example, after binding the enhancer and core promoter, the mediator complex undergoes a compositional change in which the kinase module dissociates from the complex to allow association with RNA polymerase II and transcriptional activation.[6]

The Mediator complex is located within the cell nucleus. It is required for the successful transcription of nearly all class II gene promoters in yeast.[7] It works in the same manner in mammals. The mediator functions as a coactivator and binds to the C-terminal domain of RNA polymerase II holoenzyme, acting as a bridge between this enzyme and transcription factors.[8]


Mediator complex architecture with focus on the disordered "spline" of Med 14[9]

The yeast mediator complex is approximately as massive as a small subunit of a eukaryotic ribosome. The yeast mediator is composed of 25 subunits, while the mammalian mediator complexes are slightly larger.[3] Mediator can be divided onto 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module.[10]

Mediator subunits have many intrinsically disordered regions called "splines", which may be important to allow the structural changes of mediator that change the function of the complex.[3][d] The figure shows how the splines of the Med 14 subunit connect a large portion of the complex together while still allowing flexibility.[4][e]

Mediator complexes that lack a subunit have been found or produced. These smaller mediators can still function normally in some activity, but lack other capability.[3] This indicates somewhat independent function of some of the subunits while part of the larger complex.

Another example of structural variability is seen in vertebrates, in which 3 paralogues of subunits of the cyclin-dependent kinase module have evolved by 3 independent gene duplication events followed by sequence divergence.[3]

Mediator structural model[9]

There is a report that mediator forms stable associations with a particular type of non-coding RNA, ncRNA-a.[11][f] These stable associations have also been shown to regulate gene expression in vivo, and are prevented by mutations in MED12 that produce the human disease FG syndrome.[11] Thus, the structure of a mediator complex can be augmented by RNA as well as proteinaceous transcription factors.[3]


Structural model of the tail and middle of mediator bound to RNA polymerase II[9]

Mediator was originally discovered because it was important for RNA polymerase II function, but it has many more functions than just interactions at the transcription start site.[3]

RNA polymerase II-Mediator core initiation complex

Mediator is a crucial component for transcription initiation. Mediator interacts with the pre-initiation complex, composed of RNA Polymerase II and general transcription factors TFIIB, TFIID, TFIIE, TFIIF, and TFIIH to stabilize and initiate transcription.[12] Studies of Mediator-RNA Pol II contacts in budding yeast have emphasized the importance of TFIIB-Mediator contacts in the formation of the complex. Interactions of Mediator with TFIID in the initiation complex has been shown.[10]

The Structure of a core Mediator (cMed) that's associated with a core pre-initiation complex was elucidated.[12]

RNA synthesis

The preinitiation complex, which contains mediator, transcription factors, a nucleosome[13][14][g] and RNA polymerase II, is important to position the polymerase for the start of transcription. Before RNA synthesis can occur, the polymerase must dissociate from mediator. This appears to be accomplished by phosphorylation of part of the polymerase by a kinase. Importantly, mediator and transcription factors do not dissociate from the DNA at the time polymerase begins transcription. Rather, the complex remains at the promoter to recruit another RNA polymerase to begin another round of transcription.[3][h]

There is some evidence to suggest that mediator in a yeast is involved in regulating RNA polymerase III (Pol III) transcripts of tRNAs[15] In support of that evidence, an independent report showed specific association of mediator with Pol III in Saccharomyces cerevisiae.[16] Those authors also reported specific associations with RNA polymerase I and proteins involved in transcription elongation and RNA processing, supporting other evidence of mediator's involvement in elongation and processing.[16]

Chromatin organization

Mediator is involved in "looping" of chromatin, which brings distant regions of a chromosome into closer physical proximity.[3] The ncRNA-a mentioned above[11] is involved in such looping.[i] Enhancer RNAs (eRNAs) can function similarly.[3]

In addition to the looping of euchromatin, mediator appears to be involved in formation or maintenance of heterochromatin at centromeres and telomeres.[3]

Signal transduction

TGFβ signaling at the cell membrane results in 2 different intracellular pathways. One of them depends on MED15,[j] while the other is independent of MED15.[17] In both human cells and Caenorhabditis elegans MED15 is involved in lipid homeostasis through the pathway involving SREBPs[18] In the model plant Arabidopsis thaliana the ortholog of MED15 is required for signaling by the plant hormone Salicylic acid,[19] while MED25 is required for the transcriptional activation of jasmonate and shade signalling responses.[20][21][22] Two components of the CDK module (MED12 and MED13) are involved in the Wnt signaling pathway[3] MED23 is involved in RAS/MAPK/ERK pathway[3] This abbreviated review shows the versatility of individual mediator subunits, and leads to the idea that mediator is an end-point of signaling pathways.[3]

Human disease

Involvement of mediator in various human diseases has been reviewed.[23][24][25][26][27][28][29][30][31][32][33] Since inhibiting one interaction of a disease-causing signaling pathway with a subunit of mediator may not inhibit general transcription needed for normal function, mediator subunits are attractive candidates for therapeutic drugs.[3]


Mediator interactome in Saccharomyces cerevisiae[16]

A method employing very gentle cell lysis in yeast followed by co-immunoprecipitation with an antibody to a mediator subunit (Med 17) has confirmed almost all previously reported or predicted interactions and revealed many previously unsuspected specific interactions of various proteins with mediator.[16]


The interaction network of MED1 protein from BioPlex 2.0

A discussion of all mediator subunits is beyond the scope of this article, but details of one of the subunits is illustrative of the types of information that may be gathered for other subunits.

regulation by Micro RNAs

Micro RNAs are involved in regulating the expression of many proteins. Med1 is targeted by miR-1, which is important in gene regulation in cancers.[34] The tumor suppressor miR-137 also regulates MED1.[35]

Mouse embryonic development

Null mutants die at an early gestational age (embryonic day 11.5).[36][37] By investigating hypomorphic mutants (which can survive 2 days longer), it was found that placental defects were primarily lethal and that there were also defects in cardiac and hepatic development, but many other organs were normal[37]

Mouse cells and tissues

A mediator mutation causes hairy teeth in mice

Conditional mutations can be produced in mice which affect only specific cells or tissues at specific times, so that the mouse can develop to adulthood and the adult phenotype can be studied. In one case, MED1 was found to participate in controlling the timing of events of meiosis in male mice.[38] Conditional mutants in keratinocytes show differences in skin wound healing.[39] A conditional mutant in mice was found to change dental epithelium into epidermal epithelium, which caused hair to grow associated with the incisors.[40]

Subunit composition

The Mediator complex is composed at least 31 subunits in all eukaryotes studied: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED28, MED29, MED30, MED31, CCNC, and CDK8. There are three fungal-specific components, referred to as Med2, Med3 and Med5.[41]

The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.

  • The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22.
  • The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4.
  • The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16.
  • The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.

In other species

Below is a cross-species comparison of mediator complex subunits.[41][42]

Subunit No. Human gene C. elegans gene D. melanogaster gene S. cerevisiae gene Sch. pombe gene
MED1 MED1 Sop3/mdt-1.1, 1.2 MED1 MED1 med1
Med2 [k] MED2
Med3 [k] PGD1
MED4 MED4 MED4 MED4 med4
Med5 [k] NUT1
MED6 MED6 MDT-6 MED6 MED6 med6
MED7 MED7 MDT-7/let-49 MED7 MED7 med7
MED8 MED8 MDT-8 MED8 MED8 med8
MED10 MED10 MDT-10 NUT2 med10
MED11 MED11 MDT-11 MED11 MED11 med11
MED12 MED12 MDT-12/dpy-22 MED12 SRB8 srb8
MED13 MED13 MDT-13/let-19 MED13 SSN2 srb9
MED14 MED14 MDT-14/rgr-1 MED14 RGR1 med14
MED15 MED15 mdt-15 MED15 GAL11 YN91_SCHPO [l]
MED17 MED17 MDT-17 MED17 SRB4 med17
MED18 MED18 MDT-18 MED18 SRB5 med18
MED19 MED19 MDT-19 MED19 ROX3[41] med19
MED20 MED20 MDT-20 MED20 SRB2 med20
MED21 MED21 MDT-21 MED21 SRB7 med21
MED22 MED22 MDT-22 MED22 SRB6 med22
MED23 MED23 MDT-23/sur-2 MED23
MED27 MED27 MED27 med27
MED29 MED29 MDT-19 MED29
MED31 MED31 MDT-31 MED31 SOH1 med31
CCNC CCNC cic-1 CycC SSN8 pch1
CDK8 CDK8 cdk-8 Cdk8 SSN3 srb10


  1. ^ Mediator is also referred to in scientific literature as the vitamin D receptor interacting protein (DRIP) coactivator complex and the thyroid hormone receptor-associated proteins (TRAP).
  2. ^ However note that more recently it has been found that the CDK module and MED26 cannot be present concurrently in a complex.[3]
  3. ^ The sharp bend in the DNA associated with the transcription bubble is shown in the graphical abstract and first figure of this research paper
  4. ^ Some of those changes are diagrammed in figure 1 of the review article, which can be viewed in slightly larger form by clicking it at that site.
  5. ^ Note that Med 17 (shown in blue) also has that sort of spline
  6. ^ These non-coding activating RNAs have not been mentioned yet in the ncRNA article as of 16 February 2017
  7. ^ This is the +1 nucleosome, which "covers" the transcription start site during the preinitiation phase.
  8. ^ This is diagrammed in figure 2 of the review article, which can be viewed in slightly larger form by clicking it at that site.
  9. ^ This is diagrammed in figure 3 of the review article, which can be viewed in slightly larger form by clicking it at that site. That figure also shows Pol II disengaged from mediator, etc, which remains on the DNA
  10. ^ Also known as ARC105 in Xenopus laevis, the model species in which the work was done.
  11. ^ a b c Fungal-specific
  12. ^ Protein-name in Sch. pombe


  1. ^ Kelleher RJ, Flanagan PM, Kornberg RD (June 1990). "A novel mediator between activator proteins and the RNA polymerase II transcription apparatus". Cell. 61 (7): 1209–15. doi:10.1016/0092-8674(90)90685-8. PMID 2163759. S2CID 4971987.
  2. ^ Flanagan PM, Kelleher RJ, Sayre MH, Tschochner H, Kornberg RD (April 1991). "A mediator required for activation of RNA polymerase II transcription in vitro". Nature. 350 (6317): 436–8. Bibcode:1991Natur.350..436F. doi:10.1038/350436a0. PMID 2011193. S2CID 4323957.
  3. ^ a b c d e f g h i j k l m n o p q r Allen BL, Taatjes DJ (March 2015). "The Mediator complex: a central integrator of transcription". Nature Reviews Molecular Cell Biology. 16 (3): 155–66. doi:10.1038/nrm3951. PMC 4963239. PMID 25693131.
  4. ^ a b c Robinson PJ, Trnka MJ, Pellarin R, Greenberg CH, Bushnell DA, Davis R, Burlingame AL, Sali A, Kornberg RD (September 2015). "Molecular architecture of the yeast Mediator complex". eLife. 4: e08719. doi:10.7554/eLife.08719. PMC 4631838. PMID 26402457.
  5. ^ Bernecky C, Grob P, Ebmeier CC, Nogales E, Taatjes DJ (March 2011). "Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly". PLOS Biology. 9 (3): e1000603. doi:10.1371/journal.pbio.1000603. PMC 3066130. PMID 21468301.
  6. ^ Petrenko, N; Jin, Y; Wong, KH; Struhl, K (3 November 2016). "Mediator Undergoes a Compositional Change during Transcriptional Activation". Molecular Cell. 64 (3): 443–454. doi:10.1016/j.molcel.2016.09.015. PMC 5096951. PMID 27773675.
  7. ^ Biddick R, Young ET (September 2005). "Yeast mediator and its role in transcriptional regulation". Comptes Rendus Biologies. 328 (9): 773–82. doi:10.1016/j.crvi.2005.03.004. PMID 16168358.
  8. ^ Björklund S, Gustafsson CM (May 2005). "The yeast Mediator complex and its regulation". Trends in Biochemical Sciences. 30 (5): 240–4. doi:10.1016/j.tibs.2005.03.008. PMID 15896741.
  9. ^ a b c Robinson, Philip J.; Trnka, Michael J.; Pellarin, Riccardo; Greenberg, Charles H.; Bushnell, David A.; Davis, Ralph; Burlingame, Alma L.; Sali, Andrej; Kornberg, Roger D. (24 September 2015). "Molecular architecture of the yeast Mediator complex". eLife. 4: e08719. doi:10.7554/eLife.08719. ISSN 2050-084X. PMC 4631838. PMID 26402457.
  10. ^ a b Soutourina, Julie (6 December 2017). "Transcription regulation by the Mediator complex". Nature Reviews Molecular Cell Biology. 19 (4): 262–274. doi:10.1038/nrm.2017.115. ISSN 1471-0072. PMID 29209056. S2CID 3972303.
  11. ^ a b c Lai, F; et al. (2013). "Activating RNAs associate with mediator to enhance chromatin architecture and transcription" (PDF). Nature. 494 (7438): 497–501. Bibcode:2013Natur.494..497L. doi:10.1038/nature11884. hdl:11858/00-001M-0000-0019-1122-4. PMC 4109059. PMID 23417068.
  12. ^ a b Plaschka, C.; Larivière, L.; Wenzeck, L.; Seizl, M.; Hemann, M.; Tegunov, D.; Petrotchenko, E. V.; Borchers, C. H.; Baumeister, W. (February 2015). "Architecture of the RNA polymerase II–Mediator core initiation complex". Nature. 518 (7539): 376–380. Bibcode:2015Natur.518..376P. doi:10.1038/nature14229. ISSN 0028-0836. PMID 25652824. S2CID 4450934.
  13. ^ Nagai S, Davis RE, Mattei PJ, Eagen KP, Kornberg RD (2017). "Chromatin potentiates transcription". Proc Natl Acad Sci U S A. 114 (7): 1536–154. doi:10.1073/pnas.1620312114. PMC 5320956. PMID 28137832.
  14. ^ Kornberg, RD. "The Molecular Basis of Eukaryotic Transcription". YouTube. Israel Institute for Advanced Studies. Archived from the original on 15 December 2021. Retrieved 17 February 2017.
  15. ^ Carlsten, JO; Zhu X, López MD, Samuelsson T, Gustafsson CM (February 2016). "Loss of the Mediator subunit Med20 affects transcription of tRNA and other non-coding RNA genes in fission yeast". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859 (2): 339–347. doi:10.1016/j.bbagrm.2015.11.007. PMID 26608234.CS1 maint: multiple names: authors list (link)
  16. ^ a b c d Uthe H, Vanselow JT, Schlosser A (2017). "Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae". Sci Rep. 7: 43584. Bibcode:2017NatSR...743584U. doi:10.1038/srep43584. PMC 5327418. PMID 28240253.
  17. ^ Kato Y, Habas R, Katsuyama Y, Näär AM, He X (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.
  18. ^ 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 (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.
  19. ^ Canet JV, Dobón A, Tornero P (2012). "Non-recognition-of-BTH4, an Arabidopsis mediator subunit homolog, is necessary for development and response to salicylic acid". Plant Cell. 24 (10): 4220–35. doi:10.1105/tpc.112.103028. PMC 3517246. PMID 23064321.
  20. ^ Chen, Rong; Jiang, Hongling; Li, Lin; Zhai, Qingzhe; Qi, Linlin; Zhou, Wenkun; Liu, Xiaoqiang; Li, Hongmei; Zheng, Wenguang; Sun, Jiaqiang; Li, Chuanyou (July 2012). "The Arabidopsis Mediator Subunit MED25 Differentially Regulates Jasmonate and Abscisic Acid Signaling through Interacting with the MYC2 and ABI5 Transcription Factors". The Plant Cell. 24 (7): 2898–2916. doi:10.1105/tpc.112.098277. PMC 3426122. PMID 22822206.
  21. ^ Sun, Wenjing; Han, Hongyu; Deng, Lei; Sun, Chuanlong; Xu, Yiran; Lin, Lihao; Ren, Panrong; Zhao, Jiuhai; Zhai, Qingzhe; Li, Chuanyou (November 2020). "Mediator Subunit MED25 Physically Interacts with PHYTOCHROME INTERACTING FACTOR4 to Regulate Shade-Induced Hypocotyl Elongation in Tomato". Plant Physiology. 184 (3): 1549–1562. doi:10.1104/pp.20.00587. PMC 7608172. PMID 32938743.
  22. ^ Hartman, Sjon (November 2020). "MED25 Mediates Shade-Induced Hypocotyl Elongation in Tomato". Plant Physiology. 184 (3): 1217–1218. doi:10.1104/pp.20.01324. PMC 7608160. PMID 33139486.
  23. ^ Clark AD, Oldenbroek M, Boyer TG (2015). "Mediator kinase module and human tumorigenesis". Crit Rev Biochem Mol Biol. 50 (5): 393–426. doi:10.3109/10409238.2015.1064854 (inactive 31 October 2021). PMC 4928375. PMID 26182352.CS1 maint: DOI inactive as of October 2021 (link)
  24. ^ Croce S, Chibon F (2015). "MED12 and uterine smooth muscle oncogenesis: State of the art and perspectives". Eur J Cancer. 51 (12): 1603–10. doi:10.1016/j.ejca.2015.04.023. PMID 26037152.
  25. ^ Schiano C, Casamassimi A, Rienzo M, de Nigris F, Sommese L, Napoli C (2014). "Involvement of Mediator complex in malignancy". Biochim Biophys Acta. 1845 (1): 66–83. doi:10.1016/j.bbcan.2013.12.001. PMID 24342527.
  26. ^ Schiano C, Casamassimi A, Vietri MT, Rienzo M, Napoli C (2014). "The roles of mediator complex in cardiovascular diseases". Biochim Biophys Acta. 1839 (6): 444–51. doi:10.1016/j.bbagrm.2014.04.012. PMID 24751643.
  27. ^ Utami KH, Winata CL, Hillmer AM, Aksoy I, Long HT, Liany H, Chew EG, Mathavan S, Tay SK, Korzh V, Sarda P, Davila S, Cacheux V (2014). "Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency". Hum Mutat. 35 (11): 1311–20. doi:10.1002/humu.22636. PMID 25137640. S2CID 42336634.
  28. ^ Grueter CE (2013). "Mediator complex dependent regulation of cardiac development and disease". Genomics Proteomics Bioinformatics. 11 (3): 151–7. doi:10.1016/j.gpb.2013.05.002. PMC 4357813. PMID 23727265.
  29. ^ Yang X and Yang F (2013). "Mediating Lipid Biosynthesis: Implications for Cardiovascular Disease". Trends Cardiovasc Med. 23 (7): 269–273. doi:10.1016/j.tcm.2013.03.002. PMC 3744615. PMID 23562092.
  30. ^ Napoli C, Sessa M, Infante T, Casamassimi A (2012). "Unraveling framework of the ancestral Mediator complex in human diseases". Biochimie. 94 (3): 579–87. doi:10.1016/j.biochi.2011.09.016. PMID 21983542.
  31. ^ Xu W, Ji JY (2011). "Dysregulation of CDK8 and Cyclin C in tumorigenesis". J Genet Genomics. 38 (10): 439–52. doi:10.1016/j.jgg.2011.09.002. PMID 22035865.
  32. ^ Spaeth JM, Kim NH, Boyer TG (2011). "Mediator and human disease". Semin Cell Dev Biol. 22 (7): 776–87. doi:10.1016/j.semcdb.2011.07.024. PMC 4100472. PMID 21840410.
  33. ^ Lyons MJ (2008). MED12-Related Disorders (08/11/2016 ed.). University of Washington, Seattle. PMID 20301719.
  34. ^ Jiang C, Chen H, Shao L, Wang Q (2014). "MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31". Oncol Rep. 32 (3): 1249–56. doi:10.3892/or.2014.3274. PMID 24969180.
  35. ^ Nilsson EM, Laursen KB, Whitchurch J, McWilliam A, Ødum N, Persson JL, Heery DM, Gudas LJ, Mongan NP (2015). "MiR137 is an androgen regulated repressor of an extended network of transcriptional coregulators". Oncotarget. 6 (34): 35710–25. doi:10.18632/oncotarget.5958. PMC 4742136. PMID 26461474.
  36. ^ Ito M, Yuan CX, Okano HJ, Darnell RB, Roeder RG (2000). "Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action". Mol Cell. 5 (4): 683–93. doi:10.1016/S1097-2765(00)80247-6. PMID 10882104.
  37. ^ a b Landles C, Chalk S, Steel JH, Rosewell I, Spencer-Dene B, Lalani el-N, Parker MG (2003). "The thyroid hormone receptor-associated protein TRAP220 is required at distinct embryonic stages in placental, cardiac, and hepatic development". Mol Endocrinol. 17 (12): 2418–35. doi:10.1210/me.2003-0097. PMID 14500757.CS1 maint: multiple names: authors list (link)
  38. ^ Huszar JM, Jia Y, Reddy JK, Payne CJ (2015). "Med1 regulates meiotic progression during spermatogenesis in mice". Reproduction. 149 (6): 597–604. doi:10.1530/REP-14-0483. PMC 4417004. PMID 25778538.
  39. ^ Noguchi F, Nakajima T, Inui S, Reddy JK, Itami S (2014). "Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice". PLOS ONE. 9 (8): e102271. Bibcode:2014PLoSO...9j2271N. doi:10.1371/journal.pone.0102271. PMC 4133190. PMID 25122137.
  40. ^ Yoshizaki K, Hu L, Nguyen T, Sakai K, He B, Fong C, Yamada Y, Bikle DD, Oda Y (2014). "Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair". PLOS ONE. 9 (6): e99991. Bibcode:2014PLoSO...999991Y. doi:10.1371/journal.pone.0099991. PMC 4065011. PMID 24949995.
  41. ^ a b c Bourbon HM, Aguilera A, Ansari AZ, Asturias FJ, Berk AJ, Bjorklund S, et al. (2004). "A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II". Molecular Cell. 14 (5): 553–7. doi:10.1016/j.molcel.2004.05.011. PMID 15175151.
  42. ^ Gene names derived from "UniProtKB". Retrieved 12 October 2012.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Mediator complex subunit MED14 Provide feedback

Saccharomyces cerevisiae RGR1 mediator complex subunit affects chromatin structure, transcriptional regulation of diverse genes and sporulation, required for glucose repression, HO repression, RME1 repression and sporulation [2]. This subunit is also found in higher eukaryotes and Med14 is the agreed unified nomenclature for this subunit. Med14 is found in the tail region of Mediator [5].

Literature references

  1. Gu W, Malik S, Ito M, Yuan CX, Fondell JD, Zhang X, Martinez E, Qin J, Roeder RG; , Mol Cell. 1999;3:97-108.: A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. PUBMED:10024883 EPMC:10024883

  2. Covitz PA, Song W, Mitchell AP; , Genetics. 1994;138:577-586.: Requirement for RGR1 and SIN4 in RME1-dependent repression in Saccharomyces cerevisiae. PUBMED:7851756 EPMC:7851756

  3. Jiang YW, Dohrmann PR, Stillman DJ; , Genetics. 1995;140:47-54.: Genetic and physical interactions between yeast RGR1 and SIN4 in chromatin organization and transcriptional regulation. PUBMED:7635307 EPMC:7635307

  4. Spahr H, Samuelsen CO, Baraznenok V, Ernest I, Huylebroeck D, Remacle JE, Samuelsson T, Kieselbach T, Holmberg S, Gustafsson CM; , Proc Natl Acad Sci U S A 2001;98:11985-11990.: Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells. PUBMED:11572939 EPMC:11572939

  5. Lariviere L, Seizl M, van Wageningen S, Rother S, van de Pasch L, Feldmann H, Strasser K, Hahn S, Holstege FC, Cramer P; , Genes Dev. 2008;22:872-877.: Structure-system correlation identifies a gene regulatory Mediator submodule. PUBMED:18381891 EPMC:18381891

This tab holds annotation information from the InterPro database.

InterPro entry IPR013947

Saccharomyces cerevisiae (Baker's yeast) RGR1 mediator complex subunit affects chromatin structure, transcriptional regulation of diverse genes, and sporulation. It is required for glucose repression, HO repression, RME1 repression and sporulation [ PUBMED:7851756 , PUBMED:7635307 ]. This subunit is also found in higher eukaryotes and MED14 is the agreed unified nomenclature for this subunit [ PUBMED:15175151 ].

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.

The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.

  • The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22.
  • The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4.
  • The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16.
  • The CDK8 module contains: MED12, MED13, CCNC and CDK8.

Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_13303 (release 19.0)
Previous IDs: MED14;
Type: Family
Sequence Ontology: SO:0100021
Author: Mistry J , Wood V
Number in seed: 129
Number in full: 2056
Average length of the domain: 184.70 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 14.92 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.6 25.6
Trusted cut-off 25.7 25.8
Noise cut-off 24.0 25.4
Model length: 193
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Med14 domain has been found. There are 12 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A1D6ENJ2 View 3D Structure Click here
A0A2R8QJ08 View 3D Structure Click here
A1C5W6 View 3D Structure Click here
A1DG38 View 3D Structure Click here
A2ABV5 View 3D Structure Click here
A2QFK0 View 3D Structure Click here
A3LZ54 View 3D Structure Click here
A4R0J9 View 3D Structure Click here
D4A020 View 3D Structure Click here
I1JRN1 View 3D Structure Click here
I1NC98 View 3D Structure Click here
O60244 View 3D Structure Click here
P0CB66 View 3D Structure Click here
P19263 View 3D Structure Click here
Q03570 View 3D Structure Click here
Q0CL23 View 3D Structure Click here
Q16U49 View 3D Structure Click here
Q1DZL3 View 3D Structure Click here
Q29FF7 View 3D Structure Click here
Q2HDU8 View 3D Structure Click here
Q2UMJ1 View 3D Structure Click here
Q4P0P3 View 3D Structure Click here
Q4WH96 View 3D Structure Click here
Q5AG31 View 3D Structure Click here
Q5AW92 View 3D Structure Click here
Q61IR6 View 3D Structure Click here
Q6BPK1 View 3D Structure Click here
Q6C9Z2 View 3D Structure Click here
Q6CRY2 View 3D Structure Click here
Q6ENK5 View 3D Structure Click here
Q6FKA5 View 3D Structure Click here
Q6YTR0 View 3D Structure Click here
Q75CZ2 View 3D Structure Click here
Q7Q6S8 View 3D Structure Click here
Q7S154 View 3D Structure Click here
Q9P7Y4 View 3D Structure Click here
Q9SR02 View 3D Structure Click here
Q9W0P8 View 3D Structure Click here